Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders (NDDs) in the offspring, especially in the case of drug exposure. However, little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors. We collected and manually curated sub-pathways and pathways (sub-/pathways) and drug information to propose an analytical framework for predicting drug candidates. This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs. Further, specific and pleiotropic sub-/pathways/drugs were identified using entropy, and sex bias was analyzed in conjunction with logistic regression and random forest models. We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs, showing temporal or spatial changes across fetal development. Moreover, 5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels. A user-friendly NDDP visualization website ( https://ndd-lab.shinyapps.io/NDDP ) was developed to allow researchers and clinicians to access and retrieve data easily. Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories. This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/metabolism* ; Male ; Prenatal Exposure Delayed Effects ; Fetal Development/drug effects* ; Drug Discovery/methods* ; Brain/metabolism*

Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

Objective: To understand the level and trend of health literacy among residents in Zhoushan City, Zhejiang Province from 2015 to 2023, so as to provide the reference for developing promotion strategies and interventions of health literacy. Methods: Permanent residents aged 15 to 69 years in Zhoushan City were selected as the survey subjects using a multi-stage stratified random sampling combined with population-size proportional sampling method. The residents' health literacy was investigated using the Questionnaire on the Health Literacy among Chinese Residents, and standardized by Zhoushan City population data captured from the national population census in China. The absolute increase and growth rate of health literacy level from 2015 to 2023 were calculated to investigate the changing trends in health literacy levels. Results: A total of 19 296 residents were monitored from 2015 to 2023, including 8 006 men (41.49%) and 11 290 women (58.51%), and had a mean age of (50.06±12.67) years. The health literacy levels among residents in Zhoushan City from 2015 to 2023 were 13.10%, 18.33%, 20.35%, 23.71%, 27.58%, 30.75%, 34.36%, 37.03% and 39.47%, respectively, showing an upward trend (P<0.05), with an average annual growth rate of 2.93%. The 9-year absolute increase rates of 26.37%, and the growth rate reached 201.30%. The health literacy levels of basic knowledge and concept, healthy lifestyle and behaviors and basic skills all appeared increasing trends (all P<0.05), and the 9-year absolute increase and growth rate of the basic skills were the smallest (7.64% and 34.60%). The health literacy levels of six categories of health issues all showed upward trends (all P<0.05). The health literacy levels of residents in different regions and genders showed upward trends (both P<0.05). Except for the age of 65 to 69 years, the health literacy levels among all the other age groups showed upward trends (all P<0.05). There was no significant changing trend in the health literacy level among illiterate/semi-literate residents (P>0.05), the health literacy level among residents with primary school education showed a downward trend (P<0.05), while the health literacy levels of residents with other educational levels all showed upward trends (all P<0.05). There was no significant changing trend in the health literacy level among farmers (P>0.05), while the health literacy levels among residents with other occupations showed upward trends (all P<0.05). Conclusions The health literacy level among residents in Zhoushan City steadily increased from 2015 to 2023. Health education and promotion efforts have been targeted at key populations of the elderly aged over 65 years, residents with a primary school education or below and farmers.

Objective To analyze the expression level of ATP5A1 in gastric carcinoma and its influence on the prognosis of the patients and glucose metabolism in the tumor cells.Methods We retrospectively analyzed the data of 115 patients undergoing radical resection of gastric carcinoma in our hospital from February,2013 to November,2016.ATP5A1 expression in the surgical specimens were detected using immunohistochemistry,and the long-term prognosis of the patients with high(n=58)and low ATP5A1 expression(n=57)were analyzed.In gastric carcinoma MGC803 cells,the effects of lentivirus-mediated ATP5A1 knockdown or overexpression on glucose metabolism were investigated.We also observed the growth and glucose metabolism of xenografts derived from MGC803 cells with ATP5A1 knockdown or overexpression in nude mice.Results ATP5A1 was significantly overexpressed in gastric carcinoma tissues in close correlation with blood CEA and CA19-9 levels,pathological grade,T stage and N stage(P<0.05).ATP5A1 overexpression was an independent risk factor for a significantly lowered 5-year survival rate of patients with gastric carcinoma(P<0.05).ROC curve analysis demonstrated the predictive value of high ATP5A1 expression for the patients'prognosis(P<0.001).In MGC803 cells,ATP5A1 overexpression significantly up-regulated cellular glucose uptake and lactate production and increased the protein levels of HK2,PFK1,and LDHA(P<0.05),while ATP5A1 knockdown produced the opposite changes(P<0.05).In the tumor-bearing mice,overexpression of ATP5A1 increased glucose metabolism of the tumor cells and promoted tumor growth(P<0.05).Overexpression of ATP5A1 promoted the expressions of p-JNK and p-JUN in MGC803 cells(P<0.05),and the JNK inhibitor SP600125 significantly inhibited the enhancement of cellular glucose metabolism induced by ATP5A1 overexpression(P<0.05).Conclusion High ATP5A1 expression in gastric cancer is associated a poor long-term prognosis of the patients,and its effect is mediated at least partly by promoting glucose metabolism of the cells through the JNK/JUN pathway.

Objective To analyze the risk factors affecting the prognosis of patients with advanced gastric cancer,so as to provide evidence for identifying high-risk populations and guiding clinical treatment.Methods The clinical data of 282 patients with advanced gastric cancer who admitted to Zhoushan Hospital of Traditional Chinese Medicine from January 2017 to December 2021 were retrospectively analyzed.The survival outcome of patients was obtained by telephone follow-up and regular review.Kaplan-Meier method was used to analyze the overall survival(OS).Univariate and multivariate COX regression models were used to analyze the effects of clinical features on OS in patients with advanced gastric cancer.Results The median OS of 282 patients with advanced gastric cancer was 10.0 months.Univariate analysis showed that first-line chemotherapy,traditional Chinese medicine treatment,body mass index(BMI),Karnofsky performance status(KPS)score,hemoglobin(Hb)and albumin(Alb)were significantly correlated with the survival of patients with advanced gastric cancer(P<0.05).Multivariate COX regression models analysis showed that first-line chemotherapy,BMI,KPS score and Alb were independent risk factors affecting the survival of patients with advanced gastric cancer(P<0.05).Conclusion BMI,Alb,KPS score and first-line chemotherapy are independent risk factors for predicting the prognosis of patients with advanced gastric cancer,indicating nutrition management may be an important way to improve the outcome of patients with advanced gastric cancer.

Objective To analyze the expression level of ATP5A1 in gastric carcinoma and its influence on the prognosis of the patients and glucose metabolism in the tumor cells.Methods We retrospectively analyzed the data of 115 patients undergoing radical resection of gastric carcinoma in our hospital from February,2013 to November,2016.ATP5A1 expression in the surgical specimens were detected using immunohistochemistry,and the long-term prognosis of the patients with high(n=58)and low ATP5A1 expression(n=57)were analyzed.In gastric carcinoma MGC803 cells,the effects of lentivirus-mediated ATP5A1 knockdown or overexpression on glucose metabolism were investigated.We also observed the growth and glucose metabolism of xenografts derived from MGC803 cells with ATP5A1 knockdown or overexpression in nude mice.Results ATP5A1 was significantly overexpressed in gastric carcinoma tissues in close correlation with blood CEA and CA19-9 levels,pathological grade,T stage and N stage(P<0.05).ATP5A1 overexpression was an independent risk factor for a significantly lowered 5-year survival rate of patients with gastric carcinoma(P<0.05).ROC curve analysis demonstrated the predictive value of high ATP5A1 expression for the patients'prognosis(P<0.001).In MGC803 cells,ATP5A1 overexpression significantly up-regulated cellular glucose uptake and lactate production and increased the protein levels of HK2,PFK1,and LDHA(P<0.05),while ATP5A1 knockdown produced the opposite changes(P<0.05).In the tumor-bearing mice,overexpression of ATP5A1 increased glucose metabolism of the tumor cells and promoted tumor growth(P<0.05).Overexpression of ATP5A1 promoted the expressions of p-JNK and p-JUN in MGC803 cells(P<0.05),and the JNK inhibitor SP600125 significantly inhibited the enhancement of cellular glucose metabolism induced by ATP5A1 overexpression(P<0.05).Conclusion High ATP5A1 expression in gastric cancer is associated a poor long-term prognosis of the patients,and its effect is mediated at least partly by promoting glucose metabolism of the cells through the JNK/JUN pathway.

OBJECTIVE To explore the intestinal absorption characteristics of saikosaponins. METHODS Based on everted intestinal sac model， using accumulative absorption amount （Q） and absorption rate constant （Ka） as indexes， UHPLC-MS/MS technique as a method， the absorption of saikosaponin A， B2， C， D and F from total saponins of Bupleurum chinense （8 g/mL， by crude drug） in the duodenum， jejunum and ileum was detected. RESULTS The correlation coefficients （r） of the regression equations for the absorption of saikosaponins A， B2， C and F in the duodenum， jejunum and ileum were all higher than 0.95， while the r of saikosaponin D in the above intestinal segments was lower than 0.95； compared with the absorption of the same composition in the duodenum， the Q and Ka of saikosaponin A and C circulating in jejunum and ileum for 120 min， as well as the Q and Ka of saikosaponin F circulating in the ileum for 120 min were significantly decreased （P＜0.05）. CONCLUSIONS Saikosaponin A and the other 4 saikosaponins are all absorbed in the duodenum， jejunum and ileum； among them， saikosaponin A， B2， C and F are linearly absorbed， which conforms to the zero-order absorption characteristics， but saikosaponin D shows non- linear absorption.

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.
Computational Biology ; Drugs, Chinese Herbal ; Humans ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Urinary Bladder Neoplasms/genetics*

Objective To explore the expression of nutrition information based on consumer cognitive psychology,and improve the applicability of pre-packaged food nutrition labels.Method Taking the "nutrition label" of a biscuit as an example:First,the energy (kilojoules) of the biscuit is converted into "food exchange serving";Then,the energy supply ratio of three major calorigenic nutrients of various foods in the biscuit is calculated according to the "China Food Composition Table",and the energy supply ratio of three major calorigenic nutrient in different food combinations is also calculated.Finally,we determined whether energy supply ratio of the three major calorigenic nutrients of the biscuit is similar to a mix of certain energy ratios of certain types of food.Thus,the new nutritional information expression of'nutrition labels' was determined.The applicability and operability of balanced food practice was compared between the existing and improved nutrition information expression by the'desktop deduction'method.Results The biscuit contains 1 823 k] of energy per 100 g,which is about 5 "food exchange servings".The average energy supply ratio of protein,fat,and carbohydrate of all kinds of food are as follows:The cereals were 15％,5％ and 80％ respectively;the meats were 55％,39％ and 10％ respectively;the vegetables were 27％,9％ and 58％ respectively;and the fruits were 5％,3％ and 91％,respectively.If different types of food are mixed according to their energy ratio,then the energy supply ratio of the three energy producing nutrients is different.The energy ratio of the three energy producing nutrients of the prepackaged food will always be similar to that of the mixture of some kinds of food.The biscuit is similar to 1:4 energy mixed with oil foods and cereals,which translates to about 10 g of oils and 100 g of grains,based on the'food exchange serving'.Hence,if you eat 100 g of these cookies,subtract about 10 g of fat and 100 g of cereal from your three meals per day.Conclusion The nutritional ingredient list of'prepackaged food nutrition label'should increase the expression of 'food exchange'and food category and energy proportion,so as to facilitate the practice of balanced diet by consumers.

Objective To study the effect of masked hypertension (MH) and white coat hypertension (WCH) on vascular elasticity and endothelial function in elderly patients.Methods Four hundred and eighty-seven elderly patients who underwent physical examination in our our hospital were divided into normotension group (n=128),WCH group (n=115),MH group (n=112) and hypertension group (n=132) according to their diagnostic office blood pressure and 24 h ambulatory blood pressure.The brachial artery FMD,serum NO and endothelin-1 (ET-1) levels,and cfPWV were measured.Results The FMD and serum NO level were significantly lower while the serum ET-1 level and cfPWV were significantly higher in WCH group,MH group and hypertension group than in normotension group (P＜0.05).The FMD and serum NO level were significantly higher while the serum ET-1 and cfPWV were significantly lower in WCH group and MH group than in hypertension group (P＜ 0.05).Multivariate linear stepwise regression analysis showed that WCH,MH and hypertension were the independent influencing factors for FMD,serum NO and ET-1 level and cfPWV with normotension used as reference after adjustment of confounding factors (P＜0.01).Conclusion MH and WCH are the risk factors for the decreased vascular elasticity and endothelial dysfunction in elderly patients.