Objective : To explore the role and mechanism of plasmalemma vesicle-associated protein(PLVAP) in the progression of hepatocellular carcinoma(HCC). Methods : Bioinformatic analysis, quantitative real-time PCR, Western blot and immunohistochemistry were used to analyze the expression level of PLVAP in HCC and paracancerous tissues, and its correlation with clinicopathological characteristics. Stable HCC cell lines with knockdown and overexpression of PLVAP were constructed, then cell proliferation, migration and invasion of HCC cells were examined by CCK-8, foci formation assays, wound-healing assays and Transwell assays. Western blot was used to detect the protein levels of phosphatidylinositol 3-kinase PI3K, phosphorylated phosphatidylinositol 3-kinase p-PI3K, protein kinase B AKT and phosphorylated protein kinase B p-AKT in the PI3K/AKT pathway after PLVAP knockdown and overexpression. Cell proliferation, migration and invasion were also examined in PLVAP-overexpressed cells after treatment of LY294002, an inhibitor of the PI3K/AKT pathway. Results : The expression of PLVAP was significantly higher in HCC tissues than that in adjacent non-tumor tissues(P<0.05), and was positive correlated with tumor stage, T stage, M stage, and microvascular invasion(P<0.05). Knockdown of PLVAP significantly reduced the proliferation, migration and invasion of HCC cells(P<0.001), while overexpression of PLVAP significantly increased the proliferation, migration and invasion of HCC cells(P<0.01). Western blot analysis revealed that knockdown of PLVAP decreased the protein expression levels of p-PI3K and p-AKT, overexpression of PLVAP increased the protein expression levels of p-PI3K and p-AKT, whereas the PI3K/AKT inhibitor LY294002 eliminated the effects of PLVAP on cell proliferation, migration and invasion(P<0.01). Conclusion PLVAP is highly expressed in HCC and may promote HCC progression by activating the PI3K/AKT signaling pathway.

Objective:To evaluate the protective effectiveness (VE) of the acellular pertussis vaccine (aPV) against pertussis in children aged 2 months to 6 years.Methods:A test-negative case-control study was conducted among children aged 2 months to 6 years who sought medical care for cough and underwent pertussis nucleic acid testing at sentinel surveillance hospitals in Zhejiang Province in 2024. Cases were defined as those with positive pertussis nucleic acid test results, while controls were test-negative individuals matched 1∶1 based on propensity scores using the caliper matching method. Conditional logistic regression models were used to calculate odds ratios ( ORs) and VEs. Results:Among the 658 participants, 31.76% (209 cases) tested positive for pertussis. After propensity score matching, 203 cases and 203 controls were included in the analysis. The VE of 1-2, 3, and 4 doses of aPV against pertussis was 52.46% (95% CI:-39.82%-83.84%), 65.22% (95% CI: 6.86%-87.02%), and 72.21% (95% CI: 34.33%-88.24%), respectively. For pertussis-related hospitalization, the VE of 1-3 and 4 doses was 80.95% (95% CI:31.38%-94.71%) and 86.79% (95% CI: 51.89%-96.37%). The VE for those who completed 4 doses of vaccination and had intervals of less than 2 years, 2 years, 3 years, and 4 years or more after vaccination were 91.15% (95% CI: 67.61%-97.58%), 84.70% (95% CI: 43.71%-95.84%),56.23% (95% CI:-47.58%-87.02%), and 49.92% (95% CI:-83.74%-86.35%), respectively. Conclusion:The VE of aPV against pertussis in children aged 2 months to 6 years increases with the number of doses administered, and it is more effective in preventing hospitalization due to pertussis. The VE declines rapidly over time after the last dose. It is recommended to follow the new pertussis immunization program for timely and full vaccination.

Objective:To explore the diagnostic value of ultrasound for retained products of conceptions com-plicated with uterine arteriovenous fistula(UAVF)after early pregnancy miscarriage and the predictive value for massive bleeding by constructing a risk model for bleeding.Methods:A total of 90 patients who were diagnosed by ultrasound in West China Second Hospital of Sichuan University as having retained products of conceptions complicated with UAVF after early pregnancy miscarriage from July 2013 to September 2021 were selected,among which 37 cases underwent digital subtraction angiography(DSA).Clinical and ultrasound data were collected and statistical analysis was conducted on the ultrasound parameters of whether DSA examination was accompanied by UAVF and whether there was major bleeding(spontaneous and intraoperative).We performed multivariate Lo-gistic regression analysis on parameters with statistical differences,plotted receiver operating characteristic(ROC)curve for predicting major bleeding(spontaneous and intraoperative),and calculated the area under the curve(AUC).Results:① After DSA examination,14 out of 37 patients(37.8%)were diagnosed with UAVF based on ultrasound diagnosis of pregnancy residue combined with UAVF.Univariate and multivariate Logistic an-alyses showed that the expanding inner diameter of blood vessels was an independent risk factor for residual pregnancy products combined with UAVF after early pregnancy miscarriage(OR 37.099,P=0.027).ROC curve analysis revealed that dilated vessel diameter had an AUC of 0.78,sensitivity of 64%,specificity of 91%,and an optimal cut-off value of 0.85 cm for the diagnosis of UAVF.②Out of 90 patients,44(48.9%)experienced sponta-neous massive bleeding.Univariate and multivariate Logistic analyses showed that the presence of vascular pools or dilated vessels was an independent risk factor for spontaneous massive bleeding(OR 5.163,P=0.004).③A-mong70 patients undergoing surgical treatment,7 experienced intraoperative bleeding(11.7%).Univariate and multivariate Logistic analyses showed that the enlargement of the maximum diameter of the lesion was an inde-pendent risk factor for intraoperative massive bleeding(OR 7.278,P=0.007).ROC curve analysis revealed that the AUC of the maximum diameter of the lesion for predicting the risk of intraoperative bleeding was 0.92,with a sensitivity of 100%,specificity of 82%,and an optimal threshold of 3.95 cm.Conclusions:Dilated vessel diameter in ultrasound examination parameters has high diagnostic value for residual pregnancy products combined with UAVF after early pregnancy miscarriage.Patients with vascular pools or dilated vessels and large lesions have a higher risk of spontaneous and intraoperative bleeding,and clinical prediction models can be used to assess risk of bleeding.

Objective:To explore the diagnostic value of ultrasound for retained products of conceptions com-plicated with uterine arteriovenous fistula(UAVF)after early pregnancy miscarriage and the predictive value for massive bleeding by constructing a risk model for bleeding.Methods:A total of 90 patients who were diagnosed by ultrasound in West China Second Hospital of Sichuan University as having retained products of conceptions complicated with UAVF after early pregnancy miscarriage from July 2013 to September 2021 were selected,among which 37 cases underwent digital subtraction angiography(DSA).Clinical and ultrasound data were collected and statistical analysis was conducted on the ultrasound parameters of whether DSA examination was accompanied by UAVF and whether there was major bleeding(spontaneous and intraoperative).We performed multivariate Lo-gistic regression analysis on parameters with statistical differences,plotted receiver operating characteristic(ROC)curve for predicting major bleeding(spontaneous and intraoperative),and calculated the area under the curve(AUC).Results:① After DSA examination,14 out of 37 patients(37.8%)were diagnosed with UAVF based on ultrasound diagnosis of pregnancy residue combined with UAVF.Univariate and multivariate Logistic an-alyses showed that the expanding inner diameter of blood vessels was an independent risk factor for residual pregnancy products combined with UAVF after early pregnancy miscarriage(OR 37.099,P=0.027).ROC curve analysis revealed that dilated vessel diameter had an AUC of 0.78,sensitivity of 64%,specificity of 91%,and an optimal cut-off value of 0.85 cm for the diagnosis of UAVF.②Out of 90 patients,44(48.9%)experienced sponta-neous massive bleeding.Univariate and multivariate Logistic analyses showed that the presence of vascular pools or dilated vessels was an independent risk factor for spontaneous massive bleeding(OR 5.163,P=0.004).③A-mong70 patients undergoing surgical treatment,7 experienced intraoperative bleeding(11.7%).Univariate and multivariate Logistic analyses showed that the enlargement of the maximum diameter of the lesion was an inde-pendent risk factor for intraoperative massive bleeding(OR 7.278,P=0.007).ROC curve analysis revealed that the AUC of the maximum diameter of the lesion for predicting the risk of intraoperative bleeding was 0.92,with a sensitivity of 100%,specificity of 82%,and an optimal threshold of 3.95 cm.Conclusions:Dilated vessel diameter in ultrasound examination parameters has high diagnostic value for residual pregnancy products combined with UAVF after early pregnancy miscarriage.Patients with vascular pools or dilated vessels and large lesions have a higher risk of spontaneous and intraoperative bleeding,and clinical prediction models can be used to assess risk of bleeding.

Objective:To evaluate the protective effectiveness (VE) of the acellular pertussis vaccine (aPV) against pertussis in children aged 2 months to 6 years.Methods:A test-negative case-control study was conducted among children aged 2 months to 6 years who sought medical care for cough and underwent pertussis nucleic acid testing at sentinel surveillance hospitals in Zhejiang Province in 2024. Cases were defined as those with positive pertussis nucleic acid test results, while controls were test-negative individuals matched 1∶1 based on propensity scores using the caliper matching method. Conditional logistic regression models were used to calculate odds ratios ( ORs) and VEs. Results:Among the 658 participants, 31.76% (209 cases) tested positive for pertussis. After propensity score matching, 203 cases and 203 controls were included in the analysis. The VE of 1-2, 3, and 4 doses of aPV against pertussis was 52.46% (95% CI:-39.82%-83.84%), 65.22% (95% CI: 6.86%-87.02%), and 72.21% (95% CI: 34.33%-88.24%), respectively. For pertussis-related hospitalization, the VE of 1-3 and 4 doses was 80.95% (95% CI:31.38%-94.71%) and 86.79% (95% CI: 51.89%-96.37%). The VE for those who completed 4 doses of vaccination and had intervals of less than 2 years, 2 years, 3 years, and 4 years or more after vaccination were 91.15% (95% CI: 67.61%-97.58%), 84.70% (95% CI: 43.71%-95.84%),56.23% (95% CI:-47.58%-87.02%), and 49.92% (95% CI:-83.74%-86.35%), respectively. Conclusion:The VE of aPV against pertussis in children aged 2 months to 6 years increases with the number of doses administered, and it is more effective in preventing hospitalization due to pertussis. The VE declines rapidly over time after the last dose. It is recommended to follow the new pertussis immunization program for timely and full vaccination.

Objective:To evaluate direct and indirect costs for schizophrenia,major depressive disorder(MDD)and bipolar disorder,and to compare their differences of cost composition,and to explore the drivers of the total costs.Methods:A total of 3 175 inpatients with schizophrenia,MDD,and bipolar disorder were recruited.In-patient's self-report total direct of medical costs outpatient and inpatient,out-of-pocket costs,and direct non-medical costs were regarded as direct costs.Productivity loss and other loss caused by damaging properties were defined as indirect costs.The perspectives of this study included individual and societal levels.Multivariate regression analysis was applied for detecting the factors influencing disease costs.Results:The total cost of schizophrenia was higher than those of MDD and bipolar disorder at individual and societal levels.The indirect costs of three mental disorders were higher than the direct costs,and the indirect cost ratio of bipolar disorder was higher than those of schizophre-nia and MDD.Age,gender,working condition and marital status(P＜0.05)were the important drivers of total costs.Conclusion:The economic burden of the three mental disorders is relatively heavy.Schizophrenia has heaviest disease burden,and the productivity loss due to mental disorders is the driving force of the soaring disease cost

Objective To evaluate the value of chromosomal microarray analysis (CMA) for genetic evaluation of fetal ultrasound abnormality. Methods A total of 180 pregnant women with fetal abnormality detected by prenatal ultrasound diagnosis in the first trimester during the period from January 2020 through May 2022 were enrolled as the study subjects. All prenatal fetal screening samples were subjected to G-band karyotyping and CMA. Results G-band karyotyping detected normal karyotypes in 168 samples (93.85%) and abnormal karyotypes in 11 samples (6.15%), and CMA detected 17 positive samples (9.44%) and 163 negative samples (90.56%). The seventeen positive samples included 11 pathogenic copy number variations (CNVs) and 6 variants of unknown significance (VOUS), and there were 11 CMA-positive results consistent with G-band karyotyping, and 6 additional pathogenic CNVs mainly included microdeletion and microduplication syndromes. The detection rates of pathogenic CNVs were 11.11%, 2.63%, 2.78%, 4.00%, 0, 0, 11.11% and 0 among the fetuses with abnormal structure of the cardiovascular system, the lymphatic system, the nervous system, the digestive system, the cranial and face system, the skeletal system, the urinary system, and other system (χ² =8.188, P = 0.316). All eleven fetuses with pathogenic CNVs detected by CMA were all induced for abortion. Conclusion CMA improves the detection of genetic abnormality among fetuses with ultrasound abnormality in relative to G-band karyotyping, which is feasible for prenatal cytogenetic diagnosis among fetuses with ultrasound abnormality

Orally inhaled drug products (OIDPs) play a great role in the pharmacological treatment of chronic obstructive pulmonary disease (COPD) and asthma. There is an unmet clinical need for OIDPs. Pharmacodynamics-Bioequivalence studies (PD-BE) are recommended by several national guidelines as important research methods for bioequivalence study of OIDPs. It can effectively bridge the gap between in vitro studies and PK-BE studies in evaluating the efficacy and safety consistency of generic drugs with the original drugs. There are two research methods for PD-BE, using a diastolic model or an excitation model. The different methods use different metrics to evaluate efficacy. The more commonly used metrics include Forced Expiratory Volume in the First Second (FEV1), Specific Airway Conductance (sGaw), Peripheral Airway Resistance (R5-20), and stimulant concentration/dose (PC20/PD20). PD-BE studies using FEV1 as an efficacy metric is also recommended by the FDA (Food and Drug Administration), EMA (European Medicines Agency) and NMPA (National Medical Products Administration) guidelines and is widely accepted by investigators. In such PD-BE studies, the trial protocols for different OIDPs drugs are relatively consistent in terms of trial design, trial data processing, and equivalence evaluation criteria, while there are detailed differences in terms of target population, single/multiple dosing, dose administration, and collection site design. This paper reviews the progress of PD-BE studies in the bioequivalence evaluation of OIDPs by combining national guidelines and PD-BE-related studies of OIDPs published in the last five years, with a view to providing important theoretical information for PD-BE studies of OIDPs.

Objective:To explore the effect of post-pyloric feeding by spiral nasoenteric tubes on the prognosis of critically ill patients with acute gastrointestinal injury (AGI) grade Ⅱ.Methods:A retrospective study was performed to analyze the clinical data of critically ill adult patients with AGI grade Ⅱ, who were enrolled in three randomized controlled trials conducted by Guangdong Provincial People's Hospital for post-pyloric tube placement between April 2012 and May 2019. Data including demographic characteristics, serological indicators of nutrition, the tube tip position confirmed by abdominal X-ray 24 h after tube insertion, and intensive care unit (ICU), 28-day and hospital mortality were collected. Patients were divided into the post-pyloric feeding group and gastric feeding group according to the tube tip position. Propensity score matching method was used to perform 1:1 matching, and the differences of each index between the two groups were compared after matching. Then the influencing factors of P<0.1 were included in multivariate logistic regression analysis to investigate the potential ICU mortality risk factors of critically ill patients with AGI gradeⅡ. Factors with 0.1 level of significance from the univariate analysis were considered in the multivariate analysis. Results:There were 90 patients in post-pyloric feeding group and 90 patients in the gastric feeding group. Demographics and clinical characteristics of study population were well balanced between the two groups after matching. ICU, 28-day and hospital mortality in the post-pyloric feeding group were significantly lower than those in the gastric feeding group (4.4% vs 15.6%, 14.4% vs 27.8%, 6.7% vs 17.8%, all P < 0.05). Multivariate logistic regression analysis indicated that post-pyloric feeding was an independent protective factor [odds ratio ( OR)=0.295, 95% confidence internal (95% CI): 0.091-0.959, P=0.042] and APACHEⅡ score was an independent risk factor ( OR=1.111, 95% CI: 1.025-1.203, P=0.010) for ICU mortality of critically ill patients with AGI gradeⅡ. Conclusions:Post-pyloric feeding for critically ill patients with AGI grade Ⅱ could decrease ICU mortality and is an independent protective factor against mortality.

Objectives:To investigate the prevalence of cough and its influencing factors in community children under 5 years old.Methods:From October to December 2019, we selected 3 102 community children under the age of 5 from 50 natural villages/residential communities in 14 towns/streets of Yiwu, Zhejiang Province, using multi-stage random sampling method. A face-to-face and on-site questionnaire survey was conducted among child caregivers to collect demographic data and information about children′s cough in the last 1 month. Multiple logistic regression model was used to analyze children′s cough and the influencing factors of different cough states.Results:Multivariate logistic regression model analysis results showed that compared with 0-1 year old, dispersed, caregivers with education level below high school, families with 1 child under 5 years old, Cough risk was higher in 1-2, 2-3, 3-4 years old, nurseries, caregivers with education level of high school or above, and families with more than 2 children under 5 years old. OR (95% CI) values were 1.52(1.19-1.92), 1.65(1.29-2.10), 1.86(1.36-2.54), 2.59(1.99-3.38), 1.48(1.26-1.74) and 1.35(1.13-1.62), respectively. Further analysis of the influencing factors of different states of cough, multivariate logistic regression model analysis results showed that preschool status, the number of children under 5 years old in the family and the education level of caregivers were the influencing factors of acute, prolonged and chronic cough. Age was only an influencing factor of acute and persistent cough. Conclusions:The disease burden of cough in children under 5 years old community was heavy, and the cough was related to children′s age, education level of caregivers, number of children under 5 years old in the family and childcare status.