1.Effect of Hemoglobin on Efficacy of CAR-T Therapy in Patients with Multiple Myeloma.
Zhi SHI ; Juan CHEN ; Hai-Lang XU ; Hui-Juan LOU ; Zi-Han CHEN ; Huan-Xin ZHANG ; Jiang CAO ; Zhen-Yu LI ; Zhi-Ling YAN ; Kai-Lin XU
Journal of Experimental Hematology 2023;31(3):783-787
		                        		
		                        			OBJECTIVE:
		                        			To investigate the effect of hemoglobin (Hb) on the efficacy of chimeric antigen receptor T cell therapy (CAR-T) in patients with multiple myeloma (MM).
		                        		
		                        			METHODS:
		                        			From June 2017 to December 2020, 76 MM patients who received CAR-T therapy in the Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, with complete clinical data and evaluable efficacy, were selected as the research objects. According to the receiver operating characteristic (ROC) curve, the best cut-off value was obtained. The patients were divided into groups on the basis of Hb 105.5 g/L as the cut-off value. The age, sex, serum calcium, β2-microglobulin, serum creatinine, lactate dehydrogenase (LDH), and the influencing factors of CAR-T treatment efficacy in MM patients were analyzed.
		                        		
		                        			RESULTS:
		                        			Hb was an influencing factor of efficacy. Univariate analysis showed that Hb, LDH, and albumin affected the efficacy of CAR-T therapy. Multivariate analysis showed that Hb ( OR=1.039, 95% CI: 1.002-1.078) and LDH ( OR=1.014, 95% CI: 1.000-1.027) were the influencing factors for the efficacy of CAR-T therapy.
		                        		
		                        			CONCLUSION
		                        			The efficacy of CAR-T therapy in MM patients with low Hb is poor, and Hb is a factor affecting the efficacy of CAR-T therapy.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Multiple Myeloma/drug therapy*
		                        			;
		                        		
		                        			Receptors, Chimeric Antigen
		                        			;
		                        		
		                        			Immunotherapy, Adoptive
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Hematologic Diseases
		                        			
		                        		
		                        	
2.Observation of liver indexes in patients with relapsed/refractory multiple myeloma treated with CAR-T-cells based on BCMA.
Qian SUN ; Yue Kun QI ; Kun Ming QI ; Zhi Ling YAN ; Hai CHENG ; Wei CHEN ; Feng ZHU ; Wei SANG ; De Peng LI ; Jiang CAO ; Ming SHI ; Zhen Yu LI ; Kai Lin XU
Chinese Journal of Hematology 2023;44(10):832-837
		                        		
		                        			
		                        			Objective: To observe the characteristics of the evolution of liver indexes in patients with relapsed/refractory multiple myeloma (RRMM) treated with CAR-T-cells based on BCMA. Methods: Retrospective analysis was performed of patients with RRMM who received an infusion of anti-BCMA CAR-T-cells and anti-BCMA combined with anti-CD19 CAR-T-cells at our center between June 1, 2019, and February 28, 2023. Clinical data were collected to observe the characteristics of changes in liver indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) in patients, and its relationship with cytokine-release syndrome (CRS) . Results: Ninety-two patients were included in the analysis, including 41 patients (44.6%) in the group receiving a single infusion of anti-BCMA CAR-T-cells, and 51 patients (55.4%) in the group receiving an infusion of anti-BCMA combined with anti-CD19 CAR-T-cells. After infusing CAR-T-cells, 31 patients (33.7%) experienced changes in liver indexes at or above grade 2, which included 20 patients (21.7%) with changes in one index, five patients (5.4%) with changes in two indexes, and six patients (6.5%) with changes in three or more indexes. The median time of peak values of ALT and AST were d17 and d14, respectively, and the median duration of exceeding grade 2 was 5.0 and 3.5 days, respectively. The median time of peak values of TBIL and DBIL was on d19 and d21, respectively, and the median duration of exceeding grade 2 was 4.0 days, respectively. The median time of onset of CRS was d8, and the peak time of fever was d9. The ALT, AST, and TBIL of patients with CRS were higher than those of patients without CRS (P=0.011, 0.002, and 0.015, respectively). CRS is an independent factor that affects ALT and TBIL levels (OR=19.668, 95% CI 18.959-20.173, P=0.001). The evolution of liver indexes can be reversed through anti-CRS and liver-protection treatments, and no patient died of liver injury. Conclusions: In BCMA-based CAR-T-cell therapy for RRMM, CRS is an important factor causing the evolution of liver indexes. The evolution of liver indexes after CAR-T-cell infusion is transient and reversible after treatment.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Antigens, CD19
		                        			;
		                        		
		                        			B-Cell Maturation Antigen/therapeutic use*
		                        			;
		                        		
		                        			Bilirubin
		                        			;
		                        		
		                        			Immunotherapy, Adoptive
		                        			;
		                        		
		                        			Liver
		                        			;
		                        		
		                        			Multiple Myeloma/drug therapy*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			T-Lymphocytes
		                        			
		                        		
		                        	
3.A multicenter epidemiological study of acute bacterial meningitis in children.
Cai Yun WANG ; Hong Mei XU ; Jiao TIAN ; Si Qi HONG ; Gang LIU ; Si Xuan WANG ; Feng GAO ; Jing LIU ; Fu Rong LIU ; Hui YU ; Xia WU ; Bi Quan CHEN ; Fang Fang SHEN ; Guo ZHENG ; Jie YU ; Min SHU ; Lu LIU ; Li Jun DU ; Pei LI ; Zhi Wei XU ; Meng Quan ZHU ; Li Su HUANG ; He Yu HUANG ; Hai Bo LI ; Yuan Yuan HUANG ; Dong WANG ; Fang WU ; Song Ting BAI ; Jing Jing TANG ; Qing Wen SHAN ; Lian Cheng LAN ; Chun Hui ZHU ; Yan XIONG ; Jian Mei TIAN ; Jia Hui WU ; Jian Hua HAO ; Hui Ya ZHAO ; Ai Wei LIN ; Shuang Shuang SONG ; Dao Jiong LIN ; Qiong Hua ZHOU ; Yu Ping GUO ; Jin Zhun WU ; Xiao Qing YANG ; Xin Hua ZHANG ; Ying GUO ; Qing CAO ; Li Juan LUO ; Zhong Bin TAO ; Wen Kai YANG ; Yong Kang ZHOU ; Yuan CHEN ; Li Jie FENG ; Guo Long ZHU ; Yan Hong ZHANG ; Ping XUE ; Xiao Qin LI ; Zheng Zhen TANG ; De Hui ZHANG ; Xue Wen SU ; Zheng Hai QU ; Ying ZHANG ; Shi Yong ZHAO ; Zheng Hong QI ; Lin PANG ; Cai Ying WANG ; Hui Ling DENG ; Xing Lou LIU ; Ying Hu CHEN ; Sainan SHU
Chinese Journal of Pediatrics 2022;60(10):1045-1053
		                        		
		                        			
		                        			Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Brain Abscess
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Child, Preschool
		                        			;
		                        		
		                        			Escherichia coli
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hydrocephalus
		                        			;
		                        		
		                        			Infant
		                        			;
		                        		
		                        			Infant, Newborn
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Meningitis, Bacterial/epidemiology*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Streptococcus agalactiae
		                        			;
		                        		
		                        			Streptococcus pneumoniae
		                        			;
		                        		
		                        			Subdural Effusion
		                        			;
		                        		
		                        			beta-Lactamases
		                        			
		                        		
		                        	
4.Management and short-term outcomes of neonates born to mothers infected with SARS-CoV-2 Omicron variant.
Shu Juan LI ; Lan ZHANG ; Hao YUAN ; Xiao Bo ZHANG ; Chuan Qing WANG ; Gong Bao LIU ; Ying GU ; Tong Ling YANG ; Xiao Ting ZHU ; Xiao Wen ZHAI ; Yu SHI ; Si Yuan JIANG ; Ke ZHANG ; Kai YAN ; Peng ZHANG ; Xiao Jing HU ; Qing LIU ; Rui Wei GAO ; Juan ZHAO ; Jian Guo ZHOU ; Yun CAO ; Zhi Hua LI
Chinese Journal of Pediatrics 2022;60(11):1163-1167
		                        		
		                        			
		                        			Objective: To summarize the management and short-term outcomes of neonates delivered by mothers infected with SARS-CoV-2 Omicron variant. Methods: A retrospective study was performed on 158 neonates born to mothers infected with SARS-CoV-2 Omicron variant admitted to the isolation ward of Children's Hospital of Fudan University from March 15th, 2022 to May 30th, 2022. The postnatal infection control measures for these neonates, and their clinical characteristics and short-term outcomes were analyzed. They were divided into maternal symptomatic group and maternal asymptomatic group according to whether their mothers had SARS-CoV-2 symptoms. The clinical outcomes were compared between the 2 groups using Rank sum test and Chi-square test. Results: All neonates were under strict infection control measures at birth and after birth. Of the 158 neonates, 75 (47.5%) were male. The gestational age was (38+3±1+3) weeks and the birth weight was (3 201±463)g. Of the neonates included, ten were preterm (6.3%) and the minimum gestational age was 30+1 weeks. Six neonates (3.8%) had respiratory difficulty and 4 of them were premature and required mechanical ventilation. All 158 neonates were tested negative for SARS-COV-2 nucleic acid by daily nasal swabs for the first 7 days. A total of 156 mothers (2 cases of twin pregnancy) infected with SARS-CoV-2 Omicron variant, the time from confirmed SARS-CoV-2 infection to delivery was 7 (3, 12) days. Among them, 88 cases (56.4%) showed clinical symptoms, but none needed intensive care treatment. The peripheral white blood cell count of the neonates in maternal symptomatic group was significantly higher than that in maternal symptomatic group (23.0 (18.7, 28.0) × 109 vs. 19.6 (15.4, 36.6) × 109/L, Z=2.44, P<0.05). Conclusions: Neonates of mothers infected with SARS-CoV-2 Omicron variant during third trimester have benign short-term outcomes, without intrauterine infection through vertical transmission. Strict infection control measures at birth and after birth can effectively protect these neonates from SARS-CoV-2 infection.
		                        		
		                        		
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Infant
		                        			;
		                        		
		                        			Infant, Newborn
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Pregnancy
		                        			;
		                        		
		                        			COVID-19
		                        			;
		                        		
		                        			Mothers
		                        			;
		                        		
		                        			Pregnancy Complications, Infectious/prevention & control*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			SARS-CoV-2
		                        			
		                        		
		                        	
5.Effect of Biyanning Granules on local symptoms and immune function of chronic rhinosinusitis.
Ying GAO ; Rui WANG ; Shu-Xin WEN ; Kai-Xue WEN ; Hui-Fang ZHAO ; Jian-Rong RONG ; Ye CAO ; Zhi-Hua GONG ; Ji-Qiang GUO
China Journal of Chinese Materia Medica 2022;47(17):4789-4798
		                        		
		                        			
		                        			This study discusses the effect of Biyanning Granules on local symptoms and systemic immune function of patients with chronic rhinosinusitis with nasal polyps(CRSwNP) within the 6 months of treatment by glucocorticoid nasal spray after surgical treatment. To be specific, a total of 237 CRSwNP patients, treated in Otorhinolaryngology Head and Neck Surgery in Shanxi Bethune Hospital, were enrolled. All patients were treated by nasal endoscopy and classified into hormone group(Budesonide Nasal Spray after surgery), Chinese medicine group(Biyanning Granules after surgery), and combination group(Budesonide Nasal Spray+Biyanning Granules after surgery) with random number table method, 79 cases in each group, and the treatment lasted 3 months. The follow-up was performed from the day of discharge to 12 months after the surgery. The clinical effect was observed. The visual analogue scale(VAS) scores and sino-nasal outcome test-20(SNOT-20) scale scores were used to assess patient's subjective symptoms and quality of life. Lund-Kennedy endoscopic score(LKES), Japanese T&T olfactometry, and standard olfactory test were used to evaluate the objective curative effect on patients. The levels of interleukin(IL)-21, CD4~+CD25~+Foxp3~+Treg, and CD4~+Th17 in peripheral blood were analyzed. The incidence of complications, recurrence rate, and adverse reactions during treatment were also recorded. The total effective rate after treatment in the combination group was higher than that in the hormone group and Chinese medicine group(P<0.05). VAS scores and SNOT-20 scale scores were lower in the three groups after treatment than before treatment and lower in the combination group than in the other two groups(P<0.05). The improvement in LKES and T&T standard olfactometry test was better in the combination group than in the other two groups(P<0.05). Serum levels of IL-21 and CD4~+Th17 in the three groups were lower than before treatment. The levels in the combination group were lower than those in the other two groups and lower in the hormone group than in the Chinese medicine group(P<0.05). Serum CD4~+CD25~+Foxp3~+Treg level was higher in the three groups after treatment than before, higher in the combination group than in the other two groups, and higher in the Chinese medicine group than in the hormone group(P<0.05). During the treatment, no serious adverse reactions were observed. After treatment, the combination group showed no significant difference in the incidence and recurrence rate of complications from the hormone group and Chinese medicine group. In the treatment of CRSwNP with glucocorticoid, Biyanning Granules reduced the side effects of glucocorticoid and assisted glucocorticoid in alleviating the symptoms of patients. It significantly improved the curative effect, regulated immune imbalance, accele-rated the recovery of immune function, reduced the recurrence rate of inflammatory reaction, and improved the quality of life. The combination of Chinese and western treatment is more effective than glucocorticoid alone and warrants further clinical study in large sample size.
		                        		
		                        		
		                        		
		                        			Budesonide/therapeutic use*
		                        			;
		                        		
		                        			Chronic Disease
		                        			;
		                        		
		                        			Forkhead Transcription Factors/metabolism*
		                        			;
		                        		
		                        			Glucocorticoids/therapeutic use*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Immunity
		                        			;
		                        		
		                        			Medicine, Chinese Traditional
		                        			;
		                        		
		                        			Nasal Sprays
		                        			;
		                        		
		                        			Quality of Life
		                        			;
		                        		
		                        			Rhinitis/surgery*
		                        			;
		                        		
		                        			Sinusitis/surgery*
		                        			
		                        		
		                        	
6.Mechanisms of β-sitosterol on Inhibiting the Proliferation of Hepatocellular Carcinoma Cells by Targeting CDC25B
Kai WANG ; Wei LI ; Zhi-fang LI ; Hui-qiong JI ; Zhi-wei GUO ; Jun-qiu CAO
Journal of Sun Yat-sen University(Medical Sciences) 2022;43(4):675-684
		                        		
		                        			
		                        			ObjectiveTo explore the effects and possible actions mechanisms of β-sitosterol on the proliferation of hepatocellular carcinoma (HCC) cells. MethodsThe target of β-sitosterol was predicted by SwissTarget and TargetNet data platforms. The up-regulated gene in GSE101728 HCC data set was analyzed by GEO2R, and the common gene between the target and the up-regulated gene was analyzed. According to the analysis of TCGA_LIHC data matrix, the relationship between cell division cyclin 25B (CDC25B) and clinical staging, prognosis of HCC was obtained. The activities, proliferation, cycles distribution and apoptosis of HCC cells (HepG2, Hep3B) treated with β-sitosterol were detected by CCK-8, colony-forming assay and flow cytometry. The models of nude mice with subcutaneous xenografted tumors in HepG2 were constructed and divided into control group and β-sitosterol group. The β-sitosterol group was intraperitoneally injected with β-sitosterol (50 mg/kg·d). The volume and mass of tumors were measured. The expression level of Ki67 was detected by immunohistochemistry. The levels of CDC25B protein in HepG2 and Hep3B cell lines treated with different concentrations of β-sitosterol for different action time were detected by Western blot. HepG2 and Hep3B cell lines with stable overexpression of CDC25B were constructed, and then which were treated with β-sitosterol. The activities, proliferation, cycles distribution and apoptosis of HepG2 and Hep3B cell lines were detected by the above-mentioned methods. ResultsThe expression level of CDC25B in HCC tissues was higher than that in para-carcinoma tissues (P<0.05). The expression level of CDC25B in patients with TNM staging at stage T2-4, clinical staging at stage Ⅱ-Ⅳ, G3-4 differentiation, recurrence and poor prognosis was higher than that with TNM staging at stage T1, clinical staging at stage I, G1-2 differentiation, non-recurrence and good prognosis, respectively (P<0.05). The overall survival rate in high-expression CDC25B group was lower than that in low-expression group (P<0.05). The activities of Hep3B and HepG2 cells were decreased with the increase of β-sitosterol dose and the prolongation of action time. The relative number of clone cells and the percentages of cells during S phase in Hep3B (15 μmol/L β-sitosterol) and HepG2 (18 μmol/L β-sitosterol) were significantly lower than those in control group (P<0.05), while percentage of cells during G0/G1 phase and apoptosis rate were significantly higher than those in control group (P<0.05). The volume and mass of xenografted tumors, and relative expression level of Ki67 in β-sitosterol group were significantly lower than those in the control group (P<0.05). The expression of CDC25B protein in Hep3B and HepG2 cells was decreased with the increase of β-sitosterol concentration and the prolongation of action time. The cells growth, relative number of clone cells, and percentages of cells during S phase in Hep3B and HepG2 cells were all significantly higher than those in β-sitosterol group (P<0.05), while percentage of cells during G0/G1 phase and apoptosis rate were significantly lower than those in β-sitosterol group (P<0.05). ConclusionThe β-sitosterol can promote apoptosis of HCC cells and inhibited their proliferation. The inhibition of cells proliferation may be related to inhibition of CDC25B protein. 
		                        		
		                        		
		                        		
		                        	
7.Comparison of the characteristics of NK cells after two different methods of expansion and observation of the clinical efficacy in patients who relapsed post allogeneic hematopoietic stem cell transplantation.
Xun Hong CAO ; Zhi Dong WANG ; Yu Qian SUN ; Jun KONG ; Sheng Ye LU ; Fei Fei TANG ; Yuan Yuan ZHANG ; Jing Zhi WANG ; Lan Ping XU ; Xiao Hui ZHANG ; Yu WANG ; Kai Yan LIU ; Xiao Jun HUANG ; Xiao Yu ZHAO
Chinese Journal of Hematology 2022;43(5):400-407
		                        		
		                        			
		                        			Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.
		                        		
		                        		
		                        		
		                        			Antibodies, Monoclonal/pharmacology*
		                        			;
		                        		
		                        			Graft vs Host Disease/metabolism*
		                        			;
		                        		
		                        			Hematopoietic Stem Cell Transplantation
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Killer Cells, Natural
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
8.A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data.
Xue Wei DING ; Zhi Chao ZHENG ; Qun ZHAO ; Gang ZHAI ; Han LIANG ; Xin WU ; Zheng Gang ZHU ; Hai Jiang WANG ; Qing Si HE ; Xian Li HE ; Yi An DU ; Lu Chuan CHEN ; Ya Wei HUA ; Chang Ming HUANG ; Ying Wei XUE ; Ye ZHOU ; Yan Bing ZHOU ; Dan WU ; Xue Dong FANG ; You Guo DAI ; Hong Wei ZHANG ; Jia Qing CAO ; Le Ping LI ; Jie CHAI ; Kai Xiong TAO ; Guo Li LI ; Zhi Gang JIE ; Jie GE ; Zhong Fa XU ; Wen Bin ZHANG ; Qi Yun LI ; Ping ZHAO ; Zhi Qiang MA ; Zhi Long YAN ; Guo Liang ZHENG ; Yang YAN ; Xiao Long TANG ; Xiang ZHOU
Chinese Journal of Gastrointestinal Surgery 2021;24(5):403-412
		                        		
		                        			
		                        			Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
		                        		
		                        		
		                        		
		                        			Chemotherapy, Adjuvant
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Gastrectomy
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Neoadjuvant Therapy
		                        			;
		                        		
		                        			Neoplasm Staging
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Stomach Neoplasms/surgery*
		                        			
		                        		
		                        	
9.Adherence to adjuvant with therapy imatinib in patients with gastrointestinal stromal tumor: a national multi-center cross-sectional study.
Peng ZHANG ; Jun ZHANG ; Bo ZHANG ; Wen Chang YANG ; Jun Bo HU ; Xiao Feng SUN ; Gang ZHAI ; Hao Ran QIAN ; Yong LI ; Hao XU ; Fan FENG ; Xing Ye WU ; He Li LIU ; Hong Jun LIU ; Hai Bo QIU ; Xiao Jun WU ; Yan Bing ZHOU ; Kun Tang SHEN ; You Wei KOU ; Yang FU ; Zhi Gang JIE ; Xiao Ming ZOU ; Hui CAO ; Zhi Dong GAO ; Kai Xiong TAO
Chinese Journal of Gastrointestinal Surgery 2021;24(9):775-782
		                        		
		                        			
		                        			Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.
		                        		
		                        		
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Antineoplastic Agents/therapeutic use*
		                        			;
		                        		
		                        			Chemotherapy, Adjuvant
		                        			;
		                        		
		                        			Cross-Sectional Studies
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Gastrointestinal Stromal Tumors/drug therapy*
		                        			;
		                        		
		                        			Humans
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		                        			Imatinib Mesylate/therapeutic use*
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		                        			Male
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		                        			Middle Aged
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		                        			Neoplasm Recurrence, Local/drug therapy*
		                        			
		                        		
		                        	
10.Long Noncoding RNA PVT1 Promotes Stemness and Temozolomide Resistance through miR-365/ELF4/SOX2 Axis in Glioma
Rui GONG ; Zhi-Qiang LI ; Kai FU ; Chao MA ; Wei WANG ; Jin-Cao CHEN
Experimental Neurobiology 2021;30(3):244-255
		                        		
		                        			
		                        			Long non-coding RNA (lncRNA) are a class of non-coding RNAs demonstrated to play pivotal roles in regulating tumor progression. Therefore, deciphering the regulatory role of lncRNA in the development of glioma may offer a promising therapeutic target for treatment of glioma. We performed RT-qPCR analysis on the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and miR-365 in glioma tissues and cell lines. Cell proliferation and viability was assessed with CCK8 assay. Cell migration was assessed by wound healing assay. Transwell assay was used to assess cell invasion capacity. Expression of CD133+ cells was detected by flow cytometry. Western blot assay was used to detection the expression of ELF4 and stemness-related protein SOX2, Oct4 and Nanog. Bioinformatics and dual-luciferase assay were used to predict and validate the interaction between PVT1 and miR-365. Elevated PVT1 expression was observed in glioma tissues and cells. Knockdown of PVT1 and overexpression of miR-365 inhibited proliferation, migration, invasion and promoted stemness and Temozolomide (TMZ) resistance of glioma cells. PVT1 regulated ELF4 expression by competitively binds to miR-365. PVT1 regulated the stemness and sensitivity of TMZ of glioma cells through miR-365/ELF4/ SOX2 axis. This study identified that PVT1 promoted glioma stemness through miR-365/ELF4/SOX2 axis.
		                        		
		                        		
		                        		
		                        	
            
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