This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective To compare ovulation recovery rate and metabolic indicators between ethinyl-estradiol/drospirenone(EE/DRSP)combined with orlistat and EE/DRSP alone in overweight/obese patients with polycystic ovary syndrome(PCOS).Methods This study was a randomized controlled clinical trial conducted based on the 2004 Rotterdam criteria.From October 2020 to December 2023,180 overweight/obese PCOS patients aged 20-40 were recruited from the Department of Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University.The patients were randomly divided into two groups in a 1∶2 ratio.Among them,60 patients received treatment with EE/DRSP(EE20 μg,DRSP 3 mg),while 120 patients received a combination treatment of EE/DRSP and orlistat(360 mg/d).The height,weight,waist circumference,hip circumference,and blood pressure of the patients were measured before treatment and after 12 weeks of treatment.Laboratory tests included measurements of follicle-stimulating hormone(FSH),luteinizing hormone(LH),fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),free androgen index(FAI),alanine transaminase(ALT),aspartate transaminase(AST),gamma-glutamyl transferase(GGT),fasting plasma glucose(FPG),total cholesterol(TC),triglycerides(TG),high density lipoprotein-cholesterol(HDL-C),low density lipoprotein-cholesterol(LDL-C),lipoprotein(a)[Lp(a)],sex hormone-binding globulin(SHBG),total testosterone(T),and free testosterone(FT).After 12 weeks of treatment,the medication was discontinued,and natural ovulation was observed.Results After 12 weeks of treatment,the ovulation rate of the EE/DRSP combined with orlistat group reached 70.8%,while the natural ovulation rate of the EE/DRSP group alone was only 35%,indicating that the ovulation rate was significantly increased after EE/DRSP combined with orlistat treatment.After 12 weeks of treatment,both groups showed a significant decrease in total testosterone,free testosterone,and low-density lipoprotein levels(all P<0.05),and the decrease in BMI,waist circumference,fasting insulin,and HOMA-IR in the EE/DRSP combined with orlistat group was greater than that in the EE/DRSP group alone(P<0.05).After treatment,both groups showed a significant increase in high-density lipoprotein and triglyceride levels(all P<0.05),with no significant changes in total cholesterol and fasting blood glucose(all P>0.05).Conclusion After 12 weeks of treatment,EE/DRSP combined with orlistat can significantly improve the ovulation rate of PCOS patients.It is superior to EE/DRSP alone in reducing androgen levels,body weight,insulin resistance,and low-density lipoprotein levels.

Objective To investigate the effect of individualized lifestyle intervention on sexual function in obese patients with polycystic ovarian syndrome(PCOS).Methods The study was conducted on obese patients with PCOS in the Department of Endocrinology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University from October 2022 to December 2023.There were 160 cases in both the experimental group and the control group,progesterone was administered to both groups for 3 months to regulate menstruation.For women in the experimental group received individualized comprehensive lifestyle intervention combining diet,exercise,and behavior modifications,along with dedicated follow-up and weight management.The control group received routine clinical education for lifestyle intervention aimed at weight loss.Female Sexual Function Index(FSFI)and 12-item Short-Form Health Survey(SF-12)scale were applied to evaluate the sexual function and quality of life.The clinical data that may affect sexual function were collected and sex hormone levels were measured,including anthropometric indicators,estradiol,sex hormone-binding globulin,total testosterone,bioactive testosterone,and dehydroepiandrosterone sulfate in serum.Results After 3 months of intervention,the body mass index,waist circumference,body fat percentage,insulin resistance index,total testosterone,bioactive testosterone and dehydroepiandrosterone sulfate in experimental groups were significantly lower(P<0.05),and the sex hormone binding globulin level was significantly higher(P<0.001),compared with the control group.SF-12 mental health scores,FSFI total scores,sexual desire,orgasm and sexual satisfaction scores were significantly increased in experimental groups(P<0.05),however,there were no significant differences in SF-12 physical health scores,as well as the scores of sexual arousal,vaginal lubrication,and coital pain.Conclusions Individualized lifestyle intervention can better improve the sexual function and mental health of obese patients with PCOS.

Objective To investigate the current situations of economic toxicity in hematological malignancies patients,and explore it's correlation with quality of life and psychological resilience.Methods A total of 135 hematological malignancies patients admitted in Sun Yat-sen Memorial Hospital,Sun Yat-sen University from December 2022 to October 2023 were selected as subjects.Patients were surveyed by using general information and disease-related information questionnaires,comprehensive scores for financial toxicity,European organization for research and treatment of cancer core questionnaire,connor-davidson resilience scale,social support rating sale.Correlation analysis was performed by using the Pearson method.Multiple linear regression was used to analyze the factors of economic toxicity after controlling for confounding factors.Results Economic toxicity score of 135 hematological malignancies patients was(15.95±0.84)points,of which 82.2％of them had economic toxicity.It was positively correlated with functional quality of life(r-0.464,P=＜0.001)and psychological resilience(r=0.232,P=0.007),and negatively correlated with symptomatic psychological quality(r=-0.440,P＜0.001).Multiple linear regression analysis showed that quality of life,knowledge of the treatment cost,course of treatment,patient personality and have no second caregiver were influencing factors of economic toxicity of hematological malignancies(P＜0.05).Conclusion Hematological malignancies patients have a higher level of economic toxicity,which can affect their quality of life and psychological resilience.

Objective:To investigate the correlation between expressions of serum procalcitonin (PCT), T-cell immunogloblin domain, mucin domain 4 (TIM-4) and prognosis of patients with severe pneumonia (SP) treated with bronchoalveolar lavage (BAL).Methods:Data of 497 patients with SP in the Department of Respiratory and Critical Care Medicine of the Affiliated Hospital of Yan'an University from June 2021 to June 2024 were retrospectively analyzed. Patients were divided into good prognosis group [pneumonia severity index (PSI) score<90 points, 289 cases] and poor prognosis group (PSI score≥90 points, 208 cases) according to the prognosis status of patients at 30 days after admission. The clinical data [history of smoking, alcohol consumption, history of hypertension, history of diabetes mellitus, gender, age, body mass index, PSI score after 30 d of admission, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and clinical pulmonary infection score (CPIS) after 14 days of treatment], serum PCT and TIM-4 levels were compared between both groups. Measurement data with normal distribution were expressed as xˉ± s, and t test was used for comparison between groups. Enumeration data were represented as n (%), and the composition ratio between groups was compared by χ2 test. The influencing factors of prognosis of BAL in the treatment of SP were analyzed by multivariate Logistic regression analysis. ROC curve was applied to analyze the diagnostic efficiency of serum PCT and TIM-4 on prognosis of BAL therapy. Results:Age (56.79±11.98) years, APACHEⅡscore (9.98±3.27) and CPIS score (6.54±1.81) in the good prognosis group were younger or lower than those in the poor prognosis group [(62.74±10.57) years, (13.06±4.25), (8.12±1.97)] ( t=5.734, 9.127, 9.250, respectively, P<0.001). The PCT (0.41±0.08) μg/L and TIM-4 (61.79±15.62) ng/L after treatment were higher in the poor prognosis group than those in the good prognosis group [(0.35±0.07) μg/L, (48.76±14.58) ng/L] ( t=8.876, 9.538, respectively, P<0.001). Multivariate Logistic regression analysis suggested that after excluding the interference effects of other factors, PCT ( OR=3.615, 95% CI: 1.641-7.964) and TIM-4 ( OR=4.047, 95% CI: 1.773-9.236) were influencing factors of prognosis in patients with SP receiving BAL therapy ( P=0.002, 0.001). ROC curve analysis indicated that the AUC value of PCT, TIM-4 and the combination of both in the diagnosis of prognosis of BAL therapy of SP were 0.782, 0.828 and 0.887 respectively, all of which had efficiency on predicting prognosis (all P<0.001). The sensitivity and specificity of combined prediction were 88.00% and 72.00%. Conclusion:The expressions of serum PCT and TIM-4 are closely related to the prognosis of SP patients receiving BAL. The PCT, TIM-4 and combination of both are of important reference value for prognosis prediction.

IgA vasculitis nephritis（IgAVN）is a common cause of secondary renal disease in children. Recent studies have identified several risk factors associated with the onset and prognosis of IgAVN，including older age，persistent purpura，severe gastrointestinal manifestations，and elevated levels of galactose-deficient IgA1. Based on these factors，developing predictive models for the risk and prognosis of IgAVN and formulating individualized treatment plans are essential for improving the overall therapeutic efficacy and prognosis of IgAVN.With the growing availability of medical big data，increasing attention has been directed toward the development of predictive models based on clinical variables，including general characteristics，clinical manifestations，and laboratory parameters. This review summarizes the current evidence on risk factors and predictive models for the development and prognosis of IgAVN in pediatric populations.

Urticarial vasculitis is a skin disease with urticaria-like lesions and a histopathological pattern of leukocytoclastic vasculitis. It is considered a "hidden rash" in traditional Chinese medicine. Xuanfu is the portal that regulates qi, blood, fluid, and the ascending, descending, exiting, and entering of nutrition qi and defensive qi. Collaterals are the pathways for the circulation of qi and blood. The two accompany each other, connecting zang-fu organs, reaching the surfaces of the skin, hair, and external body, circulating qi and fluid, and moistening and protecting the skin. Based on the theory of Xuanfu-collateral, this study aimed to clarify the etiology, pathogenesis, and treatment method of urticarial vasculitis. External assault by wind and Xuanfu blockage are believed to be the initiating factors of this disease. The malnutrition of Xuanfu and collaterals and accumulated dampness-heat are important links in the occurrence and development of urticarial vasculitis. It spreads from Xuanfu to the collaterals, and blockage of the collaterals is the immanent trend of this disease. Clinically, by closely adhering to the core pathogenesis of blockage of Xuanfu-collateral, treatment method such as using wind medicinals to open Xuanfu with pungent and dispersing properties, using the method of supplement deficiency and removing the blockage, and using medicinals to promote blood circulation and remove blood stasis to unblock the blocked collaterals. The herbs are flexibly added or subtracted to unblock Xuanfu and collaterals, harmonize qi and blood, thus all symptoms can be relieved. We hope that this study will provide new ideas for the treatment of urticarial vasculitis with traditional Chinese medicine.

Hepatocellular carcinoma (HCC) is one of the fastest growing cancers in the world, ranking fourth among the causes of cancer-induced death in the world. At present, the field of HCC treatment is developing rapidly, and immunotherapy has been recognized as a promising treatment method, in which T cells play a key role in HCC immunotherapy. However, in the case of virus infection or in tumor microenvironment (TME), T cells will be continuously stimulated by antigens and then fall into the state of T cell exhaustion (Tex). This state will not only reduce the immunity of patients but also lead to poor efficacy of immunotherapy. Therefore, to deeply analyze the mechanism of Tex and to explore effective strategies to reverse Tex is the key point in the immunotherapy for HCC. This review aims to summarize the mechanism of Tex in HCC patients, and the current situation and shortcomings of drug research and development to reverse Tex at this stage, in order to provide theoretical basis for the optimization of immunotherapy regimen for HCC patients.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy/methods* ; T-Lymphocytes/immunology* ; Tumor Microenvironment/immunology* ; Animals ; T-Cell Exhaustion

OBJECTIVE T o explore the prevention and control measures for the hospital-acquired pulmonary mu-cormycosis caused by Cunninghamella bertholletiae.METHODS One case of patient with pulmonary mucormyco-sis caused by Cunninghamella bertholletiae who was treated in pediatric intensive care unit(PICU)of a three-A general hospital was enrolled in the study,the process of clinical diagnosis and treatment was summarized.A ret-rospective survey regarding four aspects including people,machine,materials and environment was conducted.The related factors leading to the hospital-acquired infections in the patient were analyzed.RESULTS The child was diagnosed with severe aplastic anemia and underwent hematopoietic stem cell transplantation,the child was treated with various invasive procedures during the treatment period and was infected with pulmona-ry mucormycosis caused by the rare Cunninghamella bertholletiae.The occurrence of the pulmonary mucormyco-sis was associated with the poor management of medical textile,insufficient environmental cleaning and disinfec-tion and nonstandard invasive procedures.CONCLUSIONS The Cunninghamella bertholletiae infection is less com-mon,but the risk of death is high.It is necessary for the medical institutions to complete the prevention and con-trol measures and intensify the health care workers'capabilities in identification of the pathogenic fungus so as to reduce the incidence of pulmonary mucormycosis caused by the pathogen.