Objective:To identify serum metabolic markers for early prediction and diagnosis of gestational diabetes mellitus (GDM).Methods:A retrospective case-control study was conducted.The study subjects were from pregnant women enrolled in the Birth Cohort Study of the Women′s Hospital, Zhejiang University, from1 November 2018 to 30 March 2020.100 cases of GDM (GDM group, Age 36.03±3.91) and 150 non-GDM pregnant women matched for clinical information (control group, Age35.49±3.46) were retrospectively selected for the study. Fasting serum samples were collected at 15-20 weeks of gestation (prior to GDM diagnosis, T1 period) and 24-28 weeks of gestation (during GDM diagnosis, T2 period). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify GDM-related serum metabolic small molecules, including 1, 5-anhydroglucitol, 3-hydroxybutyric acid, phenylalanine, and isoleucine. These molecules, along with basic clinical information (age, gestational week, BMI) and standard biochemical indicators (FPG), were used to develop predictive models for the early detection of GDM at T1 and the diagnosis of GDM at T2. Statistical analysis was performed using t-tests or Mann-Whitney U-tests.Result:The results of the targeted quantitative validation study indicate: At the T1 stage, the level of 1, 5-anhydroglucitol was found to be significantly lower ( P=0.001) in the GDM group compared to the control group. Conversely, the level of isoleucine was significantly higher ( P=0.027) in the GDM group. There were no significant differences in the levels of 3-hydroxybutyrate and phenylalanine between the two groups ( P>0.05). The combination of the 4 metabolites yielded the highest predictive value (AUC) for GDM at T1, with an AUC of 0.670 (95% CI: 0.602-0.739), P<0.001.At the T2 stage, the GDM group had significantly lower levels of 1, 5-anhydroglucitol ( P<0.05) and significantly higher levels of 3-hydroxybutyric acid and isoleucine ( P<0.05) than the control group, with no significant differences in phenylalanine levels ( P=0.626). The combination of the four metabolites had the highest diagnostic value (AUC) for GDM, 0.717 (95% CI 0.651-0.783), P<0.001.The analysis of seven different combinations of GDM prediction/diagnostic models created by combining four metabolites with basic clinical information and routine biochemical indicators showed: We found that the AUC value of the GDM diagnostic model built with FPG, BMI, pre-pregnancy BMI, age, gestational week, and the 4 metabolite indicators in T2 stage was the best, 0.794 (95% CI 0.736-0.851), P<0.001, with a sensitivity of 72%;The best AUC value for the GDM prediction model built with the same indicators at T1 was 0.711(95% CI 0.646-0.776), P<0.001, with a sensitivity of 77%. Conclusions:Four metabolic small molecules, 1, 5-anhydroxyglucitol, 3-hydroxybutyric acid, phenylalanine, and isoleucine, were integrated with clinical indicators (FPG) and clinical information (age, gestational week, BMI) to develop a predictive model for GDM at gestation (T1) and a diagnostic model for GDM at gestation (T2), demonstrating promising clinical prediction and diagnostic capabilities. 1, 5-Anhydroglucitol, 3-hydroxybutyric acid, phenylalanine, and isoleucine show potential as valuable markers for the prediction and diagnosis of GDM.

Objective To explore the effects of metformin on the proliferation,migration,and epithelial-mesenchy-mal transition(EMT)of human lens epithelial cells(LEC)induced by transforming growth factor-β2(TGF-β2).Methods Immortalized human LEC(HLEB-3 cells)was selected as the cell source.Human LEC with a cell fusion degree of 80％was cultured in DMEM low-glucose medium containing 10 mg·L-1 TGF-β2 for 24 hours as the control group.The cells treated with TGF-β2 and then further treated with different concentrations of metformin were used as the experimental group.After treatment,the morphological changes of cells in each group were observed under an inverted microscope.The cytotoxicity was detected by CCK-8 assay,and the cell survival rate was calculated.The expression levels of Yes-associated protein 1(YAP1),large tumor suppressor 1(LATS1),and Vimentin in cells were detected by Western blot.The mRNA ex-pression levels of YAP1,LATS1,mammalian STE20-like kinase 1(MST1),Vimentin,and E-cadherin were detected by re-al-time quantitative polymerase chain reaction.Results The cytotoxicity test of metformin showed that when the concen-tration of metformin was greater than 15 mmol·L-1,the survival rate of human LEC significantly decreased,indicating that the concentration of metformin had a significant impact on the survival of LEC.Therefore,15 mmol·L-1 was selected for subsequent experiments.Metformin significantly inhibited the proliferation of human LEC induced by TGF-β2 in a dose-dependent manner(P＜0.001).After 24 hours of treatment with 15 mmol·L-1 metformin,the relative expression levels of YAP1 and Vimentin proteins in human LEC were lower than those in the control group(both P＜0.05),while the relative expression level of LATS1 protein was higher than that in the control group(P＜0.05).After 24 hours of treatment with 15 mmol·L-1 metformin,the relative expression levels of YAP1 and Vimentin mRNA in human LEC were lower than those in the control group,while the relative expression levels of LATS1,MST1,and E-cadherin mRNA were higher than those in the control group,with statistically significant differences(all P＜0.05).Conclusion Metformin can inhibit the prolifer-ation,migration and EMT of human LEC induced by TGF-β2 in vitro,downregulate the expression of YAP1 and Vimentin mRNA,and upregulate the expression of LATS1,MST 1 and E-cadherin.The mechanism of action may be related to its ac-tivation of the Hippo signaling pathway.

Objective:To learn about the monitoring indicators and patient management in coal-burning-borne endemic arsenic poisoning areas in Shaanxi Province, and provide a basis for consolidating and improving the prevention and control achievements.Methods:From March to December 2023, in accordance with the requirements of the "Notice of the Office of Shaanxi Provincial Health Commission on Issuing of the Monitoring Plan for Key Endemic Diseases Such as Kashin-Beck Disease" and "The Monitoring Plan for Endemic Fluorosis and Arsenic Poisoning in Shaanxi Province", a basic situation investigation was conducted in the affected villages of all counties (districts) with coal-burning-borne endemic arsenic poisoning in Shaanxi Province, and on-site visits were conducted to check the management of high arsenic coal mines. Using the simple random sampling method, 30 families in each village were selected to investigate the use of stoves and the formation of health-related behaviors. A survey on arsenic poisoning was carried out among all populations in the affected villages. According to the requirements of the provincial monitoring program, 720 people were randomly selected from 12 affected villages in 3 monitoring counties to measure their urinary arsenic level. The determination was based on the "Guidelines for the Safety of Urinary Arsenic in Population" (WS/T 665-2019). The evaluation for elimination of disease areas was carried out in accordance with the "National Health Commission Issued the Evaluation Approach for Control and Elimination of Priority Endemic Diseases (2019 edition)".Results:A total of 2 cities, 8 counties (districts), 99 townships, and 1 414 affected villages were monitored. All 53 high arsenic coal mines had stopped mining. The rate of qualified improved stoves was 99.97%; the correct utilization rate of qualified improved stoves, and the correct drying rate of corn and chili peppers provided for human consumption in the affected villages were 100.00%. A total of 2 064 138 people were examined, and 2 682 cases of arsenic poisoning were detected, all of whom were historical patients. There were no new cases of arsenic poisoning or skin cancer. There were currently 2 682 arsenic poisoning patients who had received family doctor contract services and implemented follow-up management. The geometric mean of urinary arsenic was 0.016 7 mg/L, which was lower than the safety guideline value for human urinary arsenic (0.032 mg/L).Conclusions:The monitoring indicators in the coal-burning-borne endemic arsenic poisoning areas in Shaanxi Province have reached the elimination standards. In the future, we should continue to strengthen the management of high arsenic coal mines, implement comprehensive prevention and control measures mainly focused on furnace and stove renovation and health promotion, and do a good job in patient management to continuously consolidate and improve the prevention and control achievements.

Guided by the concept of "blood-pulse-heart-spirit"， it is believed that stable angina combined with insomnia is caused by disturbance of blood vessels， which leads to loss of nourishment for the heart body and heart spirit， so the core treatment principle is to regulate the blood vessels and calm the mind. At the beginning of the disease， it shows as the liver fails to govern the free flow of qi， and disorders qi and blood； during the progress of the disease， it shows as spleen deficiency and phlegm stagnation， phlegm and blood stasis obstructing the vessels； the central mechanism of the disease shows as disturbance of blood vessels and insufficient heart yin. For the pattern of liver depression and blood stasis， pattern of phlegm and blood stasis blocking the vessels， and pattern of heart yin deficiency， it is recommended to treat by Wuzang Shenning Formula （五脏神宁方） to dredge the liver and regulate the vessels， Banxia Houpo Decoction （半夏厚朴汤） plus Gualou Xiebai Banxia Decoction （瓜蒌薤白半夏汤） to dissolve phlegm and regulate the vessels， and Yunpi Tiaoxin Decoction （运脾调心汤） to nourish the yin and regulate the vessels. Throughout the treatment， pattern differentiation and treatment is accompanied by the method of calming the mind with heavy sedatives and nourishing the blood to calm the mind， so as to achieve the purpose of regulating mind and heart together and treating the body and spirit at the same time.

Objective To explore the clinical effect of endoscopic sclerosing agent and tissue glue injection combined with ligation in the treatment of rectal ectopic varices(EV)bleeding.Method A retrospective analysis was conducted on 60 patients with rectal EV bleeding who received endoscopic treatment from January 2017 to January 2022.According to the surgical method,the patients were divided into two groups,with 30 cases in the control group receiving endoscopic ligation treatment;30 cases in the observation group were treated with endoscopic scleroing agent and tissue glue injection combined with ligation.Follow up was conducted according to a cycle of 1,3,6 and 12 months after surgery,and the following indicators were compared between the two groups of patients:successful surgical hemostasis rate,incidence of postoperative complications,mortality rate,improvement of postoperative varicose vein diameter,and postoperative response rate.Result The success rate of surgical hemostasis in the observation group was 93.3%,significantly higher than 66.7%in the control group,the incidence of abdominal pain and fever in the observation group was 10.0%and 10.0%,respectively,significantly lower than 33.3%and 36.7%in the control group,there were 2 deaths in the observation group and 9 deaths in the control group,the mortality rate in the observation group was 6.7%,significantly lower than the 30.0%in the control group,the preoperative venous diameter of the observation group was(1.60±0.36)cm,and the postoperative diameter continued to decrease,at the 12th month after surgery,the diameter was(0.78±0.31)cm,while in the control group,the preoperative venous diameter was(1.52±0.26)cm,the postoperative diameter continued to increase,and at the 12th month after surgery,the diameter was(1.55±0.36)cm,the postoperative effective rate of the observation group was significantly better than that of the control group,the differences were statistically significant(P<0.05).Conclusion The combination of endoscopic scleroing agent and tissue glue injection combined with ligation for the treatment of rectal EV bleeding has a higher success rate and effective rate of surgical hemostasis,fewer postoperative complications,lower mortality rate during follow-up observation,and satisfactory clinical efficacy.It is worth further promoting and applying in clinical practice.

ObjectiveTo understand the prevalence of hookworm infection and its relevant behavioral factors in rural areas of Tiantai County， Zhejiang Province， and to provide scientific evidence for prevention and control of hookworm disease. MethodsBy using a stratified cluster random sampling strategy， local residents aged ≥3 years was divided into 5 districts according to geographical location； furthermore， those in one administrative village （surveillance site） were investigated in each district. Species of hookworm were identified by filter paper culture in vitro， and enterobius vermicularis eggs were detected by cellophane anal swab in children aged 3‒9 year. Risk factors were determined by questionnaire. ResultsA total of 1 013 residents were investigated in 5 surveillance sites. Thirty nine cases with hookworm infection were detected， with the total infection rate of 3.85% . All species detected were determined to be Necator americanus. The infection rate significantly differed across the towns （χ²=48.32， P<0.05）， with the highest rate in Nanping Town （10.95%） . It significantly differed by age groups （χ²=65.65， P<0.05）， with the highest rate in those aged >70 years （9.75%）. Furthermore， it decreased with educational background. It was significantly associated with fertilize with fresh manure （χ²=6.87， P<0.05） and barefoot labor （χ²=157.69， P<0.05）. ConclusionThe overall infection rate of hookworm in Tiantai County remains low. Dominant species of hookworm is hookworm Necator americanus. It is necessary to strengthen the advocacy of hookworm prevention and control knowledge， improve hygiene in work and life style， and increase self-protection awareness.

Primary immune-privileged site large B-cell lymphoma(IP-DLBCLs)is a general term introduced in the 5th edition of the World Health Organization(WHO)Classification of Lymphoid Tumors and refers to a group of aggressive B-cell lymphomas that originate in sites behind the immune barrier in immunocompetent patients.Anatomical-derived immune sanctuaries(such as the blood-brain,blood-retinal,and blood-testicular barriers)and immunomodulatory systems that share the same immunophenotype and molecular characteristics cur-rently include the central nervous,vitreoretinal,and testes systems and large B-cell lymphomas.The primary immune-privileged site large B-cell lymphoma prognosis is relatively poor,with no standard treatment plan.Toll-like receptor-mediated nuclear factor kappa B(NF-κB)(via MYD88 mutation)and B-cell receptor(BCR)(via CD79B mutation)pathway activation was the core pathogenesis mechanism in all three sys-tems(central nervous,vitreoretinal,and testes),presenting a potential common treatment target.Bruton's tyrosine kinase(BTK)is a central molecule in the above signaling pathway,thus BTK inhibitors present a reasonable therapeutic drug choice for such diseases.This article re-views the mechanism of action,clinical studies,adverse reactions,and drug resistance of BTK inhibitors in primary immune-priviledged site large B-cell lymphoma treatment.

ObjectiveTo observe the effect of icariin on the recombinant Ras homolog family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway in rats with Alzheimer's disease （AD）， and to explore the mechanism of icariin in ameliorating the neuronal and dendritic damage. MethodThe β-amyloid 1-42 （Aβ_1-42， 2.5 g·L^-1） was used to induce AD in rats via lateral ventricle injection， and the rats were divided into a model group， a low-dose icariin group （0.03 g·kg^-1）， a middle-dose icariin group （0.06 g·kg^-1）， a high-dose icariin group （0.09 g·kg^-1）， and a control group. The control group and the model group were given an equal volume of normal saline at a dose of 10 mL·kg^-1. The cognitive function of rats was assessed by the Morris water maze. The pathological morphology of the rat hippocampal CA1 area was observed by Nissl staining. Dendritic spine density and dendritic length in the CA1 region of the hippocampus were observed by Golgi-Cox staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus. Western blot assay was used to detect the protein expression levels of TNF-α， IL-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus. ResultAs compared with the control group， the escape latency of the rats in the model group was increased （P<0.01）， while the number of crossing the platform and the dwelling time in the target quadrant were decreased （P<0.01）. As compared with the model group， the escape latency of the rats in the middle and high-dose icariin groups was decreased （P<0.05， P<0.01）， while the number of crossing the platform and the dwelling time in the target quadrant were increased （P<0.05， P<0.01）. As compared with the control group， the number of neurons， dendritic spine density， and dendritic length in the hippocampal CA1 area of the rats in the model group were decreased （P<0.01）. As compared with the model group， the number of neurons， dendritic spine density， and dendritic length in the hippocampus of the rats in the middle and high-dose icariin groups were increased （P<0.05， P<0.01）. As compared with the control group， the mRNA and protein expression levels of TNF-α， IL-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus of the rats in the model group were increased （P<0.01）. As compared with the model group， the mRNA and protein expression levels of TNF-α， IL-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus of the rats in the middle and high-dose icariin groups were decreased （P<0.05， P<0.01）. ConclusionIcariin improves cognitive function and neuronal and dendritic damage in AD by inhibiting the RhoA/ROCK signaling pathway.

ObjectiveTo observe the effect of Shenghuitang on serum levels of neurotransmitters in the mouse model of Alzheimer's disease （AD） and explore the mechanism of Shenghuitang in mitigating the cognitive impairment and circadian rhythm disturbance of AD. MethodTwenty-seven APP/PS1 dementia mice were randomly assigned into a model group， a donepezil （0.92×10^-4 g·kg^-1·d^-1） group， and a Shenghuitang （13.5 g·kg^-1·d^-1） group. Another nine wild-type C57BL/6JNju mice was set as the control group. The mice were administrated with corresponding drugs by gavage and the control and model groups were given the same volume of pure water. Every group was continuously treated for 4 weeks. The cognitive function and circadian rhythm of mice were evaluated by Morris water maze test and open field test. The liquid chromatography-tandem mass spectrometry （LC-MS/MS） was employed to determine the expression levels of acetylcholine （ACh）， choline acetyltransferase （ChAT）， norepinephrine （NE）， epinephrine （E）， glutamate （Glu）， 5-hydroxyindoleacetic acid （5-HIAA）， and dopamine （DA） in the serum. ResultCompared with the control group， the modeling increased the escape latency， swimming distance， time of first arrival on the platform， activity time of light environment， activity time of dark environment， and total activity time （P<0.01）， while it decreased the number of crossing the platform and the swimming time in the target quadrant （P<0.01）. Compared with the model group， donepezil and Shenghuitang decreased the escape latency， swimming distance， time of first arrival on the platform， activity time of light environment， activity time of dark environment and total activity time （P<0.05， P<0.01）， while they increased the number of crossing the platform and the swimming time in the target quadrant （P<0.05， P<0.01）. Compared with the control group， the modeling down-regulated the expression levels of ACh and ChAT in the serum （P<0.01）. Compared with the model group， donepezil and Shenghuitang up-regulated the expression levels of ACh and ChAT in the serum （P<0.05， P<0.01）. Compared with the control group， the modeling up-regulated the expression level of Glu in the serum （P<0.01） and down-regulated the expression levels of NE， 5-HIAA， and DA （P<0.01）. Compared with the model group， Shenghuitang down-regulated the expression level of Glu （P<0.05） and up-regulated the expression levels of NE， 5-HIAA， and DA （P<0.05， P<0.01）. The expression levels of NE， Glu， 5-HIAA， and DA in the donepezil group did not change significantly compared with those in the model group. The expression level of E showed no significant difference among different groups. ConclusionShenghuitang may ameliorate the cognitive impairment and circadian rhythm disturbance of AD mice by regulating the levels of neurotransmitters in the serum.

Objective:To investigate the inhibitory effect of small interfering RNA-Yes-associated protein 1 (siRNA-YAP1) on epithelial-mesenchymal transition (EMT) in human lens epithelial cells (LECs) induced by transforming growth factor-β 2 (TGF-β 2). Methods:Human LECs line (HLEB-3) was cultured and divided into normal control group and TGF-β 2 induced group.The cells in the normal control group were treated with serum-free low-glucose medium for 24 hours, and the cells in the TGF-β 2 induced group were treated with additional 10 ng/ml TGF-β 2 for 24 hours.The cultured HLEB-3 cells were divided into siRNA empty vector group, siRNA-YAP1 transfection group, siRNA empty vector+ TGF-β 2 group and siRNA-YAP1+ TGF-β 2 group, and the cells were transfected with plasmid including siRNA empty vector or siRNA-YAP1 sequence according to grouping.The relative expression levels of YAP1 mRNA and protein in various groups were detected and compared by quantitative real-time polymerase chain reaction (PCR), immunofluorescence and Western blot assay, respectively.The relative expression levels of EMT marker proteins (E-cadherin and Vimentin proteins) in various groups were detected by immunofluorescence and Western blot assay. Results:Compared with the normal control group, the expression level of E-cadherin protein was decreased (1.180±0.118 vs.0.830±0.104) and the Vimentin protein was increased (0.797±0.110 vs.1.240±0.110) in the TGF-β 2 induced group, with significant differences between the two groups ( t=3.857, P=0.018; t=-4.933, P=0.008).The relative expression levels of YAP1 mRNA and protein in the TGF-β 2 induced group were significantly increased in comparison with the normal control group (2.200±0.193 vs.1.136±0.123; 1.203±0.121 vs.0.967±0.025), with significant differences between the two groups ( t=-9.288, P<0.01; t=-3.329, P=0.029).Compared with the siRNA empty vector group, the expression levels of YAP1 mRNA and protein in the siRNA-YAP1 transfection group were significantly reduced (both at P<0.01).Compared with the siRNA empty vector+ TGF-β 2 group, the relative expression level of E-cadherin protein was significantly enhanced and the expression level of Vimentin protein was significantly reduced in the siRNA-YAP1+ TGF-β 2 group (both at P<0.01). Conclusions:YAP1 participates in the TGF-β 2 induced EMT in human LECs, and siRNA-YAP1 can suppress the EMT process.