1.Detoxification Strategies of Triptolide: A Review
Wenchen WANG ; Ming CHEN ; Shuangjie WU ; Zhenggen LIAO ; Wei DONG ; Xinli LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):278-287
Tripterygium wilfordii is a traditional Chinese medicinal herb belonging to the genus Tripterygium in the Celastraceae family, which has the effects of clearing heat and detoxifying, dispelling wind and dampness, and invigorating blood circulation to relieve pain, and is used to treat diseases such as rheumatoid arthritis, glomerulonephritis, nephrotic syndrome, lupus erythematosus, scabies, and stubborn tinea. Its chemical composition is diverse. Among them, triptolide(TP) is one of the main active and toxic components of T. wilfordii. It has significant biological activities such as anti-inflammation, anti-tumor, and immunosuppression. However, it causes serious adverse reactions such as liver and kidney function damage and reproductive system disorders. At the same time, TP has poor water solubility and low bioavailability, and the enhancement of bioavailability by increasing the dosage undoubtedly improves the exposure of the drug in non-target organs, leading to the occurrence of adverse reactions, and these largely limit the clinical application of TP. Based on this, this article extracted relevant data from the Web of Science, PubMed, and China National Knowledge Infrastructure(CNKI) databases, summarized the research on the adverse reactions of TP in recent years, and reviewed the progress of toxicity reduction research from the perspectives of structural modification, novel drug delivery systems, and compatibility. Structural modification can precisely alter the chemical structure of TP, reduce the activity of its toxic groups, and retain its biological activity while fundamentally reducing the occurrence of adverse reactions. New drug delivery systems can achieve targeted delivery of TP, increase its concentration in target organs, and reduce its exposure in non-target organs, thereby enhancing therapeutic efficacy and reducing adverse effects. In addition, the combination of TP with Chinese medicine compound, single-flavored Chinese medicine or monomer can reduce the adverse effects of TP and enhance the efficacy to different degrees, which is of clinical value. This paper systematically explains attenuation research from the above three perspectives, aiming to provide a theoretical basis for the full utilization of biological activity and drug development of TP.
2.Surveillance results of common diseases among primary and secondary school students in Yichang City in 2019 - 2022
Yi LIANG ; Zaoxia WANG ; Chi HU ; Xiaoyan MING ; Man XIAO ; Qian WU ; Zhongcheng YANG
Journal of Public Health and Preventive Medicine 2025;36(4):98-101
Objective To investigate the prevalence of common diseases among primary and secondary school students in Yichang City from 2019 to 2022, and to provide a scientific basis for formulating effective intervention measures in the future. Methods By random cluster sampling , 7 schools in urban areas and 5 schools in suburban counties were selected to screen common diseases such as myopia, dental caries, obesity and abnormal spinal curvature. Descriptive epidemiological methods were employed for statistical analysis. Results A total of 17 023 primary and secondary school students were screened from 2019 to 2022. The overall detection rate of common diseases from high to low was myopia (54.12%), caries (36.75%), overweight (15.17%), obesity (11.88%), malnutrition (5.80%), and abnormal spinal curvature (3.49%). The detection rates of myopia and abnormal curvature of the spine showed an increasing trend with years and school stages, while the detection rates of malnutrition and dental caries showed a decreasing trend with years and school stages. The detection rates of overweight and obesity showed no trend difference with years, and the detection rates of obesity showed a decreasing trend with school stages. The rates of myopia, overweight and obesity were higher in urban areas than those in suburban counties, and the rate of dental caries was higher in suburban counties than that in urban areas. The prevalence of overweight, obesity, and malnutrition in boys was higher than that in girls. The prevalence of myopia and dental caries in girls was higher than that in boys. The above differences were statistically significant (all P<0.05). Conclusion Myopia, dental caries, obesity, and abnormal curvature of the spine are the current focus of the prevention and treatment of common diseases in students. There are great differences between different regions, school stages, and genders. The “tripartite linkage” of schools, families, and communities should be achieved with the joint efforts of the education and health departments to actively take targeted intervention measures to reduce the prevalence.
3.Acupuncture regulates dynamic flux of Ca2+, Na+, and H2O2 in skeletal muscle injury induced by eccentric exercise in rats.
Xue-Lin ZHANG ; Qian ZHAO ; Ai-Shan LIU ; Ming-Liang DUAN ; Jing-Jing DING ; Hua WANG
Acta Physiologica Sinica 2025;77(1):47-61
This study aimed to investigate the effects of acupuncture on dynamic changes in Ca2+, Na+, and H2O2 flux following eccentric exercise-induced muscle injury. The total of 324 healthy male Wistar rats were randomly divided into 6 groups: control group (C), eccentric exercise group (E), eccentric exercise with acupuncture group (EA), EA with TRP channel blocker group (EAT), EA with NOX2 blocker group (EAN) and EA with placebo group (EAP). Gastrocnemius muscles were subject to lengthening contractions with percutaneous electrical stimulation, followed by immediate pretreatment with blocking agents. After 30 min, acupuncture needling was administered to the gastrocnemius muscle, and real-time dynamic changes of Ca2+, Na+ and H2O2 flux were measured with non-invasive micro-test technique during the needle retention period, immediately, 3 h, 6 h, and 24 h post-extraction respectively. Results showed that compared with the E group, acupuncture significantly increased net Ca2+ efflux (P < 0.05), extended the period of net Na+ influx, and significantly decreased net H2O2 efflux (P < 0.05). However, these effects were significantly attenuated in the EAT and EAN groups, where excessive net H2O2 efflux was observed (P < 0.001). These findings indicate that acupuncture regulates the dynamic changes of Ca2+, Na+ and H2O2 flux by activating the TRP channels and interacting with NOX2 activity following eccentric exercise-induced skeletal muscle injury.
Animals
;
Muscle, Skeletal/metabolism*
;
Rats, Wistar
;
Rats
;
Male
;
Calcium/metabolism*
;
Hydrogen Peroxide/metabolism*
;
Physical Conditioning, Animal
;
Sodium/metabolism*
;
Acupuncture Therapy
;
NADPH Oxidase 2
4.Medication rules of Astragali Radix in ancient Chinese medical books based on "disease-medicine-dose" pattern.
Jia-Lei CAO ; Lü-Yuan LIANG ; Yi-Hang LIU ; Zi-Ming XU ; Xuan WANG ; Wen-Xi WEI ; He-Jia WAN ; Xing-Hang LYU ; Wei-Xiao LI ; Yu-Xin ZHANG ; Bing-Qi WEI ; Xian-Qing REN
China Journal of Chinese Materia Medica 2025;50(3):798-811
This study employed the "disease-medicine-dose" pattern to mine the medication rules of traditional Chinese medicine(TCM) prescriptions containing Astragali Radix in ancient Chinese medical books, aiming to provide a scientific basis for the clinical application of Astragali Radix and the development of new medicines. The TCM prescriptions containing Astragali Radix were retrieved from databases such as Chinese Medical Dictionary and imported into Excel 2020 to construct the prescription library. Statical analysis were performed for the prescriptions regarding the indications, syndromes, medicine use frequency, herb effects, nature and taste, meridian tropism, dosage forms, and dose. SPSS statistics 26.0 and IBM SPSS Modeler 18.0 were used for association rules analysis and cluster analysis. A total of 2 297 prescriptions containing Astragali Radix were collected, involving 233 indications, among which sore and ulcer, consumptive disease, sweating disorder, and apoplexy had high frequency(>25), and their syndromes were mainly Qi and blood deficiency, Qi and blood deficiency, Yin and Yang deficiency, and Qi deficiency and collateral obstruction, respectively. In the prescriptions, 98 medicines were used with the frequency >25 and they mainly included Qi-tonifying medicines and blood-tonifying medicines. Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Citri Reticulatae Pericarpium were frequently used. The medicines with high frequency mainly have warm or cold nature, and sweet, pungent, or bitter taste, with tropism to spleen, lung, heart, liver, and kidney meridians. In the treatment of sore and ulcer, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to promote granulation and heal up sores. In the treatment of consumptive disease, Astragali Radix was mainly used with the dose of 37.30 g and combined with Ginseng Radix et Rhizoma to tonify deficiency and replenish Qi. In the treatment of sweating disorder, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to consolidate exterior and stop sweating. In the treatment of apoplexy, Astragali Radix was mainly used with the dose of 7.46 g and combined with Glycyrrhizae Radix et Rhizoma to dispell wind and stop convulsions. Astragali Radix can be used in the treatment of multiple system diseases, with the effects of tonifying Qi and ascending Yang, consolidating exterior and stopping sweating, and expressing toxin and promoting granulation. According to the manifestations of different diseases, when combined with other medicines, Astragali Radix was endowed with the effects of promoting granulation and healing up sores, tonifying deficiency and Qi, consolidating exterior and stopping sweating, and dispelling wind and replenishing Qi. The findings provide a theoretical reference and a scientific basis for the clinical application of Astragali Radix and the development of new medicines.
Drugs, Chinese Herbal/history*
;
Humans
;
Medicine, Chinese Traditional/history*
;
History, Ancient
;
Astragalus Plant/chemistry*
;
China
;
Astragalus propinquus
5."Component-effect" correlations in traditional Chinese medicine from holistic view: taking discovery of gintonin from ginseng as an example.
Xin-Ming YU ; Chen-Yu YU ; Hua-Ying WANG ; Wei-Sheng YUE ; Zhu-Bin ZHANG ; Wei WU ; Xiao-Bin JIA ; Bing YANG ; Liang FENG
China Journal of Chinese Materia Medica 2025;50(7):2001-2012
The holistic view is the key in the study of traditional Chinese medicine(TCM). The component structure theory is based on the holistic view to investigate the correlation between material basis and efficiency, which enriches the holistic "component-effect" research of TCM. Gintonin is a newly isolated non-saponin component of ginseng. Compared to ginsenosides, gintonin has many different pharmacological activities, and it provides new knowledge for the holistic research of ginseng. Thus, taking the discovery of gintonin from ginseng as an example, this paper explored the linkage between ginsenosides and gintonin from the perspective of "component-effect" correlations and systematically sorted out the similarities and differences between them in terms of structural characteristics, modes of action, and pharmacological activities. Starting from the collaborative interaction of TCM compounds, the study discussed the application and value of the holistic view in TCM "component-effect" research in the light of the component structure theory to provide new thoughts for the development of modern TCM research.
Panax/chemistry*
;
Drugs, Chinese Herbal/pharmacology*
;
Medicine, Chinese Traditional
;
Humans
;
Ginsenosides/pharmacology*
;
Animals
6.Correlation between differences in starch gelatinization, water distribution, and terpenoid content during steaming process of Curcuma kwangsiensis root tubers by multivariate statistical analysis.
Yan LIANG ; Meng-Na YANG ; Xiao-Li QIN ; Zhi-Yong ZHANG ; Zhong-Nan SU ; Hou-Kang CAO ; Ke-Feng ZHANG ; Ming-Wei WANG ; Bo LI ; Shuo LI
China Journal of Chinese Materia Medica 2025;50(10):2684-2694
To elucidate the mechanism by which steaming affects the quality of Curcuma kwangsiensis root tubers, methods such as LSCM, RVA, dual-wavelength spectrophotometry, LF-NMR, and LC-MS were employed to qualitatively and quantitatively detect changes in starch gelatinization characteristics, water distribution, and material composition of C. kwangsiensis root tubers under different steaming durations. Based on multivariate statistical analysis, the correlation between differences in gelatinization parameters, water distribution, and terpenoid material composition was investigated. The results indicate that steaming affects both starch gelatinization and water distribution in C. kwangsiensis. During the steaming process, transformations occur between amylose and amylopectin, as well as between semi-bound water and free water. After 60 min of steaming, starch gelatinization and water distribution reached an equilibrium state. The content of amylopectin, the amylose-to-amylopectin ratio, and parameters such as gelatinization temperature, viscosity, breakdown value, and setback value were significantly correlated(P≤0.05). Additionally, the amylose-to-amylopectin ratio was significantly correlated with total free water and total water content(P≤0.05). Steaming induced differences in the material composition of C. kwangsiensis root tubers. Clustering of primary metabolites in the OPLS-DA model was distinct, while secondary metabolites were classified into 9 clusters using the K-means clustering algorithm. Differential terpenoid metabolites such as(-)-α-curcumene were significantly correlated with zerumbone, retinal, and all-trans-retinoic acid(P<0.05). Curcumenol was significantly correlated with isoalantolactone and ursolic acid(P<0.05), while all-trans-retinoic acid was significantly correlated with both zerumbone and retinal(P<0.05). Alpha-tocotrienol exhibited a significant correlation with retinal and all-trans-retinoic acid(P<0.05). Amylose was extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and α-tocotrienol(P<0.05). Amylopectin was significantly correlated with zerumbone(P<0.05) and extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and 9-cis-retinoic acid(P<0.01). The results provide scientific evidence for elucidating the mechanism of quality formation of steamed C. kwangsiensis root tubers as a medicinal material.
Curcuma/chemistry*
;
Starch/chemistry*
;
Multivariate Analysis
;
Water/chemistry*
;
Terpenes/analysis*
;
Plant Roots/chemistry*
;
Plant Tubers/chemistry*
;
Drugs, Chinese Herbal/chemistry*
7.Research progress on prevention and treatment of hepatocellular carcinoma with traditional Chinese medicine based on gut microbiota.
Rui REN ; Xing YANG ; Ping-Ping REN ; Qian BI ; Bing-Zhao DU ; Qing-Yan ZHANG ; Xue-Han WANG ; Zhong-Qi JIANG ; Jin-Xiao LIANG ; Ming-Yi SHAO
China Journal of Chinese Materia Medica 2025;50(15):4190-4200
Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans
;
Gastrointestinal Microbiome/drug effects*
;
Carcinoma, Hepatocellular/microbiology*
;
Liver Neoplasms/microbiology*
;
Drugs, Chinese Herbal/administration & dosage*
;
Animals
;
Medicine, Chinese Traditional
8.Clinical efficacy of separation surgery in treating spinal metastases accompanied by neurological symptoms.
Qiang WANG ; Min-Hao LU ; Xing-Wu WANG ; Ming FANG ; Wu-Liang YU ; Jian-Meng LU
China Journal of Orthopaedics and Traumatology 2025;38(2):157-163
OBJECTIVE:
To explore the safety and effectiveness of separation surgery in patients with neurological symptoms of spinal metastases.
METHODS:
From January 2020 to December 2022, 14 patients with neurological symptoms of spinal metastases underwent separation surgery, including 7 males and 7 females, aged from 30 to 76 years old with an average of (61.57±12.16) years old. In comparison with eleven patients underwent conservative treatment during the same period, including 6 males and 5 femals, aged from 46 to 88 years old with an average of (66.55±12.32) years old. The changes in visual analogue scale (VAS), Frankel grades, Karnofsky scores, and quality of life score (QOL) before and after treatment were compared between two groups.
RESULTS:
Fourteen patients in the separation surgery group underwent surgery successfully, with surgery time of (218.57±50.00) minutes and intraoperative blood loss of (864.29±332.97) ml, 2 patients developed delayed hematoma and recovered well finally after emergency surgery, the follow-up time was 3 to 36 months, after separation surgery, the pain was significantly relieved, and neurological function recovered well in the patients. Three months after treatment, the VAS in the separation surgery group (1.43±0.76) scores was significantly lower than that in the conservative treatment group (8.64±0.51) scores (P<0.05);and the Frankel grades, Karnofsky scores, and QOL scores in the separation surgery group were significantly better than those in the conservative treatment group(P<0.05).
CONCLUSION
For patients with obvious neurological symptoms of spinal metastases, separation surgery not only can rapidly relieve nerve compression but also carry relatively low surgical risks, and improve the quality of life of patients.
Humans
;
Female
;
Male
;
Middle Aged
;
Aged
;
Spinal Neoplasms/complications*
;
Adult
;
Aged, 80 and over
;
Quality of Life
9.Single-position O-arm X-ray navigation assisted oblique lateral interbody fusion combined with minimally invasive percutaneous pedicle nail internal fixation for lumbar spondylolisthesis.
Kai-Kai TU ; Hui FEI ; Yu-Liang LOU ; Can-Feng WANG ; Chang-Ming LI ; Li-Shen ZHOU ; Feng HONG
China Journal of Orthopaedics and Traumatology 2025;38(5):447-453
OBJECTIVE:
To investigate the early clinical efficacy of single-position O-arm navigation-assisted oblique lateral interbody fusion(OLIF) combined with minimally invasive percutaneous pedicle screw fixation(PPS) in the treatment of lumbar spondylolisthesis.
METHODS:
A retrospective analysis was conducted on 22 patients with lumbar spondylolisthesis who underwent OLIF-PPS surgery including 11 males and 11 females with a mean age of (64.6±1.5) years old ranging from 49 to 80 years old between April 2021 and June 2023. All patients presented with lumbosacral pain, lower limb radiating pain, numbness, and had poor responses to conservative treatment. Surgical time, intraoperative blood loss, hospital stay, and postoperative complications were recorded. Clinical outcomes were evaluated using the visual analogue scale(VAS) and Oswestry disability index(ODI) preoperatively at 3 days after operation and the final follow-up. Standing lumbar anteroposterior and lateral X-rays were performed to measure disc height(DH), slippage degree, vertebral reduction rate, pedicle screw accuracy, and cage subsidence.
RESULTS:
All surgeries were successfully completed with a mean follow-up of (27.1±2.2) months (range 18 to 36 months). The mean surgical time was (76.1±12.2) min (range 60 to 93 min), intraoperative blood loss was (86.3±32.2) ml (range 40 to 113 ml), and hospital stay was (7.1±1.2) days. Postoperative VAS significantly improved from (7.2±0.7) preoperatively to (2.3±0.5) at 3 days after operation and (1.7±0.2) at the final follow-up (P<0.05). ODI decreased from (68.5±7.2)% preoperatively to (30.3±3.1)% at 3 days after operation and (16.6±1.6)% at the final follow-up (P<0.05). DH increased from (8.5±1.7) mm preoperatively to (18.1±1.4) mm at 3 days after operation and (17.2±1.1) mm at the final follow-up (P<0.05). Slippage degree improved from (24.1±4.6)% preoperatively to (10.3±4.2)% at 3 days after operation and (10.1±3.2)% at the final follow-up (P<0.05). A total of 88 pedicle screws were implanted with an excellent rate of 98% (86/88). Complications included transient left hip flexion weakness (2 cases) and left anteromedial thigh pain (1 case), all resolved during follow-up. No incision hematoma, infection, screw loosening, or cage subsidence occurred.
CONCLUSION
Single-position O-arm navigation-assisted OLIF combined with PPS demonstrates satisfactory early clinical efficacy for lumbar spondylolisthesis, with advantages including minimal invasiveness, significant pain relief, effective vertebral reduction, and low complication rates.
Humans
;
Male
;
Female
;
Spondylolisthesis/diagnostic imaging*
;
Middle Aged
;
Aged
;
Spinal Fusion/methods*
;
Lumbar Vertebrae/diagnostic imaging*
;
Minimally Invasive Surgical Procedures/methods*
;
Pedicle Screws
;
Aged, 80 and over
;
Retrospective Studies
10.Experimental study on autologous osteochondral transplantation in the treatment of recurrent anterior dislocation of the shoulder joint with articular cartilage defect in rabbits.
Tao LIU ; Sen FANG ; Fang-Xiang LIU ; Ming-Tao ZHANG ; Zhi-Tao YANG ; Bo-Rong ZHANG ; Jun-Wen LIANG ; Xi-Hao WANG ; Jin JIANG ; Xiang-Dong YUN
China Journal of Orthopaedics and Traumatology 2025;38(6):619-625
OBJECTIVE:
To explore clinical effect of autologous osteochondral transplantation (AOT) in the treatment of recurrent anterior dislocation of the shoulder joint with glenoid cartilage defect in rabbits by establishing a model of recurrent anterior dislocation of the shoulder joint with < 20% glenoid cartilage defect in rabbits.
METHODS:
Twenty-four male New Zealand white rabbits, aged 6-month-old, weighed (2.69±0.17) kg were selected. The labrum of shoulder joint of rabbits was artificially destroyed to establish a model of recurrent anterior dislocation of shoulder joint with cartilage defect. They were divided into AOT surgery group and simple suture group, with 12 rabbits in each group. AOT group were underwent AOT surgery, while simple suture group was treated with simple Bankart suture for recurrent shoulder joint dislocation. At 6 and 12 weeks after operation, 6 rabbits between two groups were sacrificed for sampling. The dietary conditions, activity conditions, mental states of rabbits and healing conditions of grafts in the specimens were observed and compared between two groups. HE staining was used to observe cell creep, cell morphology, inflammatory cell infiltration, fibrochondrocytes and their arrangement. Masson staining was used to observe the formation and arrangement of collagen fibers; Safrane-green staining was used to observe the regeneration of articular cartilage, subchondral bone and bone tissue. Bone mineral density (BMD), bone volume (BV) and trabecular thickness (Tb.Th) between two groups were measured by Micro-CT to evaluate the remodeling of shoulder glenoid bone defects by autologous osteochondral cartilage.
RESULTS:
After different surgical interventions were carried out in both groups of rabbits, at 6 weeks after the operation, the abduction, extension, internal rotation and external rotation of the shoulder joint on the operated side showed limited range of motion compared with the contralateral side, while adduction and forward flexion showed no obvious abnormalities compared with the contralateral side. At 12 weeks after operation, the range motion of tshoulder joints in both groups of rabbits had returned to the state before modeling. The effects of HE staining, Masson staining and safrane-green staining at 12 weeks after operation in both groups were stronger than the staining results at 6 weeks after operation. Moreover, the results of HE staining, Masson staining and safranin fixation green staining in AOT group at 6 and 12 weeks after operation were all higher than those in simple suture group. Micro-CT scan results at 6 and 12 weeks after operation showed that BMD (0.427±0.014), (0.466±0.032) g·cm-3, BV(116.171±3.527), (159.327±3.500) mm3, and Tb.Th (0.230±0.006), (0.285±0.009) mm in AOT group, which were higher than those of simple suture group in BMD(0.358±0.011), (0.384±0.096) g·cm-3, BV(72.657±3.903), (118.713±3.860) mm3, and Tb.Th(0.204±0.009), (0.243±0.007) mm;and the differences were statistically significant (P<0.05).
CONCLUSION
AOT procedure could effectively promote osteogenesis and fibrocartilage regeneration in the cartilage defect area of the shoulder glenoid <20%, which is conducive to reshaping the structure of the shoulder glenoid.
Animals
;
Rabbits
;
Male
;
Transplantation, Autologous
;
Cartilage, Articular/injuries*
;
Shoulder Dislocation/physiopathology*
;
Bone Transplantation
;
Shoulder Joint/surgery*


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