ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo explore the effects of the Tai Chi training on bone density， bone turnover markers， and heart rate variability for people with high-risk osteoporosis， and to provide evidence for the prevention of osteoporosis at early stage. MethodsSixty-six cases of people with high risk of osteoporosis were included， and they were divided into 33 cases each in the intervention group and the control group using the random number table method. The control group received osteoporosis health education three times a week， and the intervention group received Tai Chi training under the guidance of a trainer three times a week for 40 mins each time on the basis of the control group， and both groups were intervened for 12 weeks. Dual-energy X-ray absorptiometry was used to measure the bone density of L₁~L₄ vertebrae， bilateral femoral necks and bilateral total hips in the two groups before and after the intervention； enzyme-linked immunosorbent assay was used to determine bone turnover markers before and after the intervention， including pro-collagen type Ⅰ pro-amino-terminal prepropyl peptide （P1NP） and β-collagen type Ⅰ cross-linking carboxy-terminal peptide （β-CTX）. Seven cases with good compliance in the intervention group were selected. After wearing the heart rate sensor， they successively performed Tai Chi training and walking activities recommended by the guideline for 20 mins each， and the heart rate variability （HRV） during exercise was collected， including time-domain indexes such as standard deviation of normal sinus intervals （SDNN）， root-mean-square of the difference between adjacent RR intervals （RMSSD）， frequency-domain metrics such as low-frequency power （LF）， high-frequency power （HF）， and low-frequency/high-frequency power ratio （LF/HF）， as well as nonlinear metrics such as approximate entropy （ApEn）， sample entropy （SampEn）. ResultsFinally， 63 cases were included in the outcome analysis， including 30 cases in the intervention group and 33 cases in the control group. After the intervention， the differences of L₁~L₄ vertebrae， bone density of bilateral femoral neck and bilateral total hip in the intervention group were not statistically significant when compared with those before intervention （P＞0.05）， while the bone density of all parts of the control group decreased significantly compared with that before intervention （P＜0.05）， and the difference in the bone density of the L₁~L₄ vertebrae， bilateral femoral neck， and the right total hip before and after the intervention of the intervention group was smaller than that of the control group （P＜0.05）. The differences in P1NP and β-CTX between groups before and after intervention was not statistically significant （P＞0.05）. Compared with walking exercise， LF decreased， HF increased and LF/HF decreased during Tai Chi exercise （P＜0.05）； the time domain indexes and non-linear indexes between groups had no statistically significant difference （P＞0.05）. ConclusionTai Chi exercise can maintain lumbar， hip， and femoral bone density and improve sympathetic/parasympathetic balance in people at high risk for osteoporosis， but cannot significantly improve bone turnover markers.

ObjectiveTo investigate the differences in clinical efficacy of different medication regimens of Wangbi Tablets （尪痹片） for knee osteoarthritis （KOA） in a real-world setting， providing a basis for rational clinical use of Wangbi Tablets. MethodsA prospective registry study was conducted， involving 2，999 KOA patients registered in 30 hospitals nationwide from January 26th， 2019， to December 17th， 2021. Based on the use of Wangbi Tablets during the observation period， patients were divided into a monotherapy group （1，507 cases） and a combination therapy group （1，492 cases）， and the combination group can be further divided into Wangbi Tablets plus Chinese medicine （CM）， Wangbi Tablets plus western medicine （WM）， and Wangbi Tablets plus Chinese and western medicine （CM+WM） subgroups. The baseline data of patients in the monotherapy group and the combination group were compared， including age， gender， body weight， medication time， clinical stage， K-L grade， and others. Efficacy indicators included the Visual Analog Scale （VAS） score， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） score， and EuroQol five-dimensional （EQ-5D） health index， which were evaluated before and after 4-， 8- and 12-week treatment， and the difference before and after treatment was calculated after 4， 8 and 12 weeks of treatment. The difference between the baseline and 12 weeks of treatment of all the above indicators was used as the dependent variables， and gender， age， body mass index （BMI）， course of disease， K-L grade， and clinical stage were used as independent variables， when multiple linear regression was taken to explore the influencing factors of the efficacy. At the same time， the occurrence of major symptoms （including morning stiffness， joint swelling， soreness of waist and knees， fear of wind， and fear of cold） was counted， and the disappearance of symptoms at each time point was counted after 4， 8， and 12 weeks of treatment. ResultsAt baseline， there were no statistically significant differences in gender and age distribution between the monotherapy and combination therapy groups （P＞0.05）； the proportion of patients in the acute stage and recovery stage was higher in the monotherapy group than in the combination therapy group， while the proportion in the remission stage was lower （P＜0.05）； the VAS score was higher in the monotherapy group， and the EQ-5D index was lower （P＜0.01）， with no statistically significant difference in total WOMAC score between the two groups （P＞0.05）. Compared to those measured before treatment and at previous timepoint， the VAS score and WOMAC total score significantly decreased in both groups， while EQ-5D value increased （P＜0.05）. The difference in VAS score between baseline and after 12-week treatment was higher in the monotherapy group than the combination group， while the differences in WOMAC total score and EQ-5D value between baseline and after 4-， 8- and 12-week treatment were higher in the combination group （P＜0.05）. Multiple linear regression showed that VAS score before treatment had greatest impact on pain improvement （P＜0.01）， and compared to Wangbi Tablets monotherapy， the combination of Wangbi tablets with WM or CM had larger associations with pain improvement （P＜0.05）； and Wangbi Tablets had better efficacy when the course of treatment was ＞28 days （P＜0.01）. Wangbi Tablets plus WM had a better effect on improving the overall function of the knee joint than Wangbi Tablets alone （P＜0.01）； and the efficacy of Wangbi Tablets with a course of treatment ＞28 days was better （P＜0.05）. The improvement of quality of life of patients in the attack and remission stages was more obvious than that in the recovery stage （P＜0.01）； Wangbi Tablets plus WM or CM had a better effect on improving quality of life than Wangbi Tablets alone （P＜0.05）. Before treatment， the proportion of patients with morning stiffness， soreness of waist and knees， fear of wind and chills in the monotherapy group was higher than that in the combination group （P＜0.01）. The proportion of main symptoms in both groups decreased after 4， 8 and 12 weeks of treatment （P＜0.05）. After 4 weeks of treatment， the disappearance rate of each main symptom in the combination group was higher than that in the monotherapy group， and after 12 weeks of treatment， the disappearance rate of fear of wind in the monotherapy group was higher than that in the combination group， while the disappearance rate of joint swelling and soreness of waist and knees was lower （P＜0.05）. ConclusionWangbi Tablets， whether used alone or in combination with other medications， is effective throughout the course of KOA， with greater benefits in improving joint function and quality of life during the acute and remission stages compared to the recovery stage. Combination therapy had a faster onset of effect， but began to converge with monotherapy after 8 weeks. The best efficacy was observed with the combination of Wangbi Tablets with WM， followed by combination with CM.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

OBJECTIVE:The rabbit model of steroid-induced osteonecrosis of femoral head is the most commonly used animal model of femoral head necrosis.The pathological changes of the femoral head are close to clinical practice,however,the conditions,methods and evaluation standards of animal models reported in and outside China are not uniform,which leads to the low scientific value of animal models and is difficult to popularize.This study aimed to clarify the influence of different mold-making conditions on the establishment of steroid-induced osteonecrosis of femoral head rabbit model and analyze the appropriate conditions for the successful model establishment. METHODS:We searched the CNKI,WanFang,VIP,CBM,WoS,PubMed and EMbsae databases for the literature on the modeling of steroid-induced osteonecrosis of femoral head rabbits up to April 1,2022,completed the screening of the literature according to the inclusion and exclusion criteria and literature quality evaluation,and extracted the outcome index data in the literature.RevMan Stata and ADDIS statistical software were used to conduct a meta-analysis of the included data. RESULTS:(1)A total of 82 articles with 1 366 rabbits were included in the study.The steroid-induced osteonecrosis of femoral head modeling methods were divided into three types:steroid-alone method,steroid combined lipopolysaccharide method and steroid combined serum method.Among these,33 articles used steroid-alone method;20 articles used steroid combined lipopolysaccharide method;29 articles used steroid combined serum method.(2)Meta-analysis results showed that the three modeling methods significantly increased the rate of empty bone lacunae in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001),and significantly decreased the ratio of the trabecular bone area in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001).The order of empty bone lacunae rate of each modeling method was:steroid combined with lipopolysaccharide method>steroid-alone method>steroid combined with serum method>normal group,and the order of trabecular bone area rate of each modeling method was:normal group>steroid combined with serum method>steroid-alone method>steroid combined with lipopolysaccharide method.(3)The results of subgroup analysis suggested that the rate of empty bone lacunae in the rabbit model induced by steroid alone might be related to the rabbit variety and the type of steroid used for modeling(difference between groups P<0.05),in which the combined effect amount of New Zealand white rabbits was higher than that of Chinese white rabbits(P<0.05)and Japanese white rabbits,and the combined effect amount of dexamethasone was higher than that of other steroids.The rate of empty bone lacunae induced by steroid combined with lipopolysaccharide was related to the administration mode of lipopolysaccharide and the type of steroid(P<0.05),among which the combined effect of methylprednisolone sodium succinate was significantly higher than that of other steroids(P<0.05),and the combined effect of prednisolone was significantly lower than that of other steroids(P<0.05).The combined effect of lipopolysaccharide 100 μg/kg×twice was significantly lower than 10 μg/kg×twice and 50 μg/kg×twice(P<0.05).The rate of empty bone lacunae in the model induced by steroid combined with serum was related to serum dose and steroid type(P<0.05),among which the combined effect amount of dexamethasone sodium phosphate was significantly higher than other steroid types(P<0.05),and the combined effect amount of dexamethasone was significantly lower than other steroid types(P<0.05);the combined effect amount of serum"10 mL/kg+6 mL/kg"combined dose was lower than other serum doses(P<0.05). CONCLUSION:(1)With the rate of empty bone lacunae and the ratio of trabecular bone area as the judgment standard for the successful establishment of the model,the three modeling methods can successfully construct the rabbit steroid-induced osteonecrosis of femoral head model,of which the steroid combined with lipopolysaccharide method is the best.(2)New Zealand white rabbits and dexamethasone are recommended when selecting the steroid-alone method.Methylprednisolone sodium succinate and low-dose lipopolysaccharide are recommended when selecting the steroid combined with lipopolysaccharide method.Dexamethasone sodium phosphate is recommended when selecting the steroid combined with serum modeling method.

Objective To analyze the characteristics of pattern elements and the distribution of patterns of femoral head necrosis, hip osteoarthritis, and hip rheumatoid arthritis, in order to provide a theoretical basis for the "different diseases with the same pattern" of chronic bone diseases. Methods A cross-sectional survey was conducted to select patients with femoral head necrosis Association Research Circulation Osseous Ⅰ-Ⅱ stages, hip osteoarthritis Kellgren & Lawrence Ⅰ-Ⅱ stages, and acute or subacute hip rheumatoid arthritis who visited the Minimally Invasive Arthrology Department, Traumatology Department, and Rheumatology and Immunology Department of Beijing University of Chinese Medicine Third Affiliated Hospital from June 2020 to June 2022. The " case report form - traditional Chinese medicine pattern manifestation scale" previously developed by our team was used to collect the pattern manifestations, which were included into an Excel 2020 spreadsheet to establish a database. SPSS 20.0 software was used for factor analysis and cluster analysis to extract pattern element information, such as disease nature and location, in order to summarize the characteristics of pattern elements, the distribution of patterns, and the similarities and differences of the three kinds of early hip joint diseases.Results A total of 410 patients were included, including 150 patients with femoral head necrosis, 160 patients with hip osteoarthritis, and 100 patients with hip rheumatoid arthritis. The pattern elements of the disease nature of femoral head necrosis include phlegm (dampness), blood stasis, yang deficiency, essence deficiency, and qi deficiency. The pattern types were initially divided into four categories: syndrome of meridian obstruction (43.33％), syndrome of phlegm and blood stasis blocking collaterals (38.00％), syndrome of liver and kidney deficiency (12.00％), and syndrome of kidney essence deficiency (6.67％). The pattern elements of the disease nature of hip osteoarthritis include phlegm (dampness), blood stasis, qi deficiency, essence deficiency, yang deficiency, and cold (dampness). The pattern types were preliminarily divided into five categories: syndrome of spleen and kidney deficiency (37.50％), syndrome of meridian obstruction (26.87％), syndrome of cold and dampness obstruction (18.75％), syndrome of phlegm and blood stasis obstruction (9.38％), and syndrome of liver and kidney deficiency (7.50％). The pattern elements of the disease nature of hip rheumatoid arthritis include phlegm (dampness), blood stasis, qi deficiency, yin and yang deficiency, cold (dampness), and essence deficiency. The pattern types were preliminarily divided into four categories: syndrome of phlegm and blood stasis obstruction (34.00％), syndrome of cold and dampness obstruction (28.00％), syndrome of blood stasis blocking collaterals (23.00％), and syndrome of liver and kidney deficiency (15.00％). Overall, the top five pattern manifestations of the three kinds of hip joint diseases were hip joint pain (96.59％), tenderness (93.90％), fixed pain (87.56％), heavy joints (85.37％), and sourness of lower limbs (75.37％). The pattern elements of the disease nature include phlegm (dampness), blood stasis, qi deficiency, etc. The pattern types were preliminarily divided into five categories: syndrome of phlegm stasis blocking collaterals (33.17％), syndrome of meridian obstruction (31.95％), syndrome of cold dampness obstruction (21.46％), syndrome of liver and kidney deficiency (7.32％), and syndrome of spleen and kidney deficiency (6.10％). There were 21 similar pattern manifestations in the three kinds of early hip joint diseases, with blood stasis and spleen deficiency being the main pattern.Conclusion The common pattern characteristics of three kinds of early hip joint diseases are spleen deficiency and blood stasis. In addition, femoral head necrosis is accompanied with phlegm-dampness pattern, hip osteoarthritis is accompanied with kidney deficiency and phlegm-dampness pattern, hip rheumatoid arthritis is accompanied with kidney deficiency and cold-dampness pattern.

ObjectiveTo explore the medication characteristics and clinical efficacy of the Tenghuang Jiangu tablets in the treatment of knee osteoarthritis （KOA） in the remission stage in the real world，providing references for rational clinical use of this prescription. MethodBased on the "registration system of KOA treated with Tenghuang Jiangu tablets"，2 439 KOA cases in the remission stage were analyzed by SPSS 25.0，IBM SPSS Modeler18.0，and Apriori algorithm. To be specific，the age，body mass index （BMI），and course of treatment were described in the form of x̄±s. The information on gender，K-L grade，daily dose，and frequency of drug use was described by frequency analysis. The number of cases，course of treatment，daily dose，and drug use frequency of the single-use group and the combined-use group were described by frequency analysis，and the combination of drugs was described by frequency analysis and Apriori algorithm. Mann-Whitney U test was employed to compare the scores of Visual Analogue Scale （VAS），Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC），pain，stiffness，and joint function between the single-use group and the combined-use group. ResultThe results of clinical treatment showed that 2 439 patients with KOA in the remission stage were treated with Tenghuang Jiangu tablets，with 1 432 （58.71%） in the single-use group and 1 007 （41.29%） in the combined-use group. The average daily dose of Tenghuang Jiangu tablets was （3.90±1.44） g，and the majority of the patients were at grade Ⅱ （54.47%）. The daily average daily dose of Tenghuang Jiangu tablets in the single-use group was （3.64±1.35） g，which was lower than that in the combined-use group ［（4.26±1.48） g，P<0.05］. In the combined use，the top three western medicines were glucosamine （270 times，14.68%），sodium hyaluronate （126 times，6.85%），and imrecoxib （116 times，6.31%），and the top three Chinese medicines were Huoxuezhitong capsules/tablets/ointments （31 times，1.69%），Biqi capsules （25 times，1.36%），and Maizhiling （23 times，1.25%）. As for the overall clinical efficacy，the VAS score was （5.13±0.93） score before treatment and （2.22±1.18） score after treatment （P<0.05），with an overall average decrease of （2.91±1.14） score， and the average decrease in the single-use group was （2.76±1.43） score， which was lower than that in the combined-use group ［（3.12±1.36） score，（P<0.01）］. The WOMAC score was （31.05±11.84） score before treatment and （13.55±9.91） score after treatment （P<0.05）. The overall average decrease was （17.50±11.79） score， and the average decrease in the single-use group and combined-use group was （16.39±11.14） score and （19.08±12.50） score，respectively （P<0.01）. The patients with KOA>grade Ⅱ accounted for 91.34%（1 308/1 432） and 93.55%（942/1 007） in the single-use group and combined-use group，respectively （χ²=80.026，P<0.05）. A total of 43.37%（621/1 432） of the patients in the single-use group had other complications，lower than that in the combined-use group ［54.92%（553/1 432），（χ²=20.087，P<0.01）］. ConclusionMore than half of the patients with KOA in the remission stage are treated with Tenghuang Jiangu tablets alone，and the combination therapy is mainly applied in patients with severe conditions or other complications. In relieving knee joint pain and improving joint stiffness and joint function，both the Tenghuang Jiangu tablets alone and the combination therapy are effective.

ObjectiveTo investigate the clinical efficacy and mechanisms of Osteoking in the treatment of knee osteoarthritis （KOA） in real-world practice， so as to provide a basis for the rational clinical use of Osteoking. MethodFrom the Osteoking for knee osteoarthritis case registration system， 638 KOA cases treated with Osteoking were selected and analyzed in SPSS 26.0. The clinical data were collected from 20 hospitals in China from May 2020 to December 2021. Descriptive analyses of patient age， gender， body mass index， course of treatment and other parameters were performed. The Mann-Whitney U test was performed to compare the visual analogue scale （VAS） and Western Ontario and McMaster universities arthritis index （WOMAC） scores before and after treatment. The integrative pharmacology-based research platform of traditional Chinese medicine （TCMIP） v2.0 was used for network analysis of the core targets of Osteoking in treating knee osteoarthritis. Furthermore， 20 KOA patients treated with Osteoking in the Third Affiliated Hospital of Beijing University of Chinese Medicine from October to December in 2022 were enrolled in the treatment group， and 20 healthy volunteers in the control group. The enzyme-linked immunosorbent assay was employed to measure the serum levels of related indicators to verify the prediction results. ResultA total of 638 KOA patients were treated with Osteoking， including 429 （67.24%） receiving Osteoking alone and 209 （32.76%） receiving Osteoking combined with other therapies. The female patients （415， 65.05%） were more than the male patients （223， 34.95%）. The patients showed the mean age of （63.48±13.51） years， mean body mass index of （24.09±2.98） kg·m^-2， and mean course of treatment of （15.78±9.66） days. Most of the patients were rated as grades Ⅱ （46.24%） and Ⅲ （34.64%） in Kellgren-Lawrence （K-L） grading and in the relief stage （82.45%） in clinical staging. There was no significant correlation between clinical staging and K-L grading results. The cluster analysis identified three TCM syndromes： Qi stagnation and blood stasis， cold-dampness obstruction， and liver-kidney deficiency. The overall clinical efficacy evaluation showed that VAS score decreased from （6.01±0.85） scores before treatment to （2.54±1.73） scores after treatment （P<0.05）， and the WOMAC score decreased from （93.25±25.91） scores before treatment to （50.73±25.14） scores after treatment （P<0.05）. The network analysis predicted that Osteoking might regulate the transforming growth factor-beta （TGF-β）， tumor necrosis factor-alpha （TNF-α）， and nuclear factor-kappa B （NF-κB） signaling pathways to exert the therapeutic effect. The clinical trial showed elevated TGF-β₁ level （P<0.01） and lowered NF-κB subunit RELA and tumor necrosis factor receptor superfamily， member 1A （TNFRSF1A） levels （P<0.05） after treatment. The synergistic effects of these changes provide a multidimensional and comprehensive therapeutic efficacy for KOA， alleviating the joint pain and limited mobility in patients. ConclusionOsteoking showed significant therapeutic efficacy in treating KOA. Osteoking may act on multiple pathways involved in cartilage metabolism and inflammation. The findings provide experimental evidence and theoretical support for elucidating the multi-target mechanism of Osteoking in treating KOA.

ObjectiveTo investigate the improvement of the efficacy of Osteoking in patients with knee osteoarthritis in the onset and remission stage and to systematically explore its potential intervention mechanism， so as to provide a certain reference for improving the clinical application value of Osteoking and guiding its clinical rational drug use. MethodThrough the real-world study of the treatment of knee osteoarthritis with Osteoking， the data was obtained and entered into the "Osteoking for the treatment of knee osteoarthritis case registration system"， and 105 patients with episodic and remission knee osteoarthritis from the outpatient or inpatient orthopedic department of 20 medical institutions， including the Third Affiliated Hospital of Beijing University of Chinese Medicine， Peking Union Medical College Hospital， Wangjing Hospital of the Chinese Academy of Chinese Medical Sciences and Hunan Aerospace Hospital， from May 1， 2020 to December 31， 2021， were selected in the system. It included 60 patients treated with Osteoking and joint injection， and 45 patients treated with joint injection alone. The WOMAC osteoarthritis index score， visual analogue （VAS） pain score， individual types of pain symptoms （cold pain， hot pain， tingling， dull pain， soreness） and other TCM symptoms were observed and compared between the two groups， and statistically analyzed. In order to further elucidate the potential molecular mechanism of Osteoking combined with joint injection in the treatment of knee osteoarthritis in the treatment of onset and remission， this study used the "Bone Injury Cross Database （http：//bone-xtrans.com/database，BX-Data）" to collect the gene set of knee osteoarthritis disease， the traditional Chinese medicinal materials， chemical composition， material base， candidate target， candidate target， sodium hyaluronate candidate target data for screening， and constructed an interaction network of "disease target". ResultsAmong the 105 patients with knee osteoarthritis enrolled， 15.24% （16/105） were in the episodic period， 84.76% （89/105） were in remission， and there were no convalescent patients. There were 72 cases （68.57%） in women， 33 cases （31.43%） more than men， 60 cases in the observation group and 45 cases in the control group in 105 patients. There were 20 patients with a VAS score of 5 and 19 patients with a score of 6 in the observation group， accounting for 65.00% of the observation group. The comparative results of VAS scores between groups before and after treatment showed that the scores of the two groups were （4.42±1.01） scores， （5.00±1.02） scores.4 weeks after treatment， and （3.12±1.04） scores and （3.56±1.08） scores，8 weeks after treatment， respectively， which were lower than those before treatment （6.23±1.28） scores，（ 6.02±1.22） scores （P<0.05）， and the comparative results of the pain properties of the two groups showed that the improvement rates before and after thermal pain and tingling in the observation group were 3.3%（2/60） and 16.7%（10/60）， respectively. The control group was 2.2% （1/45）and 15.6%（7/45）［（χ²=4.034、13.583，P<0.05）］， respectively， and the improvement rate of cold pain and soreness in the observation group was 5.0%（3/60） and 3.3%（2/60）， which was higher than that of the control group . The results of comparing the WOMAC scores before and after treatment of the two groups showed that the difference between the stiffness score before and after treatment in the observation group was （1.68±1.42） scores， the difference between the score before and after treatment in the control group was （1.20±1.60） scores （P<0.05）， and the pain score before and after treatment was （3.43±2.88） scores， the difference before and after daily activity score was （12.37±10.21） scores， and the total score before and after treatment was （17.48±12.76） scores， which were also higher than those in the control group （2.82±3.29）， （10.80±9.63），（14.82±12.62） scores. The results of comparing the improvement of other symptoms before and after treatment showed that the improvement rate of less sleep and more dreams in the observation group was 28.3%（17/60）， which was significantly higher than that of the control group of 2.2%（1/45）（χ²=5.914，P<0.05）， and the improvement rates of the five symptoms of thirst and drinking， irritability， dry mouth and pharynx， dull complexion and hand， foot and mouth fever in the observation group were 3.3%（2/60）， 10.0%（6/60）， 8.3%（5/60）， 10.0%（6/60） and 5.0%（3/60）， respectively， which were higher than those in the control group -2.2%（1/45）， 2.2%（1/45）， 2.2%（1/45）， 4.5%（2/45）， -6.7%（3/45）. Through network analysis， it was found that the enrichment pathway of Henggu bone wound healing agent mainly acted on the three mechanisms of bone improvement， energy metabolism and anti-inflammatory and analgesic， and the sodium hyaluronate enrichment pathway mainly acted on the anti-inflammatory and analgesic mechanism. ConclusionThe efficacy of Osteoking combined with intra-articular injection of sodium hyaluronate in the treatment of patients with knee osteoarthritis in attack and remission is better than that of sodium hyaluronate alone， especially in anti-inflammatory and analgesic， and the two drugs have synergistic effect. Osteoking may play its role in relieving the symptoms of joint stiffness， tingling， heat pain， and less sleep and more dreams by improving bone quality and regulating the body's energy metabolism pathways， which is worthy of clinical promotion.