Abstract： ObjectiveThe study aims to explore the effects and regulatory roles of glucose transporter 1 （GLUT1） on the proliferation， migration， adhesion， and angiogenesis of human umbilical vein endothelial cells （HUVECs） under ischemia-hypoxic conditions. MethodsIn vitro experiments were conducted to subject HUVECs to an ischemia-hypoxic-mimicking environment （1% O₂， 5% CO₂， 94% N₂）. The biological characteristics of HUVECs under normoxic and ischemia-hypoxic conditions were compared by assessing cell viability， proliferation capacity， and examining the expression changes of GLUT1， HIF-1α， and VEGFA proteins under ischemia-hypoxia using Western blot technology. Further， GLUT1 was overexpressed using plasmid transfection and the proliferation， migration， adhesion， and angiogenic capabilities of HUVECs were evaluated through scratch assays， cell adhesion assays， and tube formation assays. Mitochondrial morphological changes were observed by transmission electron microscopy，and oxygen consumption rate （OCR） was detected by Seahorse metabolic analyzer to evaluate mitochondrial function. ResultsCompared with normoxic conditions， the ischemia-hypoxic environment significantly inhibited the proliferation， cell viability， migration， and adhesion capabilities of HUVECs and impaired their angiogenic potential. The expression levels of GLUT1， HIF-1α and VEGFA proteins were also markedly reduced. However， when GLUT1 expression was upregulated， the migration， adhesion， and angiogenic capabilities of HUVECs were significantly improved， and the protein expression levels of HIF-1α， VEGFA and VEGFR were increased. Transmission electron microscopy revealed that ischemic-hypoxia leads to mitochondrial swelling and matrix damage， while GLUT1 overexpression significantly alleviates mitochondrial morphology abnormalities. OCR results suggest that GLUT1 overexpression may enhance oxidative phosphorylation of endothelial cells in ischemic-hypoxic environments to improve energy metabolism. These results suggest that GLUT1 may influence the function and angiogenic potential of HUVECs by regulating glucose metabolism and energy supply. ConclusionsThis study reveals the significant regulatory role of GLUT1 in the function of HUVECs under ischemia-hypoxic conditions， potentially through modulating cellular energy metabolism and signal transduction pathways， thereby affecting cell proliferation， migration， adhesion， and angiogenesis. These findings provide a new perspective on the role of GLUT1 in cardiovascular diseases and may offer potential targets for the development of new therapeutic strategies.

Objective To analyze the disease burden of chronic kidney diseases (CKD) attributed to high body mass index (BMI) in China from 1992 to 2021 and predict the disease burden for the next decade, and to provide evidence for the prevention and treatment of CKD. Methods Using the Global Burden of Disease (GBD) database and the Joinpoint model, the average annual percentage rate change (AAPC) of the mortality rate and disability-adjusted life year (DALY) rate was calculated to describe and analyze the CKD disease burden attributed to high BMI in China from 1992 to 2021. The ARIMA model was employed to predict and analyze the change trend of the CKD disease burden. Results From 1992 to 2021, the mortality rate and DALY rate attributed to high BMI-induced chronic kidney disease showed an upward trend. Compared to 1992, the attributed number of deaths increased by 324.38%, and DALYs increased by 268.56%; the mortality rate increased by 64.00%, and the DALY rate grew by 51.62%. From 1992 to 2021, the mortality rate and DALY rate for males were lower than those for females, but the growth rate for males exceeded that of females. From 1992 to 2021, the mortality rate and DALY rate of chronic kidney disease attributed to high BMI in China increased with age. The average annual change rate of chronic kidney disease attributed to high BMI in China from 1992 to 2021 (mortality rate: 1.40 per 100,000 (95% CI: 1.04–1.76), DALY rate: 1.43 per 100 000 (95% CI: 1.17–1.70)) was higher than thHuaiyin Normal University, Huai'anher social demographic index (SDI) regions. The ARIMA model predicted that the age-standardized mortality rate increased from 2.91 per 100 000 in 2022 to 3.05 per 100 000 in 2026, and the age-standardized DALY rate increased from 69.65 per 100 000 in 2022 to 73.58 per 100 000 in 2026. Conclusion Chronic kidney disease attributed to high BMI in China is on the rise, and it will continue to grow in the future. The focus of CKD prevention and control should be on males and the elderly, while active measures should be taken to reduce the occurrence and progression of chronic kidney disease.

This paper systematically combed and verified the name， origin， producing area， quality evaluation， harvesting， processing of Euryales Semen in famous classical formulas by consulting relevant ancient materia medica， medical books， prescription books and modern literature. The results showed that Euryales Semen was first collected by materia medica under the name of Jitoushi， and since the Ming dynasty， Qianshi has been used as a proper name and continues to this day， with other aliases such as Yanhuishi. Euryale ferox， a plant of the Nymphaeaceae family， is the same as that used in the past dynasties. However， due to long-term artificial domestication， the varieties vary with the origin， including Beiqian and Suqian. The medicinal part of Euryales Semen is mature seed kernel， its origin of ancient records mainly includes Shandong， Jiangsu， Henan and other places， since the Ming and Qing dynasties， Euryales Semen produced in Suzhou has been highly praised. Since modern times， it has gradually summarized and formed the best quality evaluation method of Euryales Semen with full grains， white cross-section， powdery enough and no broken powder. The harvesting time in the past dynasties was mainly August or in autumn. The main processing methods in the past dynasties included peeling for powder， pounding powder after steaming， drying and frying. Up to now， two mainstream processing methods of cleansing and stir-frying have been formed. Based on the research results， it is recommended that the mature seed kernel of E. ferox be used in famous classical formula Yihuangtang. Combined with the processing requirements of the original formula， it is suggested to refer to the stir-frying method in the general principles of processing of the current edition of Chinese Pharmacopoeia.

Pregnancy ; Female ; Humans ; Diabetes, Gestational/diagnosis* ; Retrospective Studies ; Prognosis ; Pregnancy Outcome ; Maternal Age

Objective:To establish the animal model of cervicofacial venous malformations(VMs)by surgical reconstruction of exter-nal jugular vein in sheep.Methods:The external jugular veins of 5 sheep were dissected,and the position,course,branch and exter-nal diameter were observed and measured.The models of VMs with draining and returning veins were constructed by suturing or constric-ting the proximal part of main trunk and ligating or constricting the distal part of the jugular or branch veins.The animal model was eval-uated by Doppler ultrasound,gross observation and histological observation at the 4th week after surgery.Results:The external jugular veins of sheep is in the lateral side of bilateral neck,and the main trunk is formed by the maxillary vein and lingual facial vein.The ex-ternal diameter ranges from 6 to 12 mm,with an average external diameter of 9.3 mm.Immediately after the external jugular vein was sutured and narrowed at the proximal part of the main vein,the distal part of the vein branch was ligated or narrowed,the blood flow speed slowed down and the veins in the model area bulged.4 weeks after surgery,gross observation showed that most veins narrowed and thrombosis was formed in part of the venous lumen.The central region of some specimens was dilated,and the peripheral collateral veins were dilated in some models.Doppler ultrasonography showed that the lumens of most veins were dilated and the returning veins and the inflow veins were narrowed.Colored blood flow was seen in the lumen.Histological observation showed that the structure of vein endothelium and wall was close to the normal vein,and the vein vessel wall of some specimens was thickened.Conclusion:The VMs model estab-lished by external jugular vein of sheep basically meets the re-quirements and is expected to be used in the therapeutic meth-odology research of cervicofacial VMs.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective To conduct data mining of asthma-inducing medications in underage populations based on the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,so as to provide reference for the clinical application of related medications.Methods Adverse drug event(ADE)reports from the first quarter of 2013 to the fourth quarter of 2022 in the FAERS database were collected and screened for reports of asthma adverse events in the this population(under 18 years old),which were categorized into infants,toddlers,children,and adolescents according to different age groups,and were subjected to medication signal mining by using the reporting odds ratio method,the composite standardized method,and the information component method.Results A total of 1 915 reports were obtained after screening,involving 1 042(54.41％)males and 831(43.39％)females;the highest percentage of the reporting population was between 12 and under 18 years old,with a total of 762(39.79％);60.78％of the reports were reported by health professionals;and the results of the clinical referrals showed that serious adverse events occurred in 85.90％of the cases.306 suspected drugs were screened,52 drugs were determined to be valid signals,and 1 044 adverse events were reported,of which 16 drug inserts did not mention the risk of asthma,in order of elosulfatase alpha,canakinumab,tobramycin,vancomycin,ceftriaxone,cetirizine,phenylephrine,imiglucerase,cefuroxime,betamethasone,atropine,tadalafil,riscovastatin,cyclophosphamide,octreotide,and omeprazole.Conclusion The FAERS database was mined for adverse drug event signals and evaluated using the proportional disequilibrium method to identify 16 medicines that may trigger pharmacogenetic asthma and are not documented in the specification,which can be used to provide a good early warning for the clinic.At the same time,focusing on special populations,strengthening the assessment of lung function before medication and monitoring during and after medication,timely interventions were taken to reduce the harm of drug-derived adverse reactions and ensure the safe use of medication.

Objective Based on the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,data mining was conducted on hematological adverse events related to antibody drug conjugates(ADC),providing reference for the safe use of ADC drugs in clinical practice.Methods The report data from the third quarter of 2011 to the fourth quarter of 2022 were retrieved from the FAERS database.After data cleaning such as deduplication and name standardization,extract hematological adverse events related to ADC,and use report odds ratio method and the information component method for signal detection.Results A total of 101 610 adverse event reports were extracted,with 8 ADC drugs as the primary suspected drugs,and 5 768 ADC related hematological adverse event reports.Among them,3 423 cases of agranulocytosis were involved,and the signal intensity from strong to weak were sacituzumab govitecan(SG),gemtuzumab ozogamicin(GO),brentuximab vedotin(BV),polatuzumab vedotin(PV),enfortumab vedotin(EV),trastuzumab deruxtecan(TD),inotuzumab ozogamicin(IO)and ado-trastuzumab emtansine(TDM-1).There were 2 327 cases hematopoietic cell deficiency,with signals ranging from strong to weak were IO,SG,BV,EV,PV,TD,TDM-1,and GO.Report with clinical outcome of death of ADC drug related hematological adverse events included BV 179(16.84％),TDM-1 102(13.01％),TD 88(27.08％),GO 12(16.90％),IO 8(11.59％),EV 54(24.32％),PV 22(27.16％),and SG 84(21.05％).Adverse event time analysis showed that the number of events on the first day of TD,IO,and SG medication accounts for ≥ 40％of the total number of cases.The median time of hematological adverse events in TD,GO,IO,EV,PV,and SG was within one treatment course(21 days).Conclusion Attention should be paid to the risk of ADC drug-related hematological adverse event,during the clinical medication process,blood cell count changes should be closely monitored,and any abnormalities should be promptly diagnosed and treated.

AIM:This study aims to investigate the impact of nobiletin(NOB)on the gut microbiota and short-chain fatty acids(SCFAs)in high-fat diet-induced obese rats.METHODS:A total of 22 SD rats were randomly di-vided into the control(CON)group and high-fat diet(HFD)group.The HFD induced obesity,upon successful modeling,the rats were further divided into the HFD and NOB group,each group consisting of 6 rats.The NOB group received nobi-letin solution(100 mg·kg-1·d-1)via gavage for 21 consecutive days.Body weight was measured bi-daily,and hematoxylin-eosin(HE)staining was employed to observe pathological changes in adipose tissue and liver.Serum lipid levels were as-sessed using an auto-biochemical analyzer.Analysis of the gut microbiota was performed using 16S ribosomal RNA(rRNA)sequencing,while high-performance liquid chromatography mass spectrometry(LC-MS)was used to determine SCFAs levels in rat feces.RESULTS:Compared with CON group,HFD-fed demonstrated a substantial increase in body weight(P<0.01),accompanied by an augmentation in adipocyte diameter and the presence of hepatic cell vacuolization,indicative of cellular steatosis and inflammation.Moreover,there was a notable elevation in TG and TC levels(P<0.05).At the phylum level,the HFD rats exhibited an altered composition,characterized by an increase in Firmicutes and a con-current decrease in Bacteroidetes.At the genus level,Bacteroides,Lactobacillus and Blautia experienced a significant de-crease,while Colidextribacter showed an increase.Notably,there was a substantial reduction in the expression of propion-ic acid and butyric acid.In comparison to the HFD group,rats administered with NOB demonstrated a marked decrease in body weight(P<0.05),a reduction in adipocyte diameter,and an amelioration in hepatic cell vacuolization and cellular steatosis.Furthermore,TG and TC levels exhibited a significant decrease(P<0.05).At the phylum level,Firmicutes de-creased,and Bacteroidetes increased.At the genus level,Bacteroides,Lactobacillus and Blautia exhibited a significant in-crease,while Colidextribacter displayed a decrease.Additionally,there was an up-regulation of propionic acid and butyric acid levels in the NOB group.CONCLUSION:Nobiletin,through its multifaceted actions,demonstrates a potential anti-obesity effect by effectively reducing body weight in obese rats.This includes the regulation of gut microbiota structure,modulation of SCFAs content,and enhancement of lipid metabolism.

According to the codon characteristics of the prokaryotic system,we synthesized the optimized Rv2628c-Rv1737c nucleic acid sequence and constructed the expression plasmid pET24a-Rv2628c-Rv1737c.After sequencing,expression in E.coli was induced.The fusion protein was found in inclusion bodies.After renaturation and affinity chromatography purifi-cation,the Rv2628c-Rv1737c recombinant protein,with a molecular weight of 57 kDa and a purity exceeding 90％,was ob-tained.The recombinant protein was used to stimulate PBMC cells from different patients,and the differences in IFN-γ mRNA expression were analyzed with q-PCR.The Rv2628c-Rv1737c fusion protein stimulated patients with TB,particularly latent TB infection(LTBI).The level of IFN-γ mRNA in PBMC cells was higher than that in healthy controls(P＜0.05).Mice immu-nized with BCG+Rv2628c-Rv1737c/DMT showed significant induction of high levels of IgG antibodies.Rv2628c-Rv1737c re-combinant protein,as a latent infection antigen,is recognized by PBMCs cells infected with TB,with strong immunogenicity,and thus may serve as a potential TB subunit vaccine target antigen.This protein may be used to prevent TB infection,particu-larly latent infection,and to perform laboratory diagnosis.