Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system. Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life. Sclerotherapy has become the first-line therapy for venous system diseases. However, there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy, and improper operation will cause serious adverse consequences. Therefore, exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy. To solve the above problems, we proposed a new sclerotherapy strategy with a dual mechanism of "vascular damage and plasmin (PLA) system inhibition." We intended to construct a novel cationic surfactant (AEO_x-TA) by reacting tranexamic acid (TA), a parent structure, with fatty alcohol polyoxyethylene ether (AEO_x) by ester bonds. AEO_x-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus. Furthermore, AEO_x-TA could be degraded by esterase and release the parent drug, TA, which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis. In addition, such surfactant-based sclerosants have foam-forming properties, and they can be blended with polyvinyl alcohol (PVA) to prepare a highly stable foam formulation (AEO_x-TA/P), which can achieve a precise drug delivery and prolonged drug retention time, thereby improving drug efficacy and reducing the risk of ectopic embolism. Overall, the novel cationic surfactant AEO_x-TA provides a new avenue to resolve the bottleneck: surfactant sclerosants' efficiency is relatively low in the current sclerotherapy.

Objective To determine the mechanism by which 1,25-dihydroxyvitamin D3(VD3)regulates the Th17/Treg cell balance to improve sepsis-induced acute kidney injury(AKI).Methods C57BL/6 mice were assigned to a sham operation group(sham group),a sepsis group(CLP group),a VD3 group,a VD3+knockdown control group(VD3+sh-NC group),and a VD3+NLRP6 knockdown group(VD3+sh-NLRP6 group)(n=10 per group).A mouse model of sepsis-induced AKI was established by cecal ligation and puncture(CLP).Hematoxylin and eosin staining was used to observe pathological damage to renal tissue.ELISA was used to detect the serum creatinine(sCr),kidney injury molecule 1(KIM-1),interleukin(IL)-17,and IL-10 levels.Flow cytometry was used to determine the Th17 cell and Treg cell numbers in peripheral blood.Western blotting was used to detect the expression of vitamin D receptor(VDR)and NLRP6 pro-teins in renal tissue.Results Administration of VD3 alleviated the pathological kidney damage in CLP mice,reduced the sCr,KIM-1,and IL-17 levels and the proportion of Th 17 cells in peripheral blood.It also increased the proportion of Treg cells and the IL-10 level,and upregulated the expression of VDR and NLRP6 proteins.Knockdown of NLRP6 reversed the effect of VD3on the Th17/Treg cell imbal-ance and its renoprotective effects in CLP mice.Conclusion VD3 exerts protective effects in sepsis-induced AKI.Its mechanism likely involves the activation of VDR,leading to subsequent upregulation of NLRP6 expression,ultimately improving the Th17/Treg cell imba-lance.

Objective To determine the mechanism by which 1,25-dihydroxyvitamin D3(VD3)regulates the Th17/Treg cell balance to improve sepsis-induced acute kidney injury(AKI).Methods C57BL/6 mice were assigned to a sham operation group(sham group),a sepsis group(CLP group),a VD3 group,a VD3+knockdown control group(VD3+sh-NC group),and a VD3+NLRP6 knockdown group(VD3+sh-NLRP6 group)(n=10 per group).A mouse model of sepsis-induced AKI was established by cecal ligation and puncture(CLP).Hematoxylin and eosin staining was used to observe pathological damage to renal tissue.ELISA was used to detect the serum creatinine(sCr),kidney injury molecule 1(KIM-1),interleukin(IL)-17,and IL-10 levels.Flow cytometry was used to determine the Th17 cell and Treg cell numbers in peripheral blood.Western blotting was used to detect the expression of vitamin D receptor(VDR)and NLRP6 pro-teins in renal tissue.Results Administration of VD3 alleviated the pathological kidney damage in CLP mice,reduced the sCr,KIM-1,and IL-17 levels and the proportion of Th 17 cells in peripheral blood.It also increased the proportion of Treg cells and the IL-10 level,and upregulated the expression of VDR and NLRP6 proteins.Knockdown of NLRP6 reversed the effect of VD3on the Th17/Treg cell imbal-ance and its renoprotective effects in CLP mice.Conclusion VD3 exerts protective effects in sepsis-induced AKI.Its mechanism likely involves the activation of VDR,leading to subsequent upregulation of NLRP6 expression,ultimately improving the Th17/Treg cell imba-lance.

Objective:To analyze the clinical characteristics of patients with inflammatory bowel disea-ses(IBD)in pre-pregnancy,pregancy and loctation.Methods:The clinical data of pregnancy compli-cated with IBD in Department of Obstetrics and Gynecology of Peking University Third Hospital and deli-very from September 2011 to June 2022 were collected.The clinical characteristics of the patients were analyzed retrospectively.According to the state of diseases during pre-pregnancy,pregnancy and lactation,the patients were divided into active and remission group,and the two groups were compared interms of pre-pregnancy counseling,nutritional status,pregnancy and delivery complications,gestational week,mode of delivery,and neonatal outcome.Results:A total of 33 pregnant women with IBD were included in this study,of which 7 delivered a second child,for a total of 40 deliveries,with 36 natural pregnan-cies(90.0％)and 4 assisted reproductions(10.0％).Among the 40 cases,21 cases(52.5％)were sustained in remission in pre-pregnancy,pregnancy and lactation,and 19 cases(47.5％)in disease ac-tivity,of which 8 cases(42.1％)were due to self-withdrawal of drugs or failure to take medicine regu-larly.Compared with the activity group,the disease remission group had a higher rate of pre-pregnancy counseling(57.1％vs.15.8％,P=0.010),and higher levels of hemoglobin[(112.67±8.53)g/L vs.(102.84±5.23)g/L,P＜0.001],serum total protein[(66.58±6.34)g/L vs.(60.83±6.25)g/L,P=0.006],serum albumin[36.4(35.1,38.3)g/L vs.34.3(31.1,35.6)g/L,P=0.006],se-rum calcium[(2.25±0.10)μmol/L vs.(2.13±0.15)μmol/L,P=0.004],but a lower incidence of gestational hypertensive disorders(0 vs.31.6％,P=0.007).In 40 deliveries,there were 27 cases of vaginal delivery(67.5％),13 cases of cesarean section(32.5％).The analysis of neonatal outcomes showed 38 full-term deliveries and 2 preterm deliveries;1 case of macrosomia,1 case of small-for-gesta-tional-age,1 case of low birth weight and 3 cases of birth defects.There were 10 newborns admitted to neonatal intensive care unit,including 4 cases of neonatal infections and 2 cases of neonatal jaundice.Conclusion:Pre-pregnancy counseling and evaluation of IBD patients are very important,and good preg-nancy outcomes can be obtained through careful management during pregnancy in the most of the pa-tients.

Objective:To assess and compare the performance of limiting-antigen avidity enzyme immunoassay (LAg-Avidity EIA) and pooling PCR in the surveillance for recent infection rates of HIV-1 in men who have sex with men (MSM).Methods:Blood samples were collected from MSM selected through snowball sampling method in sentinel surveillance in 13 prefectures of Yunnan province from 2016 to 2017. The samples were tested for HIV-1 antibody. The confirmed positive samples were tested by LAg-Avidity EIA. The negative samples were tested by pooling PCR. The recent infection rates of HIV-1 were estimated by the algorithm based on LAg-Avidity EIA and pooling PCR respectively. The two results were compared.Results:During 2016-2017, a total of 5 363 blood samples were collected from MSM, in which 407 samples were HIV-1 positive (including 177 positive tested previously) and 4 956 samples were HIV-1 negative. A total of 211 samples(91.7%) were tested by LAg-Avidity EIA, 69 were confirmed to be recent infections. A total of 4 469 samples were tested by pooling PCR, 8 were confirmed to be acute infections. The recent infection rates of HIV-1 from 2016 to 2017 estimated by LAg-Avidity EIA were 3.36% and 4.84%, and the recent infection rates estimated by pooling PCR were 3.27% and 3.02% respectively. The differences in recent infection rates of HIV-1 estimated by the two algorithms were not significant.Conclusions:The recent infection rates of HIV-1 estimated by LAg-Avidity EIA and pooling PCR in sentinel surveillance in MSM in Yunnan had good consistency from 2016 to 2017. Using the two methods might have a better stability in continuous surveillance for recent infection rates of HIV-1.

Objective:To understand the infection status of HCV and Treponema pallidum (TP) in HIV/AIDS cases in Yunnan province,and identify the risk factors. Methods:Between January 1 and June 30 in 2020,a cross-sectional survey was conducted in Yunnan. Two enzyme-linked immunosorbent assay (ELISA) kits were used to detect anti-HCV, the positive results of both two kits indicated HCV infection. ELISA and syphilis toluidine red untreated serum test were applied to identify TP infection. Both Excel 2016 and SPSS 22.0 software were used for statistical analysis, and logistic regression model was conducted to identify the relevant factors of HCV and TP infection.Results:A total of 5 922 HIV/AIDS cases were included in this study, the infection rates of HCV and TP were 6.5% (383/5 922) and 5.8% (344/5 922) respectively. The co-infection rate of HCV and TP was 0.4% (22/5 922). The risk for HCV infection in HIV/AIDS cases was higher in younger age groups compared with age group ≥50 years (15-19:a OR=3.53;20-29:a OR=3.02;30-39:a OR=2.91;40-49:a OR=3.61), in males than in females (a OR=2.31), in the married and unmarried than in the divorced or widowed (married:a OR=1.61;unmarried:a OR=1.63), in other ethnic groups than in Han ethnic group (a OR=1.70), in people with lower education level than in people with education level of college and above (primary school degree and below:a OR=4.69;middle school:a OR=3.96), in people living in the central and western Yunnan than in people living in eastern Yunnan (central Yunnan:a OR=2.46; western Yunnan:a OR=7.08), in injection drug users than in MSM (a OR=131.08). The risk of TP infection in HIV/AIDS cases was higher in people with education level of college and primary school than in middle school degree (primary school and below:a OR=1.73;college and above:a OR=1.77), in people with other occupations than in farmers (a OR=1.39), in people living in eastern Yunnan than in people living in western Yunnan (a OR=1.75); in MSM than in people with heterosex (a OR=9.75). Conclusions:A certain proportion of HIV/AIDS cases reported between January and June in 2020 in Yunnan were co-infected with HCV and TP, many factors were associated with the co-infection. It is suggested to strengthen HCV and TP tests in HIV/AIDS cases and conduct active treatment of the co-infection.

Objective:To analyze the characteristics of HIV-1 molecular network in men who have sex with men (MSM) from 2016 to 2018 in Kunming, Yunnan province, explore the risk factors associated with HIV-1 transmission network and provide evidence for the effective implementation of intervention.Methods:A total of 540 samples of newly reported HIV-1 positive MSM were consecutively collected in Kunming from 2016 to 2018, the pol gene fragments were amplified by nested polymerase chain reaction (PCR). HIV-1 molecular networks were constructed according to the bootstrap value of the maximum likelihood evolutionary tree over 95% and the genetic distance less than 3%. The factors associated with the subjects entering network and network growth were further analyzed. Results:Among 459 successfully sequenced samples, seven genotypes were found, in which CRF07_BC (49.2%, 226/459) and CRF01_AE (40.3%, 185/459 ) were predominant. Other genotypes included URFs (4.8%, 22/459), CRF08_BC (3.1%, 14/459), CRF55_01B (1.7%, 8/459), B (0.7%, 3/459) and CRF68_01B (0.2%, 1/459). A total of 163 sequences entered the network, with an entry rate of 35.5%(163/459), forming 56 clusters with the number of individuals in the cluster was between 2 and 13. The analysis of the factors associated with entering network showed that the MSM who married and had multiple homosexual partners were more likely to be found in HIV-1 molecular networks. Multivariate logistic regression analysis showed that the number of sexual partners was the factor for the growth of HIV-1 molecular network. According to the criteria for the emergence of three or more newly reported cases in every year, six transmission clusters were judged as active transmission clusters, in which MSM who were not Kunming natives, had sexually transmitted diseases (STD), were divorced and students were the key targets of intervention.Conclusions:HIV-1 genotypes in MSM in Kunming were becoming complex, the risk factors associated with transmission networks in MSM in Kunming included being married and having multiple partners, the intervention targets in active transmission clusters included MSM who were not Kunming natives, had STD, were divorced and students. This study provided the basis for applying HIV-1 molecular networks to real-time intervention in this population.

Objective:To understand the characteristics of HIV-1 genotypes and drug resistance among men who have sex with men in Kunming in 2018.Methods:A total of 193 plasma samples were collected from the newly reported HIV-1 infected MSM in Kunming from January to December 2018. Viral RNA was extracted, and the gag, pol, env gene segments were amplified by nested PCR. HIV-1 genotypes and drug resistance were also analyzed. Subsequently, the evolutionary characteristics of CRF55_01B and CRF68_01B among MSM in Kunming were analyzed by Bayesian Markov Chain Monte Carlo method. Results:Multiple HIV-1 genotypes were identified among these 193 samples, including CRF07_BC (39.4%, 76/193), CRF01_AE (34.2%, 66/193), unique recombinant forms (URFs) (20.2%, 39/193), CRF08_BC (3.1%, 6/193), CRF55_01B (1.6%, 3/193), subtype B (1.0%, 2/193) and CRF68_01B (0.5%, 1/193). Results from the Bayesian evolutionary analysis showed that CRF55_01B started to spread locally after being imported from other provinces, while CRF68_01B was likely to have been brought in from the eastern provinces of China. Prevalence of HIV-1 drug resistant strains was 2.6%(5/190) before antiviral treatment, with mutation rates resistant to non-nucleoside reverse transcriptase inhibitors being the highest (2.1%, 4/190) among MSM in Kunming, 2018.Conclusion:The diversity of HIV-1 was increasing among MSM in Kunming. Although the resistance rate on pretreatment drug was relatively low, the emergence of multiple resistant strains to first-line antiviral drugs posed a challenge to antiretroviral therapy, in Kunming.

Objective: To understand the distribution of HIV-1 genotypes and the status of drug resistance among people living with HIV who had prepared to initiate antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefecture (Dehong). Methods: A total of 170 adults with HIV were recruited in Dehong from January to June 2017, before initiating ART. HIV-1 pol genes were amplified and used to analyze the HIV-1 genotypes and drug resistance. Results: A total of 147 samples were successfully sequenced. Based on the phylogenetic analysis, 12 HIV-1 genotypes were found among the subjects, including three predominant genotypes such as subtype C (29.9%, 44/147), unique recombinant forms (URFs) (27.2%, 40/147) and CRF01_AE (19.7%, 29/147). Circulating recombinant forms (CRFs) which were newly identified in this area in recent years were also found among these subjects, including CRF62_BC, CRF64_BC, CRF86_BC and CRF96_cpx. The distribution of HIV-1 genotypes between heterosexual transmission or intravenous drug use, showed statistical difference. Surveillance drug resistance mutations (SDRMs) were found among 8.8% (13/147) of the subjects. Proportion of drug resistant strains among injecting drug users (25.0%, 8/32) was higher than that among those heterosexual transmitted individuals (4.6%, 5/109, χ²=10.166, P=0.002). Conclusions Among people living with HIV-1 who had prepared to initiate ART, their HIV-1 genetics were highly complicated, with moderate prevalence rate of HIV-1 drug-resistant strains.

Bacitracin is a broad-spectrum polypeptide antibiotic, which is formed by 11 amino acids residues. Precursor amino acids supply might be the limit factor during bacitracin fermentation. First, our results demonstrated that increasing Ile and Leu supplies were regarded as the efficient strategies for the enhanced titer of bacitracin. Then, the amino acid permease YhdG, which was identified as the BCAA permease, was deleted and overexpressed in DW2, respectively. Our results showed that knocking out of permease YhdG could improve bacitracin production remarkablely. The bacitracin titer of the yhdG deficient strain DW2ΔyhdG reached 917.35 U/mL by flask fermentation, increased by 11% compared with that of DW2. In addition, the bacitracin titer was decreased by 25% in the YhdG overexpressed strain. Meanwhile, the intracellular concentrations of BCAA were higher than DW2 during the biosynthesis of bacitracin. The above results suggested that the permease YhdG might act as an exporter for branched chain amino acids in B. licheniformis DW2. Taken together, the increasing intracellular concentrations of branched chain amino acids by deleting amino acid permease YhdG could improve bacitracin titer. This study provided a new strategy for high-level production of bacitracin.