ObjectiveTo evaluate the public health governance capacity in Jiangsu Province and provide an optimized pathway for the construction of a “strong, rich, beautiful, and high-quality” new Jiangsu. MethodsA total of 806 policy documents, 658 public information reports, and 148 research literatures related to public health governance capacity in Jiangsu Province from January 1995 to December 2023 were collected. The status of current public health goverance was assessed based on the evaluation criteria suitable for public health systems, and the strengths and the weaknesses of the system were identified. ResultsThe public health governance capability of Jiangsu Province was scored at 738.3 points, ranking 3rd nationally. Maternal health care and emergency response capacities achieved leading positions nationwide, both ranking 2nd. Jiangsu had exhibited a standardized guidance in the strategic level, a well-established management mechanism, an extensive coverage in information collection, and a scientifically established health targets setting. However, bottlenecks remained, including an unclear division of responsibilities across organizational departments, an insufficient public-health workforce, the absence of a stable growth mechanism for government funding investment, and difficulties in promptly identifying public needs. ConclusionJiangsu’s public-health system demonstrates leading nationally, yet several components remain underdeveloped. Future efforts should consolidate advantages while addressing weaknesses, further diversify content and forms, establish a stable funding increase mechanism, and clarify departmental functions, thereby providing solid health support for realizing the developmental goals of a “strong, rich, beautiful and high-quality” new Jiangsu.

ObjectiveTo systematically assess the public health governance capacity in Zhejiang Province, to conduct an in-depth analysis of its strengths and weaknesses, so as to provide scientific basis and strategic recommendations for further enhancement. MethodsA systematic collection of policy documents, public information reports, and research literature related to public health governance capacity in Zhejiang Province from 2002 to 2023 was conducted (encompassing a total of 1 263 policy documents, 138 pieces of information reports and 631 research articles). Based on the evaluation criteria suitable for public health systems previously developed by the research team, the basic status and magnitude of change in public health governance capacity in Zhejiang Province was evaluated. Additionally, normative gap analyses were employed to identify the strengths and weaknesses. ResultsZhejiang Province ranked 4th nationwide in terms of public health governance capacity with a score of 733.4 points (1 000.0-point maximum). The province has effectively implemented the principle of health first (scoring 698.5 points in the assessment of health-first strategy implementation) and attached sufficient importance to health-related goals (scoring 658.2 points in the scientific rationality of goal setting). However, the implementation of inter-departmental coordination and incentive mechanisms only scored 178.7 points, the feasibility of management and monitoring mechanisms scored even lower at only 144.0 points, and the coverage of incentive mechanisms scored 286.0 points. ConclusionZhejiang Province has effectively implemented its health first strategy and attached great importance to health targets, but still needs to strengthen cross-departmental coordination mechanisms and health-oriented incentives.

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.

Background and Aims:Laparoscopic cholecystectomy(LC)is a common surgical method for the treatment of gallbladder diseases.However,some patients experience symptoms such as dyspepsia after surgery,which can affect their quality of life.Compound azinomide enteric-coated tablets,a novel drug,may improve dyspeptic symptoms after LC.This study was conducted to explore the clinical efficacy of compound azinomide enteric-coated tablets in treating post-LC dyspepsia symptoms through a multicenter clinical trial.Methods:A multicenter,superior efficacy,open-label,parallel-controlled design was used.Patients with postoperative dyspepsia were enrolled in 7 centers between January 2023 and May 2024.Patients were randomly assigned to either the observation or control groups using a random number table.The observation group received compound azinomide enteric-coated tablets,while the control group was treated with a combination of oryzae pancreatin tablets and ursodeoxycholic acid tablets.Both groups were treated for 4 weeks.The primary endpoints included gastrointestinal symptom scores and quality of life scores assessed before and at 14 and 28 d after treatment.Additionally,the incidence of adverse reactions and cost-effectiveness ratio(CER)were compared between the groups.Results:A total of 303 patients were included,with 150 in the observation group and 153 in the control group.Baseline characteristics were balanced between the groups before treatment(all P>0.05).After treatment,the observation group showed significantly higher effective rates at 14 d and 28 d than the control group(44.7%vs.29.4%;98.0%vs.73.9%,both P<0.05).The observation group also had significantly lower symptom scores and quality of life scores at both 14 and 28 d,with a significantly higher improvement rate in symptom scores compared to the control group(all P<0.05).Further analysis of the improvement rate and treatment efficacy for individual symptoms revealed that,except for the 14-d improvement in abdominal pain/discomfort,the observation group showed better improvement in all other symptoms at 14 d and in all symptoms at 28 d compared to the control group(all P<0.05).No adverse reactions were observed in either group.The CER for the observation group was 283.78 yuan/efficacy rate at 14 d and 128.57 yuan/efficacy rate at 28 d,while the control group's CER was 729.93 yuan/efficacy rate at 14 d and 290.22 yuan/efficacy rate at 28 d.Conclusion:Compound azinomide enteric-coated tablets demonstrated good clinical efficacy in treating dyspepsia symptoms after LC with excellent safety and high cost-effectiveness.Despite some limitations,the results provide a new treatment option for dyspepsia after LC.Larger-scale randomized controlled trials are needed to validate this study's conclusions further.

BACKGROUND:Ligament rupture and defect of the lateral or medial malleolus caused by high-energy injuries are common challenges in foot and ankle surgery.Their neighboring core tendons are often used as grafts to reconstruct the deficient ligaments.It is of paramount importance to investigate the mechanical properties of such tendons in the context of ligament defects to provide a suitable donor tendon.OBJECTIVE:To investigate the interactive dynamics and biomechanical alterations among their core tendons during ankle joint motions under varying degrees of lateral or medial malleolar ligament defect.METHODS:Based on CT imaging data of the left foot of a 50-year-old healthy male,a surface stereolithography model was extracted and constructed using MIMICS software.After Geomagic Wrap software was employed to fit the surfaces,a bone-cartilage-ligament-tendon ankle complex model incorporating varying degrees of ligament deficiencies was created within SOLIDWORKS software.Finite element analysis was then conducted using Ansys Workbench software,and the model's validity was verified through a simulated anterior drawer test.Following validation,the mechanical response of the ankle under the conditions of internal and external rotation,as well as inversion and eversion,was simulated.The variation and distribution patterns of the maximum Von-Mises stress in the peroneus brevis and longus tendons,as well as the anterior and posterior tibial tendons,were observed.RESULTS AND CONCLUSION:(1)In the anterior drawer test,the maximum talar displacement reached 5.208 5 mm,which was similar to the data in the previous literature,thereby the effectiveness of the model was validated.(2)Under four loading conditions,the defect of unilateral single-bundle ligaments exerted minimal influence on the maximum stress of adjacent core tendons,whereas the defect of unilateral multi-bundle ligament significantly increased the maximum tendon stress.Except for the consistently high stress across segments of the anterior tibial tendon,the high-stress regions in the long and short peroneal tendons and posterior tibial tendon were concentrated at their distal ends near the insertions.(3)Regarding the defect of the lateral malleolar ligament,the maximum stress and its variation in the peroneus brevis tendon during inversion and internal rotation were higher than those in the peroneus longus tendon.During inversion under the condition of the defect of the anterior talofibular ligament,the maximum stress in the short peroneal tendon increased by 0.951 2 MPa compared to that of normal condition,while that in the long peroneal tendon decreased by 0.065 1 MPa.Under the condition of the defect of the calcaneofibular ligament during internal rotation,the maximum stress in the short peroneal tendon increased by 2.352 9 MPa,while the maximum stress in the long peroneal tendon decreased by 0.269 2 MPa.(4)During eversion and external rotation under the defect of medial malleolar ligament,the variations in the maximum stress of the anterior and posterior tibial tendons were complex and depended on the type of ligament defect.Notably,full-thickness ligament defect significantly augmented the maximum stress in both tendons.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

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.

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 investigate the long-term outcomes of using 3D-printed preformed titanium meshes in repair and reconstruction of orbital region.Methods:A retrospective analysis was conducted on patients with tumors invading the naso-orbito-maxillary region who underwent surgical resection and repair/reconstruction with 3D-printed preformed titanium meshes. The patients were collected at three medical centers (the Third Affiliated Hospital of Sun Yat-sen University, Xijing Hospital of Air Force Military Medical University, and Shenzhen Longgang District Ear, Nose and Throat Hospital) from 2016 to 2023. Tumor extent was evaluated radiologically, and the surgical approaches, reconstruction outcomes, surgical complications, and long-term follow-up results were analyzed.Results:A total of 46 patients from the three centers were included in this study, comprising 27 males and 19 females, with an average age of 51 years (range: from 13 to 86 years). Among them, 4 patients had benign tumors, while the remaining 42 had malignant tumors. The median follow-up duration was 60.7 months (range: from 19.0 to 75.0 months). Postoperatively, symmetrical globe position was achieved in 38 cases without significant diplopia; 4 cases exhibited enophthalmos without diplopia, and 4 cases had enophthalmos with diplopia. Twelve patients received preoperative radiotherapy, and 30 patients received postoperative radiotherapy. Six patients developed enophthalmos, and 6 experienced titanium mesh exposure after radiotherapy. Following treatment completion, 3 patients underwent repair using frontal flaps, 1 using a superficial temporal artery island flap, and 2 using free flaps. All remaining patients showed no postoperative infections, and their wounds healed normally.Conclusion:The application of 3D-printed preformed titanium mesh enables precise repair of postoperative defects in patients with naso-orbital tumors, facilitating reliable reconstruction of the orbital and facial contours with straightforward operation and dependable outcomes.