ObjectiveTo explore the effects of astragalin （AST） on autophagy and apoptosis of astrocytes in the L_4-5 dorsal horn of the spinal cord in mice with inflammatory pain induced by complete Freund's adjuvant （CFA）. MethodsTwenty-four male C57BL/6 mice， aged six months， were randomly assigned to four groups： control group， saline group， CFA model group， and CFA+AST group， six mice in each group. The inflammatory pain model was established by injection of 10 µL CFA into the right lateral malleolus fossa. The saline group were injected with an equal amount of normal saline at the same site. The inflammatory pain mice in CFA+AST group were further treated with AST （60 mg/kg） intraperitoneally once a day for 21 consecutive days. Multiplex immunofluorescence staining was used to detect the coexpression of autophagy-related factors including ATG 12 and Beclin-1， apoptosis-related factors including Cleaved-Caspase3 and Caspase9， and the astrocyte marker such as GFAP in the L_4-5 spinal dorsal horn of the mice in each group. Western blot was used to examine the protein expression levels of autophagy-related proteins（ATG12， Beclin-1） and apoptosis-related proteins（Caspase 3， Caspase 9） in the L_4-5 spinal dorsal horn of mice. ResultsImmunofluorescent staining showed that in the L_4-5 dorsal horn of the spinal cord， the fluorescence intensity of ATG12 （P<0.000 1） and Beclin-1 （P<0.000 1） was significantly increased， while that of Cleaved-Caspase 3 （P<0.001） and Caspase 9 （P<0.000 1） was decreased in the CFA+AST group when compared to the CFA model group. Furthermore， AST could inhibit the activation of astrocytes. Western blot further confirmed that AST significantly upregulated the expression of ATG12 （P<0.000 1） and Beclin-1 （P<0.000 1） in the L_4-5 spinal cord of CFA mice， and downregulated the expression of Caspase 3 （P<0.01） and Caspase 9 （P<0.001）. ConclusionsAST promotes autophagy of astrocytes and inhibits their apoptosis in the L_4-5 spinal dorsal horn of CFA mice.

OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

Objective The DNA methylation microhaplotype(DMH)refers to the combination of multiple methylation sites within a very short range,and these haplotypes show wide diversity.We carried out screening and validation of age-related DMHs in mouse blood.Methods We initially constructed a theoretical dataset of DMHs based on the mouse reference genome.We then screened age-related DMHs by Spearman's rank correlation analysis,using high-throughput sequencing information for DNA methylation in mouse blood from a network database.Finally,cross-validation was performed using a validation dataset.Results A total of 6787 142 DMH sites were identified within 50 bp in the mouse genome,including 98.64%of single-digit CpG sites.A total of 5835 age-associated DMHs were screened in 58 mouse blood samples(|rho|＞0.5,P＜0.01),accounting for 0.086%of DMHs.Finally,we validated the top 100 age-associated DMHs with high correlation in 95 independent samples,Resultsing in 44 loci.Conclusions The age-associated DMHs screened in this study may be useful in future studies of apparent age prediction using mouse blood and in aging studies.

Objective: Recent studies indicate that 3 morphological types of atlanto-occipital joint (AOJ) exist in the craniovertebral junction and are associated with type II basilar invagination (BI) and atlanto-occipital instability. However, the actual biomechanical effects remain unclear. This study aims to investigate biomechanical differences among AOJ types I, II, and III, and provide further evidence of atlanto-occipital instability in type II BI. Methods: Models of bilateral AOJ containing various AOJ types were created, including I-I, I-II, II-II, II-III, and III-III models, with increasing AOJ dysplasia across models. Then, 1.5 Nm torque simulated cervical motions. The range of motion (ROM), ligament and joint stress, and basion-dental interval (BDI) were analyzed. Results: The C0–1 ROM and accompanying rotational ROM increased progressively from model I-I to model III-III, with the ROM of model III-III showing increases between 27.3% and 123.8% indicating ultra-mobility and instability. In contrast, the C1–2 ROM changes were minimal. Meanwhile, the stress distribution pattern was disrupted; in particular, the C1 superior facet stress was concentrated centrally and decreased substantially across the models. The stress on the C0–1 capsule ligament decreased during cervical flexion and increased during bending and rotating loading. In addition, BDI gradually decreased across the models. Further analysis revealed that the dens showed an increase of 110.1% superiorly and 11.4% posteriorly, indicating an increased risk of spinal cord impingement. Conclusion Progressive AOJ incongruity critically disrupts supportive tissue loading, enabling incremental atlanto-occipital instability. AOJ dysplasia plays a key biomechanical role in the pathogenesis of type II BI.

Objective:To analyze the association between body health score and the risk of hypertension among health examination population aged 40-65 years.Methods:This study was a cross-sectional study, and 1 104 people aged 40-65 years who underwent physical examination at the Physical Examination Centre of the First People′s Hospital of Fuquan City from March to November 2022 were selected. Clinical data, such as general information, physical examination, body composition and history of hypertension diseases, were collected. The body health score was reported by the Xiaomi Body Fat Scale′s accompanying exercise health software, and was calculated by combining body fat, water and other body composition data. The association between body health score and the risk of hypertension was analyzed using restricted cubic spline regression models, while a sensitivity analysis and sex-stratified analyses were performed. Multivariate logistic regression combined with stratified analysis was used to explore the association between dimensions of body composition and the risk of hypertension.Results:The body health score was significantly lower in hypertensive patients than in non-hypertensive patients among the 1 104 health examination population [52.0(30.0) vs 69.0(35.8) points] ( Z=-8.547, P<0.001). The lower the body health score, the higher the risk of hypertension ( χ2=18.48, PNonlinear<0.001). In the total population, high body mass index was associated with an increased risk of hypertension ( OR=1.744, 95% CI: 1.104-2.765), high protein content was associated with a reduced risk of hypertension ( OR=0.587, 95% CI: 0.344-0.982) (both P<0.05). Gender-stratified analyses showed that high protein content was associated with a reduced risk of hypertension only in men ( OR=0.233, 95% CI: 0.080-0.592) ( P=0.004). High body mass index was positively associated with the risk of hypertension when the body health score was ≥60 points ( OR=2.378, 95% CI: 1.255-4.542) ( P=0.008). High visceral adiposity index (VAI) was positively associated with the risk of hypertension when the body health score was <60 points ( OR=4.395, 95% CI: 1.466-13.620), and high protein content was negatively associated with the risk of hypertension ( OR=0.255, 95% CI: 0.091-0.638) (all P<0.05). Conclusions:Health examination population aged 40-65 years with lower scores of physical health are more likely to have a risk of hypertension. Men should pay attention to the impact of body protein in hypertension risk prevention and control. The effect of body mass index should be noted when body health scores are ≥60 points, and the effect of VAI and body protein should be considered when body health scores are <60 points.

Renal cell carcinoma is one of the significant diseases endangering human health. Recent findings have shown that the human microbiome plays an important role in the occurrence and development of renal cell carcinoma, influencing its regression and treatment outcome. At present, microecological research on renal cell carcinoma are still in their initial stages, and their regulatory roles and specific mechanisms still need to be further explored. This article reviews the relationship between the human microbiome and renal cell carcinoma occurrence and development, as well as its role in diagnosis and therapies.

Objective:To observe the effects of ointment and massage on inflammation, oxidative stress and angiogenesis after skeletal muscle trauma, and to explore their mechanisms.Methods:Forty-two adult male Sprague-Dawley rats were randomly divided into a blank group ( n=6), an ointment and massage (O&M) group ( n=18) and a model group ( n=18). The blunt contusion model of gastrocnemius malformation was established in both the O&M and model groups using self-made percussion instruments. Two hours after successful modeling, the anti-inflammatory pain-relieving cream was applied to the injured area, and massaged evenly and gently for 5 minutes. That was repeated with an interval of 12 hours. No treatment was given to the model and blank groups. On the 1st, 3rd and 7th days after modeling, injured gastrocnemius muscles were resected after collecting abdominal blood. Hematoxylin-eosin (HE) staining and immunofluorescent (CD34) staining were applied, and serum superoxide dismutase (SOD) and malondialdehyde (MDA) contents were detected. Results:HE staining showed that at each time point the gastrocnemius muscle fibers of the model group were significantly more swollen and deformed, collapsed and dissolved than those of the blank group, with a large number of inflamed cells. The O&M group had better recovery, with more newly-generated muscle cells, less inflammatory infiltration and more normal cell shapes than the model group. Fluorescence was stronger in the O&M and model groups than in the blank group at each time point, with that of the O&M group significantly stronger than in the model group. The average SOD and MDA levels in the model and O&M groups were significantly higher than in the blank group, and on the 1st and 3rd days the O&M group′s average SOD level was significantly higher than the model group′s average, though by the 7th day there was no significant difference. The average MDA content of the O&M group was significantly lower than the model group′s average at each time point.Conclusion:Ointment and massage can effectively reduce the local inflammatory response and oxidative stress after a skeletal muscle injury. They can accelerate local angiogenesis, promoting the repair of damaged tissues.

Objective: Recent studies indicate that 3 morphological types of atlanto-occipital joint (AOJ) exist in the craniovertebral junction and are associated with type II basilar invagination (BI) and atlanto-occipital instability. However, the actual biomechanical effects remain unclear. This study aims to investigate biomechanical differences among AOJ types I, II, and III, and provide further evidence of atlanto-occipital instability in type II BI. Methods: Models of bilateral AOJ containing various AOJ types were created, including I-I, I-II, II-II, II-III, and III-III models, with increasing AOJ dysplasia across models. Then, 1.5 Nm torque simulated cervical motions. The range of motion (ROM), ligament and joint stress, and basion-dental interval (BDI) were analyzed. Results: The C0–1 ROM and accompanying rotational ROM increased progressively from model I-I to model III-III, with the ROM of model III-III showing increases between 27.3% and 123.8% indicating ultra-mobility and instability. In contrast, the C1–2 ROM changes were minimal. Meanwhile, the stress distribution pattern was disrupted; in particular, the C1 superior facet stress was concentrated centrally and decreased substantially across the models. The stress on the C0–1 capsule ligament decreased during cervical flexion and increased during bending and rotating loading. In addition, BDI gradually decreased across the models. Further analysis revealed that the dens showed an increase of 110.1% superiorly and 11.4% posteriorly, indicating an increased risk of spinal cord impingement. Conclusion Progressive AOJ incongruity critically disrupts supportive tissue loading, enabling incremental atlanto-occipital instability. AOJ dysplasia plays a key biomechanical role in the pathogenesis of type II BI.

Objective: Recent studies indicate that 3 morphological types of atlanto-occipital joint (AOJ) exist in the craniovertebral junction and are associated with type II basilar invagination (BI) and atlanto-occipital instability. However, the actual biomechanical effects remain unclear. This study aims to investigate biomechanical differences among AOJ types I, II, and III, and provide further evidence of atlanto-occipital instability in type II BI. Methods: Models of bilateral AOJ containing various AOJ types were created, including I-I, I-II, II-II, II-III, and III-III models, with increasing AOJ dysplasia across models. Then, 1.5 Nm torque simulated cervical motions. The range of motion (ROM), ligament and joint stress, and basion-dental interval (BDI) were analyzed. Results: The C0–1 ROM and accompanying rotational ROM increased progressively from model I-I to model III-III, with the ROM of model III-III showing increases between 27.3% and 123.8% indicating ultra-mobility and instability. In contrast, the C1–2 ROM changes were minimal. Meanwhile, the stress distribution pattern was disrupted; in particular, the C1 superior facet stress was concentrated centrally and decreased substantially across the models. The stress on the C0–1 capsule ligament decreased during cervical flexion and increased during bending and rotating loading. In addition, BDI gradually decreased across the models. Further analysis revealed that the dens showed an increase of 110.1% superiorly and 11.4% posteriorly, indicating an increased risk of spinal cord impingement. Conclusion Progressive AOJ incongruity critically disrupts supportive tissue loading, enabling incremental atlanto-occipital instability. AOJ dysplasia plays a key biomechanical role in the pathogenesis of type II BI.

Objective To establish a simple model for arteriosclerosis(AS)screening to provide a viable tool for the timely identification of AS risk among residents aged 40～65 years.Methods Data were obtained from the Sleep and Chronic Diseases Program in Fuquan City.The original dataset was divided into a training subset and a validation subset(80%:20%).LASSO and logistic regression models were used to screen variables,perform multivariate regression analyses.Internal validation was performed using the Bootstrap method.Nomogram Plot was constructed,and risk score thresholds were determined based on ROC curves to classify high-risk populations.Results RS Model was established to include age,gender,napping,sleep efficiency,sleep disorders,hyperten-sion and diabetes,with AUC=74.80%and a model risk score threshold=84.20.PHC Model was established to include age,gender,napping,sleep efficiency,systolic blood pressure,fasting blood glucose,and pulse variables,with AUC=82.80%and a risk score threshold of 78.00.Decision curves showed that both models performed well in terms of calibration and actual benefits for health management.Conclusion The two AS screening models exhibit acceptable accuracy and differentiation.Therefore,it can be applied in residents'self-health management and in primary care organizations'screening work in a large scale.