AIM: To investigate the effects of agkis-trodon halys venom anti-tumor component (AHVAC-) on the biological behavior of gastric cancer MKN-28 cells. METHODS: Gastric cancer MKN-28 cells were treated with the experimental concentrations (5, 10, 15 μg/mL) of AHAVC- for 24 h. Cell proliferation and toxicity assay (cell counting kit-8, CCK-8) was used to detect the inhibition rates of the cells in different concentrations of AHVAC-. The migration ability of the cells was evaluated by wound-healing and Transwell assay. The apoptosis were observed by laser confocal microscopy with annexin V-mCherry/DAPI double staining, and the apoptosis rates were analyzed by flow cytometry with annexin V-FITC/PI double fluorescence staining. The protein level of Caspease-3 was determined by Western blot. RESULTS: Compared with normal control group, the results of AHVAC- concentration groups showed that with the increase of AHVAC- concentration, the proliferative activity of MN-28 cells decreased gradually (P<0.01), the cell migration ability decreased gradually (P<0.01), and the cell apoptosis rate increased (P<0.05). The expression of apoptosis-related protein Caspease-3 was up-regulated (P<0.01). CONCLUSION: AHVAC- inhibits proliferation and migration of gastric cancer MSN-28 cells and induces apoptosis.

Objective To explore the comparison of the predictive value of three risk assessment tools on the chemotherapy-induced nausea and vomiting(CINV)in cancer patients.Methods From January 2022 to December 2022,convenience sampling was used to select 626 cancer patients with Intravenous chemotherapy in the Department of Hepatobiliary Pancreatic Oncology of Zhejiang Cancer Hospital as the research object.CINV risk assessment of patients was performed using George teams acute CINV prediction tool,Dranitsari's CINV risk assessment and CINV nomogram model.Area under curve(AUC),sensitivity,specificity and Youden index were used to compare the predictive value of the three tools.Results Totally 622 patients were ultimately included in the study,with an overall effective rate of 99.36%.There were 51.13%(318/622)patients who experienced CINV.Specifically,patients with grade 2 or higher acute CINV accounted for 18.17%(113/622).When using the three tools for acute CINV risk assessment,the AUC was respectively 0.591,0.616 and 0.558.And Dranitsari's CINV risk assessment has the highest sensitivity,acute and delayed chemotherapy-induced nausea and vomiting prediction tool has the highest specificity.Comparatively,Dranitsari's CINV risk assessment on the Yorden index is better.Conclusion The incidence of CINV in cancer patients is at a high level.The three tools can not effectively predict the risk of acute CINV.We need to develop a localized,multi-disease,standardized CINV risk assessment model for hospital.

Hepatocellular carcinoma (HCC) has an insidious onset, and most patients are in the advanced stage when attending the hospital and thus lose the opportunity for radical surgical resection, which results in the poor prognosis of patients. With the development of clinical treatment, the treatment of advanced HCC has gradually transitioned from the relatively single and limited treatment options in the past to the new model of comprehensive treatment. In recent years, immunotherapy, represented by immune checkpoint inhibitors (ICIs), has become widely used in clinical practice. At present, a number of clinical studies have been conducted for immunotherapy combined with local and targeted antitumor therapy, and in particular, ICIs combined with targeted therapy have become a research hotspot in the field of HCC treatment. This article reviews the research advances in immunotherapy for the treatment of HCC.

Periodontology is one of the important disciplines in oral clinical medicine, which covers a wide range of subjects and intersects with many basic disciplines. Under the environment of the implementation of modular teaching in Shanghai Jiao Tong University School of Medicine, the assessment method with separate propositions for the teaching and research section is still adopted. There is a mismatch between the assessment mode and the curriculum setting; the basic subject propositions are difficult to be combined with clinical cases; the knowledge point assessment is single, and the students' ability to integrate the knowledge points cannot be assessed. The development and construction of the comprehensive examination database for periodontology was based on curriculum integration, gathering the teaching backbones of various disciplines, focusing on periodontology, radiating all related disciplines, unifying the proposition outline, proposition type, proposition principle, combining with relevant knowledge points of various disciplines based on clinical cases, and tried to apply to clinical students majoring in stomatology. The use of the examination database promotes students' ability to flexibly apply theoretical knowledge to clinical case analysis, further promotes the reform of modular teaching, lays a solid foundation for future clinical work, and meanwhile provides an important basis for directions of the teaching and research section.

Objective:To study the distribution and antibiotics resistance of the main pathogens of neonatal purulent meningitis in different regions of China.Methods:A retrospective descriptive clinical epidemiological study was conducted in children with neonatal purulent meningitis which admitted to 18 tertiary hospitals in different regions of China between January 2015 to December 2019. The test results of blood and cerebrospinal fluid, and drug sensitivity test results of the main pathogens were collected. The distributions of pathogenic bacteria in children with neonatal purulent meningitis in preterm and term infants, early and late onset infants, in Zhejiang Province and other regions outside Zhejiang Province, and in Wenzhou region and other regions of Zhejiang Province were analyzed. The chi-square test was used for statistical analysis.Results:A total of 210 neonatal purulent meningitis cases were collected. The common pathogens were Escherichia coli ( E. coli)(41.4%(87/210)) and Streptococcus agalactiae ( S. agalactiae)(27.1%(57/210)). The proportion of Gram-negative bacteria in preterm infants (77.6%(45/58)) with neonatal purulent meningitis was higher than that in term infants (47.4%(72/152)), and the difference was statistically significant ( χ2=15.54, P=0.001). There were no significant differences in the constituent ratios of E. coli (36.5%(31/85) vs 44.8%(56/125)) and S. agalactiae (24.7%(21/85) vs 28.8%(36/125)) between early onset and late onset cases (both P>0.05). The most common pathogen was E. coli in different regions, with 46.7%(64/137) in Zhejiang Province and 31.5%(23/73) in other regions outside Zhejiang Province. In Zhejiang Province, S. agalactiae was detected in 49 out of 137 cases (35.8%), which was significantly higher than other regions outside Zhejiang Province (11.0%(8/73)). The proportions of Klebsiella pneumoniae, and coagulase-negative Staphylococcus in other regions outside Zhejiang Province (17.8%(13/73) and 16.4%(12/73)) were both higher than those in Zhejiang Province (2.9%(4/137) and 5.1%(7/137)). The differences were all statistically significant ( χ2=14.82, 12.26 and 7.43, respectively, all P<0.05). The proportion of Gram-positive bacteria in Wenzhou City (60.8%(31/51)) was higher than that in other regions in Zhejiang Province (38.4%(33/86)), and the difference was statistically significant ( χ2=6.46, P=0.011). E. coli was sensitive to meropenem (0/45), and 74.4%(32/43) of them were resistant to ampicillin. E. coli had different degrees of resistance to other common cephalosporins, among which, cefotaxime had the highest resistance rate of 41.8%(23/55), followed by ceftriaxone (32.4%(23/71)). S. agalactiae was sensitive to penicillin, vancomycin and linezolid. Conclusions:The composition ratios of pathogenic bacteria of neonatal purulent meningitis are different in different regions of China. The most common pathogen is E. coli, which is sensitive to meropenem, while it has different degrees of resistance to other common cephalosporins, especially to cefotaxime.

OBJECTIVE To study the nephrotoxicity of the extracts from different parts o f Miao medicine Wikstroemia indica in healthy rats ，and to provide reference for the study of its toxicity mechanism and clinical drug use. METHODS Using 70％ ethanol as solvent ，total ethanol extract of W. indica was extracted with diacolation method. After dispersing the above extract with water，the fractions of corresponding fractions were obtained with petroleum ether ，ethyl acetate and n-butanol，and the rest was the extract of water fraction. SD rats were randomly divided into total ethanol extract group ，petroleum ether fraction group ，ethyl acetate fraction group ，n-butanol fraction group ，water fraction group and blank group ，with 12 rats in each group （half male and half female ）. The rats in the administration groups were given the corresponding dose of drug solution intragastrically （total ethanol extract 317.520 mg/kg，petroleum ether fraction 7.875 mg/kg，ethyl acetate fraction 78.435 mg/kg，n-butanol fraction 53.865 mg/kg and water fraction 76.545 mg/kg），once a day ，for conse- cutive 2 weeks，and then stopped taking drug for 2 weeks； rats in the blank group were given equal volume of 1.0％ . sodium carboxymethyl cellulose solution intragastrically. Duringthe experiment ，the general conditions of rats were observed. The samples of urine （on the 14th and 28th day ），serum and bilateral renal tissues （on the 15th and 29th day ）were taken respectively，the renal index was calculated ，the levels of @qq.com renal function indexes in serum and urine were detected ，and the pathomorphological changes of renal tissues were observed. RESULTS During administration ，compared with blank group ，the rats in the total ethanol extract group and ethyl acetate fraction group showed poisoning behavior and activity characteristics such as mental depression ，decreased activity and diet ，thin stool and decreased body mass. The mental state of the rats in the petroleum ether fraction group ，n-butanol fraction group and water fraction group were slightly worse than that in blank group，and slightly decreased activity and diet as well as thin stool ，and slowly increased body mass were found ；however，there was no significant difference in anal temperature in each group. After 2 weeks of administration ，the renal index in total ethanol extract group ，the serum levels of N-acetylglucosaminidase（NAG），urea nitrogen （BUN）and creatinine （Cr）in total ethanol extract group and ethyl acetate fraction group ，serum level of NAG in n-butanol fraction group and serum level of Cr in water fraction group ，as while as NAG levels in urine of rats in total ethanol extract group and petroleum ether fraction group ，NAG and urinary protein levels in urine of rats in ethyl acetate fraction group were increased significantly （P＜0.05 or P＜0.01）. In the pathomorphological observation ，renal tubules showed different degrees of unclear structure ，cell swelling and a few cell necrosis in the total ethanol extract group ，petroleum ether fraction group and ethyl acetate fraction group ，accompanying by glomerular pyknosis，renal tubular sclerosis and inflammatory cell infiltration ，compared with blank group. After drug withdrawal ，the mental state of rats in the administration groups were significantly improved ，the amount of activity and diet increased ，and the stool tended to be normal. Two weeks after drug withdrawal and recovery ，the levels of above indexes in serum and urine of rats in administration groups returned to be close to that in blank group （P＞0.05）；the glomerular structure of rats in each administration group gradually recovered clearly ，and cell swelling and inflammatory cell infiltration were rare in total ethanol extract group ， petroleum ether fraction group and ethyl acetate fraction group. CONCLUSIONS The total ethanol extract ，petroleum ether fraction and ethyl acetate fraction of Miao medicine W. indica have certain nephrotoxicity and reversibility. The toxic component may

Objective:To investigate how gender differences between the donor and the recipient affect the effectiveness of antithymocyte globulin (ATG) and pure peripheral blood stem cell (PBSC) hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of malignant hematological diseases.Methods:From February 2015 to September 2020, 648 hematological malignancies patients underwent myeloablative condition regimen haplo-HSCT treatment at the Bone Marrow Transplant Center of the First Affiliated Hospital of Zhejiang University. The median age was 32 (14-62) years, with 363 males (56.0% ) and 285 females (44.0% ) present. 242 cases of acute lymphoblastic leukemia (ALL) (37.3% ) , 293 cases of acute myeloid leukemia (AML) (45.2% ) , 56 cases of myelodysplastic syndrome (MDS) (8.7% ) , 27 cases of non-Hodgkin's lymphoma (NHL) (4.2% ) , and 30 cases of other hematological malignancies (4.6% ) .Results:① The 3-year overall survival (OS) , DFS, the incidence of Ⅱ-Ⅳ grade acute graft-versus-host disease (aGVHD) , the incidence of Ⅲ-Ⅳ grade aGVHD, the 3-year incidence of moderate & severe chronic GVHD (cGVHD) , severe cGVHD, the 3-year incidence of relapse, and NRM of the whole group were (73.10±1.90) % , (70.80±1.90) % , (33.96±1.87) % , (13.08±1.33) % , (35.10±2.14) % , (10.66±1.38) % , (19.43±1.67) % , and (9.80±1.24) % , respectively. ②There was no statistically significant difference between the donor-recipient gender match and donor-recipient gender mismatch groups in the 28-day cumulative neutrophil engraftment rate, 28-day cumulative platelet engraftment rate, the incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, the cumulative incidence of relapse, NRM, and incidence of moderate & severe cGVHD, severe cGVHD. ③The 28-day cumulative neutrophil engraftment rate did not differ statistically between the male-female, female-female, male-male, and female-male groups ( P=0.148) . The incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, cumulative relapse rate, and NRM, and the incidence of cGVHD were not statistically different among the four groups ( P>0.05) . The 28-day cumulative platelet engraftment rate of the female-male group was significantly lower than male-female group, and the female-female group [ (91.45±2.63) % vs. (94.77±1.75) % , P=0.004; (91.45±2.63) % vs. (95.54±2.05) % , P=0.005]. No significant difference existed in the 28-day cumulative platelet engraftment rate between the female-male group and the male-male group [ (91.45±2.63) % vs. (95.08±1.41) % , P=0.284]. ④Among patients ≤35 years old, the 3-year incidence of severe cGVHD patients receiving sister donors and sibling donors were (26.71±5.90) % and (10.33±4.43) % , respectively ( P=0.054) . Patients accepting daughter donors and son donors had a 3-year incidence of moderate and severe cGVHD that was 40.07% vs. 27.41% , respectively, among those over 35 (40.07±6.65) % vs. (27.41±4.54) % ( P=0.084) . ⑤Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate compared to the other groups [ (91.45±2.63) % vs. (95.08±0.95) % , P=0.037]. ⑥ Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate than the other groups in the ATG-Fresenius (ATG-F) 10 mg/kg group [ (89.29±4.29) % vs. (94.49±1.45) % , P=0.037]. But when compared to the other groups in the Rabbit Antihuman Thymocyte Immunoglobulin (rATG-T) 6 mg/kg group, the 28-day cumulative platelet implantation rate between female donors and male recipients was not significantly different [ (93.44±3.38) % vs. (95.62±1.26) % , P=0.404]. Conclusion:The main clinical outcomes of patients with malignant blood diseases following transplantation are unaffected by the gender combination of the donor and patient in the haplo-HSCT mode based on ATG and PBSC sources. Female donors to male recipients have a lower 28-day cumulative platelet engraftment rate and longer platelet engraftment times.

Objective:To analyze the difference of somatic mutation of DNA mismatch repair (MMR) protein deletion (dMMR) /integrity (pMMR) in colorectal cancer (CRC).Methods:A total of 93 cases of paraffin pathological tissue derived from CRC patients underwent surgical treatment and postoperative routine immunohistochemical diagnosed as dMMR in the Second Affiliated Hospital of Zhejiang University Medical College from January 2015 to January 2017 were collected and conducted the second-generation sequencing test. The expressions of 4 MMR proteins (MLH1, MSH2, MSH6 and PMS2) in CRC tissue were detected by immunohistochemistry method, and the immunohistochemistry results were re-interpreted according to the American Association of Pathologists (CAP) standard. Second-generation sequencing technology was used to detect somatic mutations of 41 genes in 93 cases of paraffin pathological CRC tissue, and Fisher′s exact test was used to analyze the gene mutation differences between groups.Results:After re-evaluation according to CAP standard, 31 cases were divided into pMMR group and 62 cases in dMMR group among the 93 CRC patients. The medium number of gene mutations in the dMMR group was 9.5, higher than 3.0 of the pMMR group ( P<0.001). Somatic mutation differences were found in 17 genes between the dMMR and pMMR groups, including breast cancer susceptibility genes 1 (BRCA1), BRCA2, MLH1, PDGFRA, PIK3CA, APC, ATM, KIT, MET, PMS2, MSH6, POLE, MSH2, PTCH1, epidermal growth factor receptors (EGFR), TP53 and ERBB2 genes. The pathogenic somatic mutation rates of BRAF, MLH1, MSH2 and MSH6 in the dMMR group were higher than those in the pMMR group [21.0% (13/62) vs 9.7% (3/31), 9.7% (6/62) vs 0 (0/31), 21.0% (13/62) vs 0 (0/31), 22.6% (14/62) vs 0 (0/31), P<0.05]. The mutation rate differences of BLM N515fs, BRAF V600E, PTCH1 R1308fs and KRAS G13D sites were statistically different between the dMMR group and the pMMR group [22.6% (14/62) vs 0 (0/31), 19.4% (12/62) vs 3.2% (1/31), 11.3% (7/62) vs 0 (0/31), 16.1% (10/62) vs 3.2% (1/31), P<0.05]. The mutation rates of 3 uncommon sites including BLM N515fs, MSH6 F1088fs and PTCH1 R1308fs were 28.2% (11/39), 15.4% (6/39) and 15.4% (6/39) in patients with dMMR who were missing MLH1 and PMS2 together, statistically different from all of 0 (0/31) in pMMR patients ( P<0.05). Conclusions:CRC Patients with dMMR have more related gene somatic mutations. The BRAF V600E mutation is closely related to dMMR. KRAS G13D, BLM N515fs and PTCH1 R1308fs mutation sites are also associated with the expression of MMR proteins.

Objective:To analyze the difference of somatic mutation of DNA mismatch repair (MMR) protein deletion (dMMR) /integrity (pMMR) in colorectal cancer (CRC).Methods:A total of 93 cases of paraffin pathological tissue derived from CRC patients underwent surgical treatment and postoperative routine immunohistochemical diagnosed as dMMR in the Second Affiliated Hospital of Zhejiang University Medical College from January 2015 to January 2017 were collected and conducted the second-generation sequencing test. The expressions of 4 MMR proteins (MLH1, MSH2, MSH6 and PMS2) in CRC tissue were detected by immunohistochemistry method, and the immunohistochemistry results were re-interpreted according to the American Association of Pathologists (CAP) standard. Second-generation sequencing technology was used to detect somatic mutations of 41 genes in 93 cases of paraffin pathological CRC tissue, and Fisher′s exact test was used to analyze the gene mutation differences between groups.Results:After re-evaluation according to CAP standard, 31 cases were divided into pMMR group and 62 cases in dMMR group among the 93 CRC patients. The medium number of gene mutations in the dMMR group was 9.5, higher than 3.0 of the pMMR group ( P<0.001). Somatic mutation differences were found in 17 genes between the dMMR and pMMR groups, including breast cancer susceptibility genes 1 (BRCA1), BRCA2, MLH1, PDGFRA, PIK3CA, APC, ATM, KIT, MET, PMS2, MSH6, POLE, MSH2, PTCH1, epidermal growth factor receptors (EGFR), TP53 and ERBB2 genes. The pathogenic somatic mutation rates of BRAF, MLH1, MSH2 and MSH6 in the dMMR group were higher than those in the pMMR group [21.0% (13/62) vs 9.7% (3/31), 9.7% (6/62) vs 0 (0/31), 21.0% (13/62) vs 0 (0/31), 22.6% (14/62) vs 0 (0/31), P<0.05]. The mutation rate differences of BLM N515fs, BRAF V600E, PTCH1 R1308fs and KRAS G13D sites were statistically different between the dMMR group and the pMMR group [22.6% (14/62) vs 0 (0/31), 19.4% (12/62) vs 3.2% (1/31), 11.3% (7/62) vs 0 (0/31), 16.1% (10/62) vs 3.2% (1/31), P<0.05]. The mutation rates of 3 uncommon sites including BLM N515fs, MSH6 F1088fs and PTCH1 R1308fs were 28.2% (11/39), 15.4% (6/39) and 15.4% (6/39) in patients with dMMR who were missing MLH1 and PMS2 together, statistically different from all of 0 (0/31) in pMMR patients ( P<0.05). Conclusions:CRC Patients with dMMR have more related gene somatic mutations. The BRAF V600E mutation is closely related to dMMR. KRAS G13D, BLM N515fs and PTCH1 R1308fs mutation sites are also associated with the expression of MMR proteins.

Objective:To explore the application effect of non-vomiting information management system in chemotherapy-induced nausea and vomiting (CINV) of cancer patients.Methods:Using the convenient sampling method, from September 2015 to December 2018, a total of 1 980 tumor patients who received chemotherapy (including intravenous chemotherapy and intravenous plus oral chemotherapy) in Department of Abdominal and Breast Oncology in Zhejiang Cancer Hospital were selected as the pre-improvement group (before the application of non-vomiting information management system) . The 332 patients who received chemotherapy from October to December 2019 were selected as the post-improvement group (after the application of non-vomiting information management system) . From May 2019, the non-vomiting information management system was constructed to form the clinical pathways, including the risk assessment module of CINV, the medical order issuance module for anti-vomiting and the follow-up system module, and the system began trial operation in October 2019. The CINV detection status, nurse satisfaction, patient satisfaction and other indexes were compared between the two groups before and after the improvement.Results:After the application of non-vomiting information management system, the detection rate of CINV of patients, nurse satisfaction and patient satisfaction increased, and the differences were statistically significant ( P<0.05) . Conclusions:The application of non-vomiting information management system is helpful to dynamically understand the occurrence of CINV in patients anytime and anywhere, give timely guidance and treatment and improve the satisfaction of nurses and patients.