OBJECTIVE To analyze the selection and rationales of comparators for pharmaceutical enterprises in their medical insurance access application， so as to provide a reference for promoting communication and consensus between enterprises and medical insurance authorities in this process. METHODS The application materials for drugs outside the catalogue that passed formal review published by the National Healthcare Security Administration from 2021 to 2025 were extracted， and then content analysis was used to systematically sort out relevant information of the declared drugs and comparators； the specific situations and rationales of pharmaceutical enterprises’ selection of comparators were analyzed. RESULTS A total of 1 341 declared drug documents were collected. Data analysis showed that 1 035 （77.18%） were submitted with positive comparators and 306 （22.82%） used blank comparators； 58 drugs （4.33%） took combination therapy as the reference， and 5 drugs （0.37%） referred to non-pharmacological （or non-single pharmacological） treatment regimens. Among competitive drugs declared by multiple enterprises， 50.00% of the enterprises submitted different comparators. A total of 4 basic conditions and 39 additional conditions were extracted as the rationales for selecting positive comparators. For blank comparators， 12 drug-related factors， 2 administrative factors， and 1 other factor were identified. More than 10% of the drugs did not state the rationale for comparator selection， and over 44% of drugs using blank comparators provided only one justification. CONCLUSIONS Pharmaceutical enterprises mainly select comparators based on their own interests in the medical insurance access application， and there are deficiencies in the adequacy and standardization of their selection basis and reasoning. It is recommended that enterprises follow the principled requirements of medical insurance authorities， and fully and normatively explain the reasons for selecting comparators in combination with the characteristics of their own products. Meanwhile， it is advisable to change the current open-ended statement form of selection reasons into a closed-ended answering mode， so as to highlight the priority of selection， standardize the declaration behavior of enterprises， and reduce communication divergences between the two parties.

ObjectiveTo construct and validate a clinical prediction model for inflammatory remission outcomes in rheumatoid arthritis （RA） patients with liver and kidney deficiency syndrome treated with Bushen Zhiwang Decoction （补肾治尪汤， BZD） based on metabolomics. MethodsA prospective cohort study was conducted， enrol-ling 60 RA patients with liver and kidney deficiency syndrome. All patients were treated with BZD and conventional-dose oral conventional synthetic disease-modifying antirheumatic drugs （csDMARDs） for 12 months. Clinical data were collected， and the change in disease activity score in 28 joints （DAS28） after treatment compared with baseline （△DAS28） was used as the primary outcome and grouping criterion. Peripheral blood samples were collected before treatment to analyze plasma metabolites. Differential analysis and least absolute shrinkage and selection operator （LASSO） regression were used to preliminarily screen differential metabolites， followed by machine learning algorithms to further identify a core metabolite combination. Based on the expression levels of the core metabolite combination， a novel metabolite index， namely the metabolomics-based inflammatory remission score （Met-IRS）， was calculated using standar-dized metabolite values， and its clinical applicability was evaluated. A clinical prediction model was constructed by integrating clinical characteristics and Met-IRS， and the model performance was assessed. ResultsAmong the 60 patients， those with △DAS28 ≥ 0.27 were assigned to the high inflammatory remission group， while those with △DAS28 ＜ 0.27 were assigned to the low inflammatory remission group， with 30 cases in each group. Compared to the low inflammatory remission group， the high inflammatory remission group showed a higher frequency of methotrexate use and a lower positive rate of rheumatoid factor （RF） （P＜0.05）. Seven core metabolites were identified as the optimal combination， including mangiferic acid， fatty acid-hydroxy fatty acid ester 40∶6， fatty acid-hydroxy fatty acid ester 18∶0， fatty acid-hydroxy fatty acid ester 36∶1， glucosylceramide， lysophosphatidylcholine 22∶5， and pregnanetriol ketone. The calculated Met-IRS comprehensively reflected the characteristics of differential metabolites and demonstrated clinical applicability. Met-IRS was significantly higher in the high inflammatory remission group than in the low inflammatory remission group， and was positively correlated with high inflammatory remission outcomes （P＜0.05）. Based on the variables Met-IRS， methotrexate use， leflunomide use， and RF positivity， a clinical prediction model for inflammatory remission in RA treatment （Cj-RTRM） was constructed. Model performance evaluation demonstrated that the model had good clinical predictive ability， with an area under the receiver operating characteristic curve （AUC） of 0.880， sensitivity 0.967， specificity 0.700 and Youden's index 0.667. ConclusionThe clinical prediction model Cj-RTRM constructed based on the metabolomics-based inflammatory remission score Met-IRS can effectively predict clinical inflammatory remission outcomes in RA patients treated with BZD and accurately identify the advantageous population for this treatment. This model provides guiding evidence for dynamic inflammation monitoring， targeted management， and identification of populations with advantages in traditional Chinese medicine.

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

Objective To investigate the clinical characteristics and research progress of the patients with pregnancy complicating paroxysmal nocturnal hemoglobinuria(PNH).Methods The clinical data of 10 case-times of pregnancy complicating PNH admitted and treated in the Third Affiliated Hospital of Guang-zhou Medical University from September 2009 to January 2023 were retrospectively analyzed."Paroxysmal nocturnal hemoglobinuria"and"pregnancy"served as the English keywords,the literatures included in PubMed were retrieved."paroxysmal nocturnal hemoglobinuria"and"pregnancy"served as the Chinese key-words,the literatures included in CNKI and Wan Fang Databases from January 1986 to December 2022 were retrieved.The clinical characteristics,pregnancy diagnosis and treatment,and pregnancy outcome of together 43 case-times pregnancies complicating with PNH in 10 case-times by retrospective analysis and 33 case-times by retrieval report were analyzed by descriptive statistic method.Results Among 43 case-times of pregnancy,the common clinical symptoms had 29 case-times of anemia(67.44％),17 case-times of thrombocytopenia(39.53％),15 case-times of soy sauce color urine(34.88％),6 case-times of fatigue(13.95％),5 case-times of abdominal pain(11.63％),8 case-times of thrombosis(18.60％)during pregnancy and childbirth and 10 cases of complicating preeclampsia(23.25％).There were 31 case-times(72.09％)of red blood cell transfusions and 11 case-times(30.23％)of platelet transfusions;19 case-times(48.83％)of glucocorticoids use and 25 case-times(46.51％)of low molecular weight heparin(LMWH)use.There were 11 case-times(25.58％)of fetal growth restriction,17 case-times of premature delivery(39.53％),in which 6 case-times(28-33+6 weeks)of early stage premature delivery,the early premature delivery rate was 13.95％,there were 11 case-times of late premature delivery(34-36+6 weeks),the rate of late premature delivery was 25.58％.There were 3 case-times(6.97％)of stillbirth.Conclusion The incidence rate of mother and infant complications and adverse outcomes in the patients with pregnancy complicating PNH is high,which should be jointly man-aged by the doctors in hematology department and obstetric doctors with the experience for treating high risk pregnancy in general hospitals.

Rheumatoid arthritis （RA） is an autoimmune disease characterized primarily by erosive arthritis， with a high prevalence and disability rate. Although significant progress has been made in the treatment of RA in recent years， challenges such as suboptimal efficacy， drug resistance， severe side effects， and high costs of long-term treatment remain， especially for patients in the early stages of RA， as well as those with RA complications， comorbidities， and severe conditions. Hosted by the China-Japan Friendship Hospital and organized by the Youth Committee of the China Association of Chinese Medicine， the 27^th session of the Clinical Dominant Disease Series （Rheumatoid Arthritis） Youth Salon invited nearly 20 experts and scholars from traditional Chinese medicine （TCM）， western medicine， and interdisciplinary fields to actively discuss the clinical needs of modern medicine and the advantageous stages and aspects of TCM in RA. Experts at the salon agreed that TCM has unique advantages in the treatment of RA， especially during the early stage， periods of low to moderate disease activity， remission phase， and in addressing complications and comorbidities. TCM can achieve both prevention and treatment by regulating the immune system and restoring immune homeostasis. The integrated approach of traditional Chinese and western medicine demonstrates significant advantages in active RA， refractory cases， and stages with severe complications， by rapidly controlling disease progression， alleviating symptoms， enhancing the quality of life， and facilitating recovery. Given the frequent occurrence of multiple comorbidities in RA， TCM shows potential in regulating immunity， alleviating symptoms， and improving physical constitution， which provides new insights into the comprehensive treatment of RA with comorbidities. However， high-quality clinical studies on integrated traditional Chinese and western medicine in RA are still lacking. It is necessary to establish large-scale clinical cohorts and biological databases to provide a scientific basis for the development of precision-targeted therapies and clinical treatment protocols. In the future， individualized treatment strategies integrating traditional Chinese and western medicine are expected to become an important direction for improving the quality of life in RA patients.

Systemic lupus erythematosus （SLE）， a refractory autoimmune disease， is among the dominant diseases where traditional Chinese medicine （TCM） shows advantages in the field of rheumatology and immunology. The China-Japan Friendship Hospital hosted the "46^th Youth Salon on Dominant Diseases （Systemic Lupus Erythematosus）" organized by the China Association of Chinese Medicine， which led to a consensus on "the advantages， challenges， interdisciplinary approaches， and translational achievements of integrated TCM and Western medical approaches in the diagnosis and treatment of SLE." The diagnosis and treatment of SLE currently face several challenges， such as frequent misdiagnosis and missed diagnosis in the early stages， difficulty in achieving treatment targets， multiple side effects from pharmacotherapy， and the lack of management strategies for special populations， all of which hinder the fulfillment of the clinical needs of patients. Integrated TCM and Western medical approaches can improve clinical symptoms such as skin erythema， aversion to cold and cold limbs， fatigue， dry mouth， restlessness， and heat sensation in the palms and soles， thereby improving patients' quality of life. The approaches also help consolidate the efficacy of conventional Western medicine， slow disease progression， reduce relapse rates， address multi-organ involvement， and prevent or treat complications. Additionally， they enhance efficacy and reduce toxicity， prevent the side effects of Western medications， help reduce hormone use， and offer distinct advantages in the individualized intervention of special populations， contributing to the whole-process management of the disease. However， evidence-based medical support for this integrated approach remains limited， and the quality of available evidence is generally low. Common evaluation systems and modern research methodologies should be adopted to clarify the efficacy of TCM in SLE treatment. Efforts should be made to carry out high-quality evidence-based medical research， strengthen the development of fundamental and pharmacological research， and further explain the distinct advantages of TCM in the diagnosis and treatment of SLE. Future efforts should focus on advancing the integration of TCM and modern medicine， incorporating multi-omics technologies， individualized stratification， and other precision medicine concepts， in combination with artificial intelligence. Moreover， interdisciplinary collaboration should be promoted to utilize modern technology in exploring the essence of TCM theories and screening effective formulae， thereby comprehensively improving the diagnosis and treatment of SLE through integrated TCM and Western medical approaches.

Systemic lupus erythematosus （SLE）， a refractory autoimmune disease， is among the dominant diseases where traditional Chinese medicine （TCM） shows advantages in the field of rheumatology and immunology. The China-Japan Friendship Hospital hosted the "46^th Youth Salon on Dominant Diseases （Systemic Lupus Erythematosus）" organized by the China Association of Chinese Medicine， which led to a consensus on "the advantages， challenges， interdisciplinary approaches， and translational achievements of integrated TCM and Western medical approaches in the diagnosis and treatment of SLE." The diagnosis and treatment of SLE currently face several challenges， such as frequent misdiagnosis and missed diagnosis in the early stages， difficulty in achieving treatment targets， multiple side effects from pharmacotherapy， and the lack of management strategies for special populations， all of which hinder the fulfillment of the clinical needs of patients. Integrated TCM and Western medical approaches can improve clinical symptoms such as skin erythema， aversion to cold and cold limbs， fatigue， dry mouth， restlessness， and heat sensation in the palms and soles， thereby improving patients' quality of life. The approaches also help consolidate the efficacy of conventional Western medicine， slow disease progression， reduce relapse rates， address multi-organ involvement， and prevent or treat complications. Additionally， they enhance efficacy and reduce toxicity， prevent the side effects of Western medications， help reduce hormone use， and offer distinct advantages in the individualized intervention of special populations， contributing to the whole-process management of the disease. However， evidence-based medical support for this integrated approach remains limited， and the quality of available evidence is generally low. Common evaluation systems and modern research methodologies should be adopted to clarify the efficacy of TCM in SLE treatment. Efforts should be made to carry out high-quality evidence-based medical research， strengthen the development of fundamental and pharmacological research， and further explain the distinct advantages of TCM in the diagnosis and treatment of SLE. Future efforts should focus on advancing the integration of TCM and modern medicine， incorporating multi-omics technologies， individualized stratification， and other precision medicine concepts， in combination with artificial intelligence. Moreover， interdisciplinary collaboration should be promoted to utilize modern technology in exploring the essence of TCM theories and screening effective formulae， thereby comprehensively improving the diagnosis and treatment of SLE through integrated TCM and Western medical approaches.

Rheumatoid arthritis （RA） is an autoimmune disease characterized primarily by erosive arthritis， with a high prevalence and disability rate. Although significant progress has been made in the treatment of RA in recent years， challenges such as suboptimal efficacy， drug resistance， severe side effects， and high costs of long-term treatment remain， especially for patients in the early stages of RA， as well as those with RA complications， comorbidities， and severe conditions. Hosted by the China-Japan Friendship Hospital and organized by the Youth Committee of the China Association of Chinese Medicine， the 27^th session of the Clinical Dominant Disease Series （Rheumatoid Arthritis） Youth Salon invited nearly 20 experts and scholars from traditional Chinese medicine （TCM）， western medicine， and interdisciplinary fields to actively discuss the clinical needs of modern medicine and the advantageous stages and aspects of TCM in RA. Experts at the salon agreed that TCM has unique advantages in the treatment of RA， especially during the early stage， periods of low to moderate disease activity， remission phase， and in addressing complications and comorbidities. TCM can achieve both prevention and treatment by regulating the immune system and restoring immune homeostasis. The integrated approach of traditional Chinese and western medicine demonstrates significant advantages in active RA， refractory cases， and stages with severe complications， by rapidly controlling disease progression， alleviating symptoms， enhancing the quality of life， and facilitating recovery. Given the frequent occurrence of multiple comorbidities in RA， TCM shows potential in regulating immunity， alleviating symptoms， and improving physical constitution， which provides new insights into the comprehensive treatment of RA with comorbidities. However， high-quality clinical studies on integrated traditional Chinese and western medicine in RA are still lacking. It is necessary to establish large-scale clinical cohorts and biological databases to provide a scientific basis for the development of precision-targeted therapies and clinical treatment protocols. In the future， individualized treatment strategies integrating traditional Chinese and western medicine are expected to become an important direction for improving the quality of life in RA patients.

BACKGROUND:Non-traumatic necrosis of the femoral head is a difficult joint disease,and preserving one's own femoral head is of great significance for young patients.Currently,there is a lack of regular and unified functional exercise plans.OBJECTIVE:To investigate the effect of hip abductor muscle exercise on the three-dimensional gait and collapse rate of patients with non-traumatic femoral head necrosis,and to provide theoretical basis for effective rehabilitation of patients with non-traumatic femoral head necrosis.METHODS:Totally 81 non-traumatic and non-surgical patients with femoral head necrosis(81 hips)admitted to the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from June 2020 to June 2022 were included.Patients were randomly divided into a control group(n=40)and a hip abductor muscle exercise group(n=41).The control group received routine physical therapy and medication treatment.The hip abductor muscle exercise group underwent hip abductor muscle exercise on the basis of the control group.The gait status(hip joint range of motion,step length difference,and ground contact time difference)of two groups of patients was evaluated using the Tecnobody balance assessment system before and 12 weeks after treatment.The BIODEX-S4 isokinetic muscle strength testing system was used to test the peak force distance of hip abduction isokinetic muscle strength.Gluteus medius width ratio was compared between two groups.The collapse rate was compared between two groups of patients 1 year after treatment.RESULTS AND CONCLUSION:(1)There was no statistically significant difference between the hip abductor muscle exercise group and the control group in terms of age,gender,side profile,body mass index,and etiology(P＞0.05).(2)Before treatment,there was no significant statistical difference in the range of motion of the affected hip joint between the two groups(P＞0.05).After treatment,the range of motion of the affected hip joint in both groups improved compared to before treatment(P＜0.05),and the range of motion of the affected hip joint in the hip abductor muscle exercise group was significantly higher than that in the control group(P＜0.05).(3)Before treatment,there was no significant statistical difference in the step length and touchdown time between the two groups(P＞0.05).12 weeks after treatment,the difference in step length and touchdown time between the two groups decreased compared to before treatment(P＜0.05),and the difference in step length and touchdown time between the hip abductor muscle exercise group after treatment was significantly greater than that of the control group(P＜0.05).(4)Before treatment,there was no significant statistical difference in gluteus medius width ratio between the two groups(P＞0.05).12 weeks after treatment,the gluteus medius width ratio of both groups increased compared to that before treatment(P＜0.05),and the gluteus medius width ratio of the hip abductor muscle exercise group was significantly higher than that of the control group(P＜0.05).(5)At 1 year after treatment,the comparison of femoral head collapse rates between the two groups showed significant statistical significance(P＜0.05),and that in the hip abductor muscle exercise group(22％)was significantly lower than that in the control group(45％).(6)It is concluded that exercise of the hip abductor muscle effectively enhances hip joint function,improves gait,and reduces the rate of femoral head collapse in patients with non-traumatic femoral head necrosis.It is recommended to use hip abductor muscle exercise as one of the basic methods for hip preservation in non-traumatic femoral head necrosis.

Objective:To evaluate the epidemiological characteristics and influencing factors of out-of-hospital sudden cardiac death (SCD) in Hangzhou from 2016 to 2019.Methods:SCD events recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019 were reviewed. Demographic and mortality data were recorded, and the distribution patterns of SCD events in terms of date, time, and population with different characteristics were observed. Time series analysis method and a distributed lag nonlinear model based on quasi-Poisson distribution were used to explore the possible nonlinear association between ambient temperature and SCD incidence.Results:A total of 4 744 out-of-hospital sudden death events were recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019. After excluding non-SCD events and observed events with missing items, 3 743 SCD events were finally included in the study. The survey results showed that the incidence of out-of-hospital SCD in Hangzhou was 96.5 cases per 100 000 person-years. Most of the people who experienced SCD were aged ≥60 years. The incidence in males (2 462 cases, 66%) was significantly higher than that in females (1 281 cases, 34%), and the proportion of events occurring during the day (2 737 cases, 73%) was significantly higher than that at night (1 006 cases, 27%), mainly occurring between 7: 00 and 9: 00. High temperature was associated with an increased risk of SCD. When the average daily temperature was higher than 25.5 ℃, the risk of SCD increased with the further increase of average daily temperature.Conclusions:SCD events mainly occur in the elderly population aged ≥60 years, with a significantly higher incidence in males than in females, and more frequently during the day than at night, mainly between 7: 00 and 9: 00 in the morning. High temperature is closely related to the risk of SCD. It is particularly important to carry out targeted SCD screening and prevention for different populations and implement appropriate prevention strategies for high-risk groups of SCD in high-temperature weather.