ObjectiveTo retrospectively analyze the epidemiological trends of birth defects in perinatal infants in Fengxian District, Shanghai from 2018 to 2022, so as to provide a scientific evidence for the formulation of related prevention and control strategies. MethodsBased on the data from the National Birth Defects Surveillance System, statistical analysis was conducted on the perinatal birth defects from monitored hospitals within the region from 2018 to 2022. ResultsFrom 2018 to 2022, a total of 20 870 perinatal infants delivered in the monitored hospitals in Fengxian District, with 472 cases with birth defects, showing a significant increase in the prevalence of birth defects (PRR=1.49, 95%CI: 1.39‒1.59). The risk of birth defects increased with maternal age, especially for advanced maternal age (PRR=1.58, 95%CI: 1.12‒2.25). Infants born to mothers with gestational diabetes had a higher prevalence of birth defects compared to those without gestational diabetes (PRR=1.99, 95%CI: 1.46‒2.70). Infants with birth defects were more likely to be born prematurely (PRR=2.07, 95%CI:1.56‒2.76). The top three types of birth defects were congenital heart disease (CHD), other anomalies of the external ear, and polydactyly. ConclusionThe prevalence of birth defects in Fengxian District monitored hospitals showed an upward trend from 2018 to 2022. Advanced maternal age and gestational diabetes were identified as risk factors for birth defects. CHD is the leading type of birth defect in Fengxian District over the five-year period. To reduce the prevalence of birth defects, it is crucial to implement comprehensive prevention and treatment measures for CHD.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Objective To study the effect of insulin on phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway in diabetic rats with myocardial ischemia reperfusion injury.Methods Diabetic rats were induced by high-sugar and high-fat diet plus intraperitoneal injection of streptozotocin (40 mg/kg).They were randomly divided into diabetic sham group (group A),diabetes ischemic reperfusion group (group B),diabetes ischemic reperfusion insulin treatment group (group C) and diabetic ischemia reperfusion + insulin Wortmaninn (PI3K inhibitors) group (group D),10 in each group.Myocardial ischemia reperfusion model in diabetic rats:heart was exposed between the third and fourth ribs of the left chest,2 mm from the lower edge of the left atrial ear,and 5-0 sterile suture was used to ligate the anterior descending coronary artery (LAD) and the great cardiac vein for 30 min,and then the perfusion was resumed for 120 min.Wortmannin (15 μg/kg) was given through femoral vein 20 min before ligation in group D,and the same amount of normal saline was given in the other 3 groups.Insulin (2 U/kg) was injected subcutaneously in group C and D 10 min before ligation,and the same amount of normal saline was injected subcutaneously in group A and group B.Plasma creatine kinase MB (CK-MB)and troponin Ⅰ (cTnⅠ) levels were measured in arterial blood after 120 min of reperfusion,and PI3K and Akt expression in myocardial tissue were detected by Western blot.Results Compared with the group A,the plasma levels of cTnI and CK-MB increased and the expressions of PI3K and phosphorylated protein kinase B (p-Akt) in myocardium decreased in the group B (P ＜ 0.05).After insulin treatment,the plasma cTnI [(0.89 ± 0.26) μg/L],CK-MB [(9.24 ±3.16) μg/L] in the myocardial tissue of the group C decreased,while the expression of PI3K (0.341 8 ±0.03 1) and p-Akt (0.673 1 ±0.028) in the myocardial tissue increased (P ＜0.05).After insulin + Wortmaninn administration,the plasma cTnI [(1.16 ±0.29) μg/L] and CK-MB [(12.57 ± 3.01) μg/L] in the group D increased,while the expression of PI3K (0.292 7 ± 0.036) and p-Akt (0.531 4 ± 0.030) in the myocardial tissue decreased,with statistically significant difference (P ＜ 0.05).Conclusions Insulin can reduce serum CK-MB and cTnⅠ levels in diabetic rats with myocardial ischemia reperfusion injury,possibly by activating PI3K/Akt signal transduction pathway,inhibiting myocardial enzyme release,and improving myocardial ischemia reperfusion injury in diabetic rats to play a protective role in myocardial cells.

Objective To explore relationship between clinical features and peripheral blood test indicators and curative effect in adult patients with acquired hemophagocytic syndrome (HPS). Methods A total of 61 adult patients with acquired HPS who were admitted to the First Affiliated Hospital with Nanjing Medical University and the Affiliated Jiangning Hospital of Nanjing Medical University from April 2014 to March 2017 were enrolled, including 38 males and 23 females, with a median age of 48 years (17-86 years). The retrospective analyses of their clinical data and laboratory examination results were made in this study. Results There was no significant difference in the therapeutic effective rate of 61 HPS patients caused by different inducements after treatment (P ＝0.184). The prothrombin time (PT) before treatment was higher than that after treatment [(12.90±1.97) s vs. (12.35±1.78) s, P＝ 0.046]; the level of lactate dehydrogenase (LDH) before treatment was higher than that after treatment (median: 476 U/L vs. 231 U/L, P ＝ 0.000); the level of D-dimer (D-D) before treatment was higher than that after treatment (median: 1.46 mg/L vs. 0.51 mg/L, P ＝ 0.007); the level of aspartate aminotransferase (AST) before treatment was higher than that after treatment (median: 54.9 U/L vs. 26.0 U/L, P＝ 0.000); the level of serum calcium before treatment was lower than that after treatment [(2.07±0.20) mmol/L vs. (2.18±0.23) mmol/L, P ＝ 0.043]. The peripheral blood platelet counts (Plt) in the effective group (32 cases) before treatment was higher than that in the ineffective group (29 cases) (median: 104.0×109/L vs. 63.5×109/L, P ＝0.007), the level of albumin (ALB) in the effective group was higher than that in the ineffective group [(35.50 ±6.17) mmol/L vs. (31.93 ±6.54) mmol/L, P ＝ 0.033], the level of serum calcium in the effective group was higher than those in the ineffective group [(2.18±0.18) mmol/L vs. (2.08±0.20) mmol/L, P ＝ 0.047], the level of prothrombin time (PT) in the effective group was lower than that in the ineffective group [(12.40±1.76) s vs. (13.43±2.06) s, P ＝ 0.041], and the level of LDH in the effective group was lower than that in the ineffective group (median: 415.0 U/L vs. 593.5 U/L, P＝ 0.032). Conclusion The lower expressions of Plt, ALB and serum calcium, and the higher expressions of PT and LDH may indicate the poor prognosis of adult acquired HPS, and there fore these patients need to be paid attention.

Objective To investigate the risk factors,clinic charactertics and survival prognosis of pulmonary embolism (PE) in patients with lung cancer.Methods The clinic data of 28 lung cancer patients with PE,hospitalized in department of respiratory and critical care medicine of Tianjin Chest Hospital between June 2012 to June 2015,were retrospectively reviewed.Eleven of them were diagnosed with primary lung cancer and PE (symptomatic group),and 17 lung cancer patients were found PE accidentally (asymptomatic group).A total of 56 lung cancer patients without PE were used as control subjects (no PE group).Data of pathological types,clinical staging of lung cancer,systemic chemotherapy,white blood cell (WBC),hemoglobin (Hb),platelet (PLT),D-dimer (DD),albumin (ALB) and C-reactive protein (CRP) were analyzed by univariate analysis in the symptomatic group and asymptomatic group.Logistic regression analysis was carried out on the statistically significant indexes to observe the influencing factors.The morphology and location of the remobilization images were analyzed in lung cancer patients with PE.The median time to embolism and survival of PE patients were compared between symptomatic group and asymptomatic group.Results The proportion of adenocarcinoma,systemic chemotherapy and stage Ⅲ + Ⅳ were significantly higher in PE group than those in no PE group (P ＜ 0.01).The ratio of white blood cells (WBC)＞ 11× 109/L (hyperleukocytosis) and albumin (ALB) ＜30 g/L and D-dimer (DD)＞ 0.5 mg/L were significantly higher in PE group than those of no PE group (P ＜ 0.05).There were no statistical differences in other indicators including clinical symptoms between the two groups (P ＞ 0.05).The logistic regression analysis showed that adenocarcinoma,chemotherapy,WBC＞ 11× 109/L and DD＞0.5 mg/L were the risk factors of lung cancer with PE (P ＜ 0.05).There was higher ratio of asymptomatic PE in lung cancer patients with PE.There were no significant differences in morphology and location of the remobilization images in symptomatic group.The median time of embolization was 3.6 months (95％ CI:3.2-4.0) in the asymptomatic group,which was significantly earlier than that in the symptomatic group (10.5 months,95％ CI:8.88-12.12,P ＜ 0.01).The median survival time was 7.2 months (95％ CI:5.86-8.56) in the asymptomatic group,which was significantly longer than that of symptomatic group (2.8 months,95％ CI:2.48-3.12,P ＜ 0.05).Conclusion Lung adenocarcinom,systemic chemotherapy,hypoproteinemia and increased D-dimer are the independent risk factors in lung cancer patients with PE.PE in lung cancer is frequently asymptomatic in the early stage.Compared to symptomatic patients,asymptomatic cases have better prognosis.

Objective To investigate whether the presence of sepsis associated encephalopathy (SAE) would predict nosocomial coma (NC) and poor outcome in patients with supratentorial intracerebral hemorrhage (SICH). Methods A retrospective cohort study was conducted. The adult acute SICH patients with or without coma admitted to intensive care unit (ICU) of Shuyang People' Hospital Affiliated to Xuzhou Medical University from December 2012 to December 2015 were enrolled. Brain computed tomography (CT) scans were analyzed and the patients were divided into pre-hospital coma (PC) and NC groups. The clinical data and the incidence of SAE of patients in two groups were compared, and the 30-day prognosis was followed up. Univariate and Cox regression analyses were performed to analyze whether SAE would predict NC and poor outcome in patients with SICH. Results A total of 330 patients with acute SICH and coma were enrolled, excluding 60 cases of infratentorial cerebral hemorrhage, 3 cases of primary intraventricular hemorrhage, and 6 cases of unknown volume hematoma. Finally, 261 patients were included, with 111 patients of NC events, and 150 patients of PC events. 69 (62.2%) SAE in SICH with NC and 33 (22.2%) SAE in SICH with PC was diagnosed, and the incidence of SAE between two groups was statistically significant (P < 0.01). Compared with PC group, SICH patients in the NC group had lower incidence of hypertension (81.1% vs. 96.0%), longer time from onset to NC [days: 2.3 (23.9) vs. 0 (0.5)] and length of ICU stay [days: 5.0 (34.0) vs. 3.0 (12.0)], higher initial Glasgow coma score (GCS, 10.2±1.5 vs. 6.6±1.6) and sequential organ failure assessment (SOFA) score [4.0 (6.0) vs. 3.0 (3.0)], lower initial National Institutes of Health Stroke Scale (NIHSS) score (19.4±6.6 vs. 30.2±6.8), as well as more frequent sepsis (78.4% vs. 38.0%), vegetative state (24.3% vs. 14.0%), acute respiratory failure (24.3% vs. 10.0%), pneumonia (37.8% vs. 24.0%), septic shock (8.1% vs. 0), acute liver failure (5.4% vs. 0), hypernatremia (8.1% vs. 0), CT indicating that more frequent vasogenic edema (64.9% vs. 16.0%) and white matter lesion (13.5% vs. 2.0%), and less mannitol usage (94.6% vs. 100.0%), and less brain midline shift (32.4% vs. 68.0%) and hematoma enlargement (8.1% vs. 30.0%), less hematoma volume (mL: 28.0±18.8 vs. 38.3±24.4) in CT, and higher 30-day mortality (54.1% vs. 26.0%) with statistical differences (all P < 0.05). It was shown by Cox regression analyses that SAE [hazard ratio (HR) = 3.5, 95% confidence interval (95%CI) = 1.346-6.765, P = 0.000] and SOFA score (HR = 1.8, 95%CI = 1.073-1.756, P = 0.008) were independent risk factors of death of SICH patients with NC, and hematoma enlargement was independent risk factor of death of SICH patients with PC (HR = 3.0, 95%CI = 1.313-5.814, P = 0.000). Conclusion SAE is the independent factor of inducing NC event and poor prognosis in SICH patients.

Objective:To establish a UPLC method for the determination of ginsenoside Rg1 , ginsenoside Re and ginsenoside Rb1 in Yi’ nianjin. Methods: The column was ZORBAX Eclipse Plus C18 (2. 1 mm × 50 mm,1. 8 μm), the flow rate was 0. 21 ml· min-1 , the column temperature was 30℃, the mobile phase consisted of acetonitrile-water with gradient elution, the detection wave-length was 203nm, and the sample size was 1μl. Results:The linear range of ginsenoside Rg1 was 0. 020 3-0. 303 9 mg·ml-1 ( r=0. 999 6), and the average recovery was 99. 05% (RSD=1. 3%, n=6). The linear range of ginsenoside Re was 0. 020 2-0. 302 7 mg·ml-1(r=0. 999 8), and the average recovery was 101. 31% (RSD=1. 1%, n=6). The linear range of ginsenoside Rb1 was 0. 020 3-0. 305 1 mg·ml-1(r=0. 999 8), and the average recovery of 100. 71% (RSD=0. 9%, n=6). Conclusion: The method is simple and accurate, and can determine the three components simultaneously. The method can be used in the quality control of Yi’ nianjin.

Anemia, Aplastic ; drug therapy ; immunology ; Animals ; Antilymphocyte Serum ; immunology ; therapeutic use ; Calcineurin Inhibitors ; immunology ; therapeutic use ; Humans ; Immunoglobulins ; immunology ; therapeutic use ; Lymphocytes ; drug effects ; immunology ; Swine

The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with adriamycin-induced cardiomyopathy and the relationship between oxidative stress and ventricular arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group, metoprolol (a selective β1 receptor blocker) group, carvedilol (a nonselective β blocker/α-1 blocker) group and adriamycin group. Models of adriamycin-induced cardiomyopathy were established by intravenously injecting adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the adriamycin, metoprolol and carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the metoprolol and carvedilol groups were then intragastrically administrated metoprolol (5 mg/kg/d) and carvedilol (5 mg/kg/d) respectively for 2 months, while those in the adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), malondialdehyde (MAD) and superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the adriamycin group compared with the control group. The incidences of triggered activity and ventricular arrhythmia were significantly higher in the adriamycin group than those in the control group (P<0.05). In the carvedilol group as compared with the adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular arrhythmia between the adriamycin group and the metoprolol group. It was concluded that carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with adriamycin-induced cardiomyopathy, which is related to the decrease in oxygen free radials.
Animals ; Anti-Arrhythmia Agents ; administration & dosage ; Antibiotics, Antineoplastic ; Carbazoles ; administration & dosage ; Cardiomyopathies ; chemically induced ; physiopathology ; prevention & control ; Doxorubicin ; Heart Rate ; drug effects ; Male ; Metoprolol ; administration & dosage ; Oxidative Stress ; drug effects ; Propanolamines ; administration & dosage ; Rabbits ; Treatment Outcome ; Ventricular Fibrillation ; chemically induced ; physiopathology ; prevention & control

The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with adriamycin-induced cardiomyopathy and the relationship between oxidative stress and ventricular arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group, metoprolol (a selective β1 receptor blocker) group, carvedilol (a nonselective β blocker/α-1 blocker) group and adriamycin group. Models of adriamycin-induced cardiomyopathy were established by intravenously injecting adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the adriamycin, metoprolol and carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the metoprolol and carvedilol groups were then intragastrically administrated metoprolol (5 mg/kg/d) and carvedilol (5 mg/kg/d) respectively for 2 months, while those in the adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), malondialdehyde (MAD) and superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the adriamycin group compared with the control group. The incidences of triggered activity and ventricular arrhythmia were significantly higher in the adriamycin group than those in the control group (P<0.05). In the carvedilol group as compared with the adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular arrhythmia between the adriamycin group and the metoprolol group. It was concluded that carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with adriamycin-induced cardiomyopathy, which is related to the decrease in oxygen free radials.