Objective: To investigate the knowledge of hepatitis C prevention and treatment and related factors among two groups of female sex workers (FSW) and men who have sex with men (MSM) in the Xizang Autonomous Region (Xizang) to provide a basis for the subsequent development of Hepatitis C publicity and education strategies. Methods: From August to September 2021, a special survey was conducted among 1 244 FSW and 234 MSM in 5 districts (counties) of 4 regions in Xizang. A one-on-one face-to-face questionnaire survey was adopted, and the χ² test and logistic regression were used to analyze the related factors of awareness of hepatitis C prevention and treatment among FSW and MSM. Results: The awareness rates of hepatitis C prevention and treatment knowledge among FSW and MSM were 35.0% (436/1 244) and 11.1% (26/234), respectively. Multivariate logistic regression analysis revealed that the positive related factors of FSW' awareness of hepatitis C prevention and treatment knowledge among those who had high school or technical secondary school education (aOR=4.72, 95%CI: 3.30-6.74) and college education or above (aOR=2.24, 95%CI: 1.58-3.18), those who experienced self-perceived risk of HCV infection (aOR=1.87, 95%CI: 1.43-2.45), negative related factors included married or cohabiting (aOR=0.58, 95%CI: 0.35-0.95), divorce or windowless (aOR=0.44, 95%CI: 0.27-0.72), no condom was used in the most recent commercial sexual activity (aOR=0.54, 95%CI: 0.43-0.69). The positive related factors of MSM's awareness of hepatitis C prevention and treatment knowledge were over 40 years old (aOR=8.65, 95%CI: 3.19-23.42) and having a self-perceived risk of HCV infection (aOR=6.25, 95%CI: 2.50-15.61). Conclusions: The awareness rate of hepatitis C prevention and treatment among FSW and MSM was relatively low in Xizang in 2021 and urgently needs to be improved. It is necessary to formulate targeted publicity strategies based on the characteristics of these two groups of people, increase publicity efforts, and expand the coverage of knowledge publicity to popularize key points about the clinical manifestations, treatment options, and transmission routes of hepatitis C, and carry out necessary warnings and education.
Humans ; Male ; Hepatitis C/therapy* ; Health Knowledge, Attitudes, Practice ; Surveys and Questionnaires ; Sex Workers/psychology* ; Homosexuality, Male ; Female ; Adult ; China ; Young Adult ; Middle Aged ; Logistic Models

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

Background::Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients.Methods::We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177 + neutrophils, and CD40L + T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs. persistent histological inflammation using Kaplan-Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. Results::We developed an ICEI for clinical diagnosis of histological healing, i.e., Y = 1.701X 1 + 0.758X 2 + 1.347X 3 - 7.745 (X 1, X 2, and X 3 represent the proportions of CD177 + neutrophils, eosinophils, and CD40L + T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905-0.979) with a sensitivity of 92.5% and a specificity of 83.6% ( P <0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781-0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748-0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing ( P <0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. Conclusions::ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC.Registration::Chinese Clinical Trial Registry, No. ChiCTR2300077792.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Objective To explore the effect of Shuanglu Tongnao Formula on neuronal ferroptosis in ischemic stroke rats and its regulatory mechanism on the silent information regulator 2 homolog 1(SIRT1)/nuclear factor erythroid 2-related fac-tor 2(Nrf2)/glutathione peroxidase 4(GPx4)signaling pathways.Methods Twenty rats were selected as sham operation group by the random number table method,and the remaining seventy rats were made ischemic stroke rat models by the middle cerebral artery occlusion method.The rats that had been successfully modeled were randomly divided into the model control group,Shuanglu Tongnao formula group,Shuanglu Tongnao formula+SIRT1 inhibitor group(Shuanglu Tongnao formula+EX527 group),with 20 rats in each group.After 14 days,the rats were scored for neurological injury;TTC staining was applied to detect the area of cerebral infarction in rats;HE staining was applied to detect pathological changes in rat brain tissue;Nissl staining was applied to detect the number of neurons in rat brain tissue;the kit was applied to detect the levels of ferri ion(Fe2+),superoxide dismutase(SOD),glutathione(GSH),and malonaldehyde(MDA)in rat brain tissue;immunohistochemistry was applied to de-tect the positive expression of acyl-CoA synthetase long-chain family member 4(ACSL4),transferrin receptor(TFR),and ferritin heavy polypeptide 1(FTH1)proteins in rat brain tissue;Western blotting method was applied to detect the expression of SIRT1,Nrf2,GPx4,and cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11)proteins in rat brain tissue.Results Compared with the sham operation group,the neurological deficit score,cerebral infarction area,the contents of Fe2+and MDA,and the protein expressions of ACSL4 and TFR in model control group were increased(P<0.05);the number of neurons,the con-tents of SOD and GSH,the protein expression of FTH1,SIRT1,Nrf2,GPx4,and SLC7A11 were all reduced(P<0.05).Compared with the model control group,the neurological deficit score,cerebral infarction area,the contents of Fe2+and MDA,and the protein expression of ACSL4 and TFR in the Shuanglu Tongnao formula group were reduced(P<0.05),and the number of neurons,the contents of SOD and GSH,the protein expressions of FTH1,SIRT1,Nrf2,GPx4,and SLC7A11 are all increased(P<0.05).The results of the SIRT1 inhibitor supplementation experiment showed that the SIRT1 inhibitor reversed the inhibitory effect of Shuan-glu Tongnao formula on neuronal ferroptosis,while also inhibited the expression of Nrf2 and GPx4(P<0.05).Conclusion The Shuanglu Tongnao formula may inhibit neuronal ferroptosis in ischemic stroke rats by activating the SIRT1/Nrf2/GPx4 signa-ling pathway.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective To investigate the application of pre-hemostatic suturing in adolescent circumcision with a stapler.Methods A total of 120 patients with long foreskin treated in our hospital were included,and they were divided into two groups by random number table method,among which the patients in the observation group received circumcision with a stapler after pre-hemostatic suturing of the foreskin vessels,and these in the control group received conventional circumcision with a stapler.The operation time,intraoperative blood loss,postoperative healing time and occurrence of postoperative hematoma of the two groups were analyzed.Results There was no significant difference in the operation time between the two groups(P＞0.05).The intraoperative blood loss in the observation group was less than that in the control group,the postoperative healing time was shorter than that in the control group,and the incidence of postoperative hematoma was lower than that in the control group,with statistically significant differences(P＜0.05).Conclusion The application of pre-hemostatic suturing in circumcision with a stapler can improve surgical safety,with ease of learning,which may increase the benefit of patients.

Objectives:The purpose of this study was to investigate the clinical efficacy of percutaneous endoscopic transforaminal lumbar interbody fusion(PE-TLIF)in patients with single-segment lumbar spinal stenosis and explore the changes of paraspinal muscles and adjacent segmental facet joints of operative segement after PE-TLIF.Methods:28 patients with L4/5 lumbar spinal stenosis treated with PE-TLIF in Beijing Chaoyang Hospital from March 2017 to March 2019 were analyzed retrospectively.The patients consisted of 12 males and 16 females with an average age of 58.0±8.7 years(41-79 years)and were followed up for 40.7±3.6 months(36-58 months).The visual analogue scale(VAS)of low back pain(VAS-LBP)and VAS of leg pain(VAS-LP)were collected at pre-operation,postoperative 1-week follow-up,3-month follow-up,12-month follow-up and the final follow-up;Oswestry disability index(ODI)was evaluated at pre-operation,post-operative 3-month follow-up,12-month follow-up and the final follow-up.CT examination was performed at pre-operation,postoperative 12-month follow-up,24-month follow-up and the final follow-up,the cross-sec-tional area(CSA)and fat infiltration(FI)score of multifidus(MF)were measured,and the degeneration degree of adjacent segmental facet joints was evaluated according to the score of facet joint degeneration.The differ-ences of MF CSA and FI score,as well as adjacent segmental facet joint degeneration were compared be-tween preoperation and postoperation.Results:The VAS-LBP score was 3(2,3)at 1-week follow-up,1(1,2)at 3-month follow-up,1(0,2)at 12-month follow-up,and 1(0,1)at the final follow-up,which was signif-icantly improved compared with the preoperative score of 7(7,8)(P＜0.05);the VAS-LP score was 2(1,3)at 1-week follow-up,1(1,2)at 3-month follow-up,1(0,1)at 12-month follow-up,and 0(0,1)at the final fol-low-up,which were significantly improved compared with the preoperative score of 6(5,7)(P＜0.05);The ODI at 3-month follow-up was 23％(19％,31％),at 12-month follow-up was 12％(8.5％,17.5％),and at the final follow-up was 7％(4％,15.6％),all significantly improved compared with the ODI before operation of 61％(55％,67％)(P＜0.05).The postoperative MF CSAs of 547.12±53.31mm2(12-month follow-up),558.35±52.37mm2(24-month follow-up),and 531.21±56.12mm2(final follow-up)were not significantly changed from the preoper-ative MF CSA of 557.06±46.72mm2(P＞0.05).There was no significant difference in FI score between pre-op-eration of 2(2,3)and 12-month follow-up of 3(2,3),24-month follow-up of 3(2,3)and the final follow-up of 3(3,3)(P＞0.05).The postoperative facet joint degeneration scores of upper segment facet joint(USFJ)of 5(4,6)at 12-month follow-up,5(4,5)at 24-month follow-up,and 5(4,6)at final follow-up were not signifi-cantly changed from the preoperative 5(4,6)(P＞0.05).And there was no significant difference either in facet joint degeneration score of lower segment facet joint(LSFJ)between pre-operation of 5(4,6)and 12-month follow-up of 5(4,5),24-month follow-up of 5(4,6)and the final follow-up of 5(4,7)(P＞0.05).Conclusions:PE-TLIF can achieve satisfactory clinical outcomes in the treatment of single-segment lumbar spinal stenosis,which has no significant effect on multifidus in the surgical segment and adjacent segmental facet joints in the mid-to long-term.

Objective:To investigate key differential expressed genes(DEGs),enriched biological functions and signaling pathways in exosomes derived from angiosarcoma cells ISOHAS and angiosarcoma stem-like cells Sphere by bioinformatics analysis,to provide new therapeutic targets for angiosarcoma.Methods:Transcriptome sequencing of exosomes derived from ISOHAS and Sphere were performed to screen for DEGs by|log2FC|>2 and FDR<0.05 as criteria.Bioinformatics analysis was used to enrich GO and KEGG pathways of DEGs to identify biological functions and signaling pathways of enriched DEGs.STRING database was used to screen key DEGs,and iPath was used to visualize to identify metabolic pathways enriched by DEGs.Results:Transcriptome sequencing results showed that 91 DEGs were identified in exosomes derived from ISOHAS and Sphere.GO and KEGG pathway enrichment analysis demonstrated that main biological functions and signaling pathways enriched by DEGs were response to glucocorticoid and TNF signaling pathway,respectively.STRING database demonstrated that TNF and IL-6 were key DEGs.iPath metabolic network analysis demonstrated that DEGs were mainly identified in lipid metabolism and nucleotide metabolism.Conclusion:Sphere-derived exosomes may influence occurrence and development of angiosarcoma by carrying key genes TNF and IL-6 to interfere with glucocorticoid response,TNF signaling pathway,lipid metabolism,nucleotide metabolism and other biological functions and signaling pathways,providing new ideas for therapeutic targets for angiosarcoma.