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【Objective】 To describe the distribution characteristics of knee and ankle joint range of motion and muscle atrophy related indexes in patients with Kashin-Beck disease (KBD) in Shaanxi Province so as to explore the correlation of knee and ankle joint range of motion (ROM) with muscle atrophy indexes and provide reference for clinical characteristics analysis of KBD patients. 【Methods】 To investigate the registered KBD patients from KBD areas in Shaanxi Province, we measured the general demographic data of the patients were collected and the ROM of the knee joint (flexion and extension), the ankle joint (dorsiflexion and plantar flexion), and the muscle atrophy related indexes such as the upper arm circumference, thigh circumference, calf circumference and grip strength. According to the population characteristics, i.e., gender, age, body mass index (BMI) and KBD grade, the median and quartile of joint ROM and muscle atrophy of KBD patients were reported, and then the differences in each index among different groups were analyzed. Partial correlation analysis was used to explore the correlation between indicators after controlling for variables such as gender, age and BMI. 【Results】 A total of 480 patients with KBD were investigated in this study, who consisted of 249 (51.9%) males and 231 (48.1%) females, with an average age of (63.10±7.32) years and an average BMI of (23.49±8.90) kg/m2. The knee flexion ROM, knee extension ROM, ankle dorsiflexion ROM and ankle plantar flexion ROM were [105.0 (95.0, 120.0)] °, [0.0 (-15.0, 0.0)] °, [5.0 (0.0, 15.0)] ° and [20.0 (15.0, 30.0)] °, respectively, in KBD patients in Shaanxi Province. The left thigh circumference, right thigh circumference, left calf circumference, right calf circumference, and upper arm circumference were [43.0 (40.0, 47.0)] cm, [43.0 (39.0, 47.0)] cm, [29.0 (27.0, 32.0)] cm, [29.5 (27.0, 32.0)] cm, [27.0 (25.0, 30.0)] cm, respectively. The left hand grip strength and right hand grip strength were [13.4 (9.5, 18.4)] kg and [13.9 (9.8, 18.2)] kg, respectively. With the increase of age, the extension range of the left and right knee joints of KBD patients showed a decreasing trend (H=31.499, 31.847; all P<0.001). The range of motion of bilateral knee flexion was higher in the normal BMI group than in the overweight or obese group, with statistically significant differences (H=7.753, 12.333; P=0.021, 0.002). The knee flexion, thigh circumference, and calf circumference of the left and right sides showed a decreasing trend under different KBD grades (H=14.345, 17.256, 8.000, 8.462, 8.558, 9.633; all P<0.05). Correlation analysis showed that knee flexion ROM was positively correlated with thigh circumference, calf circumference, and grip strength in patients with KBD (all P<0.05). There was a positive correlation between knee extension ROM and thigh circumference in patients with KBD (P<0.01). 【Conclusion】 The impaired joint ROM and muscle atrophy are serious in KBD patients in Shaanxi Province, and there is a correlation between joint motion and muscle atrophy.
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Objective:To investigate the role of a disintegrin and metalloprotease 12 (ADAM12) gene in chondrocyte injury in patients with Kashin-Beck disease (KBD) and its impact on genes related to insulin-like growth factor binding protein (IGFBP).Methods:Articular cartilage samples were obtained from 5 patients with KBD and 5 control subjects admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University. Chondrocytes were extracted and cultured in vitro. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to detect the expression levels of ADAM12 mRNA and protein in chondrocytes of patients with KBD and control subjects, respectively. Subsequently, ADAM12 gene overexpression was performed using lentivirus in chondrocytes of patients with KBD. MTT assay was used to detect changes in cell viability after ADAM12 gene overexpression, and qRT-PCR was used to detect the mRNA expression levels of chondrocyte differentiation related genes SRY-box transcription factor 9 (SOX9) and type Ⅱ collagen (COLⅡ), apoptosis-related gene B-cell lymphoma/leukaemia-2-associated X protein (BAX), and anabolic related genes IGFBP3 and IGFBP5. Results:The expression levels of ADAM12 mRNA and protein in chondrocytes of patients with KBD (0.57 ± 0.05, 0.81 ± 0.07) were significantly lower than those of control subjects (1.00 ± 0.00, 1.00 ± 0.00), and the differences were statistically significant ( t = - 24.50, - 3.61, P < 0.05). The results of MTT assay showed that the cell viability of chondrocytes in ADAM12 overexpression group (1.09 ± 0.05) was higher than that in empty vector control group (1.00 ± 0.08), and the difference was statistically significant ( t = 4.12, P = 0.031). The results of qRT-PCR showed that compared with empty vector control group, the mRNA expression levels of IGFBP3 (2.35 ± 0.79 vs 0.96 ± 0.25), IGFBP5 (2.13 ± 0.30 vs 0.98 ± 0.34), SOX9 (2.92 ± 0.51 vs 0.94 ± 0.36) and COLⅡ (6.45 ± 2.81 vs 0.87 ± 0.19) in ADAM12 overexpression group were significantly increased, and the differences were statistically significant ( t = 3.19, 5.16, 6.27, 4.10, P < 0.05); while the expression level of BAX mRNA (0.31 ± 0.06 vs 1.02 ± 0.22) was significantly decreased, and the difference was statistically significant ( t = - 11.16, P < 0.001). Conclusion:The ADAM12 gene may have a role in inhibiting apoptosis and promoting differentiation in chondrocyte injury in patients with KBD, and its overexpression can increase expression of IGFBP3 and IGFBP5.
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Objective:To investigate the impact of matrix metalloproteinase 13 (MMP13) and low-density lipoprotein receptor-related protein 1 (LRP1) on autophagy of articular chondrocytes in patients with Kashin-Beck disease (KBD).Methods:Human articular cartilage samples obtained from 4 KBD patients and 4 control subjects were collected from Shaanxi Institute for Endemic Disease Prevention and Control, and the expression levels of MMP13 and LRP1 in cartilage tissue were determined using immunohistochemistry (IHC). Chondrocytes were extracted and cultured in vitro, the mRNA and protein expression levels of LRP1 and the autophagy related genes [Beclin 1 (BECN1), microtubule associated protein 1 light chain 3 (LC3)], cartilage injury related genes [MMP13, caspase-3 (CASP3)], chondrocyte differentiation related genes [collagen type Ⅱ alpha 1 chain (COL2A1), and SRY-box transcription factor 9 (SOX9)] were detected by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot (WB), respectively. Chondrocytes from 3 KBD patients were extracted, and MMP13 gene silencing experiment was performed by RNA interference (RNAi) technology, the mRNA and protein expression levels of the above genes were detected by qRT-PCR and WB, respectively. In addition, the antagonist receptor associated protein (RAP) of LRP1 was used to block the LRP1 of human normal chondrocytes (C28/I2 cells), and qRT-PCR and WB were used to detect the mRNA and protein expression levels of LRP1, chondrocyte autophagy, differentiation and cartilage injury related genes, respectively. Results:The IHC results showed that the expression levels of MMP13 (1.67 ± 0.21, 0.59 ± 0.15, 0.51 ± 0.12) in the surface, middle, and deep layers of cartilage tissue of KBD patients were significantly higher than those of control subjects (0.25 ± 0.03, 0.26 ± 0.04, 0.06 ± 0.01), and the differences were statistically significant ( t = - 11.38, P < 0.001; t = - 3.82, - 6.26, P = 0.019, 0.003). The expression levels of LRP1 (0.10 ± 0.02, 0.03 ± 0.01, 0.17 ± 0.03) were significantly lower than those of control subjects (1.63 ± 0.40, 0.44 ± 0.12, 0.34 ± 0.08), and the differences were statistically significant ( t = 6.61, 5.61, 3.64, P = 0.003, 0.005, 0.022). The mRNA and protein expression levels of MMP13, CASP3, SOX9 in chondrocytes of KBD patients were significantly higher than those of control subjects, and the differences were statistically significant ( P < 0.05). The mRNA expression levels of LRP1, LC3, COL2A1 were significantly lower than those of control subjects, and the differences were statistically significant ( P < 0.05). After silencing the MMP13 gene in chondrocytes of KBD patients, there were no significant differences in the mRNA and protein expression levels of LRP1, BECN1, LC3, CASP3, COL2A1, and SOX9 ( P > 0.05). After blocking LRP1 with RAP, the protein expression levels of LRP1, BECN1, LC3, MMP13, COL2A1 and SOX9 in chondrocytes were significantly lower than those in control group ( P < 0.05). Conclusions:There is no direct correlation between MMP13 and abnormal autophagy of articular chondrocytes in KBD patients. After blocking LRP1, the expression of the autophagy related genes BECN1 and LC3 in chondrocytes is decreased.
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Objective:To analyze the surgical types of patients with Kashin-Beck disease (KBD) in Shaanxi Province, and to provide reference for optimizing KBD surgery.Methods:Retrospective analysis was used to investigate KBD patients who underwent surgical treatment, and the patient's information was from the Shaanxi Provincial Endemic Disease Prevention and Control Information System. Patients with incomplete surgical treatment information were excluded, and χ 2 test was used to analyze the impact of factors such as gender, education level, living area, disease severity, and social environment on the selection of different surgical types (free body enucleation or joint replacement) for KBD patients. Using propensity score method to perform a 1 ∶ 1 match on patients with different surgical types, and analyzing the influencing factors of KBD patients receiving different types of surgical treatment through multivariate logistic regression. Results:From 2018 to 2020, a total of 1 084 KBD patients in Shaanxi Province underwent surgical treatment, including 555 males (51.20%) and 529 females (48.80%), with a median age of 64 years old. There were 917 patients (84.59%) in the Guanzhong region (Tongchuan, Xi'an, Weinan, Xianyang, Baoji), 120 patients (11.07%) in the northern Shaanxi region (Yulin, Yan'an), and 47 patients (4.34%) in the southern Shaanxi region (Ankang, Hanzhong, Shangluo). The number of patients with KBD grade Ⅰ,Ⅱ, and Ⅲ was 401 (36.99%), 525 (48.43%), and 158 (14.58%), respectively. Five hundred and forty-eight patients (50.55%) underwent free body enucleation surgery, and 536 patients (49.45%) underwent joint replacement surgery. Univariate analysis showed that different genders, educational levels, living areas, disease severity, economic status, whether to relocate, type of drinking water, type of staple food, and source of staple food were the influencing factors for KBD patients to choose the type of surgery (χ 2 = 81.82, 22.38, 93.68, 22.38, 5.17, 15.68, 13.82, 39.37, 49.63, P < 0.05). Among 374 pairs of patients who underwent free body enucleation and joint replacement through propensity score matching, multivariate logistic regression analysis found that high school and above education level [odds ratio( OR) = 0.42, P = 0.008], Guanzhong region ( OR = 0.12, P < 0.001), relocation ( OR = 0.60, P = 0.004), and drinking well water ( OR = 2.15, P = 0.001) were the influencing factors for KBD patients to choose different surgical types for treatment. Conclusion:When performing surgical treatment for KBD patients in Shaanxi Province, clinicians can consider the severity of the disease, as well as factors such as the education level, living area, relocation status, and type of drinking water of KBD patients, to provide more suitable surgical types for KBD patients.
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Objective:To investigate the willingness of patients with Kashin-Beck disease (KBD) to accept drug treatment and its influencing factors in Shaanxi Province, in order to provide a reference for promoting the standardized management of KBD patients.Methods:The general information of KBD patients in Shaanxi Provincial Endemic Disease Prevention and Control Information System from January 2018 to December 2020 was collected, including gender, age (< 50, 50 - 79, ≥80 years old), ethnicity (Han nationality, others), education level (primary school and below, junior high school, senior high school and above), occupation (farmer, others), region (northern Shaanxi, central Shaanxi, southern Shaanxi), disease severity (gradeⅠ,Ⅱ,Ⅲ), etc. A face-to-face questionnaire survey was conducted to investigate the willingness of KBD patients to accept drug treatment, mainly including the willingness of patients to accept drug treatment, management services (whether the poor population, participation in medical insurance, disability assessment) and the implementation of comprehensive prevention and control measures (type of drinking water, types and sources of staple food, relocation from other places and returning farmland to forests). Multivariate logistic regression analysis was used to analyze the influencing factors of KBD patients' willingness to accept drug treatment.Results:A total of 58 501 KBD patients were included, including 51.60% (30 185/58 501) males and 48.40% (28 316/58 501) females; the median age was 64 years old; the ethnicity was mainly Han nationality, accounting for 99.87% (58 427/58 501); the education level of primary school and below accounted for 81.76% (47 831/58 501); the occupation was mainly farmers, accounting for 99.24% (58 059/58 501); mainly distributed in central Shaanxi [81.40% (47 619/58 501)]; patients with gradeⅠaccounted for 63.68% (37 254/58 501). Totally 89.02% (52 078/58 501) of KBD patients were willing to accept drug treatment. By multivariate logistic regression analysis, gender, age, education level, disease severity, region, medical insurance, disability assessment, type of drinking water, type of staple food, relocation from other places and returning farmland to forests were the influencing factors of KBD patients' willingness to accept drug treatment ( P < 0.05). Conclusions:KBD patients in Shaanxi Province have a high willingness to accept drug treatment. In the future, the standardized management of KBD patients should take into account the factors such as age, education level, disease severity and region, and implement precise drug treatment.
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Objective:To grasp the current situation of Keshan disease in Shaanxi Province, and to provide scientific basis for evaluation of local Keshan disease control and elimination.Methods:From May to November 2020, Keshan disease surveillance was carried out in all the diseased townships (towns) of 29 diseased counties (districts, cities) in Shaanxi Province. The diseased village was used as the unit to collect the demographic data of the diseased areas, and the village doctor's clues were used to investigate suspected myocardial cases, and recent outpatient or inpatient clinical examination data of Keshan disease cases were collected; suspected cases were organized for clinical physical examination, electrocardiography (ECG), chest X-ray and echocardiography examination. According to "Notice of the National Health Commission on Printing and Distributing the Evaluation Measures for the Control and Elimination of Key Endemic Diseases (2019 Edition)", the diseased compliance status was assessed.Results:There were 174 diseased townships (towns) and 2 653 diseased villages in the whole province, with a permanent population of 2 819 342 people. A total of 87 suspected cases and 29 confirmed cases of Keshan disease were found, including 27 cases of chronic Keshan disease and 2 cases of latent Keshan disease. The acute and subacute Keshan disease and new cases with disease duration less than 1 year were not detected. The ST-T changes, premature ventricular contractions, complete right bundle branch block, left ventricular hypertrophy, and atrial fibrillation were the most common ECG changes in 29 cases of Keshan disease, and the single ECG change accounted for 6.90% (2/29), two changes accounted for 44.83% (13/29), and three or more changes accounted for 48.28% (14/29). There were 1 case with normal cardiothoracic ratio in chest X-ray examination, 10, 13, and 4 cases with mild, moderate and severe enlargement, respectively; 13 cases with enlarged left atrium in echocardiography, 15 cases with enlarged left ventricle, and 6 cases with enlarged heart.Conclusions:All the diseased areas in Shaanxi Province have reached the national standard for elimination of Keshan disease. Keshan disease monitoring should be continued, self-management of patients with chronic Keshan disease and follow-up observation of patients with latent Keshan disease should be strengthened, and treatment programs for patients with Keshan disease should be actively carried out to improve the quality of life of the patients.
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Objective:To observe the effect of selenium supplementation on 10-year survival rate of chronic Keshan disease (KD).Methods:The 10-year follow-up data of 302 patients with chronic KD at the KD surveillance sites in Shaanxi Province were collected from the Shaanxi Institute for Endemic Disease Control and Research and Xi'an Jiaotong University, 170 (56.3%) cases were given selenium supplementation (oral administration of sodium selenite tablet, once a week, 1 mg/time) until the end point of follow-up as selenium supplementation group, and the rest (132 cases) were non-selenium supplementation group. Cox proportional hazards models were used to identify the independent predictors for 10-year survival rate of chronic KD. Kaplan-Meier method was used to analyze the 10-year survival rate of patients with chronic KD during the follow-up period and the Log-rank test was used to compare the 10-year survival rate between groups.Results:The follow-up deadline was October 2019. During the follow-up period, a total of 199 patients (199/302, 65.9%) of chronic KD died, including 101 patients (101/170, 59.4%) in the selenium supplementation group and 98 patients (98/132, 74.2%) in the non-selenium supplementation group. In COX proportional hazards model, after adjustment for other baseline characteristics [age, sex, body mass index (BMI), family history of KD, smoking, blood pressure, heart rate, ECG abnormalities, initial cardiothoracic ratio, left ventricular ejection fraction (LVEF), and blood selenium content], selenium supplementation and combined use of angiotensin-converting enzyme inhibitor + β receptor blocker (ACEI + BBs) were protective factors for 10-year survival in patients with chronic KD (selenium supplementation: HR = 0.39, 95% CI: 0.28 - 0.53; ACEI + BBs: HR = 0.57, 95% CI: 0.39 - 0.84). The 10-year survival rate of chronic KD patients after selenium supplementation was significantly higher than that of non-selenium supplementation group (Log-rank test, P < 0.05). Conclusion:Selenium supplementation and combined use of ACEI + BBs in chronic KD patients, are associated with better survival during the 10-year follow-up.
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There is no difference between breast conserving surgery (BCS) combined with radiotherapy and radical surgery in outcomes.However, comparing with the radical surgery, BCS has little trauma, less bleeding and lower infection rate, which makes patients′ quality of life improved.In the practice of BCS, due to the disease, patients, physicians, socio-economic, clinical, security and many other factors, there are still many controversial issuesin the doctor-patient communication, socio-economic, aesthetic, margins width, precision operation procedures of BCS.At the same time, new surgical techniques such as plastic breast conserving surgery, and new intraoperative assessment equipment such as MarginProbe system and other new technology development has brought us new ideas to solve these problems.
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Objective To evaluate the prognostic value of three different staging system based on positive lymph nodes,lymph node ratio and log odds of positive lymph nodes in breast carcinoma.Methods In 472 breast carcinoma patients,survival analysis was performed with Kaplan-Merier and COX regression model,the hazard ratio (HR) of the three staging system were compared.Results When more than 10 lymph nodes were dissected in the operation,there was statistical differences in survival among the staging systems based on lymph node ratio and log odds of positive lymph nodes (P < 0.05),while the prognosis was highly homologous between the staging systems based on positive lymph nodes in stage N0 and N1.Univariate analysis showed age,tumor size,Her2 status,estrogen receptor status and the total lymph nodes dissected were related to overall survival (all P < 0.05).COX multivariate analysis showed that the staging system based on lymph node ratio (5.495) and log odds of positive lymph nodes (4.662) had the higher HR than the N staging system (2.722).Conclusions Compared with the number of involved lymph nodes,the staging system based on lymph node ratio and log odds of positive lymph nodes were superior to the staging system based on positive lymph nodes for prognostic assessment of breast carcinoma.