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 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.

The management of hospital volunteers is one of the main tasks of medical social workers.In practical work,they are often in a dilemma due to ethical problems,which restricts the scientific development of hospital volunteer organizations.Based on the experience of frontline medical social workers in the"Guangji Boat"Volunteer Service Alliance of the Second Affiliated Hospital Zhejiang University School of Medicine,while investigating other public hospitals,this paper summarized and organized ethical issues,analyzed their causes,and proposed improvement strategies.The ethical dilemma of hospital volunteer service was mainly in the conflict between the dual relationship of human emotion and norm,the conflict between incentive mechanism and non-reward value,as well as the conflict between participation motivation and organizational goal.The ethical dilemma in the management of hospital volunteers was attributed to the lack of standardized practical operation systems.Based on the above ethical dilemmas,combined with the development experience of volunteer service in public hospitals,this paper proposed reasonable countermeasures to provide a reference for the management of hospital volunteers.

Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.

Objective:To analyze the clinical characteristics of anti-cyclic citrullinated peptide (CCP) antibody-negative rheumatoid arthritis (RA) patients.Methods:To retrospectively analyze the medical records of RA patients hospitalized in the department of rheumatology and immunity of Peking University Third Hospital from January 2013 to December 2018, we collected the baseline characteristics, joint manifestations, extra-articular manifestations, and laboratory parameters of RA patients, and compared the differences between anti-CCP antibody-negative patients and anti-CCP antibody-positive patients by U test and chi-square test. Results:A total of 486 RA patients were included in this study, including 153 anti-CCP antibody-negative patients (31.5%) and 333 anti-CCP antibody-positive patients (68.5%). Compared with anti-CCP antibody-positive group, anti-CCP antibody-negative group had shorter disease course ( U=-4.750, P<0.01) and the pro-portion of morning stiffness, shoulder or elbow joint involvement, and hand arthritis ( P<0.05) was lower, while the incidence of phlebothrombosis of leg ( χ2=4.100, P=0.043) was higher, as well as thrombocytosis ( U=-2.179, P=0.029) and elevation of CRP ( U=-2.154, P=0.03). Subgroup analysis based on RF showed that CCP RF + group had higher percentage of women ( P=0.042) and higher incidence of interstitial lung disease ( χ2=5.652, P=0.017) and secondary Sj?gren's syndrome ( χ2=11.211, P=0.001), compared with CCP RF - group. Conclusion:anti-CCP antibody-negative-patients have similar clinical char-acteristics with anti-CCP antibody-positive group, but the involvement of shoulder or elbow joint and hand arthritis are less common in anti-CCP antibody-negative group. Meanwhile the incidence of phlebothrombosis of leg is higher, and the level of platelet(PLT) and C-reactive protein (CRP) is higher, suggesting that anti-CCP antibody-negative RA may have more vident inflammatory response.

OBJECTIVETo evaluate the clinical therapeutic effects and safety of chronic fatigue syndrome treated with transcutaneous electrical acupoint stimulation (TEAS) on the conception vessel and the governor vessel.

METHODSEighty-nine patients of chronic fatigue syndrome were randomized into an observation group (46 cases) and a control group (43 cases). In the observation group, TEAS was applied at Dazhui (GV 14) and Mingmen (GV 4), Shenque (CV 8) and Guanyuan (CV 4) [the current intensity: (14±2) mA]. In the control group, the simulated TEAS was applied at the same acupoints as the observation group (the current intensity: 1 mA). The treatment was given for 30 min, once a day, 5 times a week and the treatment of 4 weeks was as 1 session in the two groups. One session of treatment was required. Before treatment and at the end of 1 session of treatment, the fatigue severity scale (FSS) was adopted to evaluate the fatigue symptoms and the somatic and psychological health report (SPHERE) was adopted to evaluate the potential symptoms and observe the safety of TEAS therapy.

RESULTSAt the end of treatment, FSS score and SPHERE score in the control group were not different significantly as compared with those before treatment (both>0.05). FSS score and SPHERE score in the observation group were reduced significantly as compared with those before treatment (both<0.01). FSS score and SPHERE score in the observation group were reduced apparently as compared with those in the control group (both<0.001). In the entire process of treatment with TEAS, no any adverse reaction occurred.

CONCLUSIONTEAS on the conception vessel and the governor vessel relieves fatigue symptoms and the potential symptoms in the patients of chronic fatigue syndrome. It is a safe therapy.

Objective To investigate the clinical efficacy of white mustard seed moxibustion on four flower points [bilateral points Geshu(BL 17) and Danshu(BL 19)] in treating night sweat.Method One hundred and twenty patients with night sweat were randomly allocated to groups A, B and C, 40 cases each. Group A received white mustard seed moxibustion on four flower points; group B, oral administration of zuogui pills; group C, application of millet paste to four flower points. After 22 days of treatment, pre-treatment and post-treatment TCM symptoms and signs of hyperhidrosis scores were compared in the three groups and the clinical therapeutic effects were compared between the three groups.ResultThere was a statistically significant pre-/post-treatment difference in the TCM symptoms and signs of hyperhidrosis score in the three groups (P<0.05). The cure rate and the total efficacy rate were 50.0% and 92.5%, respectively, in group A; 27.5% and 75.0%, respectively, in group B; 12.5% and 50.0%, respectively, in group C. There were statistically significant differences in the cure rate and the total efficacy rate, and the TCM symptoms and signs of hyperhidrosis score between group A and group B or C (P<0.05) and between groups B and C (P<0.05).Conclusion White mustard seed moxibustion on four flower points is an effective way to treat night sweat and can markedly improve its symptoms in the patients.

BACKGROUND:Tougu Xiaotong Capsule (TGXTC) is a clinical prescription for the treatment of osteoarthritis;however, its mechanism has not been ful y elucidated. Urokinase-type plasminogen activator (uPA) system participating in the degradation of the extracel ular matrix of articular cartilage and hyperplasia of joint synovium plays an important role in the pathological process of osteoarthritis. OBJECTIVE:To investigate the effects of TGXTC medicated serum on the expression of uPA, uPA receptor (uPAR), plasminogen activator inhibitors (PAIs), matrix metal oproteinase-3 (MMP-3), interleukin-1 beta (IL-1β) and tumor necrosis factor-α(TNF-α) in osteoarthritis synovial cel s of rats and to discuss the mechanism by TGXTC medicated serum prevents and cures osteoarthritis. METHODS:Rat models with knee osteoarthritis were established by injecting 4%papain into the knee joint cavity. Primary synoviocytes and osteoarthritis synoviocytes were cultured with col agenase digestion method. The cultured synoviocytes were divided into normal group, model group and TGXTC group. The western blot method was adopted to detect uPA, uPAR, PAI, MMP-3, IL-1βand TNF-αprotein expression of synoviocytes after acting by TGXTC medicated serum for 72 hours. RESULTS AND CONCLUSION:The expression of uPA, uPAR, MMP-3, IL-1βand TNF-αwere decreased, while PAI was increased in the TGXTC group, and there were significant differences when compared with model group. In a word, TGXTC can significantly inhibit the expression of uPA, uPAR, MMP-3, IL-1β, TNF-α, and improve PAI expression in synoviocytes, which may partly explain the mechanism of the treatment of Tougu Xiaotong Capsule on osteoarthritis.

BACKGROUND:Tougu Xiaotong capsule is the clinical prescription for the treatment of osteoarthritis, however, its mechanism has not been fuly elucidated. Urokinase type plasminogen activator system which participated in the degradation of the extracelular matrix of articular cartilage and hyperplasia of joint synovium plays an important role in the pathological process of osteoarthritis. OBJECTIVE: To determine the effect ofTougu Xiaotong capsule on urokinase-type plasminogen activator system in knee cartilage tissues of knee osteoarthritis rats. METHODS: Of 144 Sprague-Dawley rats, 120 rats were randomly made into models of knee osteoarthritisvia intra-articular injection of papain, and randomly assigned to model group,Zhuanggu Guanjie Wan group [1.2 g/(kg?d)], low-doseTougu Xiaotong capsule group [0.092 g/(kg?d)], moderate-doseTougu Xiaotong capsule group [0.184 g/(kg?d)] and high-doseTougu Xiaotong capsule group [0.368 g/(kg?d)]. Each group contained 24 rats. Every 2 weeks was considered as a course, with a 2-day interval, totaly 4 courses. The remaining 24 normal rats were included in the blank group. After every two courses, a batch of experimental animals was sacrificed. The pathological changes were observed folowing staining with hematoxylin and eosin. The positive cels of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and plasminogen activator inhibitor were measured by immunohistochemistry. The protein levels of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and plasminogen activator inhibitor were measured by western blot assay. RESULTS AND CONCLUSION:Mankin’s score was significantly lower in theTougu Xiaotong capsule group and Zhuanggu Guanjie Wan group compared with the model group (P < 0.01), in a time-dependent manner. Immunohistochemical staining indicated that the positive cels of urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor were significantly decreased, but plasminogen activator inhibitor was significantly increased in theTougu Xiaotong capsule group andZhuanggu Guanjie Wangroup in a time-dependent manner. Western blot assay results had an identical trend to immunohistochemistry. These indicated thatTougu Xiaotong capsule showed preventive and therapeutic effects on osteoarthritis by regulating urokinase-type plasminogen activator system.

BACKGROUND:Tougu Xiaotong Capsule has pretty good clinical therapeutic effect on osteoarthritis of early and middle periods. However, the mechanism of Tougu Xiaotong Capsule is not ful y clarified. The RhoA GTPases can regulate chondrocyte apoptosis and hypertrophy.
OBJECTIVE:To observe the Tougu Xiaotong Capsule on the expression of Rac1and Cdc42 in tumor necrosis factor-α-induced in vitro cultured rat articular chondrocytes, and to explore its mechanism of action for combating osteoarthritis.
METHODS:Knee cartilage of the 4-week-old Sprague-Dawley rats was used to stably establish in vitro culture system of chondrocytes. Passage 3 chondrocytes were identified by toluidine blue staining. Chondrocyte apoptosis was successful y induced by 20μg/L tumor necrosis factor-αand then Tougu Xiaotong Capsule at different dosage (500, 100, 20 mg/L) was given after 24-hour incubation. MTT assay was used to detect cellsurvival, flow cytrometry to measure mitochondrial membrane potential, and western blot assay to determine the protein expression of Rac1, Cdc42, Bax and Bcl-2.
RESULTS AND CONCLUSION:Tougu Xiaotong Capsule could reduce tumor necrosis factor-α-induced apoptosis of chondrocytes to improve the survival rate of the cells, and at the same time, could down-regulate the protein expression of Rac1, Cdc42 and Bax and increase the protein expression of Bcl-2 significantly (P<0.05). Tougu Xiaotong Capsule possibly plays a therapeutic efficacy on osteoarthritis by reducing promote apoptosis Rac1, Cdc42 and Bax expression and increasing apoptosis inhibiting gene Bcl-2 expression, thereby to inhibit apoptosis of chondrocytes.