Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective: To explore and validate the potential targets of Paeoniae Radix Alba (P. Radix, Bai Shao) in protecting against chemical liver injury through network pharmacology, molecular docking technology, and in vitro cell experiments. Methods: Network pharmacology was used to identify the common potential targets of P. Radix and chemical liver injury. Molecular docking was used to fit the components, which were subsequently verified in vitro. A cell model of hepatic fibrosis was established by activating hepatic stellate cell (HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1. The cells were exposed to different concentrations of total glucosides of paeony (TGP), the active substance of P. Radix, and then evaluated using the cell counting kit-8 assay, enzyme-linked immunosorbent assay, and western blot. Results: Analysis through network pharmacology revealed 13 key compounds of P. Radix, and the potential targets for preventing chemical liver injury were IL-6, AKT serine/threonine kinase 1, jun proto-oncogene, heat shock protein 90 alpha family class A member 1 (HSP90AA1), peroxisome proliferator activated receptor gamma (PPARG), PTGS2, and CASP3. Gene Ontology (GO) enrichment analysis indicated the involvement of response to drugs, membrane rafts, and peptide binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation. Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1, PTGS2, PPARG, and CASP3. Different concentrations of TGP can inhibit the expression of COL-Ⅰ, COL-Ⅲ, IL-6, TNF-α, IL-1β, HSP-90α, and PTGS2 while increasing the expression of PPAR-γ and CASP3 in activated HSC-LX2 cells. Conclusion P. Radix primarily can regulate targets such as HSP90AA1, PTGS2, PPARG, CASP3. TGP, the main active compound of P. Radix, protects against chemical liver injury by reducing the inflammatory response, activating apoptotic proteins, and promoting the apoptosis of activated HSCs.

Objective To explore the association between R611H(G/A,rs734312)variation of WFS1 gene and early-onset type 2 diabetes mellitus(T2DM).Methods A total of 181 Chinese patients with early-onset T2DM(T2DM group)and 196 non-diabetic controls(NC group)were enrolled in this study.The rs734312 variation was detected by PCR-direct sequencing.Genotypic and allelic frequencies of rs734312 and clinical variables were compared and analyzed between the two groups.Results Compared with the NC group,the frequencies of AA genotype and A allele in R611H(G→A)variation were significantly elevated in the early-onset T2DM group,AA vs GA+GG(OR 1.720,95%CI 1.100～2.680,P<0.05).A vs G(OR 1.500,95%CI 1.020～2.220,P<0.05).The remarkable differences of frequencies of genotype and allele in rs734312(G/A)were observed between Asians(China,Japan and Korea)and Caucasians(Denmark,Britain,Spain,France and Russia,P<0.01 for each).Compared with AA genotype,fasting and 2 hours postprandial insulin(FIns and 2 hIns)as well as HOMA-β were significantly rise in GG+GA genotype carriers of early-onset T2DM group(P<0.05).Conclusions The a allele of rs734312 in WFS1 may be a risk factor for early-onset T2DM in Chinese population,and the variation might be a potential genetic marker for predicting the islet β-cell dysfunction in early-onset T2DM in Chinese population.

Objective:To explore the effect of core stability training on rehabilitation of patients after lumbar fusion.Methods:From June 2018 to December 2019, 90 patients with lumbar fusion admitted to Wuxi Second Hospital Affiliated to Nanjing Medical University were selected by convenience sampling. The patients were divided into control group and training group according to the method of random number table, with 45 cases in each group. The control group received routine postoperative rehabilitation nursing, while the training group carried out postoperative core stability training nursing. The rehabilitation effects of the two groups were observed.Results:The scores of Numerical Rating Scale (NRS) in the training group were lower than those in the control group at 2, 4, 12 and 24 weeks postoperatively, and the difference were statistical ( P<0.05) . The scores of Oswestry Disability Index (ODI) in the training group 12 and 24 weeks after operation were lower than those in the control group, with statistically significant differences ( P<0.05) . Conclusions:The core stability training nursing is helpful to improve the functional recovery after lumbar fusion, reduce the degree of postoperative pain, and then increase the rehabilitation effect of patients.

This study deeply analyzes the common problems of three military medical universities in the management of undergraduate extracurricular scientific research, such as lack of communication means, limited online resources, backward laboratory opening and low utilization rate of equipment. We have built a cloud platform management system for undergraduate extracurricular scientific research. This system firstly sets up a teaching resources storage module including videos, PPTs, documents, pictures, electronic materials, question bank, etc. Then four subsystems for different roles of students, mentors, experimental teaching staff and administrators are constructed. Finally, this system realizes independent experiments by students, real-time evaluation by mentors, instrument sharing and efficient management through the seamless connection with the user terminal equipment. And the study also makes evaluation on the present usage.

Objective:To explore the clinical features and managements of novel coronavirus (2019-nCoV) infection after kidney transplantation.Methods:The authors reviewed medical history, laboratory values, imaging studies, treatment options and clinical outcomes of two confirmed hospitalized cases of COVID-19 after kidney transplant in February 2020. Both cases were middle-aged males and confirmed as COVID-19 at 11 or 12 months after transplantation. They both presented initially with moderate-to-low fever, cough and fatigue. Chest computed tomography (CT) hinted at multiple peripheral patchy ground glass opacities or patchy exudation and in bilateral multiple lobular and subsegmental with obscure boundary. Both had varying degrees of renal function and cardiac insufficiency.Results:In case 1, the dose of immunosuppressants was tapered while a higher dose of glucocorticoids was prescribed during treatment. In case 2, the dose of immunosuppressants was not tapered and continuous renal replacement therapy (CRRT) performed thrice in the early disease course due to renal insufficiency and hyperkalemia. Both cases received oxygen inhalation, lopinavir/ritonavir, oral abidor and interferonα-2b antiviral therapy, antibiotics treatment. Both cases were cured.Conclusions:The clinical manifestations and diagnosis of COVID-19 patients after kidney transplantation are not significantly different from those of other people. However, early renal function and heart function abnormalities occur. How to adjust the immunosuppressant in the treatment course of severe COVID-19 after renal transplantation should be further explored.

Objective: To explore the effect of obesity on the treatment for femoral neck fracture in patients with SuperPATH hip replacement. Methods: Seventy patients who were treated with SuperPATH hip replacement in the Second People's Hospital of Wuxi from January 2014 to January 2017 were selected in the study.Based on their body mass index(BMI), the patients were divided into obesity group(BMI≥30kg/m²) (23 cases), overweight group(BMI: 25-30kg/m²) (22 cases), and normal group(BMI: 18.5-25kg/m²)(25 cases). The incision length, operation time, blood loss, blood transfusion rate, pain score, hip joint function score, imaging measurement results and postoperative complications were compared among the three groups. Results: All 70 patients received the operation successfully.The incision length of the obesity group was (7.4±0.2)cm, which of the overweight group was (7.2±0.1)cm, which of the normal group was (7.1±0.8)cm, the difference among the three groups was statistically significant (F=24.671, P<0.001). The patients were followed up for 9-13 months.The acetabular anteversion angle, acetabular abduction angle, pain score, mobility of hip joint, walking ability score in the obesity group were (17.8±1.2)°, (40.9±3.4)°, (1.26±0.61)points, (95.43±7.89)°, (8.10±0.27)points, respectively, which in the overweight group were (16.7±3.3)°, (42.9±2.9)°, (1.23±0.58)points, (96.78±3.22)°, (8.20±0.92) points, respectively, which in the normal group were (15.8±2.7)°, (43.9±5.1)°, (1.24±0.78)points, (97.12±6.44)°, (8.20±0.48)points, respectively.The difference of acetabular abduction angle among the three groups was statistically significant (F=9.803, P=0.002). In the obesity group, there were two cases of incision infection, two cases of deep venous thrombosis and one case of pulmonary complication, the incidence rate of complications was 5%.In the overweight group, there was one case of superficial incision infection, and one case of deep vein thrombosis, the incidence rate of complications was 2%.In the normal group, there was one case of deep venous thrombosis, the incidence rate of complications was 1%.The difference of incidence rate of complications among the three groups was statistically significant(χ²=15.31, P<0.01). Conclusion Obesity increases the surgical risk of SuperPATH total hip replacement, and more attention should be attached to perioperative and post-operative treatment for such patients.

Objective To evaluate the clinical outcomes and prognosis of older human immunodeficiency virus (HIV )-infected patients under antiretroviral therapy (ART ) in China .Methods This study was carried out in a retrospective cohort of HIV-infected patients initiated ART between January 2004 and December 2012 at The First Affiliated Hospital ,China Medical University .The patients were enrolled and divided into two groups ,including <50 years group (young and middle-aged group) and≥50 years group (older group) .Immunological and virological responses and mortality were analyzed . Data were analyzed by t test ,chi-square test ,two-way analysis of variance and log-rank test .Results Totally 291 subjects were included ,among whom 97 subjects were older patients and 194 subjects were young and middle-aged patients .Male was predominate in both groups ,which accounted for 91 .8％ and 87 .6％ ,respectively .The CD4+ T lymphocyte count in the older group before treatment was (151 .9 ±96 .2) cells /μL ,which was significantly lower than that in the young and middle-aged group (183 .4 ± 93 . 5) cells/μL (t= 2 .657 , P=0 .009) .At month 12 of treatment ,the CD4+ T lymphocyte count in the older group was significantly lower than that in the young and middle-aged groups (t= 2 .120 , P=0 .035) ,while there was no statistically significant difference between the two groups at month 24 (t=1 .025 ,P=0 .299) .The percentage of CD4+ T lymphocyte count increasing to 500 cells/μL in the older and youth groups during follow-up were 11 .3％ and 16 .0％ ,respectively (χ2=1 .127 ,P =0 .376) .Log-rank analysis showed that the mean times of virus inhibition in older group and young and middle-aged group were 7 .9 (95％ CI:6 .8-8 .5) and 7 .6 (95％ CI:6 .5 -9 .3) ,respectively ,with no statistically significant difference (χ2 =0 .002 , P=0 .961) .Virological failure was reported in 4 patients (4 .1％ ) in older group and 11 patients (5 .7％ ) in young and middle-aged group . Chi-square test showed no statistically significant difference between the two groups (χ2 = 0 .15 , P= 0 .78) .During follow-up , 19 .6％ (19/97) in older group and 3 .6％ (7/194) in young and middle-aged group died .The former was significantly higher than the latter (χ2 = 21 .113 , P< 0 .01 ) .Conclusions Older patients show a poor immunologic response ,similar viral suppression and higher risk of mortality compared with young and middle-aged patients . Future research should be aimed at the feasible and specific strategy for early diagnosis and timely treatment for older patients to improve treatment efficacy and reduce mortality .

Objective To compare the short-term efficacy of AC TightRope plate and clavicular hook plate in the treatment of acromioclavicular joint dislocation.Methods A retrospective case control study was conducted to analyze the clinical data of 32 patients with acromioclavicular joint dislocation admitted to Yifu Hospital Affiliated to Nanjing Medical University from April 2016 to December 2017.There were 23 males and 9 females,aged 26-61 years [(43.5 ±9.5)years].According to Rockwood classification,there were 23 patients with type Ⅲ and 9 patients with type Ⅴ.The patients were divided into AC TightRope group and clavicular hook plate group according to different treatment methods.There were 17 patients in AC TightRope group,including 12 males and 5 females,aged (42.6 ± 10.3)years.There were 15 patients in clavicular hook plate group,including 11 males and 4 females,aged (44.5 ± 8.9)years.The incision length,operation time,intraoperative blood loss,hospitalization time,postoperative visual analogue scale (VAS) of the affected shoulder,functional recovery of shoulder joint and complications were compared between the two groups.Results All patients were followed up for 6-26 months,with an average of 15 months.There was no significant difference between the two groups in hospitalization time (P ＞ 0.05).In the AC TightRope group and clavicular hook plate group,the operation time was (41.5 ±4.2)minutes and (60.1 ± 4.2) minutes,respectively (P ＜ 0.01);the incision length was (3.6 ± 0.3) cm and (10.1 ± 0.6) cm,respectively (P ＜ 0.01);the intraoperative blood loss was (45.3 ± 11.1) ml and (78.3 ± 16.0) ml,respectively (P ＜ 0.01);the postoperative VAS of the shoulder was (1.9 ± 0.5) points and (3.1 ± 0.7) points,respectively (P ＜ 0.05);the excellent and good rate of postoperative recovery of shoulder joint function was 100％ (17/17) and 67％ (10/15),respectively (P ＜0.01).There were no complications such as surgical incision infection,intraoperative neurovascular injury or condylar fracture during the perioperative period.No serious postoperative complications such as internal fixation loosening,loss of reduction or recurrence of dislocation were found in both groups.Conclusion For acromioclavicular joint dislocation,AC TightRope can obtain good clinical effect and has obvious advantages in operation time,incision length and blood loss,with lower incidence of shoulder pain and better functional recovery compared with clavicular hook plate.

Objective To investigate the expression of minichromosome maintenance protein 7 (MCM7) in sinonasal squamous cell carcinoma (SNSCC),and evaluate its relationship with tumor differentiation and prognosis of patients.Methods Using immunohistochemistry,MCM7 expression in SNSCC and nasal polyps with chronic sinusitis (NPCRS) were studied,and relationships between markers and clinicapathological features were analyzed.Results In NPCRS,MCM7 positive cells were mainly distributed in the epithelial basal layer and the expression rate was low,whereas in SNSCC,MCM7 positive cells were diffuse and the expression rate was high.MCM7 expression was significantly higher in SNSCC than in NPCRS (P ＜ 0.001) and related to tumor differentiation (P =0.001),increasing gradually with decreasing degree of differentiation.The overall 3-and 5-year survival rates of patients with SNSCC were 61.3％ and 46％,respectively.The 3-year survival rates for patients with stage Ⅰ and Ⅳ were 90％ and 25.6％,respectively,and the 5-year survival rates were 70％ and 17.1％,respectively;the difference was statistically significant (P ＜ 0.001).The 3-and 5-year survival rates of MCM7-negative patients were 36.0％ and 18.0％,respectively,and those of MCM7-positive patients were 59.9％ and 34.2％,respectively;the difference was not statistically significant (P =0.297).Conclusion In SNSCC,MCM7 expression is significantly increased,inversely associated with the degree of tumor differeutiation,and unrelated to the survival rates of patients.