BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

Objective: To investigate if high glucose (HG) exacerbates Porphyromonas gingivalis (P.g) lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (HGFs) and to explore the underlying mechanisms. To provide a basis for the mechanism of diabetes aggravating periodontitis. Methods: HGFs were divided into four groups: the control group (basal medium), the LPS group (treated with 5 μg/mL P.g-LPS for 24 h), the HG group (treated with 25 mmol/L glucose for 24 h), and the HG+LPS group (treated with 25 mmol/L glucose + 5 μg/mL P.g-LPS for 24 h). After culturing for 24 h in the respective media, the cells were harvested for experiments. Intracellular reactive oxygen species (ROS) and mitochondrial reactive oxygen species (mtROS) were detected using 2 ', 7' - dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSOX Red staining, respectively. Fluorescence intensity was analyzed by confocal fluorescence microscopy and directly measured in cell suspension. Immunofluorescence was used to detect changes in mitochondrial DNA (mtDNA) content of HGFs. Real-time fluorescence quantitative PCR was used to detect the content of mtDNA in cytoplasm and cell supernatant. Protein expression of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway was assessed by western blot, while mRNA expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were detected by PCR. Results: Compared to the control group, both the LPS group and the HG group exhibited a significant increase in ROS and mtROS, with a more pronounced elevation in the HG+LPS group, demonstrating a synergistic effect (ROS: F = 396.5, P < 0.001; mtROS: F = 29.38, P < 0.001, CI < 1). The cytoplasmic mtDNA content was significantly elevated in the LPS group, with a more marked increase in the HG+LPS group (F = 27.85, P < 0.001). The supernatant mtDNA levels were significantly higher in both the LPS and HG groups, with a more pronounced elevation in the HG+LPS group (F = 15.26, P < 0.001). The phosphorylated proteins p-STING, p-TBK1, and p-P65 in the cGAS-STING pathway showed varying degrees of activation in the LPS and HG groups, reaching the highest levels in the HG+LPS group (p-STING: F = 52.67, P < 0.001; p-TBK1: F = 15.67, P = 0.001; p-P65: F = 9.83, P = 0.005), while p-IRF3 showed no significant differences among the groups (P = 0.072). Pro-inflammatory cytokine TNF-α was significantly higher in the HG+LPS group compared to the control group (F = 15.05, P < 0.001), and IL-1β increased in both the LPS and HG groups, with a more pronounced rise in the HG+LPS group (F = 30.98, P < 0.001). IL-6 showed no significant differences among the groups (P = 0.847). Conclusion High glucose and LPS act synergistically to enhance oxidative stress, accompanied by increased mtDNA release, which activates the cGAS-STING pathway, thereby amplifying the inflammatory response in HGFs.

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

Kidney-Yang deficiency syndrome is a common geriatric disease that underlies chronic conditions such as diabetic nephropathy, chronic kidney disease, and osteoporosis. As age progresses, the kidney-Yang deficiency syndrome showcases increasingly pronounced manifestations, emerging as a key factor in the comorbidities experienced by elderly patients and affecting their quality of life and overall health status. Traditional Chinese medicine(TCM) has been extensively utilized in the treatment of kidney-Yang deficiency syndrome, with Epimedii Folium, Cinnamomi Cortex, and Lycii Fructus widely used in clinical settings. Despite the complexity of the molecular mechanisms involved in treating kidney-Yang deficiency syndrome, the potential therapeutic value of TCM remains compelling. Delving into the mechanisms of TCM treatment of kidney-Yang deficiency syndrome by regulating the neuro-endocrine-immune system can provide a scientific basis for targeted treatments of this syndrome and lay a foundation for the modernization of TCM. The pathophysiology of kidney-Yang deficiency syndrome involves multiple systems, including the interaction of the neuro-endocrine-immune system, the decline in renal function, the intensification of oxidative stress responses, and energy metabolism disorders. Understanding these mechanisms and their interrelationships can help untangle the etiology of kidney-Yang deficiency syndrome, aiding clinicians in making more precise diagnoses and treatments. Furthermore, the research on the specific applications of TCM in research on these pathological mechanisms can enhance the international recognition and status of TCM, enabling it to exert a greater global influence.
Humans ; Yang Deficiency/physiopathology* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/physiopathology* ; Neurosecretory Systems/physiopathology* ; Animals ; Kidney/physiopathology* ; Endocrine System/physiopathology* ; Immune System/physiopathology*

OBJECTIVE: To investigate the clinical utility of novel of new hematological markers in the preoperative diagnosis of periprosthetic joint infection (PJI). METHODS: A retrospective analysis was conducted on a total of 149 patients who underwent revision of total hip arthroplasty (THA) or total knee arthroplasty (TKA) at a single center between January 2016 and June 2022, including 63 males and 86 females, aged from 47 to 93 years old with an average of (69.5±11.8) years old. Of them, 46 were diagnosed as PJI(PJI group), including 22 males and 24 females. The mean age was (71.3±12.5) years old. The body mass index (BMI) was (26.4±3.1) kg·m^-2. And 103 patients were diagnosed as aseptic prosthesis loosening (aseptic group), including 41 males and 62 females. The mean age was (68.7±11.4) years old. The BMI was (25.8±3.5) kg·m^-2. Preoperatively analyzed clinical parameters included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, globulin, albumin-to-globulin ratio (AGR), plasma D-dimer, and plasma fibrinogen. The receiver operating characteristic curve (ROC), sensitivity, and specificity analysis were employed to compare the diagnostic value of each blood marker in preoperative PJI diagnosis. RESULTS: In the PJI group, the levels of CRP were 16.6 (7.6, 4.5) mg·L^-1, ESR was 17.0 (12.8, 35.5) mm·h^-1, plasma D-dimer was 1.0 (0.5, 3.1) μg·L^-1, and plasma fibrinogen was 4.2 (3.2, 3.1) mg·L^-1;all of which were higher compared to the aseptic group with CRP at 4.2 (2.6, 7.8) mg·L^-1, ESR at 12.0(8.0, 20.0 )mm·h^-l, D-dimer at 0.4(0.2, 0.7)μg·L^-1, and fibrinogen at 2.8(2.4, 3.3 ) g·L^-1(P<0.05). However, the albumin level of 35.3 (32.3, 37.5) g·L^-1 and the WBC ratio of 1.0(0.9, 1.1) in the PJI group were significantly lower compared to the aseptic group with levels of 39.8 (36.1, 41.8) g·L^-1 and 1.4 (1.3, 1.5), respectively (P<0.05). Only the area under the curve (AUC) of AGR and plasma fibrinogen were greater than 0.8. The optimal predictive cut-1off, AUC, sensitivity and specificity were 3.4 g·L-1, 0.820, 69.57% and 84.47% for plasma fibrinogen; 1.18, 0.813, 82.61% and 78.64% for AGR, respectively. CONCLUSION AGR and plasma fibrinogen are promising blood markers for improving the diagnosis of PJI.
Humans ; Female ; Fibrinogen/metabolism* ; Male ; Middle Aged ; Aged ; Prosthesis-Related Infections/blood* ; Retrospective Studies ; Biomarkers/blood* ; Aged, 80 and over ; Arthroplasty, Replacement, Knee/adverse effects* ; Arthroplasty, Replacement, Hip/adverse effects* ; Leukocyte Count

OBJECTIVE: To analyze the clinical efficacy of manual reduction combined with 3D printing small splint external fixation and synchronous manual reduction combined with traditional small splint external fixation in the treatment of humeral shaft. METHODS: Between January 2021 and December 2022, 40 patients with humeral shaft fractures were treated with 3D printing small splints and traditional small splints. They were divided into 3D group and traditional group according to different fixation methods. Among them, there were 15 males and 5 females in the 3D group, aged from 20 to 52 years old with an average of (36.3±15.6) years old. In the traditional group there were 17 males and 3 females, aged from16 to 51 years old with an average of (32.9±17.2) years old. The occurrence of complications, duration of fracture healing, rate of fracture healing, subjective evaluation scores for brace comfort at 1 week and 4 weeks, as well as the Constant-Murley shoulder function score and Mayo elbow function score at 8 weeks and 16 weeks were compared between the two groups. RESULTS: All patients were followed up for 16 weeks. The 3D group did not experience any complications, while there were two cases of complications in the traditional group. However, this difference was not found to be statistically significant (χ²=2.105, P=0.146). The fracture healing time of the 3D group (90.1±4.5) days was significantly shorter compared to that of the traditional group (93.3±3.8) days (P<0.05). The subjective evaluation scores for brace comfort in the 3D group (53.7±2.3) points and (62.8±1.1) points were significantly higher than those in the traditional group (45.6±2.4) points and (52.3±1.4) points at 1 and 4 weeks after reduction (P<0.05). After 8 weeks of reduction, the Constant-Murley shoulder function score in the 3D group was(68.1±5.3) points, which demonstrated a statistically significant improvement compared to the traditional group(54.3±4.9) points (P<0.05). However, at 16 weeks post-reduction, there were no significant differences observed between the two groups (P>0.05). The Mayo elbow function score of the 3D group (84.1±7.5) points was significantly superior to that of the traditional group (79.5±6.8) points at 8 weeks post-reduction (P<0.05). However, there was no statistically significant difference between the two groups at 16 weeks post-reduction (P>0.05). CONCLUSION For humeral shaft fractures with conservative treatment indications, manual reduction combined with 3D printed small splints is a good choice for treatment. The patient's comfort level is higher, which can not only reduce the occurrence of complications, but also improve the fracture healing rate and joint function to a certain extent, and improve the patient's quality of life.
Humans ; Female ; Male ; Adult ; Middle Aged ; Humeral Fractures/physiopathology* ; Printing, Three-Dimensional ; Splints ; Adolescent ; Young Adult ; Fracture Healing

OBJECTIVE: Asthma imposes a significant global health burden. This study examines changes in the asthma-related disease burden from 1990 to 2021 and projects future burdens for 2050 under different scenarios. METHODS: Using data from the Global Burden of Disease 2021 study, we analyzed asthma incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. We projected the disease burden for 2050 based on current trends and hypothetical scenarios in which all risk factors are controlled. Temporal trends in age-standardized incidence, prevalence, mortality, and DALY rates were explored using Annual Percent Change. RESULTS: In 2021, the age-standardized rates for asthma incidence, prevalence, mortality, and DALYs in China were 364.17 per 100,000 (95% uncertainty interval [ UI]: 283.22-494.10), 1,956.49 per 100,000 (95% UI: 1,566.68-2,491.87), 1.47 per 100,000 (95% UI: 1.15-1.79), and 103.76 per 100,000 (95% UI: 72.50-145.46), respectively. A higher disease burden was observed among Chinese men and individuals aged 70 years or older. Compared to the current trend, a combined scenario involving improvements in environmental factors, behavioral and metabolic health, child nutrition, and vaccination resulted in a greater reduction in the disease burden caused by asthma. CONCLUSION Addressing modifiable risk factors is essential for further reducing the asthma-related disease burden.
Humans ; Asthma/mortality* ; China/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Aged ; Child ; Adolescent ; Global Burden of Disease/trends* ; Child, Preschool ; Young Adult ; Infant ; Cost of Illness ; Disability-Adjusted Life Years ; Prevalence ; Incidence ; Infant, Newborn ; Aged, 80 and over ; Risk Factors

OBJECTIVES: To propose a hypothesis that aloe-emodin may inhibit scar tissue fibrosis through thrombospondin-1(THBS1)-PI3K-Akt pathway. METHODS: By cultivating fibroblasts derived from scar tissue after cleft palate surgery in humans, aloe emodin of different concentrations (10, 20, 30, 40 and 50 μmol/L) was added to the cells which activity was detected. At the same time, transcriptome sequencing was performed on scar tissue and cells, and bioinformatics methods were used to explore potential targets and signaling pathways of scar tissue fibrosis. RESULTS: Aloe-emodin had a concentration dependent inhibitory effect on fibroblast proliferation,with the 40 μmol/L concentration group showing the most significant effect. The results of tissue and cell sequencing indicated that differentially expressed genes were significantly enriched in extracellular matrix-receptor interaction pathway, and shared a common differential gene which was THBS1. The ORA analysis results indicated that differentially expressed genes, including THBS1, were significantly enriched in the PI3K-Akt signaling pathway. CONCLUSIONS Aloe emodin may inhibit the PI3K-Akt pathway by downregulating THBS1, thereby reducing the proliferation activity of fibroblasts derived from postoperative palatal scar tissue.
Thrombospondin 1/genetics* ; Humans ; Signal Transduction/drug effects* ; Fibroblasts/cytology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Fibrosis ; Phosphatidylinositol 3-Kinases/metabolism* ; Cicatrix/metabolism* ; Cell Proliferation/drug effects* ; Anthraquinones/pharmacology* ; Cells, Cultured

ObjectiveTo evaluate the efficacy and safety of Lianhua Qingke tablets in the treatment of acute bronchitis in children with the syndrome of phlegm-heat obstructing lung. MethodA randomized， open， parallel controlled， and multi-center clinical study was conduted. Children with acute bronchitis （syndrome of phlegm-heat obstructing lung） were randomly assigned to an observation group and a control group. The control group received routine basic treatment， and the observation group was treated with Lianhua Qingke Tablets on the basis of routine basic treatment. After 7 days of treatment， the clinical efficacy， TCM efficacy， time to symptom disappearance， time to cough disappearance， and clinical safety were compared between the two groups. ResultA total of 248 children were included （124 in the observation group and 124 in the control group）. After 7 days of treatment， the total response rate in terms of clinical efficacy in the observation group was 96.8% （120/124）， which was higher than that （90.3%， 112/124） in the control group （Z=-5.034， P<0.01）. The total response rate in terms of TCM syndrome in the observation group was 97.6% （121/124）， which was higher than that （93.5%， 116/124） in the control group （χ²=-5.326， P<0.01）. The scores of physical signs and TCM symptoms in the observation group were lower than those in the control group at the time of taking medicine for 3 days and 7 days （P<0.01）. The time to symptom disappearance and the time to cough disappearance in the observation group were shorter than those in the control group （P<0.01）. Drug-related adverse reactions occurred in neither group. ConclusionLianhua Qingke tablets demonstrate a definite effect on acute bronchitis in children with the syndrome of phlegm-heat blocking lung. The tablets can significantly shorten the course of disease and relieve cough and TCM symptoms， with high safety， which is worthy of clinical application and promotion.

Objective:According to the international cooperation project of Peking University Cancer Hospital on human genetic resource management practices, combined with the development direction of human genetic resource management laws and regulations, and propose reference suggestions for medical institutions to strengthen human genetic resource management.Methods:Sort out the projects that Peking University Cancer Hospital obtained international cooperation approval on the government platform of the Ministry of Science and Technology from July 2019 to June 2023, analyze the current situation of human genetic resource management in the hospital, summarize the challenges brought by the implementation of new regulations on human genetic resource management in medical institutions, and propose corresponding suggestions.Results:A total of 1276 international cooperation projects on human genetic resources have been approved, including 345 initial declarations and 931 change declarations. Involving 453 studies, including 286 clinical trials of drugs or devices on the market, accounting for 63.13%, and 100 clinical trials of Phase I drugs, accounting for 34.97% of the market studies. On average, there are 3.14 changes per project for listed research, and 1.56 changes per project for non listed research.Conclusions:Regulations on the Management of Human Genetic Resources ( short for Rules) limit the management scope of international cooperation projects involving human genetic resources and delegate management authority to medical institutions. Adjusting the scope of application for international cooperative clinical trial filing may result in some administrative approval projects being transferred to filing. The approval process for international cooperative scientific research projects on human genetic resources has been adjusted. Suggest medical institutions to strengthen the management of samples and intellectual property outside the scope of application of Rules.Strengthen the entire process management of international cooperation in scientific research. Pay attention to and timely communicate the dynamics of human genetic resource management.