Objective: To explore the neuroprotective effects of the Shaoyao Gancao decoction (SGD) against excitatory damage in PC12 cells and the role of the Src-NR2-nNOS pathway mediation by SGD in regulating γ-aminobutyric acid (GABA)-glutamate (Glu) homeostasis. Methods: N-Methyl-d-aspartic acid (NMDA) was used to establish a PC12 cell excitability injury model. To investigate the neuroprotective effect of SGD, a cell counting kit-8 (CCK-8) assay was used to determine PC12 cell viability, Annexin V/Propidium Iodide (Annexin V/PI) double staining was used to determine PC12 cell apoptosis, and Ca2+ concentration was observed using laser confocal microscopy. GABA receptor agonists and antagonists were used to analyze the neuroprotective interactions between γ-aminobutyric acid (GABA) and NMDA receptors. Additionally, molecular biology techniques were used to determine mRNA and protein expression in the Src-NR2-nNOS pathway. We analyzed the correlations between the regulatory sites of GABA and NMDA interactions, excitatory neurotoxicity, and brain damage at the molecular level. Results: NMDA excitotoxic injury manifested as a significant decrease in cell activity, increased apoptosis and caspase-3 protein expression, and a significant increase in intracellular Ca2+ concentration. Administration of SGD, a GABAA receptor agonist (muscimol), or a GABAB receptor agonist (baclofen) decreased intracellular Ca2+ concentrations, attenuated apoptosis, and reversed NMDA-induced upregulation of caspase-3, Src, NMDAR2A, NMDAR2B, and nNOS. Unexpectedly, a GABAA receptor antagonist (bicuculline) and a GABAB receptor antagonist (saclofen) failed to significantly increase excitatory neurotoxicity. Conclusions Taken together, these results not only provide an experimental basis for SGD administration in the clinical treatment of central nervous system injury diseases, but also suggest that the Src-NR2A-nNOS pathway may be a valuable target in excitotoxicity treatment.

Objective To analyze the risk factors for extrauterine growth retardation(EUGR)in late preterm infants appropriate for gestational age.Methods The clinical data in 1 402 preterm infants appropri-ate for gestational age delivered and hospitalized in this hospital from January 2016 to June 2022 were analyzed retrospectively.They were divided into the EUGR group(n=244)and the non-EUGR group(n=1 158)ac-cording to whether or not the body weight at discharge was below the 10th percentile of the growth curve for the same gestational age at the same period based on the Fenton's preterm growth curve.The clinical data of preterm infants and mothers of the two groups were collected.The risk factors for EUGR occurrence in pre-mature infants were analyzed.Results Among 1 402 preterm infants appropriate for gestational age,EUGR occurred in 244 cases with the EUGR incidence rate of 17.4％.The EUGR incidence rate had no statistical difference among the different fetal ages of premature infants(P＞0.05).The EUGR incidence rate had sta-tistical difference among different birth weights of premature infants(P＜0.05).The logistic regression anal-ysis showed that male(OR=1.694,95％CI:1.144-2.507),low birth weight(OR=0.989,95％CI:0.988-0.991),feeding intolerance(OR=2.719,95％CI:1.234-5.990),short gestational weeks(OR=0.146,95％CI:0.103-0.207)and hospitalization duration extension(OR=1.073,95％CI:1.031-1.117)were the risk factors for EUGR occurrence in late premature infants appropriate for gestational age in discharge.The sub-group analysis showed that male,low birth weight,feeding intolerance and hospitalization duration extension were the risk factors for EUGR occurrence in the preterm infants with gestational ages of 34-＜36 weeks(P＜0.05).Low birth weight and feeding intolerance only affected the preterm infants≥36 weeks of gesta-tional age(P＜0.05).Conclusion Strengthening the pregnant duration health care and active nutritional sup-port after birth may reduce the risk of EUGR occurrence in late premature infants.

Objective::This study aimed to determine the likelihood of gestational diabetes mellitus (GDM) in subsequent pregnancy among women without GDM history and to identify risk factors for GDM in subsequent pregnancy.Methods::This retrospective cohort study involved participants who delivered twice in same hospital of 18 research centers when delivered the second baby from January 2018 to December 2018. Finally 6204 women were enrolled and 5180 women without GDM history were analyzed further. Women were categorized as non-GDM or GDM based on the blood glucose values of the subsequent pregnancy, and the characteristics and GDM risk of these groups were compared. A univariate analysis of potential risk factors was performed using the Chi-squared test and/or t-test for qualitative or quantitative variables, respectively. Associations with P values <0.1 were chosen to be included in the multivariate binary logistic regression model. Results::In primary analysis of 6204 women, the incidence of GDM in subsequent pregnancy is 48.9% (490/1002) in women with GDM history and 16.1% (835/5202) in women without GDM history. In a further analysis for 5180 women without GDM at index pregnancy, compared with the non-GDM group, the GDM group had a significantly higher age, prepregnancy body mass index, and blood glucose value at each oral glucose tolerance test (OGTT) timepoint (fasting, 1 h and 2 h) during the index and subsequent pregnancies, as well as higher weight retention during the interval between the two pregnancies ( P<0.001). Age above 35 years in subsequent pregnancy (odds ratio ( OR)=1.540, 95% confidence interval ( CI) = 1.257-1.886, P<0.001), macrosomia in index pregnancy ( OR=1.749, 95% CI=1.277-2.395, P=0.001), OGTT blood glucose values in index pregnancy (fasting, OR=2.487, 95% CI=1.883-3.285, P<0.001; 1 h, OR=1.142, 95% CI=1.051-1.241, P=0.002; 2 h, OR=1.290, 95% CI=1.162-1.432, P<0.001) and weight retention ( OR=1.052, 95% CI=1.035-1.068, P<0.001) were independent risk factors for GDM in subsequent pregnancy. Conclusion::For women without GDM history, GDM risk factors including age, macrosomia history, OGTT value, and weight retention, these can be evaluated before a subsequent pregnancy. Early warning and interventions are needed for women at high risk.

Objective::This study aimed to determine the likelihood of gestational diabetes mellitus (GDM) in subsequent pregnancy among women without GDM history and to identify risk factors for GDM in subsequent pregnancy.Methods::This retrospective cohort study involved participants who delivered twice in same hospital of 18 research centers when delivered the second baby from January 2018 to December 2018. Finally 6204 women were enrolled and 5180 women without GDM history were analyzed further. Women were categorized as non-GDM or GDM based on the blood glucose values of the subsequent pregnancy, and the characteristics and GDM risk of these groups were compared. A univariate analysis of potential risk factors was performed using the Chi-squared test and/or t-test for qualitative or quantitative variables, respectively. Associations with P values <0.1 were chosen to be included in the multivariate binary logistic regression model. Results::In primary analysis of 6204 women, the incidence of GDM in subsequent pregnancy is 48.9% (490/1002) in women with GDM history and 16.1% (835/5202) in women without GDM history. In a further analysis for 5180 women without GDM at index pregnancy, compared with the non-GDM group, the GDM group had a significantly higher age, prepregnancy body mass index, and blood glucose value at each oral glucose tolerance test (OGTT) timepoint (fasting, 1 h and 2 h) during the index and subsequent pregnancies, as well as higher weight retention during the interval between the two pregnancies ( P<0.001). Age above 35 years in subsequent pregnancy (odds ratio ( OR)=1.540, 95% confidence interval ( CI) = 1.257-1.886, P<0.001), macrosomia in index pregnancy ( OR=1.749, 95% CI=1.277-2.395, P=0.001), OGTT blood glucose values in index pregnancy (fasting, OR=2.487, 95% CI=1.883-3.285, P<0.001; 1 h, OR=1.142, 95% CI=1.051-1.241, P=0.002; 2 h, OR=1.290, 95% CI=1.162-1.432, P<0.001) and weight retention ( OR=1.052, 95% CI=1.035-1.068, P<0.001) were independent risk factors for GDM in subsequent pregnancy. Conclusion::For women without GDM history, GDM risk factors including age, macrosomia history, OGTT value, and weight retention, these can be evaluated before a subsequent pregnancy. Early warning and interventions are needed for women at high risk.

OBJEC TIVE To investigate the status and clinical characteristics of adverse drug reactions （ADRs）induced by sintilimab in order to provide references for clinical rational drug use. METHODS The cases of ADR induced by sintilimab were retrieved from the databases of PubMed ，Embase，CNKI，VIP and Wanfang. RESULTS A total of 32 literature were included ， involving 33 patients among which there were 25 males（75.76％）and 8 females（24.24％）. The incidence of ADRs was higher in patients aged over 40 years（81.82％）. The dose of sintilimab was the drug instructions recommended dose （200 mg）for 30 patients and 100 mg for a patient. The earliest ADR occurred 1 h after the first medication ，the latest ADR occurred after 14 cycles of sintilimab. The 27 cases suffered from ADR cases （81.82％）within 4 months after medication ，and no reports of ADR occurred after 12 months of medication. The major manifestations of ADR were myocarditis ，diabetes mellitus ，checkpoint inhibitor pneumonitis（CIP），cytokine release syndrome （CRS）and hypothyroid myopathy （HM），etc. CRS and HM belonged to ADRs not recorded in the drug instructions. The 29 cases of recovery and 4 deaths occurred after symptomatic treatment. CONCLUSIONS ADR caused by sintilimab often occurs within 4 months after treatment ，and it is high in males and patients over 40 years old. In clinical application of sintilimab ，attention should be paid to the occurrence of myocarditis ，diabetes mellitus ，CIP，as well as CRS and HM not recorded in the drug instructions.

Objective:To investigate the relationship between discharge readiness and nutritional status of patients undergoing gastric cancer surgery in the context of enhanced recovery after surgery (ERAS) , so as to provide individualized guidance for patients after discharge.Methods:Using the convenient sampling method, a total of 120 patients who underwent radical gastrectomy for gastric cancer from June 2020 to June 2021 in Ningbo First Hospital were selected as research objects, and they all received ERAS nursing care. One day before discharge, Nutritional Risk Screening Table and Discharge Readiness Scale were used for questionnaire analysis.Results:The total score of discharge readiness of 120 patients with gastric cancer after surgery was (81.42±6.87) . Among the three dimensions, personal status was (19.65±2.19) , adaptability was (29.67±3.10) and anticipatory support was (32.10±2.61) . 57.5% (69/120) of gastric cancer patients discharged from hospital had nutritional risk. The scores of hospital discharge readiness and the scores of each dimension in the nutritional risk group were lower than those in the non-nutritional risk group, and the differences were statistically significant ( P<0.05) . Multivariate analysis showed that nutritional status was an influencing factor for the total score of hospital discharge readiness in patients with gastric cancer surgery (standardized regression coefficient was 0.321, P<0.05) . Conclusions:Under the background of ERAS, the discharge readiness of patients after gastric cancer surgery is at a moderate level, postoperative patients are generally at nutritional risk and the discharge readiness of patients with nutritional risk is lower than that of patients without nutritional risk. Perioperative nutrition management by nursing staff can improve the discharge readiness of patients undergoing gastric cancer surgery, and continuous nutrition management should be carried out for discharged patients with nutritional risk, in order to promote home rehabilitation of patients with gastric cancer surgery.

Objective: To construct influenza B virus Vero cell adapted strain by genetic recombination technology by using the influenza B virus Vero cell adapted strain as the parent strain. Methods: The chick embryo and Vero cell were co-infected with influenza virus Vero cell adapted strain B/Malaysia/2506/2004 Va (Bv) and the vaccine strain B/massachusetts/2/2012 (BX-51B) recommended by WHO. The reassortants were screened with the anti-Bv serum. Plaque-purified reassortants were used to screen for Vero cell-adapted influenza B virus strains containing the surface antigen of the epidemic strain. Results: A Vero cell-adapted influenza B virus strain was obtained with successive passage in Vero cells. The hemagglutination inhibition test and the one-way immunogold agar diffusion test both showed that the reassortant virus was homologous to NYMC BX-51B, and sequence analysis result showed that the reassortment virus has the same HA and NA gene with the vaccine strain. Conclusion B/Malaysia/2506/2004Va (Bv) can be used as a parent strain to prepare Vero cell vaccine against influenza B virus.

Objective: To investigate the expressions of CD4⁺CD45RA⁺T cells and CD4⁺CD45RO⁺T cells in peripheral blood of patients with acute coronary syndrome (ACS) and their significance. Methods: A case-control study was conducted. Ninety-four patients receiving coronary angiography (CAG) admitted to Tianjin Chest Hospital from March 5th to April 27th in 2018 were enrolled. They were divided into non-coronary heart disease (CHD) group (n = 12), unstable angina pectoris (UAP) group (n = 27), acute non-ST elevation myocardial infarction (NSTEMI) group (n = 27) and acute ST elevation myocardial infarction (STEMI) group (n = 28) according to the patients' symptoms, electrocardiogram, troponin test and angiographic results. General data, blood routine parameters, and biochemical indicators were collected. The ratios of CD4⁺CD45RA⁺T cells and CD4⁺CD45RO⁺T cells were determined by flow cytometry. Multivariate Logistic regression was used to evaluate whether CD4⁺CD45RA⁺T cells and CD4⁺CD45RO⁺T cells were associated with STEMI. Results: Ninety-four patients were included initially. After excluding the patients who died during the intervention, 93 patients were enrolled in the data analysis finally, with 12 patients in the non-CHD group, 27 patients in the UAP group, and the same as the NSTEMI group and the STEMI group. Compared with the non-CHD group, white blood cell count (WBC) was decreased (×10⁹/L: 6.03±1.30 vs. 6.60±1.30, P > 0.05), and lymphocyte ratio was increased (0.273±0.059 vs. 0.269±0.070, P > 0.05) in patients of the UAP group; however, in the NSTEMI group and STEMI group, WBC was increased (×10⁹/L: 8.29±2.28, 9.86±2.76 vs. 6.60±1.30, both P < 0.05), and lymphocyte ratio was decreased (0.236±0.076, 0.173±0.094 vs. 0.269±0.070, P > 0.05 and P < 0.05), especially in the STEMI group [WBC (×10⁹/L): 9.86±2.76 vs. 6.60±1.30, lymphocyte ratio: 0.173±0.094 vs. 0.269±0.070, both P < 0.05]. There was no significant difference in biochemical indicators among all of the groups. Flow cytometry results showed that the ratios of CD4⁺CD45RO⁺T cells in the UAP group and NSTEMI group were higher than those in the non-CHD group (0.323±0.074, 0.319±0.078 vs. 0.314±0.058, both P > 0.05); however, the ratio of CD4⁺CD45RO⁺T cells in the STEMI group showed a decreased tendency (0.270±0.057 vs. 0.314±0.058, P > 0.05), and it was significantly lower than that in the UAP group and the NSTEMI group (0.270±0.057 vs. 0.323±0.074, 0.319±0.078, both P < 0.05). There was no significant difference in the ratio of CD4⁺CD45RA⁺T cells among all of the groups. Multivariate Logistic regression analysis showed that CD4⁺CD45RA⁺T cells ratio was not significantly correlated with the occurrence of STEMI [odds ratio (OR) = 0.976, 95% confidence interval (95%CI) was 0.907-1.050, P = 0.518], but CD4⁺CD45RO⁺T cells ratio was significantly correlated with the occurrence of STEMI (OR = 0.888, 95%CI was 0.821-0.961, P = 0.003). Conclusions There was no significant difference in the ratio of CD4⁺CD45RA⁺T cells among UAP, NSTEMI and STEMI patients, and CD4⁺CD45RO⁺T cells ratio in the STEMI group was significantly lower than that in the UAP group and NSTEMI group. CD4⁺CD45RO⁺T cells ratio may be risk factor of STEMI.

OBJECTIVE: To investigate the expressions of CD4⁺CD45RA⁺T cells and CD4⁺CD45RO⁺T cells in peripheral blood of patients with acute coronary syndrome (ACS) and their significance. METHODS: A case-control study was conducted. Ninety-four patients receiving coronary angiography (CAG) admitted to Tianjin Chest Hospital from March 5th to April 27th in 2018 were enrolled. They were divided into non-coronary heart disease (CHD) group (n = 12), unstable angina pectoris (UAP) group (n = 27), acute non-ST elevation myocardial infarction (NSTEMI) group (n = 27) and acute ST elevation myocardial infarction (STEMI) group (n = 28) according to the patients' symptoms, electrocardiogram, troponin test and angiographic results. General data, blood routine parameters, and biochemical indicators were collected. The ratios of CD4⁺CD45RA⁺T cells and CD4⁺CD45RO⁺T cells were determined by flow cytometry. Multivariate Logistic regression was used to evaluate whether CD4⁺CD45RA⁺T cells and CD4⁺CD45RO⁺T cells were associated with STEMI. RESULTS: Ninety-four patients were included initially. After excluding the patients who died during the intervention, 93 patients were enrolled in the data analysis finally, with 12 patients in the non-CHD group, 27 patients in the UAP group, and the same as the NSTEMI group and the STEMI group. Compared with the non-CHD group, white blood cell count (WBC) was decreased (×10⁹/L: 6.03±1.30 vs. 6.60±1.30, P < 0.05), and lymphocyte ratio was increased (0.273±0.059 vs. 0.269±0.070, P > 0.05) in patients of the UAP group; however, in the NSTEMI group and STEMI group, WBC was increased (×10⁹/L: 8.29±2.28, 9.86±2.76 vs. 6.60±1.30, both P < 0.05), and lymphocyte ratio was decreased (0.236±0.076, 0.173±0.094 vs. 0.269±0.070, P > 0.05 and P < 0.05), especially in the STEMI group [WBC (×10⁹/L): 9.86±2.76 vs. 6.60±1.30, lymphocyte ratio: 0.173±0.094 vs. 0.269±0.070, both P < 0.05]. There was no significant difference in biochemical indicators among all of the groups. Flow cytometry results showed that the ratios of CD4⁺CD45RO⁺T cells in the UAP group and NSTEMI group were higher than those in the non-CHD group (0.323±0.074, 0.319±0.078 vs. 0.314±0.058, both P > 0.05); however, the ratio of CD4⁺CD45RO⁺T cells in the STEMI group showed a decreased tendency (0.270±0.057 vs. 0.314±0.058, P > 0.05), and it was significantly lower than that in the UAP group and the NSTEMI group (0.270±0.057 vs. 0.323±0.074, 0.319±0.078, both P < 0.05). There was no significant difference in the ratio of CD4⁺CD45RA⁺T cells among all of the groups. Multivariate Logistic regression analysis showed that CD4⁺CD45RA⁺T cells ratio was not significantly correlated with the occurrence of STEMI [odds ratio (OR) = 0.976, 95% confidence interval (95%CI) was 0.907-1.050, P = 0.518], but CD4⁺CD45RO⁺T cells ratio was significantly correlated with the occurrence of STEMI (OR = 0.888, 95%CI was 0.821-0.961, P = 0.003). CONCLUSIONS There was no significant difference in the ratio of CD4⁺CD45RA⁺T cells among UAP, NSTEMI and STEMI patients, and CD4⁺CD45RO⁺T cells ratio in the STEMI group was significantly lower than that in the UAP group and NSTEMI group. CD4⁺CD45RO⁺T cells ratio may be risk factor of STEMI.
Acute Coronary Syndrome ; Angina, Unstable ; Case-Control Studies ; Humans ; Myocardial Infarction ; T-Lymphocytes

Background: Disruption of tight junctions between intestinal epithelial cells followed by loss of barrier function is crucial for the pathogenesis and progression of a variety of gastrointestinal disorders.Aims: To investigate the protective effect of ulinastatin on hydrogen peroxide (H2O2)-induced intestinal epithelial barrier disruption.Methods: Model of intestinal epithelial monolayer barrier was established with Caco-2 cells in vitro,and then divided into four groups: blank control group (without any intervention),H2O2 group (500 μmol/L H2O2),low-dose (500 U/mL) and high-dose (3 000 U/mL) ulinastatin groups (ulinastatin + H2O2).Level of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were detected;transepithelial electrical resistance (TEER) and flux of sodium fluorescein were measured to assess the barrier function;expression and localization of two tight junction proteins,ZO-1 and occludin were evaluated by Western blotting and immunofluorescence;ultrastructure of tight junctions was observed by transmission electron microscopy (TEM).Results: Compared with the blank control group,treatment of Caco-2 cell monolayers with H2O2 resulted in increase in level of MDA,flux of sodium fluorescein and decrease in activity of SOD,TEER and expressions of ZO-1 and occludin (P all ＜0.05).TEM and immunofluorescence showed that the brusher border of Caco-2 cells in H2O2 group was destroyed,the cell-cell junction was vague and the localization of ZO-1 and occludin was discontinuous and the fluorescence intensity was extremely low.While in ulinastatin groups,especially the high-dose group,all the indices above-mentioned were significantly improved (P all ＜0.05).Conclusions: Ulinastatin protects intestinal epithelial monolayer barrier against H2O2-induced disruption at least partially by its antioxidant activity and modulating expression and localization of tight junction proteins.