Objective:To investigate the impact of neoadjuvant immunotherapy combined with chemotherapy on the safety and efficacy of radical resection in patients with cT3-4NxM0 gastric cancer.Methods:A retrospective cohort study method was used. The clinicopathological data of 515 patients who underwent radical gastrectomy after neoadjuvant treatment at Second Department of Gastric Surgery,Fudan University Shanghai Cancer Center and Department of Gastric Surgery,Zhangzhou Hospital Affiliated to Fujian Medical University from January 2020 to June 2023 were collected. Among them,379 patients received neoadjuvant chemotherapy alone(chemotherapy group),and 136 patients received neoadjuvant immunotherapy combined with chemotherapy(immunotherapy group). There were 382 males and 133 females,with an age of (58.4±10.9)years(range:26 to 85 years). To reduce the influence of potential confounding factors,a 1∶1 propensity score matching method was adopted,and the clamp value was 0.02. The peri-operative safety,imaging and postoperative pathological tumor regression,and prognosis were compared by independent sample t-test, Mann-Whitney U test, χ 2 test or Fisher exact probability method between the two groups. The Kaplan-Meier method was used to draw survival curves, and the differences between groups were compared by Log-rank test. Results:After matching, there were 101 patients in each of the chemotherapy group and the immunotherapy group. The baseline data of the patients in the two groups were evenly distributed (all P>0.05). According to the RECIST 1.1 criteria, the complete response rate (11.9% (12/101) vs. 4.0% (4/101)), partial response rate(68.3%(69/101) vs. 53.4%(54/101)), stable disease rate (17.8%(18/101) vs. 39.6%(40/101)) and disease progression rate (2.0%(2/101) vs. 3.0%(3/101)) between the immunotherapy group and the chemotherapy group were no statistical defferences ( χ2=14.374, P=0.002), and objective response rate (80.2%(81/101) vs. 57.4%(58/101), χ2=12.203, P<0.01) in the immunotherapy group was higher than that in the chemotherapy group. The results of postoperative pathological examination showed that the immunotherapy group had a higher complete response rate (16.8%(17/101) vs. 6.9% (7/101), χ2=4.728, P=0.030) and major pathological response rate (42.6%(43/101) vs. 23.8% (24/101), χ2=8.062, P=0.005). For the two groups, the operation time (175.0(76.0)minutes vs. 160.0 (30.0)minutes, Z=-0.059, P=0.953), intraoperative blood loss (110.0 (150.0)ml vs. 100.0 (120.0)ml, Z=-0.370, P=0.712), overall incidence of postoperative complications (20.8%(21/101) vs. 18.8%(19/101), χ2=0.125, P=0.724) and incidence of severe complications (5.0%(5/101) vs. 3.0%(3/101), χ2=0.130, P=0.718) were comparable. The median follow-up time of all patients was 46 months(range: 19 to 61 months). The 3-year overall survival rate (63.2% vs. 54.4%, P=0.035) and progression-free survival rate (59.1% vs. 45.6%, P=0.022) of the immunotherapy group were higher than those of the chemotherapy group. Meanwhile, there were no statistically significant differences in the incidence of neoadjuvant-treatment-related adverse events (48.5%(49/101) vs. 40.6% (41/101), χ2=1.283, P=0.411) and the incidence of severe adverse reactions of grade 3 or above (13.9% (14/101) vs. 10.9% (11/101), χ2=0.257, P=0.522) between the two groups. Conclusion:Neoadjuvant immunotherapy combined with chemotherapy can significantly improve the imaging and postoperative pathological tumor response rates and 3-year survival rate of patients with locally advanced gastric cancer,without increasing the incidence of postoperative complications and neoadjuvant treatment-related adverse event.

Objective:To investigate the impact of neoadjuvant immunotherapy combined with chemotherapy on the safety and efficacy of radical resection in patients with cT3-4NxM0 gastric cancer.Methods:A retrospective cohort study method was used. The clinicopathological data of 515 patients who underwent radical gastrectomy after neoadjuvant treatment at Second Department of Gastric Surgery,Fudan University Shanghai Cancer Center and Department of Gastric Surgery,Zhangzhou Hospital Affiliated to Fujian Medical University from January 2020 to June 2023 were collected. Among them,379 patients received neoadjuvant chemotherapy alone(chemotherapy group),and 136 patients received neoadjuvant immunotherapy combined with chemotherapy(immunotherapy group). There were 382 males and 133 females,with an age of (58.4±10.9)years(range:26 to 85 years). To reduce the influence of potential confounding factors,a 1∶1 propensity score matching method was adopted,and the clamp value was 0.02. The peri-operative safety,imaging and postoperative pathological tumor regression,and prognosis were compared by independent sample t-test, Mann-Whitney U test, χ 2 test or Fisher exact probability method between the two groups. The Kaplan-Meier method was used to draw survival curves, and the differences between groups were compared by Log-rank test. Results:After matching, there were 101 patients in each of the chemotherapy group and the immunotherapy group. The baseline data of the patients in the two groups were evenly distributed (all P>0.05). According to the RECIST 1.1 criteria, the complete response rate (11.9% (12/101) vs. 4.0% (4/101)), partial response rate(68.3%(69/101) vs. 53.4%(54/101)), stable disease rate (17.8%(18/101) vs. 39.6%(40/101)) and disease progression rate (2.0%(2/101) vs. 3.0%(3/101)) between the immunotherapy group and the chemotherapy group were no statistical defferences ( χ2=14.374, P=0.002), and objective response rate (80.2%(81/101) vs. 57.4%(58/101), χ2=12.203, P<0.01) in the immunotherapy group was higher than that in the chemotherapy group. The results of postoperative pathological examination showed that the immunotherapy group had a higher complete response rate (16.8%(17/101) vs. 6.9% (7/101), χ2=4.728, P=0.030) and major pathological response rate (42.6%(43/101) vs. 23.8% (24/101), χ2=8.062, P=0.005). For the two groups, the operation time (175.0(76.0)minutes vs. 160.0 (30.0)minutes, Z=-0.059, P=0.953), intraoperative blood loss (110.0 (150.0)ml vs. 100.0 (120.0)ml, Z=-0.370, P=0.712), overall incidence of postoperative complications (20.8%(21/101) vs. 18.8%(19/101), χ2=0.125, P=0.724) and incidence of severe complications (5.0%(5/101) vs. 3.0%(3/101), χ2=0.130, P=0.718) were comparable. The median follow-up time of all patients was 46 months(range: 19 to 61 months). The 3-year overall survival rate (63.2% vs. 54.4%, P=0.035) and progression-free survival rate (59.1% vs. 45.6%, P=0.022) of the immunotherapy group were higher than those of the chemotherapy group. Meanwhile, there were no statistically significant differences in the incidence of neoadjuvant-treatment-related adverse events (48.5%(49/101) vs. 40.6% (41/101), χ2=1.283, P=0.411) and the incidence of severe adverse reactions of grade 3 or above (13.9% (14/101) vs. 10.9% (11/101), χ2=0.257, P=0.522) between the two groups. Conclusion:Neoadjuvant immunotherapy combined with chemotherapy can significantly improve the imaging and postoperative pathological tumor response rates and 3-year survival rate of patients with locally advanced gastric cancer,without increasing the incidence of postoperative complications and neoadjuvant treatment-related adverse event.

Objective:To establish an early warning model to assess the mortality risk of patients with heat stroke disease.Methods:The case data of patients diagnosed with heat stroke disease admitted to the comprehensive ICU of Shanshan County from January 2016 to December 2020 were selected. According to the short-term outcome (28 days) of patients, they were divided into death group (20 cases) and survival group (53 cases) . The relevant indicators with statistically significant differences between groups within 24 hours after admission were selected. By drawing the subject work curve (ROC) and calculating the area under the curve, the relevant indicators with the area under the curve greater than 0.7 were selected, Fisher discriminant analysis was used to establish an assessment model for the death risk of heat stroke disease. The data of heat stroke patients from January 1, 2021 to December 2022 in the comprehensive ICU of Shanshan County were collected for external verification. Results There were significant differences in age, cystatin C, procalcitonin, platelet count, CKMB, CK, CREA, PT, TT, APTT, heart rate, respiratory rate and GLS score among the groups. Cystatin C, CKMB, CREA, PT, TT, heart rate AUC area at admission was greater than 0.7. Fisher analysis method is used to build a functional model.Results:The diagnostic sensitivity, specificity and AUC area of the functional model were 95%, 83% and 0.937 respectively. The external validation results showed that the accuracy of predicting survival group was 85.71%, the accuracy of predicting death group was 88.89%.Conclusion:The early warning model of heat stroke death constructed by ROC curve analysis and Fisher discriminant analysis can provide objective reference for early intervention of heat stroke.

Objective:To establish an early warning model to assess the mortality risk of patients with heat stroke disease.Methods:The case data of patients diagnosed with heat stroke disease admitted to the comprehensive ICU of Shanshan County from January 2016 to December 2020 were selected. According to the short-term outcome (28 days) of patients, they were divided into death group (20 cases) and survival group (53 cases) . The relevant indicators with statistically significant differences between groups within 24 hours after admission were selected. By drawing the subject work curve (ROC) and calculating the area under the curve, the relevant indicators with the area under the curve greater than 0.7 were selected, Fisher discriminant analysis was used to establish an assessment model for the death risk of heat stroke disease. The data of heat stroke patients from January 1, 2021 to December 2022 in the comprehensive ICU of Shanshan County were collected for external verification. Results There were significant differences in age, cystatin C, procalcitonin, platelet count, CKMB, CK, CREA, PT, TT, APTT, heart rate, respiratory rate and GLS score among the groups. Cystatin C, CKMB, CREA, PT, TT, heart rate AUC area at admission was greater than 0.7. Fisher analysis method is used to build a functional model.Results:The diagnostic sensitivity, specificity and AUC area of the functional model were 95%, 83% and 0.937 respectively. The external validation results showed that the accuracy of predicting survival group was 85.71%, the accuracy of predicting death group was 88.89%.Conclusion:The early warning model of heat stroke death constructed by ROC curve analysis and Fisher discriminant analysis can provide objective reference for early intervention of heat stroke.

Objective    To explore the therapeutic effects of different surgical strategies on women with mechanical valve dysfunction during pregnancy. Methods    A total of 11 patients with mechanical valve dysfunction during pregnancy who underwent surgeries in our hospital from 2007 to 2017 were retrospectively included. The average age was 27.5±3.7 years. The prognosis of patients was analyzed according to the gestational weeks, cardiac function and the severity of mechanical valve dysfunction. Results    No death occurred. Three of them suffered subtotal hysterectomy during the surgery because of uncontrolled bleeding, and the others recovered without complications. Among the 5 patients with pregnancies <28 weeks, 1 patient was found intrauterine death before hospital admission, 2 suffered fetal loss 5 days after the cardiac surgery, and the other 2 patients continued their gestations until deliveries. Among the other 6 patients with pregnancies >28 weeks, 1 fetus died because of intracranial hemorrhage, and the other 5 survived without embryopathy or foetopathy. Conclusion    Gestation week, cardiac function and severity of mechanical valve dysfunction may be taken into account when making a treatment regimen for women with dysfunctional valve prostheses during pregnancy.

Objective:To study the dynamic evaluation value of transcranial Doppler (TCD) in cerebral circulation and brain function of sepsis patients and its predictive value of the prognosis.Methods:A retrospective analysis was performed on 98 sepsis patients admitted to our hospital from January 2017 to June 2018 who were divided into the survival group (56 cases) and death group (42 cases) according to the 28-day prognosis. The general clinical data of the patients, acute physiology and chronic health evaluation II (APACHE II), delirium assessment scale (CAM-ICU), and TCD parameters PSV, Vm, EDV, PI, RI on the first day and the third day of admission were collected, and the differences of TCD parameters at different time points were analyzed between the two groups, the area under the ROC curve (AUC) was calculated and evaluating their predictive value of sepsis outcome was evaluated.Results:APACHE Ⅱscore and the number of patients with sepsis encephalopathy were significantly higher in the death group than those in the survival group ( P < 0.05). There were no significant differences in PSV, Vm and EDV between the two groups on the first day and the third day. The PI and RI of the survival group were significantly lower than those of the death group ( P<0.01). In the survival group, PI and RI on the third day decreased significantly compared with those on the first day ( P < 0.05), while in the death group, PI and RI on the first day and the third day did not change significantly. ROC survival curves showed that Day1PI, Day3PI, Day1PI - Day3PI, Day1RI, Day3RI, Day1RI - Day3RI and APACHEⅡ predicted AUC of the prognosis of sepsis patients were 0.657, 0.835, 0.730, 0.707, 0.826, 0.705, and 0.815 ( P < 0.01). When PI cutoff value on the third day became 1.02, the sensitivity was 85.7% and the specificity was 61.3%. When RI cutoff value on the third day became 0.62, the sensitivity was 78.6% and the specificity was 71.4%. Conclusions:TCD parameters, PI and RI, are of certain value in the dynamic evaluation of cerebral circulation and brain function in sepsis patients. PI and RI on the first day and the third day and the differences between them are all valuable in predicting the prognosis, and PI and RI on the third day have greater predictive value.

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.

Objective The scope of this study was aimed to explore the relationship between serum Ghrelin levels and disease severity in non-traumatic ONFH patients. Methods 84 non-traumatic ONFH patients and 84 healthy controls were enrolled for this study in our hospital. The radiographic progression was determined by FICAT grading system. The clinical severity was evaluated by visual analogue scale(VAS),Harris hip scores(HSS). The serum APN concentrations were examined by enzyme-linked immunosorbent assay(ELISA).Serum adiponectin and IL-33 levels were also examined. The relationship between serum Ghrelin levels and radiographic severity,clinical severity and biochemical indices were investigated. Results Serum Ghrelin levels were significantly lower in ONFH patients than in healthy controls. Serum Ghrelin levels were negatively correlated with FICAT grading system. In addition,Serum Ghrelin levels were also negatively related to VAS scores and positively associated with HSS scores ,Last ,Serum Ghrelin levels were positively with adiponectin levels and negatively correlated with IL-33 levels. Conclusion Serum Ghrelin levels in non-traumatic ONFH patients were negatively associated with the disease severity. Decreased serum Ghrelin levels may reflect disease severity of non-traumatic ONFH.

Objective: To evaluate the relationship between the levels of serum uric acid (SUA) and prevalence of coronary artery disease (CAD) by Meta analysis. Methods: We searched the databases of Pub Med, Elsevier and Web of Science for internationally published cohort study for the relationship between SUA levels and CAD prevalence and conducted a general analysisby using Stata software. Results: A total of 11 cohort study including 463,918 subjects were enrolled in this study. For both male and female genders, increase SUA level was the risk factor for CAD occurrence (RR=1.11, 95% CI 1.00-1.24) and (RR=1.24, 95% CI 1.15-1.34). Dose-response Meta-analysis indicated that by 1 mg/dl SUA elevation, the risk of CAD occurrence would increase 4.8% in male and 12.4% in female, the risk in female gender was higher than male. Conclusion: SUA level has been closely related to CAD prevalence.

OBJECTIVETo explore use of interleukin-10 receptor (IL-10R) gene mutation in diagnosis and pathogenesis of neonatal inflammatory bowel disease (IBD) in 2 suspected cases.

METHODTwo cases of sibling brothers who had suspected IBD from Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University during the year 2010-2014 were enrolled in the study. The proband, male, 26 days old, weight 3.73 kg, presented with recurrent fever, increased stool frequency since 9 days of age, and was hospitalized at the age of 6 months in 2014. The proband's brother, male, 6 months old, weight 8 kg, had repeated bloody and mucous diarrhea for more than five months, recurrent fever five days, and was hospitalized in 2010. The blood samples were collected from the children and their families for IL-10 receptor genes including IL-10 receptor α subunit (IL-10RA) and β subunit (IL-10RB) PCR amplification. Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify the proband IL-10RA transcripts. Sequencing was performed on the PCR products forward and reversely. Western blot analysis was used for protein expression of the proband and normal control's IL-10RA and P-STAT3 (Tyr705) expression after IL-10 stimulation, TNF-α level was detected using Human TNF-α ELISA Kit after PBMC was cultured and stimulated.

RESULTThe proband and his brother were IBD patients. Genome sequencing showed mutation in c.537G>A, namely the exon 4 and intron 4 connections changed CA/GT for CG/GT. Sequencing of the RT-PCR products and T-A clone showed that the mutation was (c.519-537del GGTGCCGGGAAACTTCAC, p.LYS173ASNfs*7), as the splice mutation. Two gene mutations were novel mutation. The parents were the mutations carrier. Both of the children were compound heterozygous mutations in IL-10RA. The Western blot analysis showed that the patient and normal children can express IL-10RA protein, however, the function of IL-10RA had obvious defects in the patient, IL-10RA downstream signaling pathways P-STAT3 had no expression. The average level of TNF-α secreted by PBMC after LPS + IL-10 co-stimulation in patient was significantly increased as compared with control group ((2 100±356) vs. (200±50) ng/L, t=9.154, P=0.001), suggesting that interleukin-10-dependent negative feedback regulation is disrupted in the patient.

CONCLUSIONIL-10 receptor mutations can cause neonatal-IBD, for which common treatment effect is poor. Early diagnosis and allogeneic stem-cell transplantation performed may save the children's life.