[摘 要] 目的：探究甘氨胆酸（GCA）对肺腺癌A549细胞移植瘤小鼠放射治疗敏感性的影响及其机制。方法：建立A549人肺腺癌细胞裸鼠移植瘤模型，随机分为移植瘤对照组（对照组）、GCA组、放疗组（RT组）和GCA + 放疗组（GCA + RT组）。RT组和GCA + RT组接受单次10  Gy照射，GCA组及GCA + RT组连续7 d每日灌胃GCA 280  mg/kg。间隔2 d测量1次移植瘤体积，末次给药后处死小鼠并取移植瘤组织，检测移植瘤组织中超氧化物歧化酶（SOD）与谷胱甘肽过氧化物酶（GSH-Px）活性，qPCR法和WB法分别检测放疗关键基因（MCM6、ITGA6、CASP3等）mRNA和蛋白表达水平，H-E染色观察移植瘤组织的形态变化。通过GEO（GSE276500、GSE294906、GSE218171）及TCGA数据库数据验证放疗关键基因。结果：GCA单用对瘤体生长有一定抑制作用，但联合放疗的GCA + RT组相比单纯放疗组表现出放疗抵抗的效应（P < 0.05）。GCA处理显著提高移植瘤组织SOD活性（P < 0.01）、降低GSH-Px活性（P < 0.01），提示GCA可改变移植瘤抗氧化酶平衡，减弱放疗诱导的氧化应激。GCA干预上调移植瘤组织中MCM6与ITGA6 mRNA表达、下调CASP3 mRNA表达（均P < 0.05）。GCA + RT组移植瘤组织中的MCM6蛋白表达显著高于对照组（P < 0.05）。H-E染色显示，GCA组部分瘤组织坏死，而GCA + RT组坏死组织面积较RT组有所缩小。GEO和TCGA数据库验证支持MCM6、ITGA6高表达与放疗抵抗和预后不良相关。结论：GCA通过增强SOD活性、降低GSH-Px活性并上调ITGA6、MCM6的表达改变氧化应激与关键信号网络，从而削弱A549移植瘤对放疗的敏感性。

Background Per- and poly-fluoroalkyl substances (PFAS) can influence gestational diabetes mellitus (GDM); however, current studies on their association are limited and have yielded inconsistent findings. Objective To investigate the association between maternal exposure to PFAS, as measured by urinary concentrations in early pregnancy, and the risk of developing GDM. Methods Based on the Wuhu Birth Cohort in Anhui Province conducted between 2020 and 2023, this study included 1910 pregnant women. Urine samples were collected during the first trimester, and a 75 g oral glucose tolerance test (OGTT) was completed at 24–28 gestational weeks. The concentrations of six PFAS in urine were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Participants were categorized into low, medium, and high exposure groups according to tertiles of individual PFAS concentrations. Logistic regression analysis was employed to assess the potential impact of early-pregnancy PFAS exposure levels on the risk of GDM, with stratified analyses by maternal age and fetal sex. A generalized weighted quantile sum regression (gWQS) model was applied to evaluate the relative weight distribution of the six PFAS in their mixture effect. Results The logistic regression results revealed that both medium exposure to perfluorohexane sulfonate (PFHxS) (OR=1.475, 95%CI: 1.040, 2.093) and high exposure to perfluorononanoic acid (PFNA) (OR=1.430, 95%CI: 1.013, 2.018) were positively associated with diagnosed GDM. This association was more pronounced among women older than 28 years. Among pregnant women carrying male fetuses, high-level exposures to per fluorohexanoic acid (PFHxA) (OR=1.708, 95%CI: 1.006, 2.899) and PFHxS (OR=2.116, 95%CI: 1.247, 3.584) showed positive associations with diagnosed GDM. In contrast, among those carrying female fetuses, moderate perfluorooctanesulfonic acid (PFOS) exposure was associated with a lower risk of GDM (OR=0.542, 95%CI: 0.311, 0.946). The gWQS results demonstrated that PFOS (0.48) and perfluorobutane sulfonate (PFBS) (0.34) contributed the most to the mixture effect. Conclusion Early-pregnancy exposure to PFAS (particularly PFHxS and PFNA) may be an etiological factor for GDM, with maternal age and fetal sex potentially acting as effect modifiers in this association.

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.

ObjectiveThis Study was conducted to investigate the interaction mechemisms between gutmicrobiota dysregulation and ischemic stroke by establishing a rat model of ischemic stroke and employing fecal microbiota transplantation (FMT). MethodsA preliminary experiment was conducted to establish an antibiotic-induced pseudo-sterile (ABX) rat model through antibiotic treatment, and a cerebral ischemia model was prepared using the middle cerebral artery occlusion (MCAO) method. Fecal microbiota from stroke patients and healthy individuals were transplanted via FMT, followed by behavioral testing. 16S rRNA sequencing was used to analyze the microbial community, hematoxylin and eosin (HE) staining to observe histopathological status, transmission electron microscopy (TEM) to examine the tight junction structure of the small intestine, and enzyme-linked immunosorbent assay (ELISA) to detect levels of inflammatory factors and intestinal barrier-related markers. Results16S rRNA sequencing of fecal samples showed that compared with the normal control group and the metronidazole group, the abundance and diversity of fecal microorganisms in the quadruple antibiotic group were significantly reduced, indicating successful establishment of the ABX model. After transplanting fecal microbiota from stroke patients into ABX rats, significant changes in gut microbiota composition were observed. Behavioral tests revealed that the MCAO model group showed significant decreases in both horizontal movement and vertical exploration abilities. ELISA results indicated that IL-17 concentration in the ABX+mFMT (antibiotic-treated+model fecal microbiota transplantation) group was lower than in the ABX+cFMT (antibiotic-treated+control fecal microbiota transplantation) group, suggesting that IL-17 may serve as a key inflammatory indicator for evaluating the impact of stroke intervention on gut microbiota. Triphenyltetrazolium chloricle staining (TTC) staining suggested that gut microbiota intervention may increase the risk of stroke. HE staining showed that, except for the control group, all groups exhibited ischemic changes and inflammatory infiltration in brain tissues. TEM revealed that microvilli of small intestinal epithelial cells in the ABX+mFMT group were sparser than those in the ABX+cFMT group, indicating that microbial intervention affects intestinal barrier function. ConclusionThe ABX model established using broad-spectrum antibiotics showed no significant differences in physiological characteristics compared to normal rats, and the findings were consistent with those from germ-free rat models. Stroke prognosis appears to be influenced by intestinal dysbiosis, accompanied by significantly elevated levels of the pro-inflammatory cytokine IL-17, which may exacerbate neural injury via the gut-brain axis. Behavioral experiments indicated that transplantation of gut microbiota from stroke rats impaired cognitive function. Furthermore, IL-17 demonstrated sensitivity to alterations in the gut microbiota, suggesting its potential as a key therapeutic target for stroke intervention.

ObjectiveThis Study was conducted to investigate the interaction mechemisms between gutmicrobiota dysregulation and ischemic stroke by establishing a rat model of ischemic stroke and employing fecal microbiota transplantation (FMT). MethodsA preliminary experiment was conducted to establish an antibiotic-induced pseudo-sterile (ABX) rat model through antibiotic treatment, and a cerebral ischemia model was prepared using the middle cerebral artery occlusion (MCAO) method. Fecal microbiota from stroke patients and healthy individuals were transplanted via FMT, followed by behavioral testing. 16S rRNA sequencing was used to analyze the microbial community, hematoxylin and eosin (HE) staining to observe histopathological status, transmission electron microscopy (TEM) to examine the tight junction structure of the small intestine, and enzyme-linked immunosorbent assay (ELISA) to detect levels of inflammatory factors and intestinal barrier-related markers. Results16S rRNA sequencing of fecal samples showed that compared with the normal control group and the metronidazole group, the abundance and diversity of fecal microorganisms in the quadruple antibiotic group were significantly reduced, indicating successful establishment of the ABX model. After transplanting fecal microbiota from stroke patients into ABX rats, significant changes in gut microbiota composition were observed. Behavioral tests revealed that the MCAO model group showed significant decreases in both horizontal movement and vertical exploration abilities. ELISA results indicated that IL-17 concentration in the ABX+mFMT (antibiotic-treated+model fecal microbiota transplantation) group was lower than in the ABX+cFMT (antibiotic-treated+control fecal microbiota transplantation) group, suggesting that IL-17 may serve as a key inflammatory indicator for evaluating the impact of stroke intervention on gut microbiota. Triphenyltetrazolium chloricle staining (TTC) staining suggested that gut microbiota intervention may increase the risk of stroke. HE staining showed that, except for the control group, all groups exhibited ischemic changes and inflammatory infiltration in brain tissues. TEM revealed that microvilli of small intestinal epithelial cells in the ABX+mFMT group were sparser than those in the ABX+cFMT group, indicating that microbial intervention affects intestinal barrier function. ConclusionThe ABX model established using broad-spectrum antibiotics showed no significant differences in physiological characteristics compared to normal rats, and the findings were consistent with those from germ-free rat models. Stroke prognosis appears to be influenced by intestinal dysbiosis, accompanied by significantly elevated levels of the pro-inflammatory cytokine IL-17, which may exacerbate neural injury via the gut-brain axis. Behavioral experiments indicated that transplantation of gut microbiota from stroke rats impaired cognitive function. Furthermore, IL-17 demonstrated sensitivity to alterations in the gut microbiota, suggesting its potential as a key therapeutic target for stroke intervention.

Objective:To observe the effect of intensified heel anti-gravity posture stability training on the gait of stroke survivors.Methods:Thirty-six hemiplegic stroke survivors were randomly divided into a control group and an experimental group, each of 18. Both groups received conventional rehabilitation treatment (including limb positioning, limb movement training and conventional walking training), while the experimental group was additionally provided with 30 minutes of intense heel anti-gravity posture stability training 5 days a week for 4 weeks. Before and after the treatment, the subjects′ walking speed, stride frequency, step length, peak knee flexion angle and peak hip flexion angle were documented using three-dimensional gait analysis with a movement training system.Results:The average walking speed, stride rate, step length, peak hip flexion and peak knee flexion of both groups had improved significantly after the treatments. But the average walking speed [(0.46±0.06)m/s], step length [(85.05±6.68)cm], peak hip flexion angle [(34.80±2.80)°] and peak knee flexion angle [(40.55±3.58)°] of the treatment group were significantly better than those of the control group.Conclusions:Intensified heel anti-gravity posture stability training can significantly improve the walking speed, step length, hip flexion and knee flexion of hemiplegic stroke survivors.

Objective:To examine the differences in the medical quality of elderly Medicare patients in tertiary public hospitals before and after the implementation of the Diagnosis-related Group Prospective Payment System(DRG-PPS), and to explore the establishment of a long-term quality control mechanism.Methods:A total of 62, 321 inpatient first-page records was collected from Beijing Hospital, including 27, 488 cases from January to December 2019 and 34, 833 cases from January to December 2023.Firstly, the two-sample Kolmogorov-Smirnov test was applied to six sample DRG groups to analyze the statistical differences in the intra-group indicators(average per-case cost, average length of stay)among three age groups(young and middle-aged group: 18-65 years old; early elderly group: 66-79 years old; advanced elderly group: 80-99 years old)before and after the DRG-PPS reform of the medical insurance payment system.Secondly, the two-sample Kruskal-Wallis test was used to analyze the statistical differences in the indicators(total cost, medical cost, nursing cost, medical technology cost, pharmaceutical cost, consumable cost, administrative cost, and length of stay)among the three age groups within the same DRG group.Finally, the Conover test was employed for pairwise comparisons of inter-group indicators between the three groups.Results:Through the intra-group analysis of the total cost and average length of stay indicators of different age groups in the six sample DRG groups( n=6, 248), it was found that the differences were statistically significant.( Z-values for total cost in groups 1-3 was 12.69, 15.73, and 11.45, respectively; Z-values for average length of stay were 8.33, 6.73, and 3.69, respectively; all P<0.05), indicating that the DRG-PPS reform was effective in controlling hospitalization costs and length of stay.The inter-group analysis revealed statistically significant differences in total cost, nursing cost, pharmaceutical cost, consumable cost, administrative cost, and length of stay( H-values were 22.49, 41.86, 15.61, 200.56, 14.73 and 10.73, respectively; all P<0.05; ), suggesting that there were statistically significant differences in cost control among different age groups in the same DRG group.Furthermore, analysis of specific cases revealed that differences in medical costs among different age groups resulted from the combined effects of clinical practice standardization(reflected in the significant reduction of unnecessary examinations and medication)and policy interventions such as volume-based procurement excluding the adverse effects of cost containment on the medical quality of elderly patients in the six sample patient groups.No substantial rise was observed in the 31-day readmission rate, indicating that admission splitting was unlikely to have occurred. Conclusions:The implementation of the DRG-PPS contributed to cost efficiency in the sample hospital.By establishing a long-term quality control mechanism focused on DRG groups with significant cost reductions in elderly patients, abnormal cost-control behaviors can be effectively identified, and high-quality development of the hospital can be achieved while ensuring healthcare quality for elderly patients.

Objective:To investigate the anatomical characteristics of the atlantoaxial joint associated with nonuniform settlement of the C 2 lateral mass (C 2LM-NUS) and its correlation with atlantoaxial osteoarthritis. Methods:A retrospective analysis was conducted on clinical and imaging data of 522 hospitalized patients (288 males, 234 females; mean age 60.8±11.2 years; range 18-83 years) who underwent CT scans of the head/neck or cervical spine at the Second Affiliated Hospital of Army Medical University between January 1, 2022 and December 31, 2022. Multiplanar reconstruction of CT data was performed to measure the settlement of the C 2 lateral mass (C 2LMS). Patients with a difference in bilateral C 2LMS (d-C 2LMS) >1.4 mm were classified into the C 2LM-NUS group (137 cases; 71 males, 66 females; mean age 63.3±11.6 years), while the normal group included 385 patients (217 males, 168 females; mean age 59.9±11.0 years). Imaging parameters of the atlantoaxial joint were measured, including the C 1, 2 coronal inclination angle (C 1, 2 CI), atlanto-dental interval (ADI), lateral atlanto-dental interval (LADI), coronal deviation angle of the odontoid (Od-CDA), and C 1, 2 relative rotation angle (C 1, 2 RRA). Osteoarthritis prevalence was recorded. A normal C 0-C 3 finite element (FE) model was constructed using CT data from a 48-year-old female in the normal group. A C 2LM-NUS FE model was developed based on anatomical differences between the C 2LM-NUS and normal groups, and stress distribution on the C 2 lateral mass articular surface was analyzed under flexion-extension, lateral bending, and axial rotation torques. Results:The C 2LM-NUS group exhibited asymmetric atlantoaxial joint morphology, with bilateral differences in C 1, 2CI and LADI of 8.5°(5.8°, 11.3°) and 0.8(0.1, 1.4) mm, respectively, significantly greater than those in the normal group [1.7°(0.8°, 2.7°) and 0.2(0.1, 0.5) mm, P<0.05]. Od-CDA and C 1, 2RRA were 3.9°(2.0°, 5.4°) and 7.2°(5.0°, 10.0°) in the C 2LM-NUS group, exceeding the normal group's values [0°(0°, 1.0°) and 0°(0°, 5.5°), P<0.05]. The prevalence of C 2LM-NUS was 37.8% in the atlantoaxial osteoarthritis group, significantly higher than in the non-osteoarthritis group (22.8%, P<0.05). Significant differences were observed in age (68.3±9.4 vs. 58.6±10.8 years), sex distribution (50/69 vs. 238/165), and C 1, 2RRA [5.6°(0°, 8.2°) vs. 3.8°(0°, 6.2°)] between the osteoarthritis and non-osteoarthritis groups ( P<0.05). After adjusting for age, sex, and C 1, 2RRA, binary logistic regression identified C 2LM-NUS as an independent risk factor for atlantoaxial osteoarthritis [ OR=2.024, 95% CI (1.300, 3.150), P<0.001]. FE analysis demonstrated a reduced C 1, 2 range of motion in the C 2LM-NUS model, with elevated stress concentrations on the settled side lateral mass during simulated flexion-extension, lateral bending, and rotation. Conclusions:The study indicated that C 2LM-NUS is associated with asymmetric anatomical changes in the atlantoaxial joint, increasing the risk of osteoarthritis. Stress concentration on the C 2 lateral mass articular surface, caused by C 2LM-NUS, is a biomechanical contributor to this heightened risk.

Objective:To investigate the effect and mechanism of Jianpi Qinghua granule in improving skeletal muscle insulin resistance induced by long-term low-dose cadmium exposure in rats.Methods:A total of 24 SPF-grade healthy 2-month-old Sprague-Dawley rats were assigned to normal control(NC) group, cadmium exposure(Cd) group, and Jianpi Qinghua granule protection(Cd+ JPQHG) group. After 24 weeks, fasting blood glucose and insulin levels were measured, and HOMA-IR was calculated. The intraperitoneal glucose tolerance test and insulin tolerance test were conducted to assess insulin sensitivity. Skeletal muscle tissues were extracted for Western blot analysis to detect levels of insulin signaling pathway-related proteins. Immunofluorescence was used to assess the translocation of glucose transporter 4(GLUT4), and oxidative stress markers were measured.Results:Compared to the NC group, the Cd group showed significant increases in fasting plasma glucose, fasting insulin levels, and HOMA-IR after 24-week exposure. Abnormal glucose and insulin tolerance were also observed in the Cd group. The 12-week intervention with Jianpi Qinghua granule significantly improved glucose metabolism and alleviated the abnormalities in glucose and insulin tolerance. Western blot results indicated that the phosphorylation levels of PI3K and Akt in the skeletal muscle of the Cd group were significantly reduced compared to the NC group, while these levels were significantly elevated in the Cd+ JPQHG group, along with increased translocation of GLUT4 to the cell membrane. Additionally, cadmium exposure significantly increased H 2O 2 and malondialdehyde levels while decreased antioxidant enzyme activity. These oxidative stress indicators improved significantly after Jianpi Qinghua granule intervention( P<0.05). Conclusion:Jianpi Qinghua granule may improve skeletal muscle insulin resistance and glucose metabolism disorders due to long-term low-dose cadmium exposure by reducing oxidative stress, regulating the phosphorylation levels of key proteins in the insulin signaling pathway, and promoting GLUT4 translocation to the cell membrane.