Objective:To investigate the risk factors of early death after lung transplantation in patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension (PAH).Methods:A retrospective cohort study was conducted. The clinical data of 134 patients with IPF and PAH who underwent lung transplantation at Wuxi People's Hospital Affiliated to Nanjing Medical University from January 2017 to December 2020 were collected. The donor's gender, age, duration of mechanical ventilation, and cold ischemia time, the recipient's gender, age, body mass index (BMI), smoking, history of hypertension and diabetes, preoperative usage of hormones, mean pulmonary arterial pressure (mPAP), cardiac echocardiography and cardiac function, serum creatinine (SCr), N-terminal pro-brain natriuretic peptide (NT-proBNP) as well as surgical type, extracorporeal membrane oxygenation (ECMO) treatment, duration of operation, and plasma and red blood cell infusion ratio were collected. The cumulative survival rates of patients at 30, 60, and 180 days after lung transplantation were calculated by Kaplan-Meier method. The univariate and multivariate Cox proportional hazards regression models were used to analyze the effects of donor, recipient, and surgical factors on early survival in donors after lung transplantation.Results:The majority of donors were male (80.6%). There was 63.4% of the donors older than 35 years old, 80.6% of the donors had mechanical ventilation duration less than 10 days, and the median cold ischemia time was 465.00 (369.25, 556.25) minutes. The recipients were mainly males (83.6%). Most of the patients were younger than 65 years old (70.9%). Most of them had no hypertension (75.4%) or diabetes (67.9%). The median mPAP of recipients was 36 (30, 43) mmHg (1 mmHg≈0.133 kPa). There were 73 patients with single lung transplantation (54.5%), and 61 with double lung transplantation (45.5%). The survival rates of 134 IPF patients with PAH at 30, 60, 180 days after lung transplantation were 81.3%, 76.9%, and 67.4%, respectively. Univariate Cox proportional risk regression analysis showed that recipient preoperative use of hormone [hazard ratio ( HR) = 2.079, 95% confidence interval (95% CI) was 1.048-4.128], mPAP ≥ 35 mmHg ( HR = 2.136, 95% CI was 1.129-4.044), NT-proBNP ≥ 300 ng/L ( HR = 2.411, 95% CI was 1.323-4.392), New York Heart Association (NYHA) cardiac function classification Ⅲ-Ⅳ ( HR = 3.021, 95% CI was 1.652-5.523) were the risk factors of early postoperative death in patients with IPF complicated with PAH (all P < 0.05). In the multivariable Cox proportional risk regression analysis, recipient preoperative hormone usage (model 1: HR = 2.072, 95% CI was 1.044-4.114, P = 0.037; model 2: HR = 2.098, 95% CI was 1.057-4.165, P = 0.034), NT-proBNP ≥ 300 ng/L ( HR = 2.246, 95% CI was 1.225-4.116, P = 0.009) and NYHA cardiac function classification Ⅲ-Ⅳ ( HR = 2.771, 95% CI was 1.495-5.134, P = 0.001) were independent risk factors of early postoperative death in patients with IPF. Conclusions:Preoperative hormone usage, NT-proBNP ≥ 300 ng/L, NYHA cardiac function classification Ⅲ-Ⅳ are independent risk factors for early death in patients with IPF and PAH after lung transplantation. For these patients, attention should be paid to optimize their functional status before operation. Preoperative reduction of receptor hormone usage and improvement of cardiac function can improve the early survival rate of such patients after lung transplantation.

Toll-like receptor 2 (TLR2) mediated macrophages regulate the protective immune response to infectious microorganisms, but the aberrant activation of macrophages often leads to pathological inflammation, including tissue damage. In this study, we identified antagonists of TLR2 by screening 2100 natural products and subsequently identified Taspine, an aporphine alkaloid, as an excellent candidate. Furthermore, analysis of the 10 steps chemical synthesis route and structural optimization yielded the Taspine derivative SMU-Y6, which has higher activity, better solubility, and improved drug-feasible property. Mechanistic studies and seq-RNA analysis revealed that SMU-Y6 inhibited TLR2 over other TLRs, hindered the formation of TLR2/MyD88 complex, and blocked the downstream NF-κB and MAPK signaling pathway, thus suppressing the release of inflammatory cytokines. SMU-Y6 could stabilize TLR2 and bind to TLR2 protein with a K_d of 0.18 μmol/L. Additionally, SMU-Y6 could efficiently reverse the M1 phenotype macrophage polarization, reduce the production of cytokines as well as infiltration of neutrophiles and alleviate the local inflammation in mice with acute paw edema and colitis. Collectively, we reported the first aporphine alkaloid derivative that selectively inhibits TLR2 with high binding affinity and superior drug-feasible property, thus providing an urgently-needed molecular probe and potential drug candidate for inflammatory and autoimmune disease therapy.

OBJECTIVE：To investigate the e ffects of Zhuangtongyin water extract （ZTYWE）on hemorheology and blood lipid level of myocardial ischemia-reperfusion model rats ，and preliminarily explore its molecular biology foundation of reducing arrhythmia after myocardial ischemia-reperfusion. METHODS ：Totally 75 SD rats were divided into control group ，model group and ZTYWE low-dose ，middle-dose and high-dose groups. Myocardial ischemia-reperfusion model was established by ligating the left ventricle cyclotron endings for 30 min then reperfusing for 60 min. Since the first day after surgery ，control group and model group were intraperitoneally administrated with same volume normal saline ；ZTYWE low-dose ，middle-dose and high-dose groups were intraperitoneally administrated with medicine solution （6.8，13.6，27.2 g/kg），once a day ，for continuous 28 d. At the 7th， 14th，21st，28th day after surgery ，the incidence rate of arrhythmia of rats were detected. The hemorheology indicators and serum contents of TC ，TG，LDL-C，HDL-C were determined after the last administration. The morphology of myocardial tissue was observed by HE staining. The protein expressions of apoptosis-related factor FAS and FAS-L were detected by Western blotting assay. RESULTS ：Compared with control group ，the incidence rates of arrhythmia of rats in model group were significantly increased；the whole blood contrast viscosity ，hematocrit（HCT），in vitro forming length and quality of thrombosis ，platelet aggregation rate ，erythrocyte filtration index （IF），as well as the serum contents of TC ，TG and LDL-C were significantly increased；in vivo thrombus formation time as well as the serum content of HDL-C were significantly decreased ；the protein expression of FAS and FAS-L were significantly increased （P＜0.05 or P＜0.01）；obvious pathological changes were observed in myocardial tissue. Compared with model group ， the incidence rates of arrhythmia of rats in ZTYWE groups were in obvious reducing trend ； except for the HCT in 163.com low-dose ZTYWE group without significance ， the blood contrast viscosity ，HCT，in vitro forming length and quality of thrombosis ，platelet aggregation rate ，IF as well as the serum contents of TC ，TG and LDL-C were significantly decreased ；in vivo thrombus formation time as well as the serum contents of HDL-C were significantly increased ；the protein expressions of FAS and FAS-L were significantly decreased （P＜0.05 or P＜ 0.01）；the pathological changes of myocardial tissue were improved. CONCLUSIONS ：Through the promoting blood circulation and removing blood stasis effect ，Zhuangtongyin decoction can improve indexes of hemorheology index of ischemia-reperfusion model rats ，reduce the contents of TC ，TG and LDL-C ，enhace the contents of HDL-C ，down-regulate the protein expression of FAS and FAS-L ，so as to inhibit myocardial cells apoptosis and reduce arrhythmia.

OBJECTIVE： To observe the effects of Zhuangtongyin （ZTY） water extract on blood vessels diastolic and systolic function and cardiac function in rats with coronary heart disease （CHD） and its potential mechanism. METHODS： SD rats were randomly divided into control group， sham operation group， model group， positive group （Compound danshen dripping pills， 0.08 g/kg） and ZTY water extract low-dose， medium-dose and high-dose groups （6.8， 13.6， 27.2 g/kg， by weight of water extract）， with 10 rats in each group. Except for control group （no operation） and sham operation group （only open chest without ligation）， CHD model were set up in other groups by ligating the left ventricle cyclotron endings. One week after modeling， control group， sham operation group and model group were given constant volume of water intragastrically， and administration groups were given relevant medicine intragastrically； once a day， for consecutive 4 weeks. Two hours after last administration， cardiac function indexes （LVEDV， LVESV， SV， LVEF） of rats were detected in each group. The levels of inflammatory factors （CRP， IL-1β， IFN-γ and ET-1） in myocardial tissue were determined by ELISA. Histomorphological characteristics of myocardial tissue were determined by HE staining. RESULTS： The structure of myocardial fibers in control group and sham operation group was clear and orderly； there was no statistical significance in difference of each index between 2 groups （P＞0.05）. Compared with control group， myocardial fibers were disorderly arranged in model group， and the phenomena of rupture， dissolution and necrosis were observed， accompanied by infiltration of inflammatory cells. The levels of LVEDV and LVESV as well as the levels of CRP， IL-1β， ET-1 and IFN-γ were increased significantly， while the levels of SV and LVEF were decreased significantly （P＜0.05 or P＜0.01）. Compared with model group， above symptoms of rats in each administration group were improved to different extents； the levels of LVEDV and LVESV as well as the levels of CRP， IL-1β， ET-1 and IFN-γ in positive group， the levels of LVEDV in ZTY water extract medium-dose and high-dose groups， the levels of LVESV and CRP， IL-1β， ET-1， IFN-γ in ZTY water extract groups were decreased significantly. The levels of SV and LVEF in positive group， the levels of SV in ZTY water extract groups as well as the levels of LVEF in ZTY water extract medium-dose and high-dose groups were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： ZTY water extract could reduce the level of ET-1 and improve blood vessels diastolic and systolic function in CHD model rats， then restore blood supply of myocardial tissue and strengthen cardiac function， by acting on inflammation cycle.

OBJECTIVETo discuss the surgical method and clinical efficacy for open tarsometatarsal joint injuries.

METHODSFrom March 2011 to January 2015, 21 patients with open tarsometatarsal joint injuries were treated with stage-surgery method, including 14 males and 7 females with an average age of 45.6 years old ranging from 20 to 75 years. Injury site occurred in the left foot of 13 cases and right foot of 8 cases. Traffic injury was in 5 cases, crush injury in 6 cases, heavy crushing was in 10 cases. According to Myerson to classify for tarsometatarsal joint injury, 5 cases were type B2, 9 cases were type C1, and 7 cases were type C2. And according to Gustilo to typing for soft tissue injury, 5 cases were type IIB, 10 cases were type IIIA, 6 cases were type IIIB. Fracture healingand complications were observed after operation and clinical effects were evaluated according to the midfoot score of AOFAS.

RESULTSAll the patients were followed up from 11 to 40 months with an average of 16.2 months. The fracture healing time was from 10 to 16 weeks with an average of 12.3 weeks. No complications such as deep infection, nonunion and osteomyelitis were found. Midfoot score of AOFAS at last follow-up was 83.0±14.9, 9 cases got excellent results, 8 good, 2 fair, 2 poor. Two patients complicated with severe traumatic arthritis once again underwent tarsometatarsal arthrodesis.

CONCLUSIONSFor the treatment of open tarsometatarsal joint injury, reasonable debridement, comprehensive assessment for the soft tissue injury, correctly grasp the surgical indications and time of internal fixation, can reduce the incidence of deep infection and osteomyelitis.

Objective To understand the correlations between HIV-1 subtypes and changes in CD4+T cell count over time in patients with different subtypes of HIV-1 infection.Methods A total of 94 patients who were diagnosed with HIV-1 infection in Nanjing and received at least twice CD4+T cell counting test before antiretroviral therapy (ART) were recruited in this study.Descriptive analysis was used to present the rates of CD4+T cell decline for different HIV-1 subtypes.Logistic regression analysis and nonparametric test were conducted to investigate the factors responsible for CD4+T cell decline and to analyze the correlations between the rates of CD4+T cell decline and HIV-1 subtypes.Results The median monthly rate of CD4+T cell decline was-2.20 [interquartile range (IQR):-11.36-2.13] cell/μl.Of all patients,25.5% (24/94) had a significant decline (≥30%) in CD4+T cell count.Compared with the patients infected with CRF01_AE,those infected with CRF07_BC (OR=0.28,95%CI: 1.7-6.5) or other subtypes (OR=0.16,95%CI: 1.0-2.9) had a lower risk of significant decline in CD4+T cell count.In addition,results of the nonparametric test showed that the patients infected with CRF01_AE (M=-21.54,IQR:-30.97——11.92 cell/μl) had a faster CD4+T cell loss than those infected with CRF07_BC (M=-11.26,IQR:-14.06——5.63 cell/μl) (P=0.033).Conclusion HIV-1 subtype is associated with the rate of CD4+T cell decline.It is important to monitor the changes in CD4+T cell count in patients infected with CRF01_AE and to carry out timely ART.

Objective To analyze the evolutionary characteristics and predict the variation trend of neuraminidase (NA) gene of influenza A/H1N1 (09pdm) virus in China from 2009 to 2016 in order to provide the basis of assessment for flu vaccines.Methods A total of 1 141 sequences of NA gene of influenza A/H1N1 (09pdm) virus were screened out from the Global Initiative on Sharing All Influenza Data and National Center for Biotechnology Information.The phylogenetic trees and the mutations of amino acids sequences were constructed and analyzed by biological softwares.The prediction for epidemic trend of influenza was analyzed by Bayesian skyline Plot.Results Compared with the sequence of reference strain,the homology of nucleic acid sequence of NA gene decreased year by year from 2009 to 2016.The phylogenetic analysis showed that NA gene clustered nearly on the identical phylogenetic tree in one year.The positive selection pressure site of NA strain was observed by different models in each year except 2012.The dynamics analysis showed that the popularity of influenza A/H1N1 virus may continue to increase to a peak in 2017.Conclusion The amino acid encoded by NA gene of influenza A/H1N1 virus is varying gradually,so the importance of surveillance for influenza virus should be reinforced for every year.

Objective: To analyze the influence of growing experience on non-heterosexual orientation among male college students. Methods: From October to November in 2015, a total of 2 535 male students from 96 classes in 14 colleges/departments were recruited from two colleges that participated in the experimental work of AIDS prevention by cluster random sampling method. A structured questionnaire was administered in this study, including general demographic information, growing experience and Kinsey scale (to evaluate sexual orientation). Out of 2 500 questionnaires distributed in this study, 2 332 effective copies were withdrew, with the effective rate at 93.3%. Chi square test was used to analyze the differences of non-heterosexual orientation among the individuals with different social demographic characteristics. Multivariate logistic regression model was used to analyze the influencing factors of non-heterosexual orientation. Results: Among the 2 332 individuals, the proportion of self-reported non-heterosexual was 6.2% (144).The proportions of male students who identify as non-heterosexual from freshman to junior year were 5.2%(63/1216),6.9%(65/941),11.7%(13/111) and 4.7%(3/64), respectively (χ²=9.06,P=0.029). Compared with the individuals of very good relationship with parents, those with bad relationship (OR=3.3, 95%CI: 1.7-6.5) and general relationship (OR=1.7, 95%CI: 1.0-2.9) with parents had a higher risk of non-heterosexual orientation, respectively. Those encountered sexual assault had a higher risk of non-heterosexual orientation than those without encountered sexual assault (OR=5.9, 95%CI: 3.2-10.9). Conclusions This study reported a high proportion of self-reported non-heterosexual among college male students in Nanjing, and highlighted the importance of targeting students with poor parental relationships and who subjected to sexually abused.

Objective To construct the molecular transmission networks of HIV-1 CRF01 AE strains circulating in China and to analyze their characteristics. Methods Sequences of the pol genes of Chinese CRF01 AE strains were downloaded from Los Alamos database and the related demographic informa-tion was checked. Transmission networks were created by four steps,including phylogenetic tree construc-tion,transmission cluster extraction,minimum genetic distance identification and network visualization. Chi-square test was performed to analyze the differences in the distribution of different populations in the networks and the differences in the distribution of subjects with different degrees among different sub-populations. De-scriptive analysis was used to investigate the transmission links between sub-populations and various regions. Results The 2 419 sequences constituted 250 separate networks including 847 nodes and 610 edges. The number of subjects covered by different networks ranged from 2 to 25. Subjects with degree ≥2 represented only 26. 4%(224 / 847)of network-individuals,but were connected with 66. 5%(563 / 847)of all network-individuals. There were 37. 6%(669 / 1 781)of men who have sex with men(MSM),28. 4%(102 / 359) of heterosexual men,16. 1%(10 / 62)of intravenous drug users(IDUs)and 30. 4%(66 / 217)of hetero-sexual women involved in the networks(χ2 =23. 774,P﹤0. 001). The percentage of subjects with degree ≥2 was high in MSM(10. 8% ,193 / 1 781)compared to that in heterosexual men(5. 6% ,20 / 359)(P =0. 002)and heterosexual women(4. 6% ,10 / 217)(P=0. 004). Of the 669 MSM in the networks,95. 5%(639 / 669)linked to other MSM and only 2. 4% (16 / 669)linked to heterosexual women. However, 15. 1%(10 / 66)of the heterosexual women in the networks linked to MSM. Of the heterosexual men in the networks,35. 3%(36 / 102)linked to heterosexual women,9. 8%(10 / 102)linked to MSM. Of the sub-jects in the networks,20. 9%(177 / 847)linked to other regions' individuals. Conclusion The super-spreaders played an important role in the molecular transmission networks of HIV-1 CRF01 AE strains even though they were in a minority. The transmission of HIV-1 CRF01 AE strains between sub-populations and various regions was complicated and active.

OBJECTIVETo investigate the methods and clinical effects of repairing finger soft tissue defect with free vascularized flaps based on the wrist cutaneous branch of ulnar artery.

METHODSFrom February 2010 to December 2012, 16 patients with finger soft tissue defects were repaired by free vascularized flaps based on the wrist cutaneous branch of ulnar artery, including 10 males and 6 females with an average age of 38.2 years old ranging from 18 to 52 years. Among them, 5 cases caused by hot crush injury, 8 cases caused by machine crush injury, 3 cases caused by firecracker burst injury. The defect area varied from 1.3 cm x 2.3 cm to 2.6 cm x 5.0 cm. The flap area varied from 1.5 cm x 2.5 cm to 2.8 cm x 5.2 cm. The appearance and two-point discrimination of flap were observed after operation.

RESULTSAll flaps survived and wounds healed primarily. No wound infection and skin necrosis were found in donor site and recipient site. Among repair methods, direct suture in forearm donor site had 11 cases and skin graft had 5 cases. All patients were followed up from 6 to 24 months with an average of 10.8 months. The appearance of flap was not fat or clumsy, texture and color were similar to the recipient site, the sensation were good, two-point discrimination was 6 to 9 mm. The appearance of donor site were well complicated with mild scarring without dysfunction obviously.

CONCLUSIONThe free vascularized flaps based on the wrist cutaneous branch of ulnar artery has the advantages of vascular anatomy constant,thickness moderate and carry sensory nerves, etc, which is effective way to repair finger soft tissue defects.

Adolescent ; Adult ; Female ; Finger Injuries ; surgery ; Free Tissue Flaps ; Humans ; Male ; Middle Aged ; Soft Tissue Injuries ; surgery ; Ulnar Artery ; surgery ; Young Adult