Objective:To investigate the role and molecular mechanisms of signal transducer and activator of tran-scription 3(STAT3)in the paraventricular nucleus(PVN)of the hypothalamus in regulating body weight and energy metabolism in mice.Methods:AAV2/9-hSyn-Cre-EGFP virus was stereotactically injected into the PVN of STAT3Flox/Flox mice to conditionally knock out(CKO)STAT3 in the PVN.STAT3 expression was verified via immunoflu-orescence staining and Western blot.Body weight and temperature were monitored,glucose tolerance was assessed using glucose tolerance tests in mice,and morphological changes in the liver,interscapular brown adipose tissue(IBAT),in-guinal white adipose tissue(IWAT),and quadriceps muscle were evaluated via hematoxylin-eosin(HE)staining.RT-qPCR was used to measure mRNA levels of platelet-derived growth factor receptor α(PDGFRα),peroxisome prolifera-tor-activated receptor γ(PPARγ),hormone-sensitive lipase(HSL),and adipose triglyceride lipase(ATGL)in these tissues.Results:STAT3 protein expression in the PVN of CKO mice was significantly reduced,and the number of STAT3-positive neurons was also decreased.Compared to wild-type(WT)mice,CKO mice exhibited increased body weight,impaired thermogenesis in IBAT,and reduced glucose tolerance.HE staining revealed lipid droplet accumula-tion in hepatocytes of the liver,enlarged adipocytes with hypertrophic lipid droplets and leukocyte infiltration in adipose tissues,and intermuscular fat deposition in the quadriceps muscle.RT-qPCR analysis showed decreased mRNA levels of PDGFRα,HSL,and ATGL in the liver;upregulated PPARγ mRNA but downregulated HSL and ATGL mRNA in IBAT and IWAT;and reduced PPARγ and HSL mRNA levels in the quadriceps muscle of CKO mice.Conclusion:The STAT3 signaling pathway in the PVN is critical for maintaining systemic energy balance and serves as a key node in met-abolic regulation.

Acetabular fracture is a kind of intra-articular fracture with complicated anatomy and difficult treatment. The core of treatment lies in anatomic reduction and strong fixation. The low incidence and intricate anatomical structure present significant challenges for treatment of acetabular fractures. In recent years, significant progress has been made in the treatment of acetabular fractures, particularly in surgical approaches, robotic-assisted technology, the application of tranexamic acid, and treatment strategies for elderly patients, providing new therapeutic options. This article reviews the latest progress in acetabular fracture treatment research.

Objective:To investigate the application of time series models in forecasting pre-hospital emergency ambulance trips in Handan City and develop the LPro ensemble model for improved prediction accuracy to support emergency resource allocation.Methods:Pre-hospital emergency data from Handan Emergency Medical Command Center (2019-2023) were retrospectively analyzed. From 324 799 original records, 289 949 valid records were included after cleaning. The training set (2019-2022: 215 918 records) included 35 527 records in 2019, 52 015 in 2020, 61 836 in 2021, and 66 540 in 2022. The validation set (2023) contained 74 031 records. ARIMA, linear trend seasonal, exponential smoothing, and Prophet models were fitted to the training set. The LPro ensemble model was constructed using MAPE-based weighting (linear trend seasonal model: 0.38, Prophet: 0.62). Performance metrics included MAPE, RMSE, MAE, and R 2. Results:Data showed annual growth (compound annual growth rate 23.27%) and seasonal patterns (October peaks, February troughs). Ambulance dispatches increased annually with monthly cyclical patterns. For 2023 validation predictions: ARIMA (MAPE 8.76%, RMSE 619, MAE 491, R 2 0.4563), linear trend seasonal (MAPE 9.83%, RMSE 671, MAE 545, R 2 0.3608), Prophet (MAPE 8.43%, RMSE 562, MAE 503, R 2 0.5513), exponential smoothing (MAPE 8.08%, RMSE 643, MAE 410, R 2 0.4124). LPro model showed superior performance (MAPE 7.05%, RMSE 491, MAE 393, R 2 0.6570), with 16.37% lower MAPE, 12.63% lower RMSE, 21.87% lower MAE, and 19.17% higher R 2 versus Prophet. Conclusion:The LPro ensemble model substantially enhances prediction accuracy and reliability, offering scientific support for emergency resource optimization and dispatch scheduling in Handan City.

Nanobodies(Nb)have become novel probes for PET imaging instead of traditional antibodies,which have broad application prospects due to advantages of small molecular weight,strong stability and permeability,passing through the blood-brain barrier and low immunogenicity.The research progresses of structural characteristics of Nb,labeling methods of positron isotopes and application of labeled products in PET imaging were reviewed in this article.

Objective:To investigate the role and molecular mechanisms of signal transducer and activator of tran-scription 3(STAT3)in the paraventricular nucleus(PVN)of the hypothalamus in regulating body weight and energy metabolism in mice.Methods:AAV2/9-hSyn-Cre-EGFP virus was stereotactically injected into the PVN of STAT3Flox/Flox mice to conditionally knock out(CKO)STAT3 in the PVN.STAT3 expression was verified via immunoflu-orescence staining and Western blot.Body weight and temperature were monitored,glucose tolerance was assessed using glucose tolerance tests in mice,and morphological changes in the liver,interscapular brown adipose tissue(IBAT),in-guinal white adipose tissue(IWAT),and quadriceps muscle were evaluated via hematoxylin-eosin(HE)staining.RT-qPCR was used to measure mRNA levels of platelet-derived growth factor receptor α(PDGFRα),peroxisome prolifera-tor-activated receptor γ(PPARγ),hormone-sensitive lipase(HSL),and adipose triglyceride lipase(ATGL)in these tissues.Results:STAT3 protein expression in the PVN of CKO mice was significantly reduced,and the number of STAT3-positive neurons was also decreased.Compared to wild-type(WT)mice,CKO mice exhibited increased body weight,impaired thermogenesis in IBAT,and reduced glucose tolerance.HE staining revealed lipid droplet accumula-tion in hepatocytes of the liver,enlarged adipocytes with hypertrophic lipid droplets and leukocyte infiltration in adipose tissues,and intermuscular fat deposition in the quadriceps muscle.RT-qPCR analysis showed decreased mRNA levels of PDGFRα,HSL,and ATGL in the liver;upregulated PPARγ mRNA but downregulated HSL and ATGL mRNA in IBAT and IWAT;and reduced PPARγ and HSL mRNA levels in the quadriceps muscle of CKO mice.Conclusion:The STAT3 signaling pathway in the PVN is critical for maintaining systemic energy balance and serves as a key node in met-abolic regulation.

Nanobodies(Nb)have become novel probes for PET imaging instead of traditional antibodies,which have broad application prospects due to advantages of small molecular weight,strong stability and permeability,passing through the blood-brain barrier and low immunogenicity.The research progresses of structural characteristics of Nb,labeling methods of positron isotopes and application of labeled products in PET imaging were reviewed in this article.

Objective To investigate the correlation between the expression level of glypican-3(GPC3)and the immune therapy response in clinical liver cancer patients.Methods Clinical data of 232 liver cancer immunotherapy response/tolerance group patients from January 2019 to May 2023 at the General Hospital of the People's Liberation Army were collected,and the correlation between GPC3 expression levels and the efficacy of immunotherapy in liver cancer patients was statistically analyzed;TCGA database validation of immune cell infiltration in GPC3 high and low expression groups of liver cancer patients;Further,real-time fluorescence quantitative PCR(qPCR)and immunohistochemical staining methods were used to detect the expression of GPC3 and immune cell infiltration in paired tissues of liver cancer immunotherapy response/tolerance group patients,and multi-color immunofluorescence was applied to detect the expression of GPC3 and related molecules.Results Clinical evidence shows that the GPC3 positive group of liver cancer patients has a low response rate to immunotherapy.Univariate/multivariate analysis results indicate that GPC3 is an independent risk factor for tumor recurrence after liver cancer immunotherapy;The analysis of the TCGA database revealed that high expression of GPC3 in liver cancer tissue leads to increased infiltration of regulatory T cells(Tregs);Paired tissue testing of liver cancer patients and adjacent tissues revealed that the immunotherapy effect was worse in the GPC3 high expression group,and Tregs cell infiltration increased,consistent with the results of database analysis.The TCGA database analysis results showed that GPC3 was positively correlated with CCL20 and its ligand CCR6,and the multi-color immunohistochemistry results were consistent with the database analysis results.Conclusion GPC3 is highly expressed in tumor tissues of liver cancer patients and is positively correlated with immune therapy tolerance in liver cancer.GPC3 regulates Tregs cell infiltration through the CCL20-CCR6 signaling axis and is expected to serve as a biomarker for predicting the efficacy of immune therapy in clinical liver cancer patients.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

BACKGROUND:Temporomandibular joint osteoarthritis is a common oral disease with a high incidence.However,temporomandibular joint osteoarthritis is not easy to be detected in the early stage,and it is difficult to obtain clinical pathological specimens,so it is difficult to carry out related research.The application of digital 3D printing technology to animal models of Temporomandibular joint osteoarthritis increases the consistency of the animal models,thus promoting the study of temporomandibular joint osteoarthritis. OBJECTIVE:To establish a standardized animal model of temporomandibular joint osteoarthritis using novel digital technology. METHODS:According to the different modeling methods of unilateral anterior crossbite,30 female Sprague-Dawley rats were randomly divided into traditional model group,digital model group,and control group(n=10 per group).Cartilage specimens of the condyles were collected at 4 and 8 weeks after modeling.The apparent morphology was observed by stereoscopic microscope.The pathological morphology was observed by hematoxylin-eosin staining and Safranin O/fast green staining.Changes in the expression of interleukin-1β and tumor necrosis factor-α were observed by ELISA,and changes in the expression of aggrecan,type Ⅱ collagen and matrix metalloproteinase-13 were observed by immunohistochemical staining. RESULTS AND CONCLUSION:Different degrees of degeneration were observed in the digital and traditional model groups.The body mass of rats in both the model groups decreased during the 1st week after intervention and subsequently demonstrated growth trend and were significantly lower than that in the control group.The results of stereoscopic microscope showed that at 4 and 8 weeks after modeling,the deformation and defect degree of the digital model group was significantly higher than that of the traditional model group.At these two time points,the Osteoarthritis Research Society International scores of the digital model group and the traditional model group were higher than those of the control group,and the Osteoarthritis Research Society International score of the digital model group was higher than that of the traditional model group(P＜0.05).Histopathological observation showed that the modified Mankin score and Osteoarthritis Research Society International score of the two model groups were significantly higher than those of the control group of the same age at 4 and 8 weeks after modeling(P＜0.05).Immunohistochemical staining results showed that at two time points,compared with the control group of the same age,the expression of aggrecan and type Ⅱ collagen decreased in the traditional model group and the digital model group,while the expression of matrix metalloproteinase 13 increased(P＜0.05).ELISA results showed that the expression levels of inflammatory factors interleukin-1β and tumor necrosis factor-α in the traditional and digital model groups were higher than those in the control group at 8 weeks,and the expression levels of interleukin-1β and tumor necrosis factor-α in the digital model group were higher than those in the traditional model group(P＜0.05).To conclude,the personalized metal tube designed and produced by 3D printing technology can quickly guide the osteoarthritis-like lesions of the temporomandibular joint without repeated trial and adjustment,which is reproducible and suitable for promotion and application.