Metabolic syndrome is a complex group of metabolic disorders with an increasing global incidence rate,posing a serious threat to human health.Sodium-glucose linked transporter 2(SGLT2)inhibitors are a new type of oral hypoglycemic drug.SGLT2 inhibitors not only lower blood glucose level in a non-insulin-dependent manner by inhibiting glucose reabsorption by renal proximal convoluted tubular epithelial cell to promote urinary glucose excretion,but also by improving islet β cell function,reducing inflammatory responses,and inhibiting oxidative stress.In addition,SGLT2 inhibitors can reduce body weight through osmotic diuresis and increase fat metabolism;reduce blood pressure by inhibiting excessive activation of sympathetic nervous system and by improving vascular function.They can also improve blood lipids by increasing degradation of triacylglycerol;reduce blood uric acid by promoting uric acid excretion in kidney and intestine,and by reducing uric acid synthesis.This article reviews the effects and mechanisms of SGLT2 inhibitors on multiple metabolic disorders in metabolic syndrome and explores their potential application in metabolic syndrome treatment.

AIM:To investigate the effect of vaccarin(VAC)on endothelial dysfunction in type 2 diabetes mellitus(T2DM),and to uncover the underlying mechanisms.METHODS:(1)C57BL/6 mice received intraperitoneal injection of streptozotocin and were fed with a high-fat diet(21.8 kJ/kg,60%of the energy source was fat)to construct a T2DM mouse model.Thirty mice were randomly divided into control,T2DM and T2DM+VAC groups,with 10 mice in each group.The mice in T2DM+VAC group were given 1 mg/kg VAC via oral gavage for 6 weeks,while those in control and T2DM groups were given the same volume of PBS.The mRNA and protein expression levels of BCL2-interacting pro-tein 3(BNIP3),PTEN-induced kinase 1(PINK1)and parkin in the thoracic aorta were detected by RT-qPCR and West-ern blot.(2)Human umbilical vein endothelial cells(HUVECs)were stimulated by high glucose(HG;35 mmol/L glu-cose).Mitochondrial membrane potential,autophagy and mitochondrial superoxide levels were detected using JC-1,acri-dine orange(AO)and MitoSOX staining,respectively.RESULTS:Compared with control group,the mRNA and protein levels of BNIP3,PINK1 and parkin were significantly increased in the thoracic aorta of T2DM mice(P<0.05).Compared with T2DM group,the mRNA and protein levels of BNIP3,PINK1 and parkin in the thoracic aorta were significantly re-duced in T2DM+VAC group(P<0.05).The results of JC-1,AO and MitoSOX staining showed that VAC attenuated the decrease in mitochondrial membrane potential and the increase in autophagy and mitochondrial superoxide levels in HG-in-duced HUVECs.Treatment with VAC also inhibited HG-mediated mitochondrial damage in HUVECs after BNIP3 overex-pression.The effect of miR-570-3p mimic on mitochondrial damage was similar to VAC.RT-qPCR and Western blot showed that both miR-570-3p mimic and VAC significantly reduced the mRNA and protein levels of BNIP3,PINK1 and parkin.In contrast,inhibition of miR-570-3p exhibited the opposite effects.CONCLUSION:Treatment with VAC alle-viated endothelial dysfunction in T2DM by inhibiting HG-induced mitochondrial dysfunction through miR-570-3p/BNIP3.

Background and objective Bone is a common site for metastasis in lung adenocarcinoma,but the mechanism behind lung adenocarcinoma bone metastasis is still unclear.And currently,there is a lack of easily traceable and stable lung adenocarcinoma bone metastasis cell models,which limits the research on the mechanism of lung adenocarcinoma bone metastasis.The establishment of human lung adenocarcinoma cell line that are highly metastatic to bone,labeled with green fluorescent proteins(GFP)and fireflies luciferase(LUC),along with transcriptomic characterization,would be beneficial for research on lung adenocarcinoma bone metastasis and provide new experimental methods.Methods The human lung ad-enocarcinoma cell line A549-GFP-LUC was injected into nude mice via the left ventricle to construct a bone metastasis model,and was domesticated in vivo for three consecutive times to obtain the human high bone metastasis lung adenocarcinoma cell line A549-GFP-LUC-BM3;cell counting kit-8(CCK-8),colony formation assay,scratch wound assays,Transwell assay and Western blot were used to compare the proliferation and invasion abilities of A549-GFP-LUC-BM3 with the parental cells.A549-GFP-LUC-BM3 cells and parental cells were further analyzed by transcriptomic sequencing.Results Human high-bone metastatic lung adenocarcinoma cells A549-GFP-LUC-BM3 was successfully established.Compared to parental cells,this cells exhibited a significantly higher incidence of bone metastasis and enhanced in vitro proliferation,migration,and invasion abilities.Transcriptomic sequencing results revealed that the A549-GFP-LUC-BM3 cell line had 2954 differentially expressed genes compared to the parental cells,with 1021 genes up-regulated and 1933 genes down-regulated.Gene Ontology(GO)functional enrichment analysis indicated that the differentially expressed genes were primarily localized in cellular components such as the cell periphery.The molecular functions identified as significantly enriched included signaling receptor activity,cal-cium ion binding,and extracellular matrix structural constituent.Additionally,the biological processes found to be enriched were cell adhesion and biological adhesion.The enrichment analysis conducted using the Kyoto Encyclopedia of Genes and Genomes(KEGG)revealed that the differentially expressed genes were primarily involved in the metabolism of xenobiot-ics by cytochrome P450,retinol metabolism,drug metabolism-cytochrome P450,cell adhesion molecules,steroid hormone biosynthesis,and the nuclear factor kappa B(NF-κB)signaling pathway.Conclusion The highly bone-metastatic human lung adenocarcinoma cell line with GFP and luciferase double labeling was successfully established.The biological behavior and transcriptome sequencing of the cell line suggest that it has a high bone-metastatic potential.

The construction of experimental animal models plays an important supporting role in research into the mechanisms of action of Chinese medicines.There have been increasing reports of the construction and evaluation of animal models of spleen deficiency;however,the construction method have involved different standards and there has been insufficient objectification of the evaluation indexes.In this review,we summarize the construction and evaluation method of animal models of spleen deficiency from the aspects of animal selection,model establishment,macroscopic characterization,behavioral experiments,and objective indexes of spleen deficiency,with a view to providing theoretical guidance for the construction of experimental animal models of spleen deficiency and references for the selection of animal model platforms for spleen deficiency.

Objective:To investigate the efficacy of different laparoscopic surgeries for gastrointestinal stromal tumors (GIST) of gastric cardia and fundus.Methods:The retrospective cohort study was conducted. The clinicopathological data of 251 patients with GIST of gastric cardia and fundus who underwent laparoscopic radical resection in 14 medical centers, including Guangdong Provincial People′s Hospital et al, from December 2007 to December 2021 were collected. There were 123 males and 128 females, aged 58(24,87)years. Observation indicators: (1) treatment; (2) clinicopathological data of patients undergoing different laparoscopic surgeries; (3) subgroup analysis for special laparoscopic techniques. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test or ANOVA. Measure-ment data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test or Kruskal-Wallis H test. Count data were described as absolute numbers or percentages. Comparison of ordinal data was conducted using the rank sum test. Results:(1) Treatment. Of the 251 patients,202 cases underwent gastric wedge resection, 26 cases underwent special laparoscopic techniques including 10 cases with serotomy and dissection and 16 cases with transluminal gastrectomy, 23 cases underwent structural gastrectomy including 6 cases with total gastrectomy and 17 cases with proximal partial gastrectomy. There were 24 patients had postoperative complications after surgery. (2) Clinicopathological data of patients undergoing different laparoscopic surgeries. The gender (male, female), age, tumor diameter, operation time, volume of intraoperative blood loss, length of incision, time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, duration of postoperative hospital stay, cases with perioperative complications, cases with mitotic count as ≤5/50 high power field, 6?10/50 high power field, >10/50 high power field, cases be classified as very low risk, low risk, medium risk, high risk according to the National Institutes of Health risk classification, cases with tumor located at fundus and gastric cardia were 93, 109, (59±11)years, 3.50(0.40,10.00)cm, 88.00(25.00,290.00)minutes,20.00(25.00,290.00)mL, 4.00(2.00,12.00)cm, 3.00(1.00,9.00)days, 4.00(1.00,16.00)days, 5.00(1.00,18.00)days, 14, 164, 31, 7, 47, 83, 50, 22, 30, 172 in patients undergoing gastric wedge resection, respectively. The above indicators were 19, 7, (49±14)years, 2.55(0.20,5.00)cm, 101.00(59.00,330.00)minutes, 27.50(2.00,300.00)mL, 4.50(0,6.00)cm, 2.50(1.00,10.00)days, 4.00(1.00,16.00)days, 6.00(1.00,18.00)days, 3, 20, 5, 1, 15, 5, 2, 4, 24, 2 in patients undergoing special laparos-copic techniques, and 11, 12, (52±10)years, 5.00(0.80,10.00)cm, 187.00(80.00,325.00)minutes, 50.00(10.00,300.00)mL, 6.00(4.00,12.00)cm, 4.00(2.00,8.00)days, 6.00(3.00,14.00)days, 8.00(2.00,18.00)days, 7, 11, 5, 7, 2, 6, 6, 9, 13, 10 in patients undergoing structural gastrectomy. There were significant differences in the above indicators among the three groups of patients ( χ2=6.75, F=10.19, H=17.71, 37.50, 35.54, 24.68, 16.09,20.20, 13.76, χ2=13.32, Z=28.98, 32.17, χ2=82.14, P<0.05). (3) Subgroup analysis for special laparoscopic techniques. The time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, classification of tumor location (endophytic type, exophytic type, parietal type) were 4.50(1.00,10.00)days, 8.00(3.00,12.00)days, 0, 8, 2 in patients undergoing serotomy and dissection, versus 2.00(1.00,4.00)days, 3.00(1.00,6.00)days, 16, 0, 0 in patients undergoing transluminal gastrectomy. There were significant differences in time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake between them ( Z=-2.65, -3.16, P<0.05); and there was a significant difference in classification of tumor location between them ( P<0.05). Conclusions:Gastric wedge resection is the most commonly used laparoscopic technique for GIST of gastric cardia and fundus. The application of special laparoscopic techniques is focused on the GIST of cardia to preserve the function of the cardia.

With the development of precision medicine for lung cancer, targeted therapy has greatly improved the survival and prognosis of patients with advanced non-small cell lung cancer (NSCLC), but the occurrence of acquired drug resistance ultimately leads to patients with no targeted drugs available and no standard treatment options for this group of patients afterwards. The emergence of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced NSCLC. However, due to the unique features of NSCLC with epidermal growth factor receptor (EGFR) mutation, such as immunosuppressive tumor microenvironment (TME), single ICIs treatment has limited clinical benefits in NSCLC patients with EGFR mutation, and the combination of ICIs with chemotherapy and/or targeted therapies is the trend. This review further discusses potential subpopulations with EGFR mutations that may benefit from ICIs treatment, and analyzes how decisions can be made in the era of combined immunotherapy to maximize the efficacy of ICIs treatment in EGFR mutation targeted therapy for NSCLC patients with drug resistance, with the aim of achieving individualized treatment.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Immune Checkpoint Inhibitors ; Lung Neoplasms/genetics* ; Mutation ; ErbB Receptors/genetics* ; Tumor Microenvironment

OBJECTIVES: Systemic lupus erythematosus (SLE) is a multi-systemic disease with the unknown pathogenic mechanism. DNA demethylation is involved in SLE pathogenesis. Growth arrest and DNA damage inducible 45 alpha (Gadd45a) takes part in the process of DNA demethylation. Gadd45a is a DNA repair-related protein. This study aims to investigate the expressions of some proteins [including activation-induced cytidine deaminase (AID), thymine DNA glycosylase (TDG), and methyl-CpG-binding domain protein 4 (MBD4)] involving in base excision repair (BER) process in CD4⁺ T cells in patients with SLE, and to analyze the correlations between the above BER proteins and lupus disease. METHODS: From January 2019 to September 2020, 12 SLE patients and 12 healthy controls were recruited from Second Xiangya Hospital of Central South University. Peripheral blood mononuclear cells (PBMCs) were separated by Ficoll-Hypaque density gradient centrifugation and then CD4+ T cells were isolated via positive selection using Miltenyi beads. We measured the messenger RNA (mRNA) and protein expressions of AID, TDG, and MBD4 by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, respectively. RESULTS: In contrast to controls, in SLE CD4+ T cells, the mRNA and protein expressions of AID were elevated (P=0.003, P=0.022, respectively); TDG protein expression was increased (P=0.017); and MBD4 protein level was reduced (P<0.001). No visible distinctions was found in the mRNA expressions of either TDG or MBD4 between the 2 groups (both P>0.05). The mRNA and protein expressions of AID and the protein levels of TDG were positively correlated with SLE disease activity index (SLEDAI). And the mRNA and protein expressions of MBD4 were negatively correlated with SLEDAI. CONCLUSIONS In SLE CD4+ T cells, the increased expressions of AID and TDG and the decreased MBD4 expression may participate in SLE pathogenic mechanism.
Humans ; Leukocytes, Mononuclear ; Lupus Erythematosus, Systemic/metabolism* ; CD4-Positive T-Lymphocytes/metabolism* ; DNA Repair ; RNA, Messenger/metabolism*

Objective:To investigate the clinical efficacy and prognostic influencing factors of radical surgery for duodenal gastrointestinal stromal tumor (GIST).Methods:The retrospective cohort study was conducted. The clinicopathological data of 741 duodenal GIST patients who under-went radical surgery in 17 medical centers, including 121 cases in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 121 cases in Chinese PLA General Hospital, 116 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 77 cases in Fudan University Shanghai Cancer Center, 77 cases in West China Hospital, Sichuan University, 31 cases in Guangdong Provincial People′s Hospital, 24 cases in Fujian Cancer Hospital, 22 cases in Fujian Medical University Union Hospital, 25 cases in Shengjing Hospital of China Medical University, 19 cases in Xiangya Hospital, Central South University, 23 cases in Zhejiang Cancer Hospital, 17 cases in Liaoning Cancer Hospital＆Institute, 17 cases in the First Affiliated Hospital of Xiamen University, 15 cases in Sun Yat-sen University Cancer Center, 14 cases in the First Affiliated Hospital of Nanjing Medical University, 14 cases in Zhongshan Hospital Affiliated to Xiamen University and 8 cases in General Hospital of Chinese People′s Liberation Army Air Force, from January 2010 to April 2020 were collected. There were 346 males and 395 females, aged 55(range, 17?86)years. Observation indicators: (1) neoadjuvant treatment; (2) surgical and postoperative situations; (3) follow-up; (4) stratified analysis. Follow-up was conducted using outpatient examination or telephone interview. Patients were followed up once every 3?6 months during neoadjuvant therapy and once every 6?12 months after radical surgery to detect tumor recurrence and survival of patient up to April 2022. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-rank test was used for survival analysis. The COX regression model was used for univariate and multivariate analyses. Propensity score matching was done by the 1∶1 nearest neighbor matching method, and the matching tolerance was 0.02. Results:(1) Neoadjuvant therapy. Of the 741 patients, 34 cases received neoadjuvant therapy for 8(range, 3?44)months. Cases assessed as partial response, stable disease and progressive disease before the radical surgery of the 34 cases were 21, 9, 4, respectively. The tumor diameter of the 34 patients before the neoadjuvant therapy and before the radical surgery were 8.0(range, 3.0?26.0)cm and 5.3(range, 3.0?18.0)cm, with the regression rate as 31.9%(range, ?166.7% to 58.3%). (2) Surgical and postoperative situations. Of the 741 patients, 34 cases underwent radical surgery after receiving neoadjuvant therapy, and 707 cases underwent radical surgery directly. All the 741 patients underwent radical surgery successfully, in which 633, 102 and 6 cases received open surgery, laparoscopic surgery and endoscopic treatment, respectively. Of the 633 cases receiving open surgery and the 102 cases receiving laparoscopic surgery, cases with surgical resection range as pancreatoduodenectomy (PD) was 238, and cases with surgical resection range as duodenal limited resection, including duodenal wedge resection, distal gastrectomy, segmental duodenal resection, local resection of duodenal tumor or segmental duodenum combined with subtotal gastrectomy, was 497, 226, 55, 204, 12. Of the 741 patients, 131 cases had post-operative complications including 113 cases with grade Ⅰ?Ⅱ complications and 18 cases with ≥ grade Ⅲ complications of the Clavien-Dindo classification. The duration of postoperative hospital stay of the 741 patients was 13(range, 4?120)days. Of the 707 patients receiving direct radical surgery, 371 cases were evaluated as extremely low risk, low risk, medium risk of the modified National Institutes of Health (NIH) risk classification after surgery, and 336 cases were evaluated as high risk in which 205 cases receive postoperative adjuvant imatinib therapy with the treatment time as 24(range, 6?110)months. (3) Follow-up. All the 741 patients were followed up for 58(range, 7?150)months. During the follow-up, 110 patients had tumor recurrence and metastasis. The 1-, 3-, 5-year overall survival rates and 1-, 3-, 5-year disease-free survival rates of the 741 patients were 100.0%, 98.6%, 94.5% and 98.4%, 90.9%, 84.9%, respectively. The 1-, 3-, 5-year overall survival rates and 1-, 3-, 5-year disease-free survival rates of the 707 patients receiving direct radical surgery were 100.0%, 98.5%, 94.3% and 98.4%, 91.1%, 85.4%, respectively. (4) Stratified analysis. ① Analysis of prognostic factors in patients undergoing radical surgery directly. Results of univariate analysis showed that primary tumor location, tumor diameter, mitotic count, modified NIH risk classification and tumor gene information were related factors affecting the overall survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=0.43, 0.18, 0.22, 0.06, 0.29, 95% confidence intervals as 0.20?0.93, 0.09?0.35, 0.10?0.50, 0.03?0.12, 0.09?0.95, P<0.05). The primary tumor location, tumor diameter, mitotic count, modified NIH risk classification were related factors affecting the disease-free survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=0.65, 0.25, 0.25, 0.10, 95% confidence intervals as 0.41?1.03, 0.17?0.37, 0.15?0.42, 0.07?0.15, P<0.05). Results of multivariate analysis showed that primary tumor located at the horizontal segment of duodenum, mitotic count >5/50 high power field, tumor gene KIT exon 9 mutation were independent risk factors affecting the overall survival of 365 patients with primary duodenal GIST after removing 342 patients without tumor gene information who underwent direct radical surgery ( hazard ratio=2.85, 2.73, 3.13, 95% confidence intervals as 1.12?7.20, 1.07?6.94, 1.23?7.93, P<0.05). Tumor diameter >5 cm and mitotic count >5/50 high power field were independent risk factors affecting the disease-free survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=3.19, 2.98, 95% confidence intervals as 2.05?4.97, 1.99?4.45, P<0.05). ② Effect of postoperative adjuvant therapy on prognosis of high-risk patients of modified NIH risk classification. Of the 336 patients evaluated as high risk of the modified NIH risk classification, the 5-year overall survival rate and 5-year disease-free survival rate were 94.6% and 77.3% in the 205 cases with postoperative adjuvant therapy, versus 83.2% and 64.4% in the 131 cases without postoperative adjuvant therapy, showing significant differences between them ( χ2=8.39, 4.44, P<0.05). Of the 205 patients evaluated as high risk of the modified NIH risk classification who received postoperative adjuvant therapy, there were 106 cases receiving postoperative adjuvant therapy <36 months, with the 5-year overall survival rate and 5-year disease-free survival rate were 87.1% and 58.7%, and there were 99 cases receiving post-operative adjuvant therapy ≥36 months, with the 5-year overall survival rate and 5-year disease-free survival rate were 100.0% and 91.5%. There were significant differences in the 5-year overall survival rate and 5-year disease-free survival rate between the 106 patients and the 99 patients ( χ2=13.92, 29.61, P<0.05). ③ Comparison of clinical efficacy of patients with different surgical methods. Before propensity score matching, cases with primary tumor located at bulb, descending, horizontal, ascending segment of duodenum, cases with tumor diameter ≤5 cm and >5 cm were 95, 307, 147, 34, 331, 252, in the 583 patients receiving open surgery with complete clinical data, versus 15, 46, 17, 5, 67, 16 in the 83 patients receiving laparoscopic surgery with complete clinical data, showing no significant difference in the primary tumor location ( χ2=0.94, P>0.05), and a significant difference in the tumor diameter ( χ2=17.33, P<0.05) between them. After propensity score matching, the above indicator were 16, 39, 20, 8, 67, 16 in the 83 patients receiving open surgery, versus 15, 46, 17, 5, 67, 16 in the 83 patients receiving laparoscopic surgery, showing no significant difference between them ( χ2=1.54, 0.00, P>0.05). Cases with postoperative complications, cases with grade Ⅰ?Ⅱ complica-tions and ≥grade Ⅲ complications of the Clavien-Dindo classification, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate were 17, 12, 5, 11(range, 5?120)days, 92.0%, 100.0% in the 83 patients receiving open surgery, versus 9, 7, 2, 11(range, 5?41)days, 91.6%, 97.3% in the 83 patients receiving laparoscopic surgery, showing no signi-ficant difference in postoperative complications, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate ( χ2=2.91, Z=3 365.50, χ2=3.02, 1.49, P>0.05) between them. There was no significant difference in complications of the Clavien-Dindo classification between them ( P>0.05). ④ Comparison of clinical efficacy of patients with primary tumor located at the descending segment of duodenum who underwent surgery with different surgical resection scopes. Before propensity score matching, cases with tumor diameter ≤5 cm and >5 cm, cases with tumor located at opposite side of mesangium and mesangium were 71, 85, 28, 128 in the 156 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 92, 41, 120, 13 in the 133 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing significant differences between them ( χ2=16.34, 150.10, P<0.05). After propensity score matching, the above indicator were 28, 13, 16, 25 in the 41 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 28, 13, 16, 25 in the 41 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing no significant difference between them ( χ2=0.00, 0.00, P>0.05). Cases with postopera-tive complications, cases with grade Ⅰ?Ⅱ complications and ≥grade Ⅲ compli-cations of the Clavien-Dindo classification, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate were 13, 11, 2, 15(range, 9?62)days, 94.2%, 64.3% in the 41 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 9, 8, 0, 15(range, 7?40)days, 100.0%, 78.8% in the 41 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing no significant difference in post-operative complica-tions, the 5-year overall survival rate and 5-year disease-free survival rate ( χ2=0.99, 0.34, 1.86, P>0.05) between them. There was no significant difference in complications of the Clavien-Dindo classification ( P>0.05) and there was a significant difference in duration of postopera-tive hospital stay ( Z=614.50, P<0.05) between them. Conclusions:The clinical efficacy of radical surgery for duodenal GIST are ideal. Primary tumor located at the horizontal segment of duodenum, mitotic count >5/50 high power field, tumor gene KIT exon 9 mutation are independent risk factors affec-ting the overall survival of patients undergoing direct radical surgery and tumor diameter >5 cm and mitotic count >5/50 high power field are independent risk factors affecting the disease-free survival of patients. There is no significant difference in the short-term efficacy and long-term prognosis between patients undergoing open surgery and laparoscopic surgery. For patients with primary tumor located at the descending segment of duodenum, the duration of postoperative hospital stay is longer in patients undergoing PD compared with patients undergoing duodenal limited resection. For patients evaluated as high risk of the modified NIH risk classification, posto-perative adjuvant therapy and treatment time ≥36 months are conducive to improving the prognosis of patients.

Objective:To study the clinical efficacy of chimeric antigen receptor T-cell (CART) treatment followed by a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with B-cell acute lymphoblastic leukemia (ALL) who relapsed following the first HSCT.Methods:Retrospective analysis of the clinical characteristics and prognosis of 41 patients with B-cell ALL who received a second allo-HSCT from October 2015 to June 2020 in Hebei Yanda Lu Daopei Hospital. After the first HSCT, all patients received CD19-CART, or CD22-CART treatment following a relapse of bone marrow morphology or extramedullary leukemia.Results:A total of 41 patients (male, 21; female, 20) were included in this study. The median age at the second HSCT was 16 (3-46) years. There were 31 cases of bone marrow recurrence (75.6%) , 5 cases of extramedullary recurrence (12.2%) , and 5 cases of bone marrow and extramedullary recurrences (12.2%) . After relapse, 35 patients (85.4%) received CD19-CART treatment, 2 patients received CD22-CART treatment (4.9%) , and 4 patients received CD19-CART and CD22-CART treatments (9.8%) . The expected 3-year overall survival (OS) , leukemia-free survival, cumulative relapse incidence, and non-relapse mortality (NRM) of patients after the second HSCT were 48.9% (95% CI 23.0%-70.6%) , 41.8% (95% CI 17.3%-64.9%) , 8.8% (95% CI 2.9%-26.4%) , and 51.1% (95% CI 31.2%-83.6%) , respectively. The 1-year OS of patients who relapsed ≤6 months and >6 months after the first HSCT were 45.0% (95% CI 12.7%-73.5%) and 75.0% (95% CI 51.4% -88.8%) ( P=0.017) , respectively. Conclusion:CART bridging in the second HSCT enables some B-cell ALL patients who relapsed after the first HSCT to achieve long-term survival. However, because of the high NRM, further modifications could help improve the outcome.

OBJECTIVE: To explore the causes of oocyte vitrification and its application in assisted reproduction. METHODS: We retrospectively analyzed the data of 26 patients with 27 cycles of oocyte vitrification cryopreservation undergoing intracytoplasmic sperm injection (ICSI) and embryo transfer between January, 2008 and October, 2018. The causes of oocyte vitrification and the outcomes of ICSI and clinical pregnancy were analyzed. RESULTS: The causes of oocytes vitrification included mainly azoospermia or severe spermatogenesis disorder of the husband, failure to obtain sperms from the husband, failure of the husband to be present on the day of oocyte retrieval and acute diseases of the husband to not allow sperm collection. A total of 274 oocytes were frozen in 27 oocyte retrieval cycles, and 217 eggs were thawed in 19 cycles with a survival rate of 81.11% (176/217). The normal fertilization rate, cleavage rate and high-quality embryo rate was 74.81% (98/131), 89.80% (88/98) and 36.73% (36/98), respectively. Fifteen patients underwent embryo transfer, and the clinical pregnancy rate and live birth rate was 53.33% (8/15) and 33.33% (5/15), respectively. Compared with patients below 35 years of age, the patients aged above 35 years had significantly lower oocyte survival rate after thawing (82.76% 74.42%, =0.211), clinical pregnancy rate (77.78% 16.67%, =0.041) and live birth rate (55.56% 0, =0.044). CONCLUSIONS Oocytes vitrification can be used as a remedy for infertile couples who fail to provide sperms due to male factors on the day of oocyte retrieval. Vitrification of the oocytes does not significantly affect the fertilization rate or the clinical pregnancy rate. The survival rate of the thawed oocytes is related to the age of the wife, and an age younger than 35 years can be optimal for achieving favorable clinical pregnancy outcomes after oocyte vitrification.
Adult ; Cryopreservation ; Embryo Transfer ; Female ; Humans ; Male ; Oocytes ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Vitrification