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.

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.

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.

Objective:To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests.Methods:Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope ? hybridization and electron microscopy. Results:All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri′s bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope ? hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions:The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.

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.

Objective To investigate the effect of chemokine CXC ligand 9(CXCL9)on cognitive function impairment in patients with breast cancer brain metastases undergoing whole-brain radiotherapy(WBRT)using bioinformatics methods.Methods The mRNA of breast cancer brain metastases datasets GSE43837 and GSE12276 and Alzheimer's disease(AD)dataset GSE161199 were screened and downloaded from GEO database.Limma method and Venn diagrams were used to identify common differentially expressed genes(DEGs),and protein-protein interaction and functional prediction through GeneMANIA website assays were performed.A total of 42 patients with breast cancer brain metastases who first visited the Department of Radiotherapy at the First Affiliated Hospital of Hebei North University from January 2021 to January 2023 were selected.Patients were divided into normal cognitive function group and cognitive function impairment group based on cognitive status.Enzyme-linked immunosorbent assay(ELISA)was employed to detect serum CXCL9 levels one week before and three months after radiotherapy.The mini-mental state examination(MMSE)was used to assess patients'cognitive function.Results The DEGs from datasets GSE43837 and GSE12276 included PKP1,POLDIP2,SPAG5,ALDOC,PTPRZ1,PKIA,TLCD1,CPE,PMP22 and CXCL9.The DEGs from GSE161199 included RPS16,CD79A,LYPD3,RPL28,HBG2,RPL23AP7,TRNR,CXCL9.Venn diagram showed that CXCL9 was a common DEG between breast cancer brain metastasis and AD.Functional enrichment analysis indicated that CXCL9 was involved in cellular responses to chemokines,negative regulation of immune system processes,negative regulation of vascular morphogenesis,Toll-like receptor signaling pathway,nucleotide oligomerization domain(NOD)-like receptor signaling pathway,and JAK-STAT signaling pathway.Before radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 61.9%and 38.1%,respectively,with a statistically significant difference in MMSE scores[(24.53±2.19)vs.(28.89±1.36),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had a significantly increased number of brain metastases and significantly lower Karnofsky performance status(KPS)scores and serum CXCL9 levels(P＜0.05).Three months after radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 47.6%and 52.4%,respectively,with a statistically significant difference in MMSE scores[(25.16±1.98)vs.(28.18±1.08),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had significantly lower CXCL9 levels(P=0.003).In patients with normal cognitive function,CXCL9 levels were remarkably lower after radiotherapy compared to those before radiotherapy(P=0.009).Conclusions Patients with cognitive function impairment had significantly lower CXCL9 levels than those with normal cognitive function,and whole-brain radiotherapy may be related to a certain degree of reduction in CXCL9 levels.

Objective To study the differences and mechanisms of damage to the reproductive organs of male rats by single and compound exposure to microwaves at 2.856 and 9.375 GHz.Methods A total of 40 male Wistar rats were randomly divided into sham group,S10 group,X10 group and SX5 group.Microwavesat 2.856 and 9.375 GHz were used to expose the rats for 6 min in the S10 and X10 groups with an average power density of 10 mW/cm2,respectively.The SX5 group was sequentiallyexposed to 2.856 and 9.375 GHz microwaves with an average power density of 5 mW/cm2 for 6 min.At 1 and 7 d after exposure,the sperm viability and serum sex hormones were detected by light microscopy and electron microscopy,and testicular tissue structure and oxidative stress and energy metabolism levels were examined.Results The sperm viability,testosterone(T),follicle stimulating hormone(FSH),and inhibin B(INHB)decreased in the S10 and X10 groups at 1 and 7 d after exposure(P＜0.01),and in the SX5 group at 7 d after exposure(P＜0.05).The LH decreased in all the exposure groups at 1 d after exposure(P＜0.01),and increased in the S10 and X10 groups at 7 d after exposure(P＜0.05).The spermatogenic epithelium of testicular tissue was lax,spermatogenic cells were edematous and vacuolated,chromatin condensed and shifted side by side,and the damage was significant in the S10 and X10 groups as compared with the SX5 group.The superoxide dismutase(SOD)activity in testis tissue decreased and malondialdehyde(MDA)content increased at 1 and 7 d after exposure in the S10 group(P＜0.01).In the X10 group,the SOD decreased at 1 d after exposure(P＜0.01).The lactate dehydrogenase(LDH)and succinate dehydrogenase(SDH)activity and adenosine triphosphate(ATP)content in testis tissue decreased at 1 and 7 d after exposure in the S10 and X10 groups(P＜0.05).In the SX5 group,the LDH and SDH decreased at 1 d after exposure(P＜0.05).Conclusion Single and combined exposure to S-band and X-band microwaves can cause damage to male reproductive organs.The S-band causes damage more significantly than that of X-band.Single-frequency microwave high-intensity exposure causes damage more significantly than that of multi-frequency microwave prolonged combined exposure.The damage is closely related to oxidative stress and energy metabolism.