Objective To provide suggestions for the clinical efficacy evaluation method of manual therapy for knee osteoarthritis(KOA)by analyzing the current status of the use of outcome indicators in randomized controlled trials(RCTs)of manual therapy for KOA.Methods RCTs about manual treatment of KOA were retrieved from CNKI,Wanfang Data,VIP,SinoMed,PubMed,Cochrane Library,Scopus and Web of Science from March 2014 to March 2024.Two researchers screened literature,extracted literature features,analyzed the RCT indicator domain,measurement tools,and measurement time points for manual treatment of KOA.Results A total of 134 articles were included,with a sample size of 17 659.A total of 138 outcome indicators were used to classify the outcome indicators:64 symptoms and signs(46.4%),54 physical and chemical examinations(39.1%),11 quality of life(8.0%),2 psychological status indicators(1.4%),2 safety indicators(1.4%),2 muscle strength testing indicators(1.4%)and 3 other indicators(2.2%).Among 134 articles,there were a total of 36 measurement time points,with a research time span of 1 hour to 1 year after treatment;91 articles(67.9%)used"clinical efficacy"as the outcome measure;27 articles(20.1%)were evaluated for safety and reported adverse events.Conclusion The RCT outcome indicators of manual therapy for KOA lack representativeness,integrality,objectivity and specificity.The rigorism of the outcome indicators should be improved from the aspects of representativeness,integrality,objectivity and specificity,in order to achieve a complete evaluation effect on disease research.

Osteoarthritis (OA), the most prevalent joint disease of late life, is closely linked to cellular senescence. Previously, we found that the senescence of fibroblast-like synoviocytes (FLS) played an essential role in the degradation of cartilage. In this work, single-cell sequencing data further demonstrated that cartilage acidic protein 1 (CRTAC1) is a critical secreted factor of senescent FLS, which suppresses mitophagy and induces mitochondrial dysfunction by regulating SIRT3 expression. In vivo, deletion of SIRT3 in chondrocytes accelerated cartilage degradation and aggravated the progression of OA. Oppositely, intra-articular injection of adeno-associated virus expressing SIRT3 effectively alleviated OA progression in mice. Mechanistically, we demonstrated that elevated CRTAC1 could bind with NRF2 in chondrocytes, which subsequently suppresses the transcription of SIRT3 in vitro. In addition, SIRT3 reduction could promote the acetylation of FOXO3a and result in mitochondrial dysfunction, which finally contributes to the degradation of chondrocytes. To conclude, this work revealed the critical role and underlying mechanism of senescent FLSs-derived CRTAC1 in OA progression, which provided a potential strategy for the OA therapy.

New Medical Sciences, as a crucial initiative in transforming and upgrading medical education and healthcare services in China, has promoted deep integration of public health with multiple disciplines. However, the public health discipline still faces numerous challenges such as disease prevention system reconstruction, insufficient technological innovation, and the shortage of professional talents. To address these issues, this paper discusses the current status, challenges, and development of the public health discipline in the context of New Medical Sciences, and proposes strategies including reforming talent cultivation models, enhancing practical capabilities, strengthening faculty development, promoting the innovation of scientific research and social service, actively utilizing artificial intelligence technology, and optimizing international cooperation. These measures aim to achieve innovative development in the public health discipline, and better serve the Healthy China strategy and global public health initiatives.

Objective To provide suggestions for the clinical efficacy evaluation method of manual therapy for knee osteoarthritis(KOA)by analyzing the current status of the use of outcome indicators in randomized controlled trials(RCTs)of manual therapy for KOA.Methods RCTs about manual treatment of KOA were retrieved from CNKI,Wanfang Data,VIP,SinoMed,PubMed,Cochrane Library,Scopus and Web of Science from March 2014 to March 2024.Two researchers screened literature,extracted literature features,analyzed the RCT indicator domain,measurement tools,and measurement time points for manual treatment of KOA.Results A total of 134 articles were included,with a sample size of 17 659.A total of 138 outcome indicators were used to classify the outcome indicators:64 symptoms and signs(46.4%),54 physical and chemical examinations(39.1%),11 quality of life(8.0%),2 psychological status indicators(1.4%),2 safety indicators(1.4%),2 muscle strength testing indicators(1.4%)and 3 other indicators(2.2%).Among 134 articles,there were a total of 36 measurement time points,with a research time span of 1 hour to 1 year after treatment;91 articles(67.9%)used"clinical efficacy"as the outcome measure;27 articles(20.1%)were evaluated for safety and reported adverse events.Conclusion The RCT outcome indicators of manual therapy for KOA lack representativeness,integrality,objectivity and specificity.The rigorism of the outcome indicators should be improved from the aspects of representativeness,integrality,objectivity and specificity,in order to achieve a complete evaluation effect on disease research.

New Medical Sciences, as a crucial initiative in transforming and upgrading medical education and healthcare services in China, has promoted deep integration of public health with multiple disciplines. However, the public health discipline still faces numerous challenges such as disease prevention system reconstruction, insufficient technological innovation, and the shortage of professional talents. To address these issues, this paper discusses the current status, challenges, and development of the public health discipline in the context of New Medical Sciences, and proposes strategies including reforming talent cultivation models, enhancing practical capabilities, strengthening faculty development, promoting the innovation of scientific research and social service, actively utilizing artificial intelligence technology, and optimizing international cooperation. These measures aim to achieve innovative development in the public health discipline, and better serve the Healthy China strategy and global public health initiatives.

Patients with severe tumors do not refer to the patients with end-stage tumors,but rather to the patients with a performance status(PS)score between 2 and 4 in certain stages due to various reasons,such as acute or chronic comorbidities,tumor itself,or treatment-related adverse events.To these patients,there is a high probability of achieving survival benefit and/or improvement in PS scores after synergistic management of available life-support technologies and anti-tumor therapies based on dynamic and precise testing.Elderly patients with tumors frequently present with one or more chronic illnesses and have poor toler-ance and compliance to treatment.Moreover,their treatment regimens often lack high-quality clinical evidence,making them more susceptible to developing severe tumors.The management of severe tumors in the elderly is based on three basic diagnosis and treatment technologies:dynamic and precise detection,powerful life support technologies,and skillful application of current anti-tumor treatments.In specific clinical practice,the following 7 flexible and individualized treatment strategies should be adopted for different tumor types:1.concurrent management of cancer and comorbidities,2.upgrading and downgrading of anti-tumor drugs based on PS score,3.dynamic accurate detection,4.skillful combinations for increasing efficacy and reducing toxicity,5.complete overview,paying equal attention to systemic therapy and local therapy,6.safety first in medication for the elderly,7.multi-discipli-nary participation,individualized and comprehensive treatment.This article introduced the concept of severe tumors in the elderly and the associated management strategies,to increase awareness and provide feasible guidance for clinical practice.

Objective To investigate the differences in blood pressure phenotypes,renal pathological changes,and related pathogenic pathways in genetically diverse hypertensive mice obtained from 13 strains.Methods The genotypes of Cckbr+/+,Cckbr+/-and Cckbr-/-were obtained by hybridization of 13 strains of genetically diverse mice with Cckbr-/-mice.Blood pressure was measured with a noninvasive blood pressure analysis system(BP-2000).The expression of CCKBR protein in mouse kidney tissue was detected by Western Blot,and the pathological changes in mouse kidney tissue were detected by hematoxylin-eosin(HE)staining and immunohistochemistry(IHC).The pathogenic pathways related to essential hypertension were screened by RNA sequencing.Results In three specific mouse strains(A/J,LOT,and FIM),the systolic blood pressure(SBP)was significantly different between the Cckbr-/-and Cckbr+/+groups.HE staining and IHC showed that hypertension caused a certain degree of renal injury in the mice.Gene Ontology(GO)and pathway enrichment analysis showed that differentially expressed genes were enriched in metabolic processes and circadian rhythm regulation.Conclusions Genetically diverse mice can effectively simulate the genetic background of the population and provide a new resource for studying the pathogenic genes related to essential hypertension.

"Tendon Constraining Bone"is an essential theory in osteology and traumatology of traditional Chinese medicine,originating from the statement in Suwen(Plain Questions)that"convergent tendon controlling bones and joints".Since the Yuan and Ming dynasties,the theory of"Tendon Constraining Bone"was formed based on the understanding of anatomical relationships and the need for pathogenesis interpretation,developed by medical practitioners such as ZHU Danxi and ZHANG Jie.The"Tendon Constraining Bone"theory summarizes the physiological connections between tendons and bones and between tendons and zang-fu organs and meridians.Tendons and bones are structurally connected and functionally related,reflected in sturdy bones and tough tendons,upright bones and soft tendons with smoothly-flowing qi and blood,all tendons being related to joints,and thews being related to bones.Tendons and bones are related by meridians and zang-fu organs,specifically reflected in the Yangming channel governing the nourishment of tendons,liver governing tendons,kidneys governing bones,Taiyang channel governing tendons,and Shaoyang channel governing bones.The abnormality of"Tendon Constraining Bone"is the general pathogenesis of various tendon and bone diseases,and it can be caused by changes in the tendon and bone structure,nourishment deficiency,or the pathogenic qi retention.The pathological manifestations of abnormal"Tendon Constraining Bone"are manifested in form and state.Abnormalities in form can manifest as tendon rupture,bone fractures,tendon dislocation,and bone dislocation,whereas abnormalities in state can manifest as tendon urgency,bone pain,tendon laxity,and bone softness.The"Tendon Constraining Bone"theory has influenced the development of treatment principles such as combining motion and quiescence,paying equal attention to bone and flesh,and combining internal and external treatment.This theory has guided the application of basic treatment method such as connecting and rectifying tendons and bones,smoothing tendons and relieving bones,and nourishing tendons and strengthening bones.Therefore,the"Tendon Constraining Bone"theory can significantly guide tendon and bone disease diagnosis and treatment.

Objective To observe the effect of microRNA-155 (miR-155) on the inflammatory response of rat alveolar macrophages induced by lipopolysaccharide (LPS). Methods The alveolar macrophages NR8383 of rat were cultured in vitro, the macrophages in logarithmic growth phase were harvested to conduct experiment. ① The 1 mg/L LPS was used to stimulate the rat alveolar macrophages for 3, 6, 12, and 24 hours, a phosphate buffer solution (PBS) control group was also set up. Enzyme linked immunosorbent assay (ELISA) was used to detect the dynamic changes of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the supernatant, and real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the dynamics expression of miR-155 in the cells, which confirmed the optimal time for LPS stimulation was 12 hours. ② Carboxyfluorescein (FAM) labeled mimic (FAM mimic) and inhibitor (FAM inhibitor) were used to transfect the alveolar macrophage, and the transfection effect was observed under inverted fluorescence microscope 6 hours later to confirm the optimal transfection concentration of mimic was 20 nmol/L, and the optimal transfection concentration of inhibitor was 100 nmol/L. miR-155 mimic and miR-155 inhibitor were transfected to alveolar macrophages respectively at the optimal transfection concentration for 24 hours, and 1 mg/L LPS was used to stimulate the cells for 12 hours. A mimic negative control + LPS group and an inhibitor negative control + LPS group were set up. The expressions of IL-1β and TNF-α in the supernatant were determined by ELISA to observe the regulation of miR-155 on inflammatory response of alveolar macrophages. Results ① After stimulation of 1 mg/L LPS on alveolar macrophages, the contents of IL-1β and TNF-α in the supernatant and the expression of miR-155 in the cells were increased gradually with time prolongation, IL-1β and TNF-α contents peaked at 12 hours, and the expression of miR-155 peaked at 24 hours [as compared with PBS control group, IL-1β (ng/L): 910.43±36.09 vs. 22.66±7.84, TNF-α (ng/L): 3 138.39±394.10 vs. 233.92±8.84, miR-155 (2-ΔΔCt): 7.82±0.30 vs. 1, all P < 0.05]. ② Under inverted fluorescence microscope, after 20 nmol/L FAM mimic or 100 nmol/L FAM inhibitor transfected alveolar macrophages for 6 hours, a large number of cells showed green fluorescence, indicating that the transfection was successful. The expression of miR-155 in the cells transfected with 20 nmol/L miR-155 mimic was up-regulated by (236.73±46.49) times as much as that in the negative control group (P < 0.05), and the levels of IL-1β and TNF-α in the supernatant of the cells stimulated by 1 mg/L LPS for 12 hours were significantly lower than those in the negative control group [IL-1β (ng/L): 324.37±36.59 vs. 799.31±39.44, TNF-α (ng/L): 1 554.01±342.48 vs. 3 020.49±418.30, both P < 0.05]. The miR-155 activity was significantly inhibited in the cells transfected with 100 nmol/L miR-155 inhibitor, and the expression of miR-155 was decreased by (4.00±3.26)% as compared with the negative control group, but the difference was not statistically significant (P > 0.05), and the levels of IL-1β and TNF-α in the supernatant of the cells stimulated by 1 mg/L LPS for 12 hours were significantly higher than those in the negative control group [IL-1β (ng/L): 1 358.98±212.04 vs. 878.68±53.42, TNF-α (ng/L): 4 225.57±281.11 vs. 2 881.32±286.08, both P < 0.05]. Conclusion In LPS induced inflammatory response of alveolar macrophages, miR-155 plays an obvious inhibitory role.

Most of the current experiments are obsolete and verified,the students are not interested in and the experiments are out of touch with the actual work.These are the common problems in the experiment teaching of occupational health and occupational medicine.By taking the students who majored in preventive medicine as the subjects,this study aimed to explore the effects of independent designed experiment teaching mode,which was based on dividing the groups before class,choosing the projects by students themselves,deciding the design of the program via the discussion of teacher and students and doing the experimental reports and sharing the experience.The results showed that,in the premise of the preliminary master of the theory and basic skills of occupational health and occupational medicine,carrying out independent designed experiments in the last three weeks of semester,to a certain extent,could arouse students' interest in learning,cultivate their abilities of independent thinking,practice,problem analysis and solution,and team cooperation.However,restricted by lack of teachers,inadequate equipment and high cost and other factors,this teaching mode is only suitable for small class.