1.Clinical Observation on Shuangye San in the Treatment of Type 2 Diabetes Mellitus Complicated with Non-alcoholic Fatty Liver Disease of Spleen Deficiency and Phlegm Stasis Type
Dao-Cheng ZHOU ; Gui-Ji RUAN ; You-You SHUAI ; Wen-Hua XU ; De-Liang LIU ; Heng-Xia ZHAO ; Hui-Lin LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(10):2687-2694
		                        		
		                        			
		                        			Objective To observe the clinical efficacy of Shuangye San(the prescription mainly composed of Mori Folium and Nelumbinis Folium)in the treatment of type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)of spleen deficiency and phlegm stasis type.Methods A total of 80 patients with T2DM complicated with NAFLD of spleen deficiency and phlegm stasis type were randomly divided into a treatment group and a control group,with 40 cases in each group.The control group was treated with conventional western medicine for lowering blood glucose and lipid,protecting liver and lowering enzymes.The treatment group was treated with the granules of Shuangye San orally on the basis of treatment for the control group.The course of treatment lasted for three months.The changes of traditional Chinese medicine(TCM)syndrome scores,homeostasis model assessment of insulin resistance(HOMA-IR),fasting insulin(FINS),fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),glycosylated hemoglobin(HbA1C),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),liver function indicators and B-ultrasound grading of fatty liver in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After three months of treatment,the total effective rate of the treatment group was 85.00%(34/40),and that of the control group was 70.00%(28/40).The intergroup comparison(tested by chi-square test)showed that the efficacy of the treatment group was significantly superior to that of the control group(P<0.01).(2)After treatment,the scores of TCM symptoms of obese physique,heaviness and weakness in the limbs,shortness of breath and unwilling to talk,tightness and stabbing pain in the chest,abdominal distension and poor appetite in the two groups were decreased compared with those before treatment(P<0.05),and the decrease of TCM syndrome scores in the treatment group was significantly superior to that in the control group(P<0.05).(3)After treatment,the levels of glucose and lipid metabolism indicators of FINS,HOMA-IR,FBG,2hPG,HbA1C,TC,TG and LDL-C in the two groups were significantly decreased compared with those before treatment(P<0.05),and the level of HDL-C was significantly increased compared with that before treatment(P<0.05).The decrease of FINS,HOMA-IR,FBG,2hPG,HbA1C,TC,TG and LDL-C levels and the increase of HDL-C levels in the treatment group were significantly superior to those in the control group(P<0.05).(4)After treatment,the levels of liver function indicators of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and gamma-glutamyl transpeptidase(GGT)in the two groups were significantly decreased compared with those before treatment(P<0.05),and the decrease of liver function indicators in the treatment group was significantly superior to that in the control group(P<0.05).(5)After treatment,the B-ultrasound grading of fatty liver of the two groups was significantly improved compared with that before treatment(P<0.05),and the improvement of fatty liver B-ultrasound grading in the treatment group was significantly superior to that in the control group,and the difference was statistically significant(P<0.05).(6)During the treatment,there were no adverse reactions such as impairment of liver and kidney function and abnormalities in routine blood,urine and stool test in the two groups.Conclusion Shuangye San exerts certain effect in the treatment of T2DM complicated with NAFLD of spleen deficiency and phlegm stasis type.It can alleviate the clinical symptoms of patients,correct the disorder of glucose and lipid metabolism,and improve liver function and fatty liver B-ultrasound grading.
		                        		
		                        		
		                        		
		                        	
2. Inhibition of MAPK pathway-induced apoptosis in renal cancer cells by ethanol extraction of Dysosma versipellis
Gan-Hua YOU ; Lian HE ; Kai LI ; Meng YANG ; Zhou WEN ; Wang-Pei LIU ; Jian-Guo ZHU
Chinese Pharmacological Bulletin 2023;39(12):2305-2313
		                        		
		                        			
		                        			 Aim To explore the effects of ethanol extraction of Dysosma versipellis on the proliferation and apoptosis of renal clear cell carcinoma OS-RC-2 cells and the underlying mechanism. Methods After treated with Dysosma versipellis, the proliferation of OS-RC-2 cells was detected by the CCK-8 assay and clone formation assay. The migration rate of cells was detected by thewound healing assay and Transwell assay. The level of ROS was detected by the reactive oxygen detection kit. The common targets between Dysosma versipellis and ROS were obtained by the network pharmacology. The above common targets were analyzed by KEGG. The apoptosis rate and cell cycle were detected by the flow cytometry, and the key proteins of MAPK signaling pathway and the levels of apoptosis related proteins were measured by Western blot. Results The results showed that Dysosma versipellis significantly inhibited the cell viability and migration ability of 0S-RC-2 cells, and up-regulated the level of ROS. Network pharmacology analysis showed a total of 165 common targets between Dysosma versipellis and ROS. KEGG analysis of the common targets revealed that there were significant changes in the MAPK signaling pathway. The results of Western blot showed that after treated with Dysosma versipellis, the protein level of JNK and the ratio of p-ERK/ERK were down-regulated. Besides, the protein level of caspase-9 and Bcl-2 declined, while the levels of cleaved caspase-9 and Bax were promoted. The flow cytometry results showed that Dysosma versipellis could significantly promote the apoptosis rate,down-regulate the cells in Gl-phase,while up-regulate the cells in G2/M-phase. The results of the rescue experiment showed that co-administration of NAC and Dysosma versipellis could significantly reverse the cell viability and apoptosis rate, the level of apop-totic related proteins, as well as the protein levels of MAPK pathway,when compared to treated with Dysosma versipellis alone in OS-RC-2. Conclusion In summary, Dysosma versipellis may inhibit the MAPK signaling pathway via the changes in ROS,further promoting apoptosis rate and decline cell proliferation in OS-RC-2 cell line. 
		                        		
		                        		
		                        		
		                        	
3.Analysis of clinical presentation and genetic characteristics of malignant infantile osteopetrosis.
Ang WEI ; Guang Hua ZHU ; Mao Quan QIN ; Chen Guang JIA ; Bin WANG ; Jun YANG ; Yan Hui LUO ; Yuan Fang JING ; Yan YAN ; Xuan ZHOU ; Tian You WANG
Chinese Journal of Pediatrics 2023;61(11):1038-1042
		                        		
		                        			
		                        			Objective: To investigate the clinical presentation and genetic characteristics of malignant infantile osteopetrosis. Methods: This was a retrospective case study. Thirty-seven children with malignant infantile osteopetrosis admitted into Beijing Children's Hospital from January 2013 to September 2022 were enrolled in this study. According to the gene mutations, the patients were divided into the CLCN7 group and the TCIRG1 group. Clinical characteristics, laboratory tests, and prognosis were compared between two groups. Wilcoxon test or Fisher exact test were used in inter-group comparison. The survival rate was estimated with the Kaplan-Meier method and the Log-Rank test was used to compare the difference in survival between groups. Results: Among the 37 cases, there were 22 males and 15 females. The age of diagnosis was 0.5 (0.2, 1.0) year. There were 13 patients (35%) and 24 patients (65%) with mutations in CLCN7 and TCIRGI gene respectively. Patients in the CLCN7 group had an older age of diagnosis than those in the TCIRGI group (1.2 (0.4, 3.6) vs. 0.4 (0.2, 0.6) years, Z=-2.60, P=0.008). The levels of serum phosphorus (1.7 (1.3, 1.8) vs. 1.1 (0.8, 1.6) mmol/L, Z=-2.59, P=0.010), creatine kinase isoenzyme (CK-MB) (457 (143, 610) vs. 56 (37, 82) U/L, Z=-3.38, P=0.001) and the level of neutrophils (14.0 (9.9, 18.1) vs. 9.2 (6.7, 11.1) ×109/L, Z=-2.07, P=0.039) at diagnosis were higher in the CLCN7 group than that in the TCIRG1 group. However, the level of D-dimer in the CLCN7 group was lower than that in the TCIRGI group (2.7 (1.0, 3.1) vs. 6.3 (2.5, 9.7) μg/L, Z=2.83, P=0.005). After hematopoietic stem cell transplantation, there was no significant difference in 5-year overall survival rate between the two groups (92.3%±7.4% vs. 83.3%±7.6%, χ²=0.56, P=0.456). Conclusions: TCIRGI gene mutations are more common in children with osteopetrosis. Children with TCIRGI gene mutations have younger age, lower levels of phosphorus, CK-MB, and neutrophils and higher level of D-dimer at the onset. After hematopoietic stem cell transplantation, patients with CLCN7 or TCIRGI gene mutations have similar prognosis.
		                        		
		                        		
		                        		
		                        			Child
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Osteopetrosis/therapy*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Genes, Recessive
		                        			;
		                        		
		                        			Phosphorus
		                        			;
		                        		
		                        			Chloride Channels/genetics*
		                        			;
		                        		
		                        			Vacuolar Proton-Translocating ATPases/genetics*
		                        			
		                        		
		                        	
4.Inhibition of GAS5 promoted invasion, migration and epithelial-mesenchymal transition of colorectal cancer cells via miR-21/PTEN/Akt axis.
Bing Hong XIONG ; Sha Sha LI ; Zi Yang REN ; Zhe ZHANG ; Ya Zhou LIU ; Yue SUN ; Jun Lin CHI ; Hua You LUO
Chinese Journal of Oncology 2022;44(11):1168-1174
		                        		
		                        			
		                        			Objective: To explore the effect of growth arrest-specific5 (GAS5) inhibition on the proliferation, colony formation, invasion, migration andepithelial-mesenchymal transition(EMT), cancer cell stem of HCT-116 and its mechanism. Methods: The colorectal carcinoma (CRC) cell HCT116 was divided into blank control, negative control (NC), si-GAS5 and si-GAS5+ miR-21 inhibitor groups. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to test the expressions of miR-21 and GAS5 at 48 h after transfection. The binding site of GAS5 and miR-21 was determined by luciferase reporter array. Cell proliferation ability was detected by CCK-8 assay. Cell colony ability was detected by colony formation assay. Cell invasion and migration abilities were detected by Transwell assay. Cell cycle and apoptosis were examined by flow cytometer (FCM). The protein levels of EMT associated factors including Snail, N-cadherin, vimentin, E-cadherin, stem cell related factors including CD44, SOX2, Oct2, and PTEN/Akt signal pathway associated factors were examined by western blotting. Results: The expression levels of miR-21 in blank, NC, si-GAS5 group were 1.00±0.10, 1.00±0.10, 1.80±0.20, the absorbance values were 0.51±0.02, 0.50±0.01 and 0.65±0.01, the cell clones were 90±4, 91±5, 200±8, the invaded cells were 118±3, 119±3, 150±4, the migrated cells were 110±2, 108±2, 127±2, the cell ratios in G(1) phase were (49.3±2.1)%, (50.1±2.0)% and (42.2±1.1)%, the cell ratios in S phase were (19.2±1.2)%, (20.2±1.1)% and (28.3±2.2)%, the cell apoptotic ratios were (14.4±2.2)%, (14.5±2.1)% and (7.2±1.3)%. These results indicated that inhibition of GAS5 up regulated the expression level of miR-21, promoted cell proliferation, invasion and migration, decreased G(1)-phase cells and increased S-phase cells, and suppressed cell apoptosis (P<0.05). Moreover, inhibition of GAS5 up regulated the expressions of Snail, N-cadherin, vimentin, Sox2, CD44, Oct2 and p-Akt in HCT-116 cells (P<0.05), while down regulated the expressions of E-cadherin and PTEN (P<0.05). Inhibition of miR-21 reversed the impact of GAS5 knockdown on PTEN/Akt signaling pathway (P<0.05). Conclusion: GAS5 can act as a competing endogenous RNA for miR-21, and down regulation of GAS5 can promote the development of CRC by activating the miR-21/PTEN/Akt signaling pathway and promoting the acquisition of EMT and tumor cell stemness.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Cadherins/metabolism*
		                        			;
		                        		
		                        			Cell Line, Tumor
		                        			;
		                        		
		                        			Cell Movement/genetics*
		                        			;
		                        		
		                        			Cell Proliferation/genetics*
		                        			;
		                        		
		                        			Colorectal Neoplasms/pathology*
		                        			;
		                        		
		                        			Epithelial-Mesenchymal Transition/genetics*
		                        			;
		                        		
		                        			Gene Expression Regulation, Neoplastic
		                        			;
		                        		
		                        			MicroRNAs/metabolism*
		                        			;
		                        		
		                        			Proto-Oncogene Proteins c-akt/metabolism*
		                        			;
		                        		
		                        			PTEN Phosphohydrolase/metabolism*
		                        			;
		                        		
		                        			Vimentin/metabolism*
		                        			
		                        		
		                        	
5.Clinical Characteristic, Diagnosis and Treatment of Acute Lymphoblastic Leukemia Combined with Pneumocystis Carinii Pneumonia in Children.
Shao-Fen LIN ; Le-Le HOU ; Jian WANG ; Lyu-Hong XU ; Yong LIU ; You-Gang MAI ; Jian-Pei FANG ; Dun-Hua ZHOU
Journal of Experimental Hematology 2022;30(4):1079-1085
		                        		
		                        			OBJECTIVE:
		                        			To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment.
		                        		
		                        			METHODS:
		                        			Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized.
		                        		
		                        			RESULTS:
		                        			The male-to-female ratio of the five children was 1∶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-β-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died.
		                        		
		                        			CONCLUSION
		                        			PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.
		                        		
		                        		
		                        		
		                        			Caspofungin/therapeutic use*
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Child, Preschool
		                        			;
		                        		
		                        			Dyspnea
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Pneumonia, Pneumocystis/therapy*
		                        			;
		                        		
		                        			Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*
		                        			;
		                        		
		                        			Respiratory Sounds
		                        			;
		                        		
		                        			Retrospective Studies
		                        			
		                        		
		                        	
6.Efficacy of laparoscopic proximal gastrectomy with double-tract reconstruction versus laparoscopic total gastrectomy with Roux-en-Y reconstruction for early upper gastric cancer.
Guang Lin QIU ; Chao WEI ; Meng Ke ZHU ; Shao Ning HAN ; Xiao Wen LI ; Hai Jiang WANG ; Pan Xing WANG ; Jia Huang LIU ; Hua You ZHOU ; Xin Hua LIAO ; Xiang Ming CHE ; Lin FAN
Chinese Journal of Gastrointestinal Surgery 2022;25(5):412-420
		                        		
		                        			
		                        			Objective: To compare clinical efficacy between laparoscopic radical proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopic radical total gastrectomy with Roux-en-Y reconstruction (LTG-RY) in patients with early upper gastric cancer, and to provide a reference for the selection of surgical methods in early upper gastric cancer. Methods: A retrospective cohort study method was carried out. Clinical data of 80 patients with early upper gastric cancer who underwent LPG-DTR or LTG-RY by the same surgical team at the Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2021 were retrospectively analyzed. Patients were divided into the DTR group (32 cases) and R-Y group (48 cases) according to surgical procedures and digestive tract reconstruction methods. Surgical and pathological characteristics, postoperative complications (short-term complications within 30 days after surgery and long-term complications after postoperative 30 days), survival time and nutritinal status were compared between the two groups. For nutritional status, reduction rate was used to represent the changes in total protein, albumin, total cholesterol, body mass, hemoglobin and vitamin B12 levels at postoperative 1-year and 2-year. Non-normally distributed continuous data were presented as median (interquartile range), and the Mann-Whitney U test was used for comparison between groups. The χ(2) test or Fisher's exact test was used for comparison of data between groups. The Mann-Whitney U test was used to compare the ranked data between groups. The survival rate was calculated by Kaplan-Meier method categorical, and compared by using the log-rank test. Results: There were no statistically significant differences in baseline data betweeen the two groups, except that patients in the R-Y group were oldere and had larger tumor. Patients of both groups successfully completed the operation without conversion to laparotomy, combined organ resection, or perioperative death. There were no significant differences in the distance from proximal resection margin to superior margin of tumor, postoperative hospital stay, time to flatus and food-taking, hospitalization cost, short- and long-term complications between the two groups (all P>0.05). Compared with the R-Y group, the DTR group had shorter distal margins [(3.2±0.5) cm vs. (11.7±2.0) cm, t=-23.033, P<0.001], longer surgery time [232.5 (63.7) minutes vs. 185.0 (63.0) minutes, Z=-3.238, P=0.001], longer anastomosis time [62.5 (17.5) minutes vs. 40.0 (10.0) minutes, Z=-6.321, P<0.001], less intraoperative blood loss [(138.1±51.6) ml vs. (184.3±62.1) ml, t=-3.477, P=0.001], with significant differences (all P<0.05). The median follow-up of the whole group was 18 months, and the 2-year cancer-specific survival rate was 97.5%, with 100% in the DTR group and 95.8% in the R-Y group (P=0.373). Compared with R-Y group at postoperative 1 year, the reduction rate of weight, hemoglobin and vitamin B12 were lower in DTR group with significant differences (all P<0.05); at postoperative 2-year, the reduction rate of vitamin B12 was still lower with significant differences (P<0.001), but the reduction rates of total protein, albumin, total cholesterol, body weight and hemoglobin were similar between the two groups (all P>0.05). Conclusions: LPG-DTR is safe and feasible in the treatment of early upper gastric cancer. The short-term postoperative nutritional status and long-term vitamin B12 levels of patients undergoing LPG-DTR are superior to those undergoing LTG-RY.
		                        		
		                        		
		                        		
		                        			Albumins
		                        			;
		                        		
		                        			Anastomosis, Roux-en-Y/adverse effects*
		                        			;
		                        		
		                        			Cholesterol
		                        			;
		                        		
		                        			Gastrectomy/methods*
		                        			;
		                        		
		                        			Hemoglobins
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Laparoscopy/methods*
		                        			;
		                        		
		                        			Postoperative Complications/etiology*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Stomach Neoplasms/pathology*
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Vitamin B 12
		                        			
		                        		
		                        	
7. Research progress of HPK1 protein kinase in tumor
Lei MIAO ; Rui ZUO ; Xiao-Jun JI ; Qiu-Hua ZHOU ; Chang-You MA ; Jian WU ; Dan XU
Chinese Pharmacological Bulletin 2022;38(9):1292-1296
		                        		
		                        			
		                        			 Hematopoietic progenitor kinase 1 ( HPK1 ) , also known as MAP4K1 , is a serine/threonine protein kinase and a member of the MAP4K family of mammalian Ste20-related pro¬tein kinases.Recent studies have found that HPK1 is assoeiated with the occurrence and progression of a variety of tumors, and may play an important role in some malignant tumors.This pa¬ per reviews the HPK1 signaling pathway, its relationship with tumor and drug development progress, so as to provide referenee for the research of HPK1 protein kinase. 
		                        		
		                        		
		                        		
		                        	
8.Survival outcomes and prognostic factors of patients with salvage surgery for hypopharyngeal carcinoma after radiotherapy.
Qi HUANG ; Zhen Hua WU ; Lei ZHOU ; Quan Jie YOU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(2):191-196
		                        		
		                        			
		                        			Objective: To investigate the survival outcomes and prognostic factors of patients with salvage surgery for hypopharyngeal carcinoma after radiotherapy. Methods: A retrospective analysis was performed, including 26 patients treated in Ningbo Medical Center Lihuili Hospital between January 2010 and December 2015. All patients were males, aged 48-83 years, of whom 8 cases were local residual after radiotherapy alone, 8 cases were local recurrence after postoperative radiotherapy, 2 cases were residual of cervical lymph nodes after radiotherapy alone, 2 cases were recurrence of cervical lymph nodes after radiotherapy alone, 2 cases were recurrence of cervical lymph nodes after postoperative radiotherapy and 4 cases were recurrence of tracheal stoma. The salvage operations included: local resection, local resection with neck dissection, simple neck dissection, tumor resection of tracheostomy, and additional repair according to the defect. Chi square test was used for recurrence and metastasis analysis, Kaplan-Meier method for survival analysis, Log-rank test for univariate analysis, and Cox regression model for multivariate analysis. Results: The complication rate of salvage surgery was 23.1% (6/26). The recurrence rate was 65.4% (17/26) and the distant metastasis rate was 42.3% (11/26) in the 5-year follow-up after salvage surgery. Patient's age and tumor invasion extent were correlated with recurrence. Initial treatment, tumor persistence or recurrence after radiotherapy, recurrence location and tumor invasion extent were correlated with distant metastasis (all P<0.05). Overall, 3 year and 5 year survival rates were 42.3% and 23.1% respectively. Age, recurrence location, surgical margin and tumor invasion extent were related to prognosis (χ²=6.56, 10.68, 9.32, and 7.90 respectively, all P<0.05). Multivariate analysis showed that surgical margin and tumor invasion extent were independent risk factors for prognosis (OR (95%CI) = 3.19 (1.03-9.84), 14.37 (2.46-84.08), both P<0.05). Conclusion: Salvage surgery is the first choice for patients with recurrence after radiotherapy for hypopharyngeal carcinoma. Safe surgical margin should be ensured, especially in tumors invading muscle, bone tissue or lymph node capsule.
		                        		
		                        		
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Carcinoma, Squamous Cell/surgery*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypopharyngeal Neoplasms/surgery*
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Neoplasm Recurrence, Local/surgery*
		                        			;
		                        		
		                        			Neoplasm Staging
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Salvage Therapy
		                        			;
		                        		
		                        			Survival Rate
		                        			
		                        		
		                        	
9.Evaluation of low-quality fundus image enhancement based on cycle-constraint adversarial network
Xueting ZHOU ; Weihua YANG ; Xiao HUA ; Qijing YOU ; Jing SUN ; Jianxin SHEN ; Cheng WAN
Chinese Journal of Experimental Ophthalmology 2021;39(9):769-775
		                        		
		                        			
		                        			Objective:To propose and evaluate the cycle-constraint adversarial network (CycleGAN) for enhancing the low-quality fundus images such as the blurred, underexposed and overexposed etc.Methods:A dataset including 700 high-quality and 700 low-quality fundus images selected from the EyePACS dataset was used to train the image enhancement network in this study.The selected images were cropped and uniformly scaled to 512×512 pixels.Two generative models and two discriminative models were used to establish CycleGAN.The generative model generated matching high/low-quality images according to the input low/high-quality fundus images, and the discriminative model determined whether the image was original or generated.The algorithm proposed in this study was compared with three image enhancement algorithms of contrast limited adaptive histogram equalization (CLAHE), dynamic histogram equalization (DHE), and multi-scale retinex with color restoration (MSRCR) to perform qualitative visual assessment with clarity, BRISQUE, hue and saturation as quantitative indicators.The original and enhanced images were applied to the diabetic retinopathy (DR) diagnostic network to diagnose, and the accuracy and specificity were compared.Results:CycleGAN achieved the optimal results on enhancing the three types of low-quality fundus images including the blurred, underexposed and overexposed.The enhanced fundus images were of high contrast, rich colors, and with clear optic disc and blood vessel structures.The clarity of the images enhanced by CycleGAN was second only to the CLAHE algorithm.The BRISQUE quality score of the images enhanced by CycleGAN was 0.571, which was 10.2%, 7.3%, and 10.0% higher than that of CLAHE, DHE and MSRCR algorithms, respectively.CycleGAN achieved 103.03 in hue and 123.24 in saturation, both higher than those of the other three algorithms.CycleGAN took only 35 seconds to enhance 100 images, only slower than CLAHE.The images enhanced by CycleGAN achieved accuracy of 96.75% and specificity of 99.60% in DR diagnosis, which were higher than those of oringinal images.Conclusions:CycleGAN can effectively enhance low-quality blurry, underexposed and overexposed fundus images and improve the accuracy of computer-aided DR diagnostic network.The enhanced fundus image is helpful for doctors to carry out pathological analysis and may have great application value in clinical diagnosis of ophthalmology.
		                        		
		                        		
		                        		
		                        	
10.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
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		                        			Female
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		                        			Gastrectomy
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		                        			Humans
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		                        			Male
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		                        			Neoadjuvant Therapy
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		                        			Neoplasm Staging
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		                        			Prognosis
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		                        			Retrospective Studies
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		                        			Stomach Neoplasms/surgery*
		                        			
		                        		
		                        	
            
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