ObjectiveTo investigate the effect of Tougu Xiaotong capsules （TGXTC） on the regulation of chondrocyte PANoptosis， delay of chondrocyte degeneration， and improvement of the symptoms in knee osteoarthritis （KOA）. MethodsIn vivo experiments： 50 male C57BL/6 mice were randomly assigned into five groups （n=10 per group）： sham operation group， model group， low-dose TGXTC group （7.2 g·kg^-1）， high-dose TGXTC group （14.4 g·kg^-1）， and diclofenac sodium group （0.05 g·kg^-1）. Except for the sham group， KOA models were established in all other groups using the modified Hulth method. Following successful model induction， the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg^-1 for 6 weeks， while the diclofenac sodium group received 0.05 g·kg^-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score； micro-computed tomography （micro-CT） was used to scan the knee， hematoxylin-eosin （HE） staining and safranin O-fast green staining were used to observe the morphology of cartilage， transmission electron microscopy （TEM） was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence （IF） co-localization assays was performed to detect the co-localization of cleaved Caspase-3， receptor-interacting protein 3 （RlPK3）， and the N-terminal domain of gasdermin D （GSDMD-N） in cartilage tissue， while western blot was employed to detect the expression levels of cleaved Caspase-3， RIPK3， and GSDMD-N. In vitro experiments： The knee cartilages of 4-week-old SD rats were isolated， and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups： the control group， the model group （pretreated with 10 mg·L^-1 lipopolysaccharide （LPS） for 24 h followed by treatment with 1 μmol·L^-1 nigericin for 4 h）， and the TGXTC treatment group （pretreated with 10 mg·L^-1 LPS for 24 h， followed by exposure to 1 μmol·L^-1 nigericin for 4 h and subsequently treated with 100 mg·L^-1 TGXTC for an additional 24 h）. The levels of reactive oxygen species （ROS）， apoptosis， necroptosis， and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection， AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels （IL-1β and IL-18） were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis， including cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3. ResultsCompared with the sham group， the Lequesne MG scores were significantly up-regulated（P<0.01） in the model group， and the pathological changes of cartilage were significantly， with joint spaces narrower， osteophyte formation increased， secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis， necroptosis， and pyroptosis， along with markedly elevated expression of cleaved Caspase-3， RlPK3， and GSDMD-N in cartilage tissue （P<0.01）. In addition， The mean fluorescence intensities of ROS， orange-red fluorescence in AO/EB staining， green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group （P<0.01） . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased （P<0.01）. The expression of PANoptosis related proteins （cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3） were also significantly upregulated（P<0.05）. Compared to the model group， the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score， an increase in joint space， a decrease in osteophyte formation， diminished cartilage damage， reduced release of ROS， and alleviation of apoptotic， necroptotic， and pyroptotic processes in chondrocytes. Additionally， mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased （P<0.05）. Furthermore， the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions （P<0.05）. Similar results were observed in chondrocytes： cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3 exhibited significant decreases as well （P<0.05）. ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.

Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

ObjectiveTo investigate the effect of Tougu Xiaotong capsules （TGXTC） on the regulation of chondrocyte PANoptosis， delay of chondrocyte degeneration， and improvement of the symptoms in knee osteoarthritis （KOA）. MethodsIn vivo experiments： 50 male C57BL/6 mice were randomly assigned into five groups （n=10 per group）： sham operation group， model group， low-dose TGXTC group （7.2 g·kg^-1）， high-dose TGXTC group （14.4 g·kg^-1）， and diclofenac sodium group （0.05 g·kg^-1）. Except for the sham group， KOA models were established in all other groups using the modified Hulth method. Following successful model induction， the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg^-1 for 6 weeks， while the diclofenac sodium group received 0.05 g·kg^-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score； micro-computed tomography （micro-CT） was used to scan the knee， hematoxylin-eosin （HE） staining and safranin O-fast green staining were used to observe the morphology of cartilage， transmission electron microscopy （TEM） was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence （IF） co-localization assays was performed to detect the co-localization of cleaved Caspase-3， receptor-interacting protein 3 （RlPK3）， and the N-terminal domain of gasdermin D （GSDMD-N） in cartilage tissue， while western blot was employed to detect the expression levels of cleaved Caspase-3， RIPK3， and GSDMD-N. In vitro experiments： The knee cartilages of 4-week-old SD rats were isolated， and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups： the control group， the model group （pretreated with 10 mg·L^-1 lipopolysaccharide （LPS） for 24 h followed by treatment with 1 μmol·L^-1 nigericin for 4 h）， and the TGXTC treatment group （pretreated with 10 mg·L^-1 LPS for 24 h， followed by exposure to 1 μmol·L^-1 nigericin for 4 h and subsequently treated with 100 mg·L^-1 TGXTC for an additional 24 h）. The levels of reactive oxygen species （ROS）， apoptosis， necroptosis， and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection， AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels （IL-1β and IL-18） were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis， including cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3. ResultsCompared with the sham group， the Lequesne MG scores were significantly up-regulated（P<0.01） in the model group， and the pathological changes of cartilage were significantly， with joint spaces narrower， osteophyte formation increased， secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis， necroptosis， and pyroptosis， along with markedly elevated expression of cleaved Caspase-3， RlPK3， and GSDMD-N in cartilage tissue （P<0.01）. In addition， The mean fluorescence intensities of ROS， orange-red fluorescence in AO/EB staining， green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group （P<0.01） . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased （P<0.01）. The expression of PANoptosis related proteins （cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3） were also significantly upregulated（P<0.05）. Compared to the model group， the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score， an increase in joint space， a decrease in osteophyte formation， diminished cartilage damage， reduced release of ROS， and alleviation of apoptotic， necroptotic， and pyroptotic processes in chondrocytes. Additionally， mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased （P<0.05）. Furthermore， the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions （P<0.05）. Similar results were observed in chondrocytes： cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3 exhibited significant decreases as well （P<0.05）. ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.

ObjectiveTo analyze the willingness to receive human papilloma virus (HPV) vaccine and its influencing factors among adult women in Qinghai Province, so as to provide scientific basis for the formulation of targeted health intervention strategies. MethodsA multi-stage whole cluster random sampling method was used to conduct a questionnaire survey on the willingness to receive HPV vaccine in eight cities or states of Qinghai Province from December 2024 to January 2025. Hierarchical multiple regression analyses were used to identify the influencing factors associated with HPV vaccination willingness. ResultsThe results of the 923 participants participated the questionnaire survey revealed that adult women’s HPV vaccination willingness scores differed statistically significant by educational level (F=9.596, P<0.001) and occupation (F=8.494, P<0.001). The hierarchical multiple regression modeling showed that perception of susceptibility (β=0.078, P<0.05), cues to action(β=0.134, P<0.05), and subjective norms (β = 0.407, P<0.001) were positively associated with HPV vaccination willingness among adult women, while perceptual disorder (β =-0.113, P<0.001) was negatively associated with it. ConclusionThe willingness to receive HPV vaccine among adult women in Qinghai Province is influenced by perception of susceptibility, perceptual disorder, cues to action, and subjective norms. Policy makers and public health agencies should therefore adopt targeted strategies, such as optimizing health education, improving vaccine accessibility, lowering barriers to vaccination, and reinforcing supportive social networks, to increase HPV vaccine uptake and ultimately achieve the goal of effective prevention, control, and elimination of cervical cancer.

Objective:To describe the safety of using the Chinese-made robotic laparoscopic surgery system for laparoscopic sacrocolpopexy in the treatment of severe pelvic organ prolapse.Methods:A pilot descriptive clinical study was conducted, enrolling 16 severe pelvic organ prolapse patients at Peking University First Hospital from April 2023 to January 2024. Patients who consented to participate in this study underwent laparoscopic sacrocolpopexy for severe pelvic organ prolapse using Chinese-made robotic laparoscopic surgery system. Preoperative clinical basic data and perioperative data of the patients were collected, summarizing the data on perioperative bleeding and complications, and reviewed the surgical learning experience. The evaluation indicators related to the learning experience included: (1) efficiency evaluation: including equipment docking time, total surgery time, suturing time, mechanical arm operation time and hysterectomy time, which were timed and recorded during surgery; (2) equipment operability evaluation: including equipment operation task load assessment and intraoperative operation feeling score. The cumulative sum analysis method was used to quantify surgery time and fit the learning curve.Results:Sixteen patients were successfully enrolled and underwent surgery, including total hysterectomy with bilateral salpingo-oophorectomy or salpingectomy plus sacrocolpopexy, or sacrocolpopexy alone (for one case without uterus). The age of 16 cases was (56.7±7.6) years (ranged from 44 to 67 years), with body mass index of (25.4±2.5) kg/m2. Concurrent procedures included anterior vaginal wall repair in 12 cases (12/16), posterior vaginal wall repair in 13 cases (13/16), tension-free vaginal tape obturator system in 1 case (1/16), and recto-uterine pouch hernia repair in 4 cases (4/16). The total surgery time was (355.8±91.1) minutes, with docking time at (6.7±4.9) minutes, robotic operative time at (267.6±81.4) minutes, robotic suturing time at (155.6±53.9) minutes, and hysterectomy time at (112.0±45.3) minutes. Learning curve analysis revealed inflection points at 6 cases for total surgery time ( P<0.001, R2=0.944) and robotic operative time ( P<0.001, R2=0.982), 5 cases for docking time ( P<0.001, R2=0.989), and 6 cases for robotic suturing time ( P<0.001, R2=0.907). Hysterectomy time had an inflection point at 5 cases ( P=0.023, R2=0.700). Median blood loss was 30 ml (range: 10-1 000 ml), with severe bleeding in one patient (1/16). No conversions to open surgery or laparoscopy occurred, and no severe perioperative or postoperative complications were reported. Conclusion:The Chinese-made robotic laparoscopic surgery system demonstrates excellent short-time safety and ease of operation for laparoscopic sacrocolpopexy.

The study was conducted among 120 general practitioners (GPs) in Shanghai Fengxian District from August 2022 to March 2024, the participants were randomly divided into two age-matched groups with 60 GPs in each group. The intervention group completed a 3-month SPOC (Small Private Online Course)program, including two weeks of narrative medicine theory (concepts, questioning skills, parallel medical record writing, and professionalism) followed by monthly writing practices (three parallel records per month) and group discussions. Both groups performed routine clinical tasks, while the control group received no narrative medicine training. Baseline data were collected, Jefferson Empathy Scale scores, and Doctor-Patient Communication Skills Evaluation Scale scores were evaluated pre- and post-intervention. There were no significant differences in empathy ( P>0.05) or communication skills ( P>0.05) between two groups before the intervention. Post-intervention, both groups showed improved empathy (both P<0.05) and communication skills (both P<0.05) after intervention, while the intervention group were outperforming the control group in both measures ( P<0.05). These findings suggest that SPOC-based narrative competence training effectively enhances the empathy and doctor-patient communication abilities of general practitioners.

WDFY1 is a member of the protein family containing the WD repeat and FYVE structural domains,acting as a junction that assists the recruitment of downstream molecules by Toll-like receptor 3/4(TLR3/TLR4)and promotes the body's natural anti-viral and anti-bacterial immune response.In recent years,the role of WDFY1 has been successively reported in various disease models,such as neurological diseases,autophagy and tumors.This paper aims to provide a comprehensive review of the current state of WDFY1 research,encompassing its expression distribution,cell biological function and its role in disease development,and take a prospect on the potential of WDFY1 as a target in rheumatoid arthritis.

BACKGROUND:Our previous research found that Tougu Xiaotong Capsules can be used not only for the treatment of osteoarthritis,but also for rheumatoid arthritis and gouty arthritis.However,the specific mechanism of action of"Same Treatment for Different Diseases"is still unclear.OBJECTIVE:To identify the main effects and mechanisms of Tougu Xiaotong Capsules in the treatment of osteoarthritis,rheumatoid arthritis and gouty arthritis with the treating principle of"Same Treatment for Different Diseases"by the methodologies of integrated pharmacology,molecular docking techniques and molecular dynamics simulation.METHODS:The active chemical components of Tougu Xiaotong Capsules and their corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Swiss Target Prediction database.The disease genes for osteoarthritis,rheumatoid arthritis and gouty arthritis were obtained from the GeneCards and OMIM databases.Cytoscape 3.7.2 software was used to construct a drug-component-disease-target network diagram and a protein-protein interaction network.Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted using the Daivd database.Molecular docking simulations were performed on the CB-DOCK2 website,and molecular dynamics simulations were carried out using the GROMACS 2020.6 software.RESULTS AND CONCLUSION:(1)A total of 50 active components of Tougu Xiaotong Capsules were screened,with 184 potential targets and 29 intersection targets across the three types of arthritis.(2)The gene ontology enrichment analysis of the intersection targets indicated that the key gene functions of Tougu Xiaotong Capsules in treating the three types of arthritis were found to be cellular response to lipopolysaccharide,inflammatory response,extracellular matrix,protein binding,and zinc ion binding.(3)Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified key pathways as interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,NOD-like receptor and Toll-like receptor signaling pathways.(4)Six core targets[interleukin-6,interleukin-1β,prostaglandin endoperoxide synthase 1,prostaglandin endoperoxide synthase 2,cytochrome P450 1A2(CYP1A2)and C-X-C chemokine ligand 8]were determined based on the protein-protein interaction network.(5)Molecular docking results confirmed that(+)-catechin,β-sitosterol,kaempferol,myricetin,and wallichilide had good structure-activity relationships.Molecular dynamics simulations further confirmed the stable binding of CYP1A2 with wallichilide,corroborating the network pharmacology and molecular docking results.Therefore,Tougu Xiaotong Capsules may regulate the interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,and other signaling pathways by targeting interleukin-1β,prostaglandin endoperoxide synthase 1,prostaglandin endoperoxide synthase 2 and CYP1A2,exert an effect of"Same Treatment for Different Diseases"on osteoarthritis,rheumatoid arthritis and gouty arthritis.

WDFY1 is a member of the protein family containing the WD repeat and FYVE structural domains,acting as a junction that assists the recruitment of downstream molecules by Toll-like receptor 3/4(TLR3/TLR4)and promotes the body's natural anti-viral and anti-bacterial immune response.In recent years,the role of WDFY1 has been successively reported in various disease models,such as neurological diseases,autophagy and tumors.This paper aims to provide a comprehensive review of the current state of WDFY1 research,encompassing its expression distribution,cell biological function and its role in disease development,and take a prospect on the potential of WDFY1 as a target in rheumatoid arthritis.

Objective:To describe the safety of using the Chinese-made robotic laparoscopic surgery system for laparoscopic sacrocolpopexy in the treatment of severe pelvic organ prolapse.Methods:A pilot descriptive clinical study was conducted, enrolling 16 severe pelvic organ prolapse patients at Peking University First Hospital from April 2023 to January 2024. Patients who consented to participate in this study underwent laparoscopic sacrocolpopexy for severe pelvic organ prolapse using Chinese-made robotic laparoscopic surgery system. Preoperative clinical basic data and perioperative data of the patients were collected, summarizing the data on perioperative bleeding and complications, and reviewed the surgical learning experience. The evaluation indicators related to the learning experience included: (1) efficiency evaluation: including equipment docking time, total surgery time, suturing time, mechanical arm operation time and hysterectomy time, which were timed and recorded during surgery; (2) equipment operability evaluation: including equipment operation task load assessment and intraoperative operation feeling score. The cumulative sum analysis method was used to quantify surgery time and fit the learning curve.Results:Sixteen patients were successfully enrolled and underwent surgery, including total hysterectomy with bilateral salpingo-oophorectomy or salpingectomy plus sacrocolpopexy, or sacrocolpopexy alone (for one case without uterus). The age of 16 cases was (56.7±7.6) years (ranged from 44 to 67 years), with body mass index of (25.4±2.5) kg/m2. Concurrent procedures included anterior vaginal wall repair in 12 cases (12/16), posterior vaginal wall repair in 13 cases (13/16), tension-free vaginal tape obturator system in 1 case (1/16), and recto-uterine pouch hernia repair in 4 cases (4/16). The total surgery time was (355.8±91.1) minutes, with docking time at (6.7±4.9) minutes, robotic operative time at (267.6±81.4) minutes, robotic suturing time at (155.6±53.9) minutes, and hysterectomy time at (112.0±45.3) minutes. Learning curve analysis revealed inflection points at 6 cases for total surgery time ( P<0.001, R2=0.944) and robotic operative time ( P<0.001, R2=0.982), 5 cases for docking time ( P<0.001, R2=0.989), and 6 cases for robotic suturing time ( P<0.001, R2=0.907). Hysterectomy time had an inflection point at 5 cases ( P=0.023, R2=0.700). Median blood loss was 30 ml (range: 10-1 000 ml), with severe bleeding in one patient (1/16). No conversions to open surgery or laparoscopy occurred, and no severe perioperative or postoperative complications were reported. Conclusion:The Chinese-made robotic laparoscopic surgery system demonstrates excellent short-time safety and ease of operation for laparoscopic sacrocolpopexy.