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

OBJECTIVE To compare the ability of ultra-high-resolution CT(U-HRCT)and multi-slice spiral CT(MSCT)to display key vocal transmission structures in the middle ear.METHODS Subjects with normal middle ear structures who underwent 0.1 mm layer thickness U-HRCT and 0.625 mm layer thickness MSCT scans at the same time in Beijing Friendship Hospital affiliated to Capital Medical University from December 2019 to August 2024 were retrospectively enrolled.Two experienced head and neck radiologists reconstruct standard transsectional,coronal images based on the thinnest layer thickness.According to the 5-point method,16 key sound transmission structures of the middle ear,including malleus,incus and stapes,as well as joints,ligaments and tendons,were evaluated for image quality scoring.The standard deviation(SD)value,signal noise ratio(SNR),and contrast noise ratio(CNR)of bone in the malleus region and intratympanic gas were measured and calculated on the two examination images.RESULTS Thirty patients(47 sides)with normal middle ear structure were included,including 18 males and 12 females.The two physicians compared the results of U-HRCT in showing malleus head,malleus neck,malleus handle,incus body,long process,and short process,5 points accounted for 100%,and the 5-point scores of incudomalleolar joint space,incudostapedial joint space,stapes footplate and annular ligament were 100%,98.29%,75.83%and 77.83%,respectively,which were significantly higher than those of MSCT(P<0.001).In addition,U-HRCT showed higher scores for lenticular process,stapes head,anterior arch of stapes,posterior arch of stapes,annular ligament,stapes muscle,and tendo musculi tensoris tympani than MSCT(P<0.001),and the lenticular process showed a 100%display rate.There was no significant difference in the SNR between the two groups(P>0.05),but the SD value of the malleus in U-HRCT was 161.6±36.4,which was significantly lower than that in MSCT(297.8±128.1),and the difference was statistically significant(P<0.001).CONCLUSION U-HRCT can clearly visualize the key sound transmission structures of the middle ear,and its visualization ability is significantly better than that of MSCT.

Objective To investigate the effect of bone metastasis on the efficacy of immune check-point inhibitors(ICI)in treatment of advanced non-small cell lung cancer(NSCLC).Methods A retro-spective analysis was conducted in 248 patients with advanced NSCLC who received ICI therapy.The patients were divided into bone metastasis group(110 cases)and non-bone metastasis group(138 ca-ses)based on the presence of bone metastasis.Clinical characteristics,objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),and overall survival(OS)were compared between the two groups.The correlations of factors such as bone metastasis with the survival prognosis of NSCLC patients were analyzed using the Cox proportional hazards regression mod-el.A total of 60 treatment-naive NSCLC patients with bone metastasis were selected from research ob-jects,with 30 patients receiving ICI combined with conventional chemotherapy(combination group)and 30 patients receiving conventional chemotherapy alone(chemotherapy group).The therapeutic effects and incidence of treatment emergent adverse events(TEAE)were compared between the two groups.Results There were no statistically significant differences in ORR and DCR between the bone metastasis and non-bone metastasis groups(P＞0.05).The PFS of the bone metastasis group(5.53 months)was shorter than that of the non-bone metastasis group(7.72 months)(x2=3.674,P=0.045).However,there was no statistically significant difference in OS between the bone me-tastasis group and the non-bone metastasis group(16.98 versus 17.56 months,x2=1.333,P=0.248).Multivariate Cox regression analysis showed that bone metastasis was an independent prog-nostic factor for PFS in NSCLC patients(HR=1.52,95％CI,1.10 to 1.98,P=0.003),but not a prognostic factor for OS(P＞0.05).The ORR and DCR in the combination group were 43.33％and 93.33％,respectively,which were higher than 26.67％and 76.67％in the chemotherapy group(P＜0.05).The PFS in the combination group was longer than that in the chemotherapy group(x2=4.023,P=0.036).However,there was no statistically significant difference in OS be-tween the two groups(x2=1.235,P=0.267).There were no statistically significant differences in the overall incidence of TEAEs or the incidence of≥grade 3 TEAE between the two groups(P＞0.05).Conclusion Although the occurrence of bone metastasis has an adverse effect on the effica-cy of ICI therapy in advanced NSCLC,patients with bone metastasis can still achieve better thera-peutic effects through ICI combined with chemotherapy compared with chemotherapy alone.

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.