1.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
		                        		
		                        			
		                        			Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
		                        		
		                        		
		                        		
		                        	
2.Efficacy and safety of BTK inhibitor combined with bendamustine and rituximab in the first-line treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma.
Shu Chao QIN ; Rui JIANG ; Ye Qin SHA ; Jing Yan QIU ; Hong Ling MI ; Yi MIAO ; Wei WU ; Li WANG ; Lei FAN ; Wei XU ; Jian Yong LI ; Hua Yuan ZHU
Chinese Journal of Hematology 2023;44(2):158-161
3.To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia.
Xiao Shuai ZHANG ; Bing Cheng LIU ; Xin DU ; Yan Li ZHANG ; Na XU ; Xiao Li LIU ; Wei Ming LI ; Hai LIN ; Rong LIANG ; Chun Yan CHEN ; Jian HUANG ; Yun Fan YANG ; Huan Ling ZHU ; Ling PAN ; Xiao Dong WANG ; Gui Hui LI ; Zhuo Gang LIU ; Yan Qing ZHANG ; Zhen Fang LIU ; Jian Da HU ; Chun Shui LIU ; Fei LI ; Wei YANG ; Li MENG ; Yan Qiu HAN ; Li E LIN ; Zhen Yu ZHAO ; Chuan Qing TU ; Cai Feng ZHENG ; Yan Liang BAI ; Ze Ping ZHOU ; Su Ning CHEN ; Hui Ying QIU ; Li Jie YANG ; Xiu Li SUN ; Hui SUN ; Li ZHOU ; Ze Lin LIU ; Dan Yu WANG ; Jian Xin GUO ; Li Ping PANG ; Qing Shu ZENG ; Xiao Hui SUO ; Wei Hua ZHANG ; Yuan Jun ZHENG ; Qian JIANG
Chinese Journal of Hematology 2023;44(9):728-736
		                        		
		                        			
		                        			Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Imatinib Mesylate/adverse effects*
		                        			;
		                        		
		                        			Incidence
		                        			;
		                        		
		                        			Antineoplastic Agents/adverse effects*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Pyrimidines/adverse effects*
		                        			;
		                        		
		                        			Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Benzamides/adverse effects*
		                        			;
		                        		
		                        			Leukemia, Myeloid, Chronic-Phase/drug therapy*
		                        			;
		                        		
		                        			Aminopyridines/therapeutic use*
		                        			;
		                        		
		                        			Protein Kinase Inhibitors/therapeutic use*
		                        			
		                        		
		                        	
4. Treatment advice of small molecule antiviral drugs for elderly COVID-19
Min PAN ; Shuang CHANG ; Xiao-Xia FENG ; Guang-He FEI ; Jia-Bin LI ; Hua WANG ; Du-Juan XU ; Chang-Hui WANG ; Yan SUN ; Xiao-Yun FAN ; Tian-Jing ZHANG ; Wei WEI ; Ling-Ling ZHANG ; Jim LI ; Fei-Hu CHEN ; Xiao-Ming MENG ; Hong-Mei ZHAO ; Min DAI ; Yi XIANG ; Meng-Shu CAO ; Xiao-Yang CHEN ; Xian-Wei YE ; Xiao-Wen HU ; Ling JIANG ; Yong-Zhong WANG ; Hao LIU ; Hai-Tang XIE ; Ping FANG ; Zhen-Dong QIAN ; Chao TANG ; Gang YANG ; Xiao-Bao TENG ; Chao-Xia QIAN ; Guo-Zheng DING
Chinese Pharmacological Bulletin 2023;39(3):425-430
		                        		
		                        			
		                        			 COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly. 
		                        		
		                        		
		                        		
		                        	
5.Effects of electroacupuncture pretreatment on GABAA receptor of fastigial nucleus and sympathetic nerve activity in rats with myocardial ischemia reperfusion injury.
Shuai-Ya WANG ; Qi SHU ; Pian-Pian CHEN ; Fan ZHANG ; Xiang ZHOU ; Qian-Yi WANG ; Jie ZHOU ; Xia WEI ; Ling HU ; Qing YU ; Rong-Lin CAI
Chinese Acupuncture & Moxibustion 2023;43(6):669-678
		                        		
		                        			OBJECTIVE:
		                        			To observe the effects of electroacupuncture (EA) pretreatment on cardiac function, sympathetic nerve activity, indexes of myocardial injury and GABAA receptor in fastigial nucleus in rats with myocardial ischemia reperfusion injury (MIRI), and to explore the neuroregulatory mechanism of EA pretreatment in improving MIRI.
		                        		
		                        			METHODS:
		                        			A total of 60 male SD rats were randomly divided into a sham operation group, a model group, an EA group, an agonist group and an agonist+EA group, 12 rats in each group. The MIRI model was established by ligation of the left anterior descending coronary artery. EA was applied at bilateral "Shenmen" (HT 7) and "Tongli" (HT 5) in the EA group and the agonist+EA group, with continuous wave, in frequency of 2 Hz and intensity of 1 mA, 30 min each time, once a day for 7 consecutive days. After intervention, the MIRI model was established. In the agonist group, the muscone (agonist of GABAA receptor, 1 g/L) was injected in fastigial nucleus for 7 consecutive days before modeling, 150 μL each time, once a day. In the agonist+EA group, the muscone was injected in fastigial nucleus 30 min before EA intervention. The data of electrocardiogram was collected by PowerLab standard Ⅱ lead, and ST segment displacement and heart rate variability (HRV) were analyzed; the serum levels of norepinephrine (NE), creatine kinase isoenzyme MB (CK-MB) and cardiac troponin I (cTnI) were detected by ELISA; the myocardial infarction area was measured by TTC staining; the morphology of myocardial tissue was observed by HE staining; the positive expression and mRNA expression of GABAA receptor in fastigial nucleus were detected by immunohistochemistry and real-time PCR.
		                        		
		                        			RESULTS:
		                        			Compared with the sham operation group, in the model group, ST segment displacement and ratio of low frequency to high frequency (LF/HF) of HRV were increased (P<0.01), HRV frequency domain analysis showed enhanced sympathetic nerve excitability, the serum levels of NE, CK-MB and cTnI were increased (P<0.01), the percentage of myocardial infarction area was increased (P<0.01), myocardial fiber was broken and interstitial edema was serious, the positive expression and mRNA expression of GABAA receptor in fastigial nucleus were increased (P<0.01). Compared with the model group, in the EA group, ST segment displacement and LF/HF ratio were decreased (P<0.01), HRV frequency domain analysis showed reduced sympathetic nerve excitability, the serum levels of NE, CK-MB and cTnI were decreased (P<0.01), the percentage of myocardial infarction area was decreased (P<0.01), myocardial fiber breakage and interstitial edema were lightened, the positive expression and mRNA expression of GABAA receptor in fastigial nucleus were decreased (P<0.01). Compared with the EA group, in the agonist group and the agonist+EA group, ST segment displacement and LF/HF ratio were increased (P<0.01), HRV frequency domain analysis showed enhanced sympathetic nerve excitability, the serum levels of NE, CK-MB and cTnI were increased (P<0.01), the percentage of myocardial infarction area was increased (P<0.01), myocardial fiber breakage and interstitial edema were aggravated, the positive expression and mRNA expression of GABAA receptor in fastigial nucleus were increased (P<0.01).
		                        		
		                        			CONCLUSION
		                        			EA pretreatment can improve the myocardial injury in MIRI rats, and its mechanism may be related to the inhibition of GABAA receptor expression in fastigial nucleus, thereby down-regulating the excitability of sympathetic nerve.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Rats, Sprague-Dawley
		                        			;
		                        		
		                        			Cerebellar Nuclei
		                        			;
		                        		
		                        			Electroacupuncture
		                        			;
		                        		
		                        			Myocardial Reperfusion Injury/therapy*
		                        			;
		                        		
		                        			Receptors, GABA-A/genetics*
		                        			;
		                        		
		                        			RNA, Messenger
		                        			
		                        		
		                        	
6.Predictive model of early urinary continence recovery based on prostate gland MRI parameters after laparoscopic radical prostatectomy.
Hai MAO ; Fan ZHANG ; Zhan Yi ZHANG ; Ye YAN ; Yi Chang HAO ; Yi HUANG ; Lu Lin MA ; Hong Ling CHU ; Shu Dong ZHANG
Journal of Peking University(Health Sciences) 2023;55(5):818-824
		                        		
		                        			OBJECTIVE:
		                        			Constructing a predictive model for urinary incontinence after laparoscopic radical prostatectomy (LRP) based on prostatic gland related MRI parameters.
		                        		
		                        			METHODS:
		                        			In this study, 202 cases were included. All the patients were diagnosed with prostate cancer by prostate biopsy and underwent LRP surgery in Peking University Third Hospital. The preoperative MRI examination of all the patients was completed within 1 week before the prostate biopsy. Prostatic gland related parameters included prostate length, width, height, prostatic volume, intravesical prostatic protrusion length (IPPL), prostate apex shape, etc. From the first month after the operation, the recovery of urinary continence was followed up every month, and the recovery of urinary continence was based on the need not to use the urine pad all day long. Logistic multivariate regression analysis was used to analyze the influence of early postoperative recovery of urinary continence. Risk factors were used to draw the receiver operator characteristic (ROC) curves of each model to predict the recovery of postoperative urinary continence, and the difference of the area under the curve (AUC) was compared by DeLong test, and the clinical net benefit of the model was evaluated by decision curve analysis (DCA).
		                        		
		                        			RESULTS:
		                        			The average age of 202 patients was 69.0 (64.0, 75.5) years, the average prostate specific antigen (PSA) before puncture was 12.12 (7.36, 20.06) μg/L, and the Gleason score < 7 points and ≥ 7 points were 73 cases (36.2%) and 129 cases (63.9%) respectively, with 100 cases (49.5%) at T1/T2 clinical stage, and 102 cases (50.5%) at T3 stage. The prostatic volume measured by preoperative MRI was 35.4 (26.2, 51.1) mL, the ratio of the height to the width was 0.91 (0.77, 1.07), the membranous urethral length (MUL) was 15 (11, 16) mm, and the IPPL was 2 (0, 6) mm. The prostatic apex A-D subtypes were 67 cases (33.2%), 80 cases (39.6%), 24 cases (11.9%) and 31 cases (15.3%), respectively. The training set and validation set were 141 cases and 61 cases, respectively. The operations of all the patients were successfully completed, and the urinary continence rate was 59.4% (120/202) in the 3 months follow-up. The results of multivariate analysis of the training set showed that the MUL (P < 0.001), IPPL (P=0.017) and clinical stage (P=0.022) were independent risk factors for urinary incontinence in the early postoperative period (3 months). The nomogram and clinical decision curve were made according to the results of multivariate analysis. The AUC value of the training set was 0.885 (0.826, 0.944), and the AUC value of the validation set was 0.854 (0.757, 0.950). In the verification set, the Hosmer-Lemeshow goodness-of-fit test was performed on the model, and the Chi-square value was 5.426 (P=0.711).
		                        		
		                        			CONCLUSION
		                        			Preoperative MUL, IPPL, and clinical stage are indepen-dent risk factors for incontinence after LRP. The nomogram developed based on the relevant parameters of MRI glands can effectively predict the recovery of early urinary continence after LRP. The results of this study require further large-scale clinical research to confirm.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Prostate/surgery*
		                        			;
		                        		
		                        			Prostatectomy/adverse effects*
		                        			;
		                        		
		                        			Prostatic Neoplasms/pathology*
		                        			;
		                        		
		                        			Urinary Incontinence/etiology*
		                        			;
		                        		
		                        			Laparoscopy/methods*
		                        			;
		                        		
		                        			Magnetic Resonance Imaging/adverse effects*
		                        			;
		                        		
		                        			Recovery of Function
		                        			;
		                        		
		                        			Retrospective Studies
		                        			
		                        		
		                        	
7.Clinical efficacy of combined therapy in children with stage 4 neuroblastoma.
Wei-Ling LIANG ; Xiao-Fan YE ; Gong ZHONG ; Jian-Jun CHEN ; Kang-Lin DAI ; Ka Leung Daniel CHEUK ; Shu MO ; Bo-Shen WANG ; Chun-Yu LI ; Xuan-Zhu JIANG ; Zhi-Yuan XU ; Li ZHOU ; Irene CHAN ; Jian-Liang CHEN ; Patrick CHU ; Pui Wah Pamela LEE ; Chi Fung Godfrey CHAN
Chinese Journal of Contemporary Pediatrics 2022;24(7):759-764
		                        		
		                        			OBJECTIVES:
		                        			To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma.
		                        		
		                        			METHODS:
		                        			A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021.
		                        		
		                        			RESULTS:
		                        			The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years.
		                        		
		                        			CONCLUSIONS
		                        			Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.
		                        		
		                        		
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Child, Preschool
		                        			;
		                        		
		                        			Combined Modality Therapy
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Infant
		                        			;
		                        		
		                        			Neuroblastoma/drug therapy*
		                        			;
		                        		
		                        			Positron-Emission Tomography
		                        			;
		                        		
		                        			Radionuclide Imaging
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
8.Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study.
Wei SHEN ; Zhi ZHENG ; Xin-Zhu LIN ; Fan WU ; Qian-Xin TIAN ; Qi-Liang CUI ; Yuan YUAN ; Ling REN ; Jian MAO ; Bi-Zhen SHI ; Yu-Mei WANG ; Ling LIU ; Jing-Hui ZHANG ; Yan-Mei CHANG ; Xiao-Mei TONG ; Yan ZHU ; Rong ZHANG ; Xiu-Zhen YE ; Jing-Jing ZOU ; Huai-Yu LI ; Bao-Yin ZHAO ; Yin-Ping QIU ; Shu-Hua LIU ; Li MA ; Ying XU ; Rui CHENG ; Wen-Li ZHOU ; Hui WU ; Zhi-Yong LIU ; Dong-Mei CHEN ; Jin-Zhi GAO ; Jing LIU ; Ling CHEN ; Cong LI ; Chun-Yan YANG ; Ping XU ; Ya-Yu ZHANG ; Si-Le HU ; Hua MEI ; Zu-Ming YANG ; Zong-Tai FENG ; San-Nan WANG ; Er-Yan MENG ; Li-Hong SHANG ; Fa-Lin XU ; Shao-Ping OU ; Rong JU
Chinese Journal of Contemporary Pediatrics 2022;24(2):132-140
		                        		
		                        			OBJECTIVES:
		                        			To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China.
		                        		
		                        			METHODS:
		                        			A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined.
		                        		
		                        			RESULTS:
		                        			The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05).
		                        		
		                        			CONCLUSIONS
		                        			It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
		                        		
		                        		
		                        		
		                        			Female
		                        			;
		                        		
		                        			Fetal Growth Retardation
		                        			;
		                        		
		                        			Gestational Age
		                        			;
		                        		
		                        			Hospitalization
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Incidence
		                        			;
		                        		
		                        			Infant
		                        			;
		                        		
		                        			Infant, Newborn
		                        			;
		                        		
		                        			Infant, Premature
		                        			;
		                        		
		                        			Infant, Very Low Birth Weight
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Risk Factors
		                        			
		                        		
		                        	
9.Chaihu Guizhi Decoction plus or minus formula combined with capecitabine inhibits IL-6/STAT3 signaling to suppress triple-negative breast cancer xenografts in nude mice.
Yu Xiao FANG ; Shu Mei WANG ; Qian YANG ; Song Fan YOU ; Xiang Ling XING
Journal of Southern Medical University 2022;42(6):905-912
		                        		
		                        			OBJECTIVE:
		                        			To investigate the effect of Chaihu Guizhi Decoction (CHGZD) combined with capecitabine on growth and apoptosis of subcutaneous triple-negative breast cancer xenografts in nude mice and explore the possible mechanism.
		                        		
		                        			METHODS:
		                        			Nude mouse models bearing subcutaneous triple-negative breast cancer xenografts were randomized into 6 groups (n=10) for treatment with distilled water (model group), low (10.62 g/kg), medium (21.23 g/kg) and high (42.46 g/kg) doses of CHGZD, capecitabine (0.2 mg/kg), or the combination of CHGZD (42.46 g/kg) and capecitabine (0.2 mg/k) once daily for 21 consecutive days. The general condition of mice was observed, and after 21-day treatments, the tumors were dissected for measurement of tumor volume and weight and histopathological examination with HE staining. Serum IL-6 levels of the mice were determined with enzyme-linked immunosorbent assay (ELISA), and the expression levels of IL-6, STAT3, p-STAT3, Bax, Bcl-2 and cyclin D1 in the tumor tissues were detected using real-time PCR and Western blotting.
		                        		
		                        			RESULTS:
		                        			Compared with those in the model group, the tumor-bearing mice receiving treatments with CHGZD showed significantly increased food intake with good general condition, sensitive responses, increased body weight, and lower tumor mass (P < 0.01). Compared with capecitabine treatment alone, treatment with CHGZD alone at the medium and high doses and the combined treatment all resulted in significantly higher tumor inhibition rates (P < 0.01), induced obvious tumor tissue degeneration and reduced the tumor cell density. Treatments with CHGZD, both alone and in combination with capecitabine, significantly decreased serum IL-6 level, lowered the mRNA expression levels of IL-6 and STAT3, the protein expressions of IL-6, STAT3 and P-STAT3 (P < 0.05), and the mRNA and protein expressions of Bcl-2 and cyclin D1 (P < 0.05), and increased the mRNA and protein expressions of Bax in the tumor tissues (P < 0.05).
		                        		
		                        			CONCLUSION
		                        			CHGZD combined with capecitabine can significantly inhibit tumor growth in nude mice bearing triple-negative breast cancer xenografts, the mechanism of which may involve the inhibition of IL-6/STAT3 signaling pathway and regulation of Bax, Bcl-2 and cyclin D1 expressions to suppress tumor cell proliferation and differentiation and induce cell apoptosis.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Capecitabine/pharmacology*
		                        			;
		                        		
		                        			Cyclin D1/metabolism*
		                        			;
		                        		
		                        			Drugs, Chinese Herbal
		                        			;
		                        		
		                        			Heterografts
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Interleukin-6/metabolism*
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Mice, Nude
		                        			;
		                        		
		                        			Proto-Oncogene Proteins c-bcl-2/metabolism*
		                        			;
		                        		
		                        			RNA, Messenger/metabolism*
		                        			;
		                        		
		                        			STAT3 Transcription Factor/metabolism*
		                        			;
		                        		
		                        			Signal Transduction
		                        			;
		                        		
		                        			Triple Negative Breast Neoplasms/drug therapy*
		                        			;
		                        		
		                        			bcl-2-Associated X Protein/metabolism*
		                        			
		                        		
		                        	
10.The Clinical Significance of Oligoclonal Bands in Patient with Multiple Myeloma.
Jia-Hui LIU ; Hui-Shou FAN ; Wen-Qiang YAN ; Jing-Yu XU ; Ling-Na LI ; Yan XU ; Shu-Hua YI ; De-Hui ZOU ; Lu-Gui QIU ; Gang AN
Journal of Experimental Hematology 2022;30(5):1453-1463
		                        		
		                        			OBJECTIVE:
		                        			To investigate the clinical value of oligoclonal bands (OB) in patients with multiple myeloma (MM).
		                        		
		                        			METHODS:
		                        			The laboratory test and clinical data of 624 newly diagnosed MM patients admitted to Blood Diseases Hospital of Chinese Academy of Medical Sciences from January 2013 to December 2019 were retrospectively analyzed, including 30 patients with OB, and the clinical characteristics, treatment effects and survival of OB and non-OB patients were analyzed and compared.
		                        		
		                        			RESULTS:
		                        			OB occurred in 11.8% (22/187) of patients who received autologous stem cell transplantation(ASCT) and only 1.8% (8/437) of patients who did not receive ASCT (P=0.000). The median time to the appearance of oligoclonal bands was 3.2(0.6-10.5) months after transplantation. The M protein types of oligoclonal bands mainly include IgG κ, IgG λ, IgM λ and λ light chains. In the presence of oligoclonal bands, 90% of patients were evaluated as complete remission (CR) and above. There were no statistically significant differences in disease stage, tumor burden, and genetic abnormalities between OB and non-OB patients. Among the all patients, the prognosis of OB patients was significantly better than that of non-OB patients, and OB patients showed deeper disease remission (significantly higher CR rate, MRD negative rate, and longer MRD negative duration). Among patients who underwent ASCT, OB patients showed earlier immune recovery, but the depth of treatment response and survival outcomes were similar between OB and non-OB patients, it was no statistically difference. Although OB patients showed earlier immune reconstitution, this did not translate into better survival, suggesting that the better prognosis of OB patients was mainly related to deeper and durable remission rather than early immune reconstitution. Further analysis in patients who received ASCT and obtained MRD negative indicated that there was no additional survival benefit in patients with OB.
		                        		
		                        			CONCLUSION
		                        			The better prognosis of OB patients may be related to the deeper treatment response, but not to the early immune reconstitution. The appearance of OB is only a sign of deep remission and early immune reconstitution in patients, it cannot be translated into survival benefit of MM patients.
		                        		
		                        		
		                        		
		                        			Hematopoietic Stem Cell Transplantation
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Immunoglobulin G
		                        			;
		                        		
		                        			Immunoglobulin M
		                        			;
		                        		
		                        			Multiple Myeloma
		                        			;
		                        		
		                        			Oligoclonal Bands
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Transplantation, Autologous
		                        			
		                        		
		                        	
            
Result Analysis
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