Objective To observe the clinical efficacy and safety of adalimumab(AD A)injection combined with methotrexate(MTX)tablets in the treatment of patients with rheumatoid arthritis(RA),and the effects of joint function,serum rheumatoid factor(RF),anti-citrullinated peptide(CCP)antibody and tumor necrosis factor-α(TNF-α).Methods The RA patients were divided into control group and treatment group according to cohort method.All patients were given intra-articular injection of prednisolone acetate injection at initial dose of 5 mg every time,once every week for 4 weeks,and then adjusted dose every 2 weeks according to the disease conditions.On this basis,the control group received oral MTX tablets 10 mg once a week,and the treatment group was combined with subcutaneous injection of ADA injection 40 mg twice a week.Both groups were treated continuously for 3 months.The clinical efficacy,clinical characteristics(swollen joint count,tender joint count,morning stiffness time),joint function[disease activity scale(DAS)-28 score,joint pain degree score],serum RF,anti-CCP antibody and TNF-α levels before and after treatment were compared between the two groups.Results The treatment group and control group included 52 and 45 cases,respectively.After treatment,the total effective rates of treatment group and control group were 92.31％(48 cases/52 cases)and 75.56％(34 cases/45 cases),respectively,and the difference was statistically significant(P＜0.05).After treatment,the swollen joint counts in treatment group and control group were 4.31±1.08 and 5.56±1.25;the tender joint counts were 6.19±1.68 and 7.92±1.43;the morning stiffness times were(44.47±11.06)and(58.63±12.46)min;the DAS28 scores were(2.67±0.73)and(3.35±0.86)points;the joint pain scores were(2.47±0.76)and(3.29±0.85)points;serum RF levels were(80.25±24.31)and(114.46±27.63)U·mL-1;serum anti-CCP antibody levels were(7.41±1.48)and(9.90±1.72)RU·mL-1;the levels of serum TNF-α were(24.16±6.33)and(34.92±7.98)pg·mL-1.Compared with control group,the above indexes of treatment group had statistical significance(all P＜0.001).The adverse drug reactions in the treatment group mainly included loss of appetite,headache and erythema at the injection site.The adverse drug reactions in the control group included loss of appetite and nausea and vomiting.The total incidences of adverse drug reactions in the treatment group and the control group were 5.77％and 4.44％,respectively,and the difference was not statistically significant(P＞0.05).Conclusion The treatment of RA with ADA injection combined with MTX tablets is more effective than using MTX tablets alone,and the former one can more significantly improve joint function and reduce levels of inflammatory markers,and without increasing the incidences of adverse drug reactions.

Objective To observe the clinical efficacy and safety of adalimumab(AD A)injection combined with methotrexate(MTX)tablets in the treatment of patients with rheumatoid arthritis(RA),and the effects of joint function,serum rheumatoid factor(RF),anti-citrullinated peptide(CCP)antibody and tumor necrosis factor-α(TNF-α).Methods The RA patients were divided into control group and treatment group according to cohort method.All patients were given intra-articular injection of prednisolone acetate injection at initial dose of 5 mg every time,once every week for 4 weeks,and then adjusted dose every 2 weeks according to the disease conditions.On this basis,the control group received oral MTX tablets 10 mg once a week,and the treatment group was combined with subcutaneous injection of ADA injection 40 mg twice a week.Both groups were treated continuously for 3 months.The clinical efficacy,clinical characteristics(swollen joint count,tender joint count,morning stiffness time),joint function[disease activity scale(DAS)-28 score,joint pain degree score],serum RF,anti-CCP antibody and TNF-α levels before and after treatment were compared between the two groups.Results The treatment group and control group included 52 and 45 cases,respectively.After treatment,the total effective rates of treatment group and control group were 92.31％(48 cases/52 cases)and 75.56％(34 cases/45 cases),respectively,and the difference was statistically significant(P＜0.05).After treatment,the swollen joint counts in treatment group and control group were 4.31±1.08 and 5.56±1.25;the tender joint counts were 6.19±1.68 and 7.92±1.43;the morning stiffness times were(44.47±11.06)and(58.63±12.46)min;the DAS28 scores were(2.67±0.73)and(3.35±0.86)points;the joint pain scores were(2.47±0.76)and(3.29±0.85)points;serum RF levels were(80.25±24.31)and(114.46±27.63)U·mL-1;serum anti-CCP antibody levels were(7.41±1.48)and(9.90±1.72)RU·mL-1;the levels of serum TNF-α were(24.16±6.33)and(34.92±7.98)pg·mL-1.Compared with control group,the above indexes of treatment group had statistical significance(all P＜0.001).The adverse drug reactions in the treatment group mainly included loss of appetite,headache and erythema at the injection site.The adverse drug reactions in the control group included loss of appetite and nausea and vomiting.The total incidences of adverse drug reactions in the treatment group and the control group were 5.77％and 4.44％,respectively,and the difference was not statistically significant(P＞0.05).Conclusion The treatment of RA with ADA injection combined with MTX tablets is more effective than using MTX tablets alone,and the former one can more significantly improve joint function and reduce levels of inflammatory markers,and without increasing the incidences of adverse drug reactions.

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.
Pregnancy ; Female ; Humans ; Male ; Vas Deferens/abnormalities* ; Azoospermia/surgery* ; Epididymis/surgery* ; Retrospective Studies ; Tertiary Care Centers ; China ; Semen

In the orthodontics process, intervention and sliding of an orthodontic bracket during the orthodontic process can arise large response of the labio-cheek soft tissue. Soft tissue damage and ulcers frequently happen at the early stage of orthodontic treatment. In the field of orthodontic medicine, qualitative analysis is always carried out through statistics of clinical cases, while quantitative explanation of bio-mechanical mechanism is lacking. For this purpose, finite element analysis of a three-dimensional labio-cheek-bracket-tooth model is conducted to quantify the bracket-induced mechanical response of the labio-cheek soft tissue, which involves complex coupling of contact nonlinearity, material nonlinearity and geometric nonlinearity. Firstly, based on the biological composition characteristics of labio-cheek, a second-order Ogden model is optimally selected to describe the adipose-like material of the labio-cheek soft tissue. Secondly, according to the characteristics of oral activity, a two-stage simulation model of bracket intervention and orthogonal sliding is established, and the key contact parameters are optimally set. Finally, the two-level analysis method of overall model and submodel is used to achieve efficient solution of high-precision strains in submodels based on the displacement boundary obtained from the overall model calculation. Calculation results with four typical tooth morphologies during orthodontic treatment show that: ① the maximum strain of soft tissue is distributed along the sharp edges of the bracket, consistent with the clinically observed profile of soft tissue deformation; ② the maximum strain of soft tissue is reduced as the teeth align, consistent with the clinical manifestation of common damage and ulcers at the beginning of orthodontic treatment and reduced patient discomfort at the end of treatment. The method in this paper can provide reference for relevant quantitative analysis studies in the field of orthodontic medical treatment at home and abroad, and further benefit to the product development analysis of new orthodontic devices.
Humans ; Periodontal Ligament/physiology* ; Orthodontic Wires ; Cheek ; Ulcer ; Tooth ; Finite Element Analysis

Objective:To evaluate the efficacy and tolerability of the dual therapy of dolutegravir (DTG) plus lamivudine (3TC) as a switch simplified strategy in treatment-experienced human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients.Methods:Treatment-experienced HIV/AIDS patients who switched to a dual therapy containing DTG (50 mg, once daily) plus 3TC (300 mg, once daily) were included in Beijing You′an Hospital, Capital Medical University from September 2016 to May 2019. HIV RNA, CD4 + T lymphocyte count, blood lipid indexes, renal function indexes were collected when patients changed the treatment regimen (baseline) and after 48 weeks of treatment. Efficacy (HIV RNA<50 copies/mL) and safety of the dual therapy were analyzed. Statistical comparisons were performed using the Wilcoxon matched-pairs signed rank test. Results:The reasons for 33 patients switching the treatment regimen were virologic failure (four cases, 12.1%), simplification of regimen (11 cases, 33.3%), and drug toxicity (18 cases, 54.5%). The patients were treated with anti-retroviral therapy (ART) for 2.13 (1.05, 4.23) years before regimens switching. Twenty-nine (87.9%) patients were virologically suppressed at baseline, and four (12.1%) patients were virological failure. After switching to DTG plus 3TC, all 33 patients showed HIV RNA<50 copies/mL after 48 weeks of treatment. The baseline CD4 + T lymphocyte count was 543 (363, 595)/μL. After switching the treatment regimens for 48 weeks, CD4 + T lymphocyte count was significantly increased to 625 (455, 651)/μL, and the difference was statistically significant ( Z=3.14, P=0.002). Compared with baseline, low-density lipoprotein-cholesterol was increased after 48 weeks of treatment (2.35(1.80, 3.08) mmol/L vs 3.12(2.74, 3.87) mmol/L), while triglyceride (2.21(1.27, 4.37) mmol/L vs 1.61(1.20, 2.22) mmol/L), the ratio of total cholesterol to high-density lipoprotein-cholesterol (5.02 (4.13, 6.40) vs 4.70 (3.55, 5.35)) and estimated glomerular filtration rate (106.4(78.2, 118.2) mL/(min·1.73 m 2) vs 88.6 (75.7, 107.9) mL/(min·1.73 m 2)) were decreased. The differences were all statistically significant ( Z=4.89, 2.37, 2.09 and 2.83, respectively, all P<0.050). No patient discontinued due to adverse events. Conclusions:The use of dual therapy containing DTG and 3TC is effective and well-tolerated in treatment-experienced HIV/AIDS patients under any prior ART without significant adverse events.

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; China/epidemiology* ; Heart Valve Prosthesis Implantation ; Humans ; Severity of Illness Index ; Treatment Outcome

Objective To evaluate the effect of the different Child-Pugh classification on the recurrence and survival of hepatocellular carcinoma (HCC) recipients after liver transplantation. Methods Clinical data of 125 HCC recipients undergoing liver transplantation were retrospectively analyzed. The 3-year disease-free survival (DFS) and overall survival (OS) rates were calculated by Kaplan-Meier survival curve. The independent risk factors probably affecting the recurrence and survival of HCC recipients after liver transplantation were identified by using Cox's proportional hazards regression model. Results The median follow-up time was 25.6 months. The 3-year DFS and OS rates were 68.4% and 65.7% for all patients. The 3-year DFS and OS rates in 113 patients with Child-Pugh class A/B HCC were 68.6% and 66.2%, whereas 66.7% and 65.6% for 12 patients with Child-Pugh class C HCC with no statistical significance (all P>0.05). Cox's proportional hazards regression model demonstrated that vascular invasion (P=0.001)and the number of tumors>3 (P=0.025) were the independent risk factors for the postoperative recurrence of HCC in recipients undergoing liver transplantation. Alpha fetoprotein (AFP)>400μg/L (P=0.035), vascular invasion (P=0.031) and number of tumors>3 (P=0.008) were the independent risk factors affecting the survival of HCC patients. Conclusions The postoperative prognosis does not significantly differ between Child-Pugh class C and A/B HCC patients after liver transplantation. AFP, vascular invasion and number of tumors are the risk factors affecting the clinical prognosis of HCC patients after liver transplantation. Liver transplantation is an efficacious treatment for HCC patients with Child-Pugh class C.

【Objective】To explore clinical manifestations and features of renal uric acid excretion in gout patients with obesity.【Methods】Totally 228 primary gout patients were enrolled and divided into three groups according to body mass index（BMI）. Clinical and fasting blood biochemical analysis data were collected. Indices of renal uric acid excretion were calculated according to 24 h urinary uric acid and urinary creatinine.【Results】The obese group（n = 44）was younger than overweight group（n = 88）and non-overweight group（n = 96）［43（32，57）years vs 55（45，65）years，58（45，67）years］，with earlier onset age［37（26，48）years vs 48（38，59）years］，higher serum uric acid［594（522，697）μmol/L vs 511（372，653）μmol/L］and had more hypercholesterolemia（56.8% vs 31.3%）and low density lipoproteinemia（59.1% vs 47.9%）compared with non-overweight group. The ratio of hypertriglyceridemia（43.5% and 37.5% vs 17.7%）and metabolic syndrome（50.0% and 36.4% vs 12.5%）in the overweight and obese group were both higher than non- overweight group. Fraction excretion of uric acid（FEUA）in obese group［5.5（3.6，7.4）% vs 7.0（5.2，9.8）%］was lower than non-overweight group，and the glomerular filtration load of uric acid［5.3（4.2，7.5）mg·min- 1 ·1.73 m- 2 vs 3.5（2.2，5.2）mg·min-1·1.73 m-2］in obese group was higher than that in non-overweight group（All P < 0.0167）. Multivariate regression analysis showed that overweight or obesity were negatively correlated with FEUA（All P < 0.05）.【Conclusion】High uric acid load of serum and glomerular filtration in gout patients with obesity may be due to the relative insufficiency of renal uric acid excretion.

Eight limonoids were isolated from 95% ethanol extracts of neem(Azadirachta indica) seeds by various chromatographic methods. By comparison of their spectroscopic data with those reported in the literatures, these limonoids were determined as salannin(1), 1-detigloyl-1-isobutylsalannin(2), salannol-3-acetate(3), salannol(4), spirosendan(5), 1-detigloyloxy-3-deacetylsalannin-1-en-3-one(6), nimbin(7) and 6-deacetylnimbin(8). Compounds 2 and 5 were firstly isolated from this genus and 5 represented the only example of its type. And 6 is a new natural product. 6 showed inhibitory activity against HeLa and HL-60 cells, with IC₅₀ of(21.61±4.37) and(27.33±5.74) μmol·L⁻¹, respectively. Both 7 and 8 mildly inhibited the growth of HeLa cells, with IC₅₀ of (33.15±5.24) and (38.56±6.41) μmol·L⁻¹, respectively.
Azadirachta ; chemistry ; HL-60 Cells ; HeLa Cells ; Humans ; Limonins ; isolation & purification ; pharmacology ; Phytochemicals ; isolation & purification ; pharmacology ; Plant Extracts ; Seeds ; chemistry

Arsenic trioxide (ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resistance mechanism is required. In this study, we established an ATO-resistant human epidermoid carcinoma cell line, KB/ATO, from its parental KB-3-1 cells. In addition to ATO, KB/ATO cells also exhibited cross-resistance to other anticancer drugs such as cisplatin, antimony potassium tartrate, and 6-mercaptopurine. The arsenic accumulation in KB/ATO cells was significantly lower than that in KB-3-1 cells. Further analysis indicated that neither application of P-glycoprotein inhibitor, breast cancer resistant protein (BCRP) inhibitor, or multidrug resistance protein 1 (MRP1) inhibitor could eliminate ATO resistance. We found that the expression level of ABCB6 was increased in KB/ATO cells. In conclusion, ABCB6 could be an important factor for ATO resistance in KB/ATO cells. The ABCB6 level may serve as a predictive biomarker for the effectiveness of ATO therapy.