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Run-Nan Xu,1 Jian-Xiong Ma,2 Xin Zhang,1 Ze-Dong Liao,2 Yi-Jia Fu,1 Bo-Dong Lv2 1The Second Affiliated Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Urology, School of Medicine, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Bo-Dong Lv, Department of Urology, School of Medicine, The Second Affiliated Hospital, Zhejiang University, 88 Jiefang Road, Shangcheng District, Hangzhou City, Zhejiang Province, People’s Republic of China, Tel +8613805722233, Email lbd168@zju.edu.cnIntroduction: Erectile dysfunction (ED) is a prevalent condition in urology, primarily managed with PDE5 inhibitors (PDE5Is). However, approximately 20% of patients do not experience improvement in overall sexual satisfaction (OS) after taking PDE5Is. Among these, traditional Chinese medicine (TCM) has emerged as a complementary approach, with formulas like Hongjing I granules (HJIG) showing promise in preliminary studies. This study aims to rigorously evaluate the effectiveness and safety of HJIG in mild to moderate ED cases, assessing improvement in both sexual function and TCM pattern alignment.Methods: This study is a randomized, double-blind, placebo-controlled multicentre trial. Recruitment will be conducted from patients who have a strong willingness to try using only traditional Chinese medicine treatment (This is very common in traditional Chinese medicine hospitals.). A total of 100 patients diagnosed with mild to moderate ED caused by qi deficiency and blood stasis will be recruited and randomly assigned to receive one of two treatments: HJIG (N = 50) or placebo (N = 50). Patients will receive 8 weeks of treatment and a 16-week follow-up starting from the fourth week of treatment. Outcome measures, including the International Index of Erectile Function-Erectile Function domain (IIEF-EF) score, Sexual Encounter Profile (SEP), and Traditional Chinese Medicine symptom score, will be evaluated.Discussion: The expected outcome of this trial is that the use of the herbal formula HIJG alone can improve overall sexual satisfaction (OS) in patients with mild to moderate ED, while also improving their traditional Chinese medicine symptom scores. This will provide evidence-based support for the use of Chinese medicine in the treatment of ED in China.Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000041127, Registered on 19 December 2020, https://www.chictr.org.cn/showproj.html?proj=46469.Trial Status: Recruitment began in March 2021, therefore 80 patients have been recruited. It is expected to finish recruiting in December 2023.Keywords: erectile dysfunction, traditional Chinese medicine, Chinese herbal formula, Hongjing I granules, clinical trials, clinical protocols, alternative medicine

Objective: To determine the key factors influencing intraoperative-acquired pressure injury (IAPI)., Methods: Researchers assessed 413 surgical patients in a Shanghai tertiary hospital using an information collection form and an IAPI occurrence record form. Analysis took place using the classification and regression tree algorithm and multiple logistic regression., Results: A total of 43 surgical patients (10.4%) had IAPI, including 32 stage 1 cases (74.4%), and 11 stage 2 cases (25.6%). The multiple logistic regression analysis indicated that operation duration, surgical position, preoperative hypertension, and preoperative Braden Scale risk score were independently associated with IAPI development. The decision tree showed that preoperative Braden Scale score, surgical position, operation grade, operation duration, age, prealbumin level, and body mass index were important factors and that preoperative Braden Scale score was the most critical decision variable. The cross-validation method was used to indicate a model accuracy of 91.8%., Conclusions: The decision tree effectively identified key factors for IAPI, complementing the logistic regression analysis and providing a scientific basis for the further development of structural risk assessment, prevention, and treatment strategies for IAPI., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

(1) Background: Epidemiological studies on the relationship between serum copper and hypertension are contradictory. We assessed the relationship between serum copper and blood pressure among adults in the United States. (2) Methods: We divided hypertension into two categories: treated hypertension and untreated hypertension. Linear or logistic regression analysis was applied to investigate the association between serum copper concentrations and blood pressure levels. (3) Results: As compared to quartile 1, the odds ratios (ORs) for untreated hypertension in quartiles 2, 3, and 4 were 1.02 (0.74-1.42), 1.23 (0.88-1.72), and 1.08 (0.74-1.58), respectively, in multivariable analysis (all p > 0.05). In non-hypertension, as compared with quartile 1, the β (95% CI) of systolic blood pressure for quartiles 2, 3, and 4 was -0.92 (-2.07-0.23), -0.05 (-1.30-1.20), and -0.48 (-1.83-0.88), respectively, in multivariable analysis (all p > 0.05). As compared to quartile 1, the ORs for treated hypertension in quartiles 2, 3, and 4 were 1.36 (0.88-2.10), 1.35 (0.87-2.09), and 1.56 (0.98-2.47), respectively, upon multivariable analysis including antihypertensive medication use as a covariate (all p > 0.05). Furthermore, 1SD increase in serum copper was non-significantly associated with 1.16 (0.97-1.37)-fold increased risk of hypertension in multivariable analysis ( p = 0.096). (4) Conclusion: In the present study, we discovered that the serum copper concentration was not related with hypertension or blood pressure levels. Antihypertensive drug use may distort the correlation between copper and blood pressure levels. Information on antihypertensive drug use may be taken into account when identifying new risk factors for hypertension.

The intestinal epithelial barrier plays an important role during human immunodeficiency virus (HIV) disease progression. However, the extent to which the intestinal epithelial barrier is damaged in immunological non-responders (INRs) and immunological responders (IRs) is largely unknown. In this study, we investigated and compared the levels of intestinal gland damage and related molecules, including the tight junction protein claudin-1, apoptosis marker caspase-3, HIV DNA, CD4 + T cell count, and inflammation marker tumor necrosis factor-α (TNF-α) among the IRs (n = 10), INRs (n = 8), and healthy controls (HCs, n = 7). Intestinal damage was not completely restored in both INRs and IRs and was more serious in INRs than that in IRs. Moreover, intestinal damage was positively correlated with HIV DNA levels and negatively correlated with CD4 + T cell counts. These results provide insight into understanding the characteristics of intestinal epithelial barrier damage between IRs and INRs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Penis cavernosa fibrosis is an important cause of refractory erectile dysfunction.Its exact pathogenesis remains incompletely elucidated, and conventional treatment is not effective, seriously affecting the quality of life, physical and mental health of men. With the deepening of research, the progress of two-dimensional shear wave elastography (2D-SWE) and molecular imaging provides the possibility for the early diagnosis, grading and staging of cavernous fibrosis. Studies on stem cell therapy, energy-based treatments, targeted therapy, and traditional Chinese medicine show promising applications in the anti-penile cavernous fibrosis. This article reviews the research progress in the diagnosis and treatment of penile cavernosis fibrosis.

Objective: A comprehensive immune landscape for HBV infection is pivotal to achieve HBV cure., Design: We performed single-cell RNA sequencing of 2 43 000 cells from 46 paired liver and blood samples of 23 individuals, including six immune tolerant, 5 immune active (IA), 3 acute recovery (AR), 3 chronic resolved and 6 HBV-free healthy controls (HCs). Flow cytometry and histological assays were applied in a second HBV cohort for validation., Results: Both IA and AR were characterised by high levels of intrahepatic exhausted CD8+ T (Tex) cells. In IA, Tex cells were mainly derived from liver-resident GZMK+ effector memory T cells and self-expansion. By contrast, peripheral CX3CR1+ effector T cells and GZMK+ effector memory T cells were the main source of Tex cells in AR. In IA but not AR, significant cell-cell interactions were observed between Tex cells and regulatory CD4+ T cells, as well as between Tex and FCGR3A+ macrophages. Such interactions were potentially mediated through human leukocyte antigen class I molecules together with their receptors CANX and LILRBs, respectively, contributing to the dysfunction of antiviral immune responses. By contrast, CX3CR1+GNLY+ central memory CD8+ T cells were concurrently expanded in both liver and blood of AR, providing a potential surrogate marker for viral resolution. In clinic, intrahepatic Tex cells were positively correlated with serum alanine aminotransferase levels and histological grading scores., Conclusion: Our study dissects the coordinated immune responses for different HBV infection phases and provides a rich resource for fully understanding immunopathogenesis and developing effective therapeutic strategies., Competing Interests: Competing interests: ZZ is a founder of Analytical Bioscience and an advisor for InnoCare. All financial interests are unrelated to this study. The remaining authors declare no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cardiovascular disease (CVD) is a constellation of heart, brain, and peripheral vascular diseases with common soil hypothesis of etiology, and its subtypes have been well-established in terms of the albumin-mortality association. However, the association between albumin and the mortality of CVD as a whole remains poorly understood, especially the non-linear association. We aimed to investigate the association of albumin levels with long-term mortality of CVD as a whole., Materials and Methods: This study included all CVD patients who participated in the National Health and Nutrition Examination Survey (NHANES 2011-2014). CVD was defined as coronary heart disease, stroke, heart failure, or any combination of these two or three diseases. Serum albumin was tertile partitioned: tertile 1, <4.1; tertile 2, 4.1-4.3; and tertile 3, >4.3 g/dl. COX proportional hazards model was used to assess the association between the serum albumin levels and CVD mortality. Restricted cubic spline (RCS) curves were used to explore the non-linear relationship., Results: A total of 1,070 patients with CVD were included in the analysis, of which 156 deaths occurred during a median 34 months of follow-up. On a continuous scale, per 1 g/dl albumin decrease was associated with an adjusted HR (95% CI) of 3.85 (2.38-6.25). On a categorical scale, as compared with tertile 3, the multivariable adjusted hazard ratio (95% CI) was 1.42 (0.74-2.71) for the tertile 2, and 2.24 (1.20-4.16) for the tertile 1, respectively, with respect to mortality. RCS curve analysis revealed a J-shaped association between albumin and CVD mortality., Conclusion: A J-shaped association between low serum albumin levels and increased long-term mortality of CVD has been revealed. This J-shaped association's implications for CVD prevention and treatment are deserving of being further studied., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Zhang, He, Li, Xu, Wang, Jiang, Chen and He.)

Recent studies highlighted that CD8+ T cells are necessary for restraining reservoir in HIV-1-infected individuals who undergo antiretroviral therapy (ART), whereas the underlying cellular and molecular mechanisms remain largely unknown. Here, we enrolled 60 virologically suppressed HIV-1-infected individuals, to assess the correlations of the effector molecules and phenotypic subsets of CD8+ T cells with HIV-1 DNA and cell-associated unspliced RNA (CA usRNA). We found that the levels of HIV-1 DNA and usRNA correlated positively with the percentage of CCL4+CCL5- CD8+ central memory cells (T CM ) while negatively with CCL4-CCL5+ CD8+ terminally differentiated effector memory cells (T EMRA ). Moreover, a virtual memory CD8+ T cell (T VM ) subset was enriched in CCL4-CCL5+ T EMRA cells and phenotypically distinctive from CCL4+ T CM subset, supported by single-cell RNA-Seq data. Specifically, T VM cells showed superior cytotoxicity potentially driven by T-bet and RUNX3, while CCL4+ T CM subset displayed a suppressive phenotype dominated by JUNB and CREM. In viral inhibition assays, T VM cells inhibited HIV-1 reactivation more effectively than non-T VM CD8+ T cells, which was dependent on CCL5 secretion. Our study highlights CCL5-secreting T VM cells subset as a potential determinant of HIV-1 reservoir size. This might be helpful to design CD8+ T cell-based therapeutic strategies for cure of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Li, Zhen, Wang, Huang, Zou, Zheng, Huang, Meng, Jin, Li, Zhou, Fu, Zhang, Li, Yang, Wang, Yang, Song, Fan, Jiao, Xu, Zhang, Zhou, Yuan, Huang, Qin, Wu, Shi, Wang and Zhang.)

To obtain a comprehensive scenario of T cell profiles and synergistic immune responses, we performed single-cell RNA sequencing (scRNA-seq) on the peripheral T cells of 14 individuals with chronic human immunodeficiency virus 1 (HIV-1) infection, including nine treatment-naive (TP) and eight antiretroviral therapy (ART) participants (of whom three were paired with TP cases), and compared the results with four healthy donors (HD). Through analyzing the transcriptional profiles of CD4 + and CD8 + T cells, coupled with assembled T cell receptor sequences, we observed the significant loss of naive T cells, prolonged inflammation, and increased response to interferon-α in TP individuals, which could be partially restored by ART. Interestingly, we revealed that CD4 + and CD8 + Effector-GNLY clusters were expanded in TP cases, and persistently increased in ART individuals where they were typically correlated with poor immune restoration. This transcriptional dataset enables a deeper understanding of the pathogenesis of HIV-1 infection and is also a rich resource for developing novel immune targeted therapeutic strategies., (© 2022. The Author(s).)

Background: Populations of natural killer cells lacking CD56 expression [CD56 neg natural killer (NK) cells] have been demonstrated to expand during human immunodeficiency virus (HIV)-1 infection. However, their phenotypic and functional characteristics have not been systematically analyzed, and their roles during disease progression remain poorly understood., Methods: In this study, 84 donors, namely 34 treatment-naïve HIV-1-infected patients (TNs), 29 HIV-1-infected patients with successful antiretroviral therapy (ARTs), and 21 healthy controls (HCs), were enrolled. The phenotypic and functional characteristics of CD56 neg NK cells were analyzed using single-cell RNA-sequencing (scRNA-seq) and flow cytometry. A potential link between the characteristics of CD56 neg NK cells and the clinical parameters associated with HIV-1 disease progression was examined., Results: The frequency of the CD56 neg NK cell population was significantly increased in TNs, which could be partially rescued by ART. Flow cytometry analyses revealed that CD56 neg NK cells were characterized by high expression of CD39, TIGIT, CD95, and Ki67 compared to CD56 dim NK cells. In vitro assays revealed reduced IFN-γ and TNF-α secretion, as well as decreased expression of granzyme B and perforin in CD56 neg NK cells. In line with the data obtained by flow cytometry, scRNA-seq analysis further demonstrated impaired cytotoxic activities of CD56 neg NK cells. Notably, a negative correlation was observed between CD39, CD95, and Ki67 expression levels in CD56 neg NK cells and CD4 + T cell counts., Conclusions: The results presented in this study indicate that the CD56 neg NK cell population expanded in HIV-1-infected individuals is dysfunctional and closely correlates with HIV-1 disease progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cao, Zhang, Wan, Li, Mu, Guo, Zhou, Shen, Zhang, Fan, Jiao, Xu, Zhou, Yuan, Wang, Wang and Song.)

Background: B cell follicles are immune-privileged sites where intensive HIV-1 replication and latency occur, preventing a permanent cure. Recent study showed that CXCR5 + NK cells in B cell follicles can inhibit SIV replication in African green monkeys, but this has not been reported in HIV-1 infected patients., Methods: Lymphocytes and tissue sections of lymph node were collected from 11 HIV-1 positive antiretroviral therapy (ART)-naive and 19 HIV-1 negative donors. We performed immunofluorescence and RNA-scope to detect the location of CXCR5 + NK cells and its relationship with HIV-1 RNA, and performed flow cytometry and RNA-seq to analyze the frequency, phenotypic and functional characteristics of CXCR5 + NK cells. The CXCL13 expression were detected by immunohistochemistry., Findings: CXCR5 + NK cells, which accumulated in LNs from HIV-1 infected individuals, expressed high levels of activating receptors such as NKG2D and NKp44. CXCR5 + NK cells had upregulated expression of CD107a and β-chemokines, which were partially impaired in HIV-1 infection. Importantly, the frequency of CXCR5 + NK cells was inversely related to the HIV-1 viral burden in LNs. In addition, CXCL13-the ligand of CXCR5-was upregulated in HIV-1 infected individuals and positively correlated with the frequency of CXCR5 + NK cells., Interpretation: During chronic HIV-1 infection, CXCR5 + NK cells accumulated in lymph node, exhibit altered immune characteristics and underlying anti-HIV-1 effect, which may be an effective target for a functional cure of HIV-1., Competing Interests: Declaration of Competing Interest The authors have declared that no conflict of interest exists., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Mesenchymal stem cell (MSC) infusion was reported to improve liver function in patients with decompensated liver cirrhosis (DLC); however, whether the medication can improve outcome of these patients is poorly understood., Methods: This prospective, open-labeled, randomized controlled study enrolled 219 patients with HBV-related DLC who were divided into control group (n = 111) and umbilical cord-derived MSC (UC-MSC)-treated group (n = 108), then all of them received a follow-up check from October 2010 to October 2017. The treated patients received three times of UC-MSC infusions at 4-week intervals plus conventional treatment that was only used for control group. The overall survival rate and HCC-free survival rate were calculated as primary endpoints and the liver function and adverse events associated with the medication were also evaluated., Results: During the follow-up check period from 13 to 75th months, there was a significantly higher overall survival rate in the treated group than the control group, while the difference of the hepatocellular carcinoma event-free survival rate between the treated and control groups was not observed during the 75-month follow-up. UC-MSC treatment markedly improved liver function, as indicated by the levels of serum albumin, prothrombin activity, cholinesterase, and total bilirubin during 48 weeks of follow-up. No significant side effects or treatment-related complications were observed in the UC-MSC group., Conclusions: Therapy of UC-MSC is not only well tolerated, but also significantly improves long-term survival rate, as well as the liver function in patients with HBV-related DLC. UC-MSC medication, therefore, might present a novel therapeutic approach for the disease., (© 2021. The Author(s).)