1. MW-9, a chalcones derivative bearing heterocyclic moieties, ameliorates ulcerative colitis via regulating MAPK signaling pathway
Zhao WU ; Nan-Ting ZOU ; Chun-Fei ZHANG ; Hao-Hong ZHANG ; Qing-Yan MO ; Ze-Wei MAO ; Chun-Ping WAN ; Ming-Qian JU ; Chun-Ping WAN ; Xing-Cai XU
Chinese Pharmacological Bulletin 2024;40(3):514-520
		                        		
		                        			
		                        			 Aim To investigate the therapeutic effect of the MW-9 on ulcerative colitis(UC)and reveal the underlying mechanism, so as to provide a scientific guidance for the MW-9 treatment of UC. Methods The model of lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cells was established. The effect of MW-9 on RAW264.7 cells viability was detected by MTT assay. The levels of nitric oxide(NO)in RAW264.7 macrophages were measured by Griess assay. Cell supernatants and serum levels of inflammatory cytokines containing IL-6, TNF-α and IL-1β were determined by ELISA kits. Dextran sulfate sodium(DSS)-induced UC model in mice was established and body weight of mice in each group was measured. The histopathological damage degree of colonic tissue was assessed by HE staining. The protein expression of p-p38, p-ERK1/2 and p-JNK was detected by Western blot. Results MW-9 intervention significantly inhibited NO release in RAW264.7 macrophages with IC50 of 20.47 mg·L-1 and decreased the overproduction of inflammatory factors IL-6, IL-1β and TNF-α(P<0.05). MW-9 had no cytotoxicity at the concentrations below 6 mg·L-1. After MW-9 treatment, mouse body weight was gradually reduced, and the serum IL-6, IL-1β and TNF-α levels were significantly down-regulated. Compared with the model group, MW-9 significantly decreased the expression of p-p38 and p-ERK1/2 protein. Conclusions MW-9 has significant anti-inflammatory activities both in vitro and in vivo, and its underlying mechanism for the treatment of UC may be associated with the inhibition of MAPK signaling pathway. 
		                        		
		                        		
		                        		
		                        	
2.Mechanism of Kechuanting granules in suppressing IL-33/ILC2s and pathogenic T cells to intervene in allergic airway inflammation
Nan-Ting ZOU ; Zhao WU ; Xiao-Dong YAN ; Chun-Fei ZHANG ; Hao-Hong ZHANG ; Qing-Yan MO ; Ming-Qian JU ; Jin-Zhu XU ; Chun-Ping WAN
Chinese Pharmacological Bulletin 2024;40(7):1350-1357
		                        		
		                        			
		                        			Aim To investigate the mechanisms of Ke-chuanting granules(KCT)inhibiting the IL-33/ILC2s pathway and pathogenic T cells to intervene in allergic airway inflammation.Methods Network pharmacolo-gy was utilized to analyze the potential targets and mechanisms of KCT-treated asthma.Allergic asthma models were induced in mice using OVA.Lung histo-pathology was conducted to observe injury changes.ELISA and quantitative PCR were utilized to measure key inflammatory factors and their mRNA expression levels in Th2-type asthma.Western blot was used to detect the phosphorylation levels of relevant proteins in the MAPK pathway.Flow cytometry was performed to evaluate the proportions of ILC2s,Th1,Th 17,Th2 and Treg cells.Results Network pharmacology iden-tified 227 main active components and 143 key targets of KCT in treating asthma,primarily enriched in signa-ling pathways such as MAPK and IL-17.Further vali-dation experiments demonstrated that KCT significantly alleviated lung inflammatory injury in asthmatic mice,reduced the number of B cells,production of I L-4,TNF-α and TGF-β,downregulated JNK phosphoryla-tion levels in lung tissue,as well as mRNA levels of Il-33,Bcl11b,Rorα,Tcf-7,Jun,Mapk3 and Mapk14.KCT intervention reduced the numbers of ILC2s and Th 17 cells in lungs and spleens of mice,and inhibited Th2 cell infiltration in lungs.Conclusions KCT ex-hibits therapeutic effects on allergic airway inflamma-tion in asthma,closely associated with the inhibition of the IL-33/ILC2s pathway,pathogenic T cell subsets,and JNK-MAPK signaling pathway.
		                        		
		                        		
		                        		
		                        	
3.Improvement of the Mouse Model of Chronic Obsessive-compulsive Disorder Induced by Quinpirole
Yu-chong LUO ; Chun-ren WEI ; Xiao CHEN ; Mo-yan LI ; Sheng-lin WEN
Journal of Sun Yat-sen University(Medical Sciences) 2022;43(3):412-421
		                        		
		                        			
		                        			ObjectiveTo obtain a mouse model of chronic obsessive-compulsive disorder with a shorter modeling time and longer symptom duration, we improved an existing method to obtain a simple and stable mouse model of chronic obsessive-compulsive disorder. Methods22 mice were randomly divided into experimental group (n=11) and control group (n=11) . The mice were injected subcutaneously with 0.75 mg/kg quinpirole solution or the same amount of saline in the neck for 19 consecutive days and were put into the compulsive behavior training device. The drinking behavior and drinking volume of the two groups were recorded during training, and the effects of quinpirole on the behavior of mice were evaluated. After training, behavioral studies such as open field test, elevated plus maze test and new object recognition test were conducted to evaluate the anxiety state and cognitive ability of the mice after modeling. In addition, immunofluorescence experiments were performed to explore the neural mechanism of behavioral changes in mice. ResultsQuinpirole injection combined with behavioral training for 19 days could effectively induce compulsive checking behavior without anxiety or cognitive decline in mice (P<0.001), and this behavior lasted more than 28 days after training. In this model, several brain regions on the cortical-striatum-thalamic-cortical circuit were activated (P<0.000 1). ConclusionChronic quinpirole administration combined with behavior training can effectively construct a mouse model of OCD with an obvious and stable phenotype, and effectively shorten the time required for modeling. 
		                        		
		                        		
		                        		
		                        	
4.Effects of chloropicrin fumigation on soil and growth and development of Panax notoginseng.
Long LI ; Rong-Feng PU ; Ming-Hua LI ; Chun-Yan DAI ; Kai ZHENG ; Zheng-Qiang JIN ; Chen-Bing MO ; Xiu-Ming CUI ; Ye YANG
China Journal of Chinese Materia Medica 2022;47(3):635-642
		                        		
		                        			
		                        			The continuous cropping obstacle of Panax notoginseng is serious, and effective control measures are lacking. Soil disinfection with chloropicrin(CP) has been proven to be effective in reducing the obstacles to continuous cropping of other crops. In order to ascertain the effect of CP in the continuous cropping of P. notoginseng, this paper explored the influences of CP at different treatment concentrations(0,30,40,50 kg/Mu, 1 Mu≈667 m~2) on soil macro-element nutrients, soil enzyme activity, growth and development of P. notoginseng, and the accumulation of medicinal components. The results showed that CP fumigation significantly increased the content of total nitrogen, alkali-hydrolyzable nitrogen, ammonium nitrogen, nitrate nitrogen, and available phosphorus in the soil, but it had no significant effect on potassium content. The soil protease activity showed a trend of first increasing and then decreasing with the prolonging of the treatment time. Both the soil urease and acid phosphatase activities showed a trend of first decreasing and then increasing with the prolonging of the treatment time. The higher the CP treatment concentration was, the lower the urease and acid phosphatase activities would be in the soil. The protease activity was relatively high after CP40 treatment, which was better than CP30 and CP50 treatments in promoting the nitrogen-phosphorus-potassium accumulation in P. notoginseng. The seedling survival rates after CP0, CP30, CP40, and CP50 tratments in October were 0, 65.56%, 89.44%, and 83.33%, respectively. Compared with the CP30 and CP50 treatments, CP40 treatment significantly facilitated the growth and development of P. notoginseng, the increase in fresh and dry weights, and the accumulation of root saponins. In summary, CP40 treatment accelerates the increase in soil nitrogen and phosphorus nutrients and their accumulation in P. notoginseng, elevates the seedling survival rate of P. notoginseng, enhances the growth and development of P. notoginseng, and promotes the accumulation of medicinal components. CP40 treatment is therefore recommended in production.
		                        		
		                        		
		                        		
		                        			Fumigation
		                        			;
		                        		
		                        			Growth and Development
		                        			;
		                        		
		                        			Hydrocarbons, Chlorinated
		                        			;
		                        		
		                        			Panax notoginseng
		                        			;
		                        		
		                        			Soil
		                        			
		                        		
		                        	
5.Visual Electrophysiological Diagnosis and Treatment Technology for Early Intervention of Urinary Incontinence After TUERP
Dao-sheng LUO ; Jian-jun LU ; Wei-ning LIANG ; Yan-chuan ZOU ; Jun-hua MO ; Shu-er CHEN ; Chun-hua DENG
Journal of Sun Yat-sen University(Medical Sciences) 2022;43(6):878-883
		                        		
		                        			
		                        			ObjectiveTo summarize the effect of visual electrophysiological diagnosis and treatment technology on postoperative urinary incontinence in early intervention after transurethral enucleation and resection of the prostate (TUERP). MethodsTotally 86 patients with benign prostatic hyperplasia (BPH) who underwent TUERP in the Puji Branch Hospital of Dongguan People's Hospital from December 2020 to June 2022 were selected as the treatment group, who received electrophysiological treatment after postoperative removal of the catheter on the 6th day after surgery, while 79 cases who received no electrophysiological treatment after surgery were selected as the control group. The urinary incontinence rates of the two groups on the 6th day, at 1 month and 3 months after surgery were observed. ResultsThere was no statistical difference between the two groups in the preoperative basic data. The rates of urinary incontinence after removal of the catheter in the two groups on the 6th day after surgery were 13 cases (15.1%) in the treatment group and 12 cases (15.2%) in the control group. There was no significant difference between the two groups (P >0.05), and the overall postoperative urinary incontinence rate in the two groups was 15.2% (25/165). At one month after surgery, only 4 cases (4.65%) had slight urinary incontinence in the treatment group, while 13 cases (16.5%) in the control group still had urinary incontinence, and the difference between the two groups was statistically significant ( P=0.019). After follow-up to three months after operation, there was no case of urinary incontinence in the treatment group, and there were still 7 cases (8.86%) of urinary incontinence in the control group. The difference between the two groups was statistically significant (P=0.005). ConclusionThe early intervention of visual electrophysiological diagnosis and treatment technology can effectively prevent the occurrence of urinary incontinence after TUERP, and has good value in clinical application. 
		                        		
		                        		
		                        		
		                        	
6.Proliferative lesions with mesonephric features in the gynecologic tract: a clinicopathological analysis of sixteen cases.
Na MO ; Chun Yan HE ; Hai Yun YU ; Xiao Tao BIAN ; Yu Lan JIN
Chinese Journal of Pathology 2022;51(10):1000-1006
		                        		
		                        			
		                        			Objective: To investigate the clinicopathological features of proliferations with mesonephric features (PMF) of the gynecologic tract. Methods: A retrospective analysis was performed on the clinical and pathological data of 16 cases with PMF that were diagnosed from October 2016 to January 2022 at a single institution. The relevant literature was reviewed. Results: Among the 16 cases, with an average of 53 years (31-68 years), there were 5 cases of mesonephric hyperplasia, 4 cases of mesonephric adenocarcinoma and 7 cases of mesonephric-like adenocarcinoma. The five cases of mesonephric hyperplasia were located in the lateral wall of the cervix and composed of simple tubules with growth patterns of diffuse or lobular clusters, without obvious stromal reaction. Four cases of mesonephric adenocarcinoma consisted of a mixture of papillary, cribriform, solid and other architectures, the nuclei resembling these of papillary thyroid carcinoma, and strong fibroproliferative reaction. They were located deep in the cervical and vaginal stroma. One of the tumors showed atypical mesonephric hyperplasia adjacent to the tumor. Five uterine and two ovarian mesonephric-like adenocarcinoma cases had similar histological morphology with mesonephric adenocarcinoma, but no mesonephric remnants/mesonephric hyperplasia were found near the tumors. In addition, four (4/5) uterine mesonephric-like adenocarcinoma cases originated from the endometrium with secondary involvement of myometrium, including one case with clear demarcation between the normal endometrium and the neoplastic glands. One (1/5) uterine mesonephric-like adenocarcinoma case was mainly located in the deep myometrium, along with adenomyosis around the tumor, without mesonephric remnants. Two ovarian mesonephric-like adenocarcinoma cases were associated with endometriotic cyst/endometrioid cystadenoma, including one case with an abrupt transition between normal epithelium and atypical mesonephric cells within the single individual cyst directly adjacent to tumor. All mesonephric hyperplasia and mesonephric adenocarcinoma cases were positive for GATA3, PAX8 and CD10 in a varying degree, and negative for ER, PR and TTF1. Although mesonephric-like adenocarcinoma showed a considerable overlap of immunohistochemical expression with mesonephric adenocarcinoma, seven mesonephric-like adenocarcinoma cases were positive for TTF1 and negative for GATA3. Conclusions: PMF is a class of rare proliferative lesions with morphological and immunophenotypic characteristics of mesonephric duct. Its commonly involved site, microscopic morphology, associated benign and/or atypical lesions, and immunophenotype may contribute to its diagnosis and differential diagnosis.
		                        		
		                        		
		                        		
		                        			Adenocarcinoma/pathology*
		                        			;
		                        		
		                        			Biomarkers, Tumor/analysis*
		                        			;
		                        		
		                        			Cervix Uteri/pathology*
		                        			;
		                        		
		                        			Diagnosis, Differential
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hyperplasia/pathology*
		                        			;
		                        		
		                        			Precancerous Conditions/pathology*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			
		                        		
		                        	
7.Mechanism of hepatic fibrosis associated with Echinococcus: a review
Ren-jie ZHANG ; Hua-sheng PANG ; Jing-zhong LI ; Zhao-hui LUO ; Lin AI ; Peng SONG ; Yu-chun CAI ; Yan LU ; Xiao-jin MO ; Mu-xin CHEN ; Jia-xu CHEN
Chinese Journal of Schistosomiasis Control 2022;34(6):646-653
		                        		
		                        			
		                        			 Echinococcosis is a zoonotic parasitic disease caused by Echinococcus infections, and this disorder may cause fibrosis of multiple vital organs, which may further progress into cirrhosis. Early-stage hepatic fibrosis is reversible, and unraveling the mechanisms underlying hepatic fibrosis induced by Echinococcus infections is of great significance for the prevention and treatment of early-stage hepatic fibrosis. Recently, the studies pertaining to hepatic fibrosis associated with Echinococcus infections focus on cytokines and immune cells. This review summarizes the advances in the mechanisms underlying host immune cells- and cytokines-mediated hepatic fibrosis in humans or mice following Echinococcus infections. 
		                        		
		                        		
		                        		
		                        	
8.Prognostic Value of Serum Epstein-Barr Virus Antibodies and Their Correlation with TNM Classification in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma
Wan-Ru ZHANG ; Yu-Yun DU ; Chun-Yan GUO ; Han-Xing ZHOU ; Jie-Yi LIN ; Xiao-Han MENG ; Hao-Yuan MO ; Dong-Hua LUO
Cancer Research and Treatment 2021;53(4):991-1003
		                        		
		                        			 Purpose:
		                        			This study assessed the correlation between Epstein-Barr virus (EBV) biomarkers and the eighth American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), IgA antibodies against Epstein-Barr nuclear antigen 1, and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients. 
		                        		
		                        			Materials and Methods:
		                        			Serum EBV antibody levels were measured by enzyme-linked immunosorbent assay in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS). 
		                        		
		                        			Results:
		                        			Rta-IgG and Zta-IgA levels were positively correlated with the N category and clinical stage. Patients with high Rta-IgG levels (> 29.07 U/mL) showed a significantly inferior prognosis as indicated by PFS (77% vs. 89.8%, p=0.004), distant metastasis–free survival (DMFS) (88.3% vs. 95.8%, p=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤ 1,500 copies/mL), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p < 0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T category (T3-4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS, and LRFS (both p < 0.05). 
		                        		
		                        			Conclusion
		                        			Rta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T category or low EBV DNA level. 
		                        		
		                        		
		                        		
		                        	
9.Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China.
Yan MA ; Dong Shan ZHU ; Ren Bo CHEN ; Nan Nan SHI ; Si Hong LIU ; Yi Pin FAN ; Gui Hui WU ; Pu Ye YANG ; Jiang Feng BAI ; Hong CHEN ; Li Ying CHEN ; Qiao FENG ; Tuan Mao GUO ; Yong HOU ; Gui Fen HU ; Xiao Mei HU ; Yun Hong HU ; Jin HUANG ; Qiu Hua HUANG ; Shao Zhen HUANG ; Liang JI ; Hai Hao JIN ; Xiao LEI ; Chun Yan LI ; Min Qing LI ; Qun Tang LI ; Xian Yong LI ; Hong De LIU ; Jin Ping LIU ; Zhang LIU ; Yu Ting MA ; Ya MAO ; Liu Fen MO ; Hui NA ; Jing Wei WANG ; Fang Li SONG ; Sheng SUN ; Dong Ting WANG ; Ming Xuan WANG ; Xiao Yan WANG ; Yin Zhen WANG ; Yu Dong WANG ; Wei WU ; Lan Ping WU ; Yan Hua XIAO ; Hai Jun XIE ; Hong Ming XU ; Shou Fang XU ; Rui Xia XUE ; Chun YANG ; Kai Jun YANG ; Sheng Li YUAN ; Gong Qi ZHANG ; Jin Bo ZHANG ; Lin Song ZHANG ; Shu Sen ZHAO ; Wan Ying ZHAO ; Kai ZHENG ; Ying Chun ZHOU ; Jun Teng ZHU ; Tian Qing ZHU ; Hua Min ZHANG ; Yan Ping WANG ; Yong Yan WANG
Biomedical and Environmental Sciences 2020;33(12):893-905
		                        		
		                        			Objective:
		                        			Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.
		                        		
		                        			Methods:
		                        			A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( 
		                        		
		                        			Results:
		                        			Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks.
		                        		
		                        			Conclusion
		                        			Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			COVID-19/virology*
		                        			;
		                        		
		                        			China/epidemiology*
		                        			;
		                        		
		                        			Comorbidity
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Severity of Illness Index
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
10.Light and heat of moxibustion for knee osteoarthritis:a multi-center randomized controlled trial.
Mo LIAO ; Ling LUO ; Qi DING ; Jia ZUO ; Ling-Ling GUO ; Chun-Yan GOU ; Cai-Rong ZHANG ; Yong TANG ; Shu-Guang YU
Chinese Acupuncture & Moxibustion 2020;40(6):623-628
		                        		
		                        			OBJECTIVE:
		                        			To explore the clinical therapeutic effect of light and heat of moxibustion for knee osteoarthritis (KOA).
		                        		
		                        			METHODS:
		                        			A total of 216 patients with KOA were randomized into a traditional moxibustion group (72 cases, 8 cases dropped off), a moxibustion light group (72 cases, 9 cases dropped off) and a moxibustion heat group (72 cases, 10 cases dropped off).The special light-heat separation moxibustion cup was applied, the patients in the traditional moxibustion group received the treatment of moxibustion, the patients in the moxibustion light group received the treatment of moxibustion light and the patients in the moxibustion heat group received the treatment of moxibustion heat. The acupoint selection of the three groups was Neixiyan (EX-LE 4), Dubi (ST 35) and Zusanli (ST 36), the treatment was given 20 min each time, 3 times a week, 4 weeks were required totally, and the follow-up surveys were made 4 and 8 weeks after treatment. The scores of Western Ontario and McMaster University osteoarthritis index (WOMAC) and visual analogue scale (VAS) were observed before treatment, after 2 and 4 weeks of treatment, 4 and 8 weeks after treatment. The therapeutic effects were evaluated according to the criterion of patient global assessment (PGA) after 4 weeks of treatment and 8 weeks after treatment.
		                        		
		                        			RESULTS:
		                        			Compared with before treatment, the pain scores, stiffness scores, physical function scores and total scores of WOMAC were reduced after 2, 4 weeks of treatment and 4 weeks after treatment in the three groups (<0.05). The pain scores, stiffness scores, physical function scores and total scores of WOMAC were reduced 8 weeks after treatment in the traditional moxibustion group and the moxibustion heat group (<0.05). The stiffness score, physical function score and total score of WOMAC were reduced 8 weeks after treatment in the moxibustion light group (<0.05). The pain score, physical function score and total score of WOMAC in the traditional moxibustion group after 4 weeks of treatment were lower than the moxibustion light group (<0.05). Compared with before treatment, the VAS scores were reduced after 2, 4 weeks of treatment and 4 , 8 weeks after treatment in the three groups (<0.05). The improvement rates in the traditional moxibustion group and the moxibustion heat group after 4 weeks of treatment and 8 weeks after treatment were superior to the moxibustion light group (<0.05).
		                        		
		                        			CONCLUSION
		                        			The light and heat of moxibustion have therapeutic effect for KOA, and the therapeutic effect of moxibustion heat is superior to moxibustion light.
		                        		
		                        		
		                        		
		                        			Acupuncture Points
		                        			;
		                        		
		                        			Hot Temperature
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Light
		                        			;
		                        		
		                        			Moxibustion
		                        			;
		                        		
		                        			Osteoarthritis, Knee
		                        			;
		                        		
		                        			therapy
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		                        			Treatment Outcome
		                        			
		                        		
		                        	
            
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