ObjectiveTo improve the quality and service performance of community visual health services in Shanghai, and to establish a set of reasonable and effective evaluation index system for community visual health services. MethodsCentered on the national and Shanghai-based visual health policies and based on the current status and development trends of community visual health service program in Shanghai, the candidate indicators were formed through literature review and expert interviews, firstly. The framework of an evaluation index system was formulated through qualitative research successively, which was further revised and perfected using the Delphi method. Coefficient weights were calculated using the analytic hierarchy process (AHP), culminating in the establishment of the community visual health evaluation index system, lastly. ResultsA total of 22 visual health experts from district-level center for disease control, hospital ophthalmology and leaders in charging of visual health service in community health centers participated in the Delphi questionnaire survey, with a questionnaire recovery rate of 100% and an expert authority coefficient of 0.86, indicating high credibility. After a round of correspondence to experts’ importance ratings and discussions, a comprehensive evaluation index system comprising 3 primary indicators, 12 secondary indicators, and 47 tertiary indicators, along with 5 additional indicators, was finalized. ConclusionAn index system tailored to effective evaluation for community visual health initiatives was drawn up in this study, which can promote the capacity building in community eye health services, facilitating the high-quality development of visual health courses, and enhancing residents’ eye health.

AIM:This study aimed to confirm the glycolytic inhibitory activity of 3-bromopyruvic acid(3BP)and to assess whether this inhibition could ameliorate hypoxia-induced pulmonary hypertension in rats.METHODS:PAH model rats were generated from normal SD rats via exposure to normal pressure and hypoxia.Intervention groups I and II(6 rats per group)were then intraperitoneally injected with 3BP(15 mg/kg),and the normal and hypoxia groups(6 rats per group)were given the same amount of normal saline for a total of 21 d.The average pulmonary artery pressure of the rats in each group was measured via right heart catheterisation,and hilar tissue measurements.The right ventricle(RV),left ventricle,and interventricular septum(LV+S)were weighed,and the ratio of RV/(LV+S)was calculated as an index of right ventricular hypertrophy.Right lower lung tissues were fixed in 4%paraformaldehyde-PBS buffer,sec-tioned in conventional paraffin(5 μm thick),stained with HE and Masson,photographed under a microscope.Then the thickness ratio of the tunica media and the area ratio of collagen fibres were calculated.The expression of pyruvate kinase isozyme type M2(PKM2),nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),and pyruvate de-hydrogenase(PDH)proteins in the hilar tissues of each group were detected by western blot,whereas interleukin-1β(IL-1β)and IL-18 contents were detected using ELISA,and lactic acid content was detected using a lactic acid kit.RE-SULTS:The results showed that 3-brpa effectively inhibited glycolysis and significantly improved hypoxia-induced pulmo-nary hypertension in rats.Compared with the hypoxia group,in intervention group II,PKM2 expression was decreased(P<0.05),PDH expression increased significantly(P<0.01),and NLRP3 expression was decreased(P<0.05).The IL-18 and IL-1β contents decreased(P<0.05 or P<0.01,respectively).Pulmonary hemodynamic indexes showed that the pro-portion of the right ventricle and the mean pressure of the pulmonary artery decreased(P<0.05 or P<0.01,respectively).The HE and Masson staining results showed that the thickness ratio of the tunica media and the area ratio of collagen fibres decreased significantly(P<0.01).Lactic acid content was significantly decreased(P<0.01).CONCLUSION:This study showed that 3BP can inhibit glycolysis and alleviate hypoxia-induced pulmonary hypertension in rats.

AIM:This study aimed to confirm the glycolytic inhibitory activity of 3-bromopyruvic acid(3BP)and to assess whether this inhibition could ameliorate hypoxia-induced pulmonary hypertension in rats.METHODS:PAH model rats were generated from normal SD rats via exposure to normal pressure and hypoxia.Intervention groups I and II(6 rats per group)were then intraperitoneally injected with 3BP(15 mg/kg),and the normal and hypoxia groups(6 rats per group)were given the same amount of normal saline for a total of 21 d.The average pulmonary artery pressure of the rats in each group was measured via right heart catheterisation,and hilar tissue measurements.The right ventricle(RV),left ventricle,and interventricular septum(LV+S)were weighed,and the ratio of RV/(LV+S)was calculated as an index of right ventricular hypertrophy.Right lower lung tissues were fixed in 4%paraformaldehyde-PBS buffer,sec-tioned in conventional paraffin(5 μm thick),stained with HE and Masson,photographed under a microscope.Then the thickness ratio of the tunica media and the area ratio of collagen fibres were calculated.The expression of pyruvate kinase isozyme type M2(PKM2),nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),and pyruvate de-hydrogenase(PDH)proteins in the hilar tissues of each group were detected by western blot,whereas interleukin-1β(IL-1β)and IL-18 contents were detected using ELISA,and lactic acid content was detected using a lactic acid kit.RE-SULTS:The results showed that 3-brpa effectively inhibited glycolysis and significantly improved hypoxia-induced pulmo-nary hypertension in rats.Compared with the hypoxia group,in intervention group II,PKM2 expression was decreased(P<0.05),PDH expression increased significantly(P<0.01),and NLRP3 expression was decreased(P<0.05).The IL-18 and IL-1β contents decreased(P<0.05 or P<0.01,respectively).Pulmonary hemodynamic indexes showed that the pro-portion of the right ventricle and the mean pressure of the pulmonary artery decreased(P<0.05 or P<0.01,respectively).The HE and Masson staining results showed that the thickness ratio of the tunica media and the area ratio of collagen fibres decreased significantly(P<0.01).Lactic acid content was significantly decreased(P<0.01).CONCLUSION:This study showed that 3BP can inhibit glycolysis and alleviate hypoxia-induced pulmonary hypertension in rats.

Background::The effect of bariatric surgery on type 2 diabetes mellitus (T2DM) control can be assessed based on predictive models of T2DM remission. Various models have been externally verified internationally. However, long-term validated results after laparoscopic sleeve gastrectomy (LSG) surgery are lacking. The best model for the Chinese population is also unknown.Methods::We retrospectively analyzed Chinese population data 5 years after LSG at Beijing Shijitan Hospital in China between March 2009 and December 2016. The independent t-test, Mann–Whitney U test, and chi-squared test were used to compare characteristics between T2DM remission and non-remission groups. We evaluated the predictive efficacy of each model for longterm T2DM remission after LSG by calculating the area under the curve (AUC), sensitivity, specificity, Youden index, positive predictive value (PPV), negative predictive value (NPV), and predicted-to-observed ratio, and performed calibration using Hosmer–Lemeshow test for 11 prediction models. Results::We enrolled 108 patients, including 44 (40.7%) men, with a mean age of 35.5 years. The mean body mass index was 40.3 ± 9.1 kg/m 2, the percentage of excess weight loss (%EWL) was (75.9 ± 30.4)%, and the percentage of total weight loss (% TWL) was (29.1 ± 10.6)%. The mean glycated hemoglobin A1c (HbA1c) level was (7.3 ± 1.8)% preoperatively and decreased to (5.9 ± 1.0)% 5 years after LSG. The 5-year postoperative complete and partial remission rates of T2DM were 50.9% [55/108] and 27.8% [30/108], respectively. Six models, i.e., "ABCD", individualized metabolic surgery (IMS), advanced-DiaRem, DiaBetter, Dixon et al’s regression model, and Panunzi et al’s regression model, showed a good discrimination ability (all AUC >0.8). The "ABCD" (sensitivity, 74%; specificity, 80%; AUC, 0.82 [95% confidence interval [CI]: 0.74–0.89]), IMS (sensitivity, 78%; specificity, 84%; AUC, 0.82 [95% CI: 0.73–0.89]), and Panunzi et al’s regression models (sensitivity, 78%; specificity, 91%; AUC, 0.86 [95% CI: 0.78–0.92]) showed good discernibility. In the Hosmer–Lemeshow goodness-of-fit test, except for DiaRem ( P <0.01), DiaBetter ( P <0.01), Hayes et al ( P = 0.03), Park et al ( P = 0.02), and Ramos-Levi et al’s ( P <0.01) models, all models had a satifactory fit results ( P >0.05). The P values of calibration results of the "ABCD" and IMS were 0.07 and 0.14, respectively. The predicted-to-observed ratios of the "ABCD" and IMS were 0.87 and 0.89, respectively. Conclusion::The prediction model IMS was recommended for clinical use because of excellent predictive performance, good statistical test results, and simple and practical design features.

Background: Pleuropterus multiflorum Thunb. cv. “Heshouwu”(HSW) has been used as a classical material for both medicine and food in China for millennia. Recently, the cultivation region of HSW has shifted from Guangdong to Sichuan, Guizhou, and other regions. The investigation of geographic variation in bioactive metabolite contents and their relationship with soil mineral elements holds academic significance. Objective: This study aimed to investigate the variations in the distribution of active components in HSW across diverse planting regions and their relationship with soil mineral elements. Methods: A reliable quantitative analysis based on ultrahigh-performance liquid chromatography with triple-quadrupole mass spectrometry (UPLC-QQQ-MS) was developed to assess the levels of 15 bioactive metabolites in 60 HSW samples collected from 4 distinct regions. A total of 43 soil mineral elements in corresponding 60 soil samples were quantified by inductively coupled plasma mass spectrometry (ICP-MS). Orthogonal partial least squares-discriminant analysis (OPLS-DA), heatmap analysis, Pearson correlation analysis, and random forest (RF) regression were conducted based on the above quantitative data. Results: The content of stilbene glycosides displayed a wider range of variation compared with emodin and physcion among different regions. Eight compounds were screened as the differential metabolites in HSW samples from various sources using the supervised OPLS-DA analysis. Among these, 2 important functional compounds including physcion and 2, 3, 5, 4′-tetrahydroxystilbene-2-O-(6″-O-ace-tyl)-glucoside (THSG-5) are the most abundant in HSW samples from Deqing, a geographical indicative production region. Pearson correlation analysis indicated that the impact of soil mineral elements on the levels of stilbene glycosides is greater compared to that on anthraquinones. A negative correlation was observed between the levels of elements Na, Zn, Ba, Ti, and 2, 3, 5, 4′-tetrahydroxysilbene 2-O-glucoside (THSG-1). Conversely, a positive correlation was found between the contents of elements Na, Ce, Ti, and physcion and THSG-5, 2 components that exhibited higher levels in Deqing. Furthermore, an RF algorithm was employed to establish an interrelationship model, effectively forecasting the abundance of the majority of differential metabolites in HSW samples based on the content data of soil mineral elements. Conclusions: The variation of stilbene glycosides is wider than emodin and physcion in HSW. The levels of metabolites in HSW samples are influenced by soil mineral elements, with stilbene glycosides being more susceptible to such influences compared to anthraquinones. Specifically, THSG-1 shows a negative association withmost soil mineral elements, notably Na, Zn, Ba, and Ti, whereas the content of physcion displays a positive correlation.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.
Humans ; White Matter/diagnostic imaging* ; Diffusion Tensor Imaging/methods* ; Alzheimer Disease/complications* ; Reproducibility of Results ; Cognition ; Cognitive Dysfunction/complications* ; Brain/diagnostic imaging*

Objective:To investigate the effect and mechanism of bone marrow-derived mesenchymal stem cells (MSCs) in alleviating renal injury in unilateral ureteral obstruction (UUO) model.Methods:MSCs were cultured, and then transplanted into a UUO model through the tail vein. Histology, cell apoptosis, peritubular capillary (PTC) loss and β-catenin expression were examined on the fourteen day after surgery.Results:Renal interstitial fibrosis in the MSCs group was significantly attenuated compared with that in the UUO group (HE: 1.60 ± 0.35 vs. 3.34 ± 0.23; MASSON: 21.32 ± 7.54 vs. 51.08 ± 4.45). Moreover, MSCs treatment inhibited the loss of peritubular capillaries (PTC) (13.56 ± 4.65 vs. 60.16 ± 10.24), cell apoptosis (14.32 ± 3.54 vs. 28.16 ± 6.21) and β-catenin expression (29.33 ± 6.45 vs. 39.51 ± 8.42).Conclusions:MSCs infusion is a promising therapeutic strategy for promoting kidney repair in chronic renal fibrosis model. The mechanism maybe that it inhibits the loss of peritubular capillaries (PTC) , cell apoptosis and β-catenin expression.

Objective:To detect the expression level of RAB39B gene and the effect of RAB39B on autophagy and α-synuclein, and then investigate the role of RAB39B gene mutation c.536dupA in the pathogenesis of Parkinson′s disease.Methods:Based on the novel RAB39B gene c.536 dupamutation identified in the previous work, the recombinant expression plasmid (pcDNA3.1-HA-RAB39B-536) of RAB39B gene with this mutation and wild-type recombinant expression plasmid (pcDNA3.1-HA-RAB39B) of RAB39B gene were constructed, and the recombinant expression plasmid was transfected into N2a cells with liposome as experimental group. The control group was made up with N2a cells transfected with plasmid pcDNA3.1-HA-RAB39B. Real-time polymerase chain reaction, Western blotting, immunofluorescence and immunoprecipitation techniques were used to detect the expression level of mutant RAB39B gene and the effects of RAB39B on autophagy and α-synuclein.Results:In the N2a cell model, the transcription level of mutant RAB39B was about twice that of wild type RAB39B, while the protein level of mutant RAB39B (0.30±0.00) was significantly lower than that of wild type (1.50±0.25, t=8.313, P<0.05). After adding proteasome inhibitor MG132, the protein level of mutant RAB39B increased (0.70±0.10, t=6.925, P<0.05); the level of microtubule-associated protein 1 light chain 3 BⅡ/Ⅰ of mutant RAB39B (3.11±0.30) was significantly lower than that of wild type (7.03±0.20, t=18.831, P<0.05); overexpression of wild type and mutant RAB39B did not affect the level of endogenous α-synuclein; overexpression of wild-type RAB39B resulted in elevated level of exogenous wild-type (p.A53T; from 0.60±0.11 to 1.25±0.08, t=8.254, P<0.05) and mutant (from 0.55±0.08 to 1.15±0.08, t=9.293, P<0.05) α-synuclein. Conclusions:The stability of the RAB39B protein decreased with the appearance of c.536 dupA mutation, the mutant protein may be degraded through the ubiquitin-proteasome pathway, and this mutation may affect the autophagy level of cells. RAB39B protein may interact with α-synuclein in vivo and may be involved in the maintenance of the stable level of α-synuclein.