ObjectiveTo explore the potential mechanism of Banxia Xiexin Decoction （半夏泻心汤， BXD） in the treatment of diabetic gastroparesis （DGP）. MethodsA total of 29 SD rats were randomly divided into four groups， blank group （5 rats） and model group， BXD group and metformin group （8 rats in each group）. Except for the blank group， rats were administered intraperitoneally with 1% streptozotocin （STZ） solution and were fed a high-sugar， high-fat diet to establish the DGP rat model. After successful modeling， the BXD group was treated with BXD at 6.68 g/（kg·d） by gavage， the metformin group was treated with metformin hydrochloride at 105 mg/（kg·d） by gavage， and the blank group and the model group were treated with normal saline at 6.68 ml/（kg·d） by gavage， for 8 weeks. After the last administration， fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， total cholesterol （TC）， triglycerides （TG） were measured and gastric emptying rate was calculated. ELISA was used to detect the levels of gastrointestinal hormones motilin （MTL） and gastrin （GAS）， as well as inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β） and interleukin-10 （IL-10） in gastric tissue. Oil red O staining was performed to observe liver pathological morphology. Hematoxylin and eosin （HE） staining was used to observe gastric antrum tissue morphology. Immunofluorescence staining was used to detect liver X receptor α （LXRα） levels in the liver. Western Blot was used to detect the protein levels of LXRα in liver tissue， and of janus kinase 2 （JAK2）， phospho-janus kinase 2 （p-JAK2）， signal transducer and activator of transcription 3 （STAT3） and phospho-signal transducer and activator of transcription 3 （p-STAT3） in gastric antrum tissue. Quantitative real-time polymerase chain reaction （qPCR） was used to measure the mRNA expression of LXRα in liver tissue and JAK2， STAT3 in gastric antrum tissue. ResultsCompared with the blank group， the model group showed significant hepatic fatty degeneration， gastric antrum tissue structure destruction， and increases in FBG， HbA1c， TC， and TG levels； the average fluorescence intensity， protein level， and mRNA expression of LXRα in liver tissue were reduced； the gastric emptying rate and gastric tissue GAS and MTL levels decreased； inflammatory factors including TNF-α， IL-6， IL-1β in gastric tissue increased， IL-10 decreased； in gastric antrum tissue， the mRNA expression of p-JAK2/JAK2， p-STAT3/STAT3， and JAK2 and STAT3 increased （P＜0.01）. Compared with the model group， both the BXD group and the metformin group showed improved liver and gastric antrum tissue pathology； FBG， HbA1c， TC， and TG levels decreased， while LXRα fluorescence intensity， protein level， and mRNA expression in liver tissue significantly increased； the gastric emptying rate and the levels of GAS and MTL in gastric tissue were markedly higher； the levels of TNF-α， IL-6， and IL-1β decreased， whereas IL-10 levels increased， p-JAK2/JAK2， p-STAT3/STAT3， and the mRNA expression of JAK2 and STAT3 in gastric antrum tissue decreased （P＜0.05 or P＜0.01）. The BXD group showed higher level than the metformin group in FBG， HbA1c， and TG levels， lower level in gastric emptying rate and gastric tissue GAS content， and higher level in gastric tissue TNF-α， IL-6， IL-1β levels； there was also a decrease in IL-10 levels， and a reduction in LXRα fluorescence intensity and mRNA expression in liver tissue， as well as in p-JAK2/JAK2 levels in gastric antrum tissue （P＜0.05 or P＜0.01）. ConclusionBXD can reduce blood glucose and lipid levels in DGP model rats while improving gastric function and alleviating gastric tissue inflammation. Its mechanism may be related to the regulation of LXRα expression in liver tissue and the JAK2/STAT3 pathway in gastric antrum tissue.

AIM: To compare the efficacy of simple autologous blood coverage with ILM flap tamponade combined with autologous blood coverage after pars plana vitrectomy(PPV)with internal limiting membrane(ILM)peeling in treating macular hole retinal detachment(MHRD)of high myopia patients with moderately long axial length.METHODS: This retrospective study enrolled 45 patients(45 eyes)with high myopia and MHRD, and axial lengths of 26-29 mm treated at our institution between January 1, 2020 and January 1, 2024. Patients were divided into two groups based on surgical technique: group A(24 eyes)underwent PPV with ILM peeling, ILM flap tamponade, autologous blood coverage, and silicone oil injection; group B(21 eyes)received PPV with ILM peeling followed by autologous blood coverage and silicone oil injection. Intraocular pressure, best-corrected visual acuity(BCVA), retinal reattachment and macular hole closure status were compared at 1 wk, 1, 3, and 6 mo postoperatively. Silicone oil removal was performed at 6 mo postoperatively, with additional 2-month follow-up.RESULTS:At 8-month postoperative follow-up, both groups achieved complete retinal reattachment. Macular hole closure rates showed no significant intergroup difference(88% vs 86%, P=0.860). Significant improvement in BCVA was observed in both groups compared to preoperative values, with the group B demonstrating better visual outcomes than the group A(P<0.001). Transient parafoveal subretinal fluid persistence was noted in 2 eyes of the group A(resolved spontaneously at 5 and 8 mo post-PPV, respectively), and 1 eye of the group B(resolved by 4 mo post-PPV). Serial optical coherence tomography(OCT)monitoring revealed no macular hole reopening, with complete subretinal fluid resolution confirmed in all cases at final follow-up.CONCLUSION:For high myopic MHRD patients with moderately long axial length, both surgical approaches effectively promote macular hole closure and retinal reattachment. However, the autologous blood coverage technique demonstrates better BCVA than the combined ILM tamponade.

ObjectiveTo systematically evaluate the public health governance capacity of 40 cities in Jiangsu, Zhejiang, and Anhui Provinces, providing a scientific evaluation basis for building a "Healthy Yangtze River Delta". MethodsA comprehensive collection of policy documents, public information reports, and research literature related to public health governance capacity in Jiangsu, Zhejiang, and Anhui Provinces was conducted, totaling 6 920 policy documents, 1 720 information reports, and 1 200 literature pieces. Based on the evaluation standards for an appropriate public health system established by the research team, the basic status of public health governance capacity was assessed to identify the strengths and weaknesses of the 40 cities. ResultsIn 2022, the public health governance capacity score for the 40 cities in Jiangsu, Zhejiang, and Anhui Provinces was (562.5±38.0) points. In terms of specific areas, the emergency response field received the highest score of (791.4±49.7) points, while the chronic disease prevention and control field received the lowest score of (368.2±29.6) points. The Jiangsu-Zhejiang-Anhui region has largely achieved the strategic priority of health, gradually improved public health legal regulations, and established a basic organizational framework with a solid foundation for information and data infrastructure. However, challenges still need to be addressed, such as unstable government funding for public health, unclear departmental responsibilities, and barriers to information interoperability. ConclusionThe public health governance capacity of the 40 cities in Jiangsu, Zhejiang, and Anhui Province has been at a moderate level, but disparities have still existed across regions and fields. In the future, while continuing to deepen existing advantages, it is essential to accurately identify the causes of problems, establish a long-term and stable investment mechanism, enhance information connectivity mechanisms, further clarify departmental responsibilities, and promote the achievement of the "Healthy Yangtze River Delta" goal.

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Human naïve pluripotent stem cells (PSCs) hold great promise for embryonic development studies. Existing induction and culture strategies for these cells, heavily dependent on MEK inhibitors, lead to widespread DNA hypomethylation, aberrant imprinting loss, and genomic instability during extended culture. Here, employing high-content analysis alongside a bifluorescence reporter system indicative of human naïve pluripotency, we screened over 1,600 chemicals and identified seven promising candidates. From these, we developed four optimized media-LAY, LADY, LUDY, and LKPY-that effectively induce and sustain PSCs in the naïve state. Notably, cells reset or cultured in these media, especially in the LAY system, demonstrate improved genome-wide DNA methylation status closely resembling that of pre-implantation counterparts, with partially restored imprinting and significantly enhanced genomic stability. Overall, our study contributes advancements to naïve pluripotency induction and long-term maintenance, providing insights for further applications of naïve PSCs.
Humans ; DNA Methylation/drug effects* ; Genomic Instability ; Pluripotent Stem Cells/metabolism* ; Cell Culture Techniques/methods* ; Cells, Cultured

Background A large body of cross-sectional studies have indicated a correlation between exposure to benzene series and increased rates of menstrual abnormalities in female workers, but these findings are confusing as evidence in the field of preventive medicine. Objective To provide a more rigorous scientific basis for early prevention of reproductive function impairment through systematic review of independent studies. Methods A comprehensive search was conducted for scientific articles published between January 1987 and July 2022, encompassing databases such as PubMed, Medline, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and CQVIP. A meta-analysis was conducted on literature that met the stringent criteria for case-control studies, featuring well-defined and consistent datasets. A meticulous investigation was executed to ascertain the collective odds ratio (OR) linked to menstrual abnormalities, encompassing diverse categories such as component, dosage, cumulative exposure dosage, and age groups. The prevalence and corresponding risk fractions were estimated by calculating frequency distributions and attributing risk percentages (AR). Results A total of 53 papers of case-control studies were included in the meta-analysis, involving 27068 benzene series-exposed female workers and 22857 control female workers. During inhalation exposure to benzene series, benzene, toluene, and xylene all increased the risk of female menstrual abnormalities (OR=3.46, 95%CI: 2.79, 4.30, AR=29.37%). The OR value elevated with the increase of joint exposure concentration (OR=2.57-4.33), the OR value of the low cumulative exposure group was lower than that of the high cumulative exposure group (OR=2.81 vs 3.86, P < 0.01), and the OR value of the group aged 18 to 36 years old was higher than that of the group aged 18 to 45 years old (OR=5.83 vs 2.93, P < 0.01). The OR value discrepancy was apparent among the groups with single and multi-components of benzene, toluene, and xylene at different concentrations (OR=2.39-6.42, 95%CI: 1.26, 9.06). The symptom dimensions of menstrual abnormalities with a higher AR were abnormal menstrual volume (AR=47.12%), followed by abnormal menstrual cycle (AR=38.68%). The symptoms that were greatly influenced by the exposures were: irregular menstrual cycle (OR=3.33, 95%CI: 2.94, 3.79, AR=51.25%, n=1103), menorrhagia (OR=3.02, 95%CI: 2.76, 3.30, AR=46.73%, n=2262), dysmenorrhea (OR=3.22, 95%CI: 2.69, 3.84, AR=44.18%, n=3183), and prolonged menstrual duration (OR=2.20, 95%CI: 1.99, 2.43, AR=37.02%, n=1452). Conclusion Through inhalation exposure to benzene series, a higher concentration of combined benzene, toluene, and xylenes may increase the risk of menstrual abnormalities in female workers of childbearing age. The OR value of menstrual abnormalities is varied by chemical composition, exposure dose, cumulative exposure dose, and age. Volume and cycle of menstruation are affected by the exposure, and the most common symptoms are dysmenorrhea, menorrhagia, irregular cycle.

ObjectiveTo investigate the protective effect of total lignans of Arctii Fructus on the retinal tissue in the rat model of type 2 diabetes mellitus. MethodWistar rats were randomized into normal， model， solvent， Shuangdan Mingmu Capsules （618 mg·kg^-1）， and low-， medium-， and high-dose （100， 200， 400 mg·kg^-1， respectively） total lignans of Arctii Fructus groups， with 16 rats in each group. The rat model was established by streptozotocin （STZ） combined with a high-fat diet and administrated with corresponding drugs by gavage once a day for 14 weeks. At the 14^th week， blood was sampled for the collection of serum from the abdominal aorta after anesthesia， and bilateral eyeballs were collected and frozen. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of the retinal tissue in rats. The pathological changes of retinal vascular network in rats were observed by retinal vascular tissue digestion and mounting The levels of vascular endothelial growth factor （VEGF）， tumor necrosis factor-α （TNF-α）， and intercellular adhesion molecule-1 （ICAM-1） in the serum were determined by the ELISA kit. ResultCompared with the normal group， the solvent group showed pathological changes in the retinal tissue， reduced retinal ganglion cells （P<0.01）， and retinal thinning （P<0.01）， decreased E/P value in retinal blood vessels （P<0.01）， and elevated serum levels of VEGF， TNF-α， and ICAM-1 （P<0.01）. Compared with the model group， the total lignans of Arctii Fructus increased the retinal ganglion cells （P<0.01）， thickened the retina （P<0.01）， and lowered the serum levels of VEGF， TNF-α， and ICAM-1 （P<0.05， P<0.01）. ConclusionTotal lignans of Arctii Fructus may lower the VEGF， TNF-α， and ICAM-1 levels to protect the retina.

Objective:To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes.Methods:Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis.Results:Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA ( P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA ( P<0.01), and the GPA group had fewer affected nerves than the other two groups ( P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group ( P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) ( OR=6.85, 95% CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes ( OR=0.13, 95% CI 0.02-0.89). Conclusions:The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.