Single-Nucleus RNA Sequencing Unravels Early Mechanisms of Human Becker Muscular Dystrophy.

OBJECTIVE: The transcriptional heterogeneity at a single-nucleus level in human Becker muscular dystrophy (BMD) dystrophic muscle has not been explored. Here, we aimed to understand the transcriptional heterogeneity associated with myonuclei, as well as other mononucleated cell types that underly BMD pathogenesis by performing single-nucleus RNA sequencing. METHODS: We profiled single-nucleus transcriptional profiles of skeletal muscle samples from 7 BMD patients and 3 normal controls. RESULTS: A total of 17,216 nuclei (12,879 from BMD patients and 4,337 from controls) were classified into 13 known cell types, including 9 myogenic lineages and 4 non-myogenic lineages, and 1 unclassified nuclear type according to their cell identities. Among them, type IIx myonuclei were the first to degenerate in response to dystrophin reduction. Differential expression analysis revealed that the fibro-adipogenic progenitors (FAPs) population had the largest transcriptional changes among all cell types. Sub-clustering analysis identified a significantly compositional increase in the activated FAPs (aFAPs) subpopulation in BMD muscles. Pseudotime analysis, regulon inference, and deconvolution analysis of bulk RNA-sequencing data derived from 29 BMD patients revealed that the aFAPs subpopulation, a distinctive and previously unrecognized mononuclear subtype, was profibrogenic and expanded in BMD patients. Muscle quantitative real-time polymerase chain reaction and immunofluorescence analysis confirmed that the mRNA and protein levels of the aFAPs markers including LUM, DCN, and COL1A1 in BMD patients were significantly higher than those in controls, respectively. INTERPRETATION: Our results provide insights into the transcriptional diversity of human BMD muscle at a single-nucleus resolution and new potential targets for anti-fibrosis therapies in BMD. ANN NEUROL 2024.

Association of cardiovascular health metrics with all-cause and cardiovascular disease mortality in chronic kidney disease: A cohort study.

BACKGROUND AND AIMS: Since the global burden of chronic kidney disease (CKD) is rising rapidly, the study aimed to assess the association of cardiovascular health (CVH) metrics with all-cause and cardiovascular disease (CVD) mortality among individuals with CKD. METHODS AND RESULTS: The cohort study included 5834 participants with CKD from the National Health and Nutrition Examination Survey 1999-2018. A composite CVH score was calculated based on smoking status, physical activity, body mass index, blood pressure, total cholesterol, diet quality, and glucose control. Primary outcomes were all-cause and CVD mortality as of December 31, 2019. Multivariable-adjusted Cox proportional hazards models were used to estimate the association between CVH metrics and deaths in CKD patients. During a median follow-up of 7.2 years, 2178 all-cause deaths and 779 CVD deaths were documented. Compared to participants with ideal CVH, individuals with intermediate CVH exhibited a 46.0% increase in all-cause mortality (hazard ratio, 1.46; 95% confidence interval: 1.17, 1.83), while those with poor CVH demonstrated a 101.0% increase (2.01; 1.54, 2.62). For CVD mortality, individuals with intermediate CVH experienced a 56.0% increase (1.56; 1.02, 2.39), and those with poor CVH demonstrated a 143.0% increase (2.43; 1.51, 3.91). Linear trends were noted for the associations of CVH with both all-cause mortality (P for trend <0.001) and CVD mortality (P for trend = 0.02). CONCLUSIONS: Lower CVH levels were associated with higher all-cause and CVD mortality in individuals with CKD, which highlights the importance of maintaining good CVH in CKD patients.

Repeated transvaginal natural orifice transluminal endoscopic surgery: An initial Chinese experience.

AIMS: To investigate the perioperative outcomes and sexual function of patients undergoing repeated transvaginal natural orifice transluminal endoscopic surgery (vNOTES). METHODS: We retrieved the records of patients who underwent vNOTES twice at our institute between April 2019 and December 2022 and analyzed their baseline information and perioperative complications, and compared the pre- and postoperative sexual function of both vNOTES. RESULTS: Patients' mean age and body mass index were 29.00 ± 3.59 and 30.4 ± 4.00 years and 21.89 ± 3.69 and 22.76 ± 3.88 kg/m2 , respectively, when receiving the first and second vNOTES. Ectopic pregnancy was the most frequent indication for vNOTES, with 7 cases in the first vNOTES and 11 cases in repeated vNOTES. The interval between the two vNOTESs ranged from 9 days to 38 months. The operation duration (63.33 ± 13.71 vs. 67.33 ± 22.51 min, p = 0.723), intraoperative estimated blood loss (32.00 ± 20.42 vs. 30.00 ± 9.26 mL, p = 0.429), and duration of postoperative hospital stay (2.20 ± 0.56 vs. 2.40 ± 0.51 days, p = 0.082) of both vNOTESs were comparable. No significant differences were found in any of the domains in the comparison of pre-first and post-first vNOTES, pre-second and post-second vNOTES, and pre-first and post-second vNOTES female sexual function index. None of the patients delivered after the second vNOTES. CONCLUSION: Repeated vNOTES is safe and feasible. No significant change in the patients' sexual function was found in our cohort after the first and second vNOTES.

High-sensitivity C-reactive protein and risk of type 2 diabetes: A nationwide cohort study and updated meta-analysis.

OBJECTIVE: To prospectively examine the association of high sensitivity C-reactive protein (hs-CRP) with incident type 2 diabetes mellitus (T2DM) among middle-aged and elderly Chinese, and validate the association in an updated meta-analysis of prospective studies. METHODS: We used data from the China Health and Retirement Longitudinal Study, started in 2011-2012 with follow ups in 2013-2014 and 2015-2016. Multivariable Cox proportional hazard regressions were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between hs-CRP level and incident T2DM. An updated meta-analysis was conducted to combine our estimates with those in previous prospective studies. RESULTS: Included in the analyses were 7985 participants (mean age: 59.38 years; men: 46.73%). Higher hs-CRP was associated with increased risk of T2DM (multivariable-adjusted HR, 1.30; 95% CI: 1.03, 1.64 for comparing extreme quartiles). The association was stronger in participants with body mass index (BMI) of 24.0 kg/m2 or higher than those with a BMI lower than 24.0 kg/m2 (p for interaction = 0.038). In a meta-analysis of 28 cohorts, 2 case-cohort, and 6 nested case-control studies among 125,356 participants with 10,759 cases, the pooled relative risk for T2DM was 1.77 (95% CI: 1.60, 1.96) for the highest versus lowest level of hs-CRP. CONCLUSIONS: Hs-CRP was associated with higher risk of T2DM in middle-aged and elderly Chinese, and this association was confirmed by an updated meta-analysis of prospective studies. Our findings highlight the role of elevated hs-CRP in the development of T2DM.

Evaluation of the use versus nonuse of urinary catheterization during laparoscopic adnexal surgery: A randomized controlled trial.

We conducted a randomized controlled trial to assess the feasibility and safety of performing gynecological single-port transumbilical laparoscopic-assisted adnexal surgery without urethral catheterization in a day surgery setting. A total of 153 patients with adnexal disease were enrolled in this prospective randomized controlled trial (RCT). All subjects performed single-port transumbilical laparoscopic-assisted adnexal surgery between March 2021 and July 2022 in a day surgery center. After completion of the baseline survey, participants were randomized into one of three groups. Participants were randomized into one of three groups: uncatheterized (n = 51), intermittent catheterized (n = 51), or indwelling catheterized (n = 51). The primary outcomes were the incidence of lower urinary tract symptoms (LUTS) and microscopic hematuria, and the secondary outcomes included the incidence of urinary tract infection (UTI), the incidence of urinary retention, the incidence of bladder injury, the time till first urination, the time till first ambulation, the time till first exhaust, the time till first feeding and Kolcaba comfort score. The incidence of postoperative LUTS in the uncatheterized group (17.65%) was lower than that in the intermittent catheterized group (52.94%) and the indwelling catheterized group (84.31%), and there was significant difference between the two catheterized groups (P < 0.001). In the patients without vaginal manipulation, the incidence of microscopic hematuria in the uncatheterized group (0%) was lower than that in the intermittent catheterized group (37.50%) and the indwelling catheterized group (38.89%) (P < 0.05). There were no significant differences in the first urination time, first ambulation time, first exhaust time, first feeding time, and comfort score among the three groups (P > 0.05). Moreover, no urinary retention, UTI and bladder injury were recorded in the three groups. Gynecological single-port laparoscopic adnexal surgery without urinary catheter is safe and feasible in a day surgery ward, which can reduce the incidence of postoperative LUTS and microscopic hematuria.

Real-world effectiveness of cytology and HPV-based screening strategy in cervical cancer screening: A cross-sectional population-based study in Chengdu, China.

Cervical cancer poses a significant health challenge in developing countries, emphasizing the need for appropriate screening strategies to accelerate the elimination of this disease. This study summarized the results of a large-scale community-based cervical cancer screening program conducted in Chengdu, China, to understand the prevalence of HPV infection and cervical lesions in the population, and to compare the real-world effectiveness of two different screening methods implemented in the program. From January 2021 to December 2022, a total of 363,376 women aged 35-64 years in Chengdu received free screenings. Among these participants, 70.1% received cytology screening and 29.9% received HPV testing combined with 16/18 genotyping and cytology triage. Ultimately, 824 cases of high-grade lesions and cervical cancer were detected, with a total detection rate of cervical cancer and precancerous lesions of 226.8 per 100,000. The follow-up rate of patients with high-grade lesions and above was 98.9%, and the treatment rate was 86.6%. The overall high-risk HPV infection rate was 11.7%, with the HPV 16/18 infection rate of 1.4%. The rate of abnormal cytology results was 2.8%. The attendance rates for colposcopy and histopathology were 71.6% and 86.1%, respectively. By calculating the age-standardized rates to eliminate the different age composition between the two group, the HPV-based screening strategy had a higher rate of primary screening abnormalities (3.4% vs. 2.8%, P<0.001), higher attendance rates of colposcopy (76.5% vs. 68.9%, P<0.001) and histopathological diagnosis (94.1% vs. 78.0%, P<0.001), higher percentage of abnormal colposcopy results (76.0% vs. 44.0%, P<0.001), and higher detection rate of cervical precancerous lesions and cancer (393.1 per 100,000 vs. 156.4 per 100,000, P<0.001) compared to cytology screening. Our study indicates that the combination of HPV testing with 16/18 genotyping and cytology triage has demonstrated superior performance in cervical cancer screening compared to cytology alone in large-scale population.

Association between maternal HIV infection and the risks of preterm birth and low birth weight in Chengdu, China: a propensity score matching approach.

OBJECTIVES: To estimate the effect of HIV infection on the risk of preterm birth (PTB) and low birth weight (LBW) among Chinese pregnancy women. DESIGN: A retrospective cohort study included HIV-positive pregnant women who gave birth to singletons in Chengdu between 2011 and 2020 and and HIV-negative pregnant women who delivered singletons at the Chengdu Women's and Children's Central Hospital in 2020. SETTING: Data of pregnant women living with HIV were extracted from China's Information System of Prevention of Mother-to-Child Transmission of HIV Management. Additionally, information for HIV-negative pregnant women was extracted from the electronic medical record system of the Chengdu Women's and Children's Central Hospital. PARTICIPANTS: 755 HIV-positive women and 15,094 HIV-negative pregnant women were included. PRIMARY OUTCOME MEASURES: PTB and LBW rates, which were defined by gestational weeks and birth weight. RESULTS: The incidences of PTB and LBW (13.51% and 14.17%, respectively) were significantly higher in the HIV-positive group compared with the HIV-negative group (6.82% and 4.65%). Propensity score matching was performed to improve comparability of the two groups, resulting in 1590 pregnancies with 558 HIV-positive and 1032 HIV-negative women in the final analysis. Conditional logistic regression was used to estimate the effect of maternal HIV status on adverse pregnancy outcomes. After propensity score matching and controlling the potential confounders, HIV infection was strongly associated with higher chances of LBW and PTB with adjusted odd ratios (95% confidence interval) of 2.53 (1.74 to 3.68) and 1.95 (1.33 to 2.85), respectively. CONCLUSIONS: HIV infection was significantly associated with increased risks of PTB and LBW in Chinese pregnant women. Future studies should focus on investigating the mechanisms underlying the association between HIV infection and adverse birth outcomes, and on identifying strategies to reduce the incidence of PTB and LBW in pregnant women living with HIV.

Perioperative outcomes of and predictors for conversion from transvaginal natural orifice transluminal endoscopic tubal surgeries: A retrospective cohort study of 619 patients.

OBJECTIVE: To assess the perioperative outcomes of vNOTES tubal surgeries and to identify predictors of surgical conversion. METHODS: A single-center retrospective cohort study was performed on 619 patients who underwent vNOTES tubal surgeries in our institute from December 2018 to October 2021. Patients were categorized into "converted" or "non-converted" groups based on whether conversion occurred. t-test and χ2 test were performed on demographic and clinicopathologic data to compare their perioperative outcomes. Logistic regression was built to identify predictors for surgical conversions. RESULTS: The conversion and complication rates of the vNOTES tubal surgeries in the present study were 3.07% and 4.85%, respectively. The "converted group" has a significantly higher percentage of patients with severe pelvic adhesions (9/19 [47.4%]) and pelvic endometriosis (2/19 [10.5%]), which significantly predicates surgical conversion. The "converted group" also had a longer duration of surgery (140.94 ± 88.73 min, P = 0.002) and an increased proportion of "converted from vNOTES" patients experienced more than 50 ml of intraoperative blood loss (7/19 [36.9%]). Four patients had intraoperative rectal injuries, and no Clavien-Dindo III-V postoperative complications occurred. CONCLUSION: vNOTES tubal surgeries are safe due to low conversion and complication rates. Severe pelvic adhesion and endometriosis are predictors for surgical conversions.

Extracellular pollutant degradation feedback regulates intracellular electron transfer process of exoelectrogens: Strategy and mechanism.

Exoelectrogens possess extraordinary degradation ability to various pollutants through extracellular electron transfer (EET). Compared with extracellular electron release process, intracellular electron transfer network is not yet fully recognized. Especially, controversy remains regarding the role of CymA, an essential electron-transfer hub of Shewanella oneidensis MR-1, in EET process. In this study, we thoroughly surveyed the intracellular transfer strategies during EET through dye decolorization. Loss of CymA severely impaired the reduction ability of S. oneidensis MR-1 to methyl orange (MO), but hardly affected the decolorization of aniline blue (AB). Complement of cymA fully restored the MO decolorization ability of ΔcymA mutant. The contribution of CymA to extracellular decolorization was subjected to MO concentrations. The defect in the decolorization ability of ΔcymA mutant was not evident at low MO concentration, but severe at high MO concentration. Further investigation revealed that EET rate determined the significance of CymA in the extracellular bioremediation by S. oneidensis MR-1. Coupled with MO concentrations increasing from 15 to 120 mg/L, the initial electron transfer rates of S. oneidensis MR-1 increased accordingly from 2.69 × 104 to 11.21 × 104 electrons CFU-1 s-1, which led to a gradual increase of the dependencyCymA. Thus, we first revealed that extracellular degradation performance could feedback regulate the intracellular electron transfer process of S. oneidensis MR-1. This work is helpful to fully understand the complex EET process of exoelectrogens and facilitates the application of exoelectrogens in bioremediation of environmental pollutants.

Lung injury after cardiopulmonary bypass: Alternative treatment prospects.

Although the lung injury caused by cardiopulmonary bypass (CPB) has been extensively investigated, the incidence and mortality of lung injury after CPB remain a prominent clinical problem. The poor outcome has been attributed to multifactorial etiology, including the systemic inflammatory response and ischemia reperfusion (I/R) injury during CPB. Lung injury after CPB is a complex pathophysiological process and has many clinical manifestations of mild to severe disease. Which is associated with prognosis. To alleviate this lung injury, interventions that address the pathogenesis are particularly important. This review summarizes the pathogenesis, mechanism and treatment options of lung injury after CPB, such as lung protection with intralipid.

Reliability of Non-Contact Infrared Thermometers for Fever Screening Under COVID-19.

Purpose: Fever is one of the most typical clinical symptoms of coronavirus disease 2019 (COVID-19), and non-contact infrared thermometers (NCITs) are commonly used to screen for fever. However, there is a lack of authoritative data to define a "fever" when an NCIT is used and previous studies have shown that NCIT readings fluctuate widely depending on ambient temperatures and the body surface site screened. The aim of this study was to establish cut-off points for normal temperatures of different body sites (neck, forehead, temples, and wrist) and investigate the accuracy of NCITs at various ambient temperatures to improve the standardization and accuracy of fever screening. Patients and Methods: A prospective investigation was conducted among 904 participants in the outpatient and emergency departments of Chengdu Women's and Children's Central Hospital. Body temperature was measured using NCITs and mercury axillary thermometers. A receiver operating characteristic curve was used to determine the accuracy of body temperature detection at the four body surface sites. Data on participant characteristics were also collected. Results: Among the four surface sites, the neck temperature detection group had the highest accuracy. When the neck temperature was 37.35°C as the optimum fever diagnostic threshold, the sensitivity was 0.866. The optimum fever diagnostic thresholds for forehead, temporal, and wrist temperature were 36.65°C, 36.65°C, and 36.75°C, respectively. Moreover, triple neck temperature detection had the highest sensitivity, up to 0.998, whereas the sensitivity of triple wrist temperature detections was 0.949. Notably, the accuracy of NCITs significantly reduced when the temperature was lower than 18°C. Conclusion: Neck temperature had the highest accuracy among the four NCIT temperature measurement sites, with an optimum fever diagnostic threshold of 37.35°C. Considering the findings reported in our study, we recommend triple neck temperature detection with NCITs as the fever screening standard for COVID-19.

Association between dyslipidemia and risk of type 2 diabetes mellitus in middle-aged and older Chinese adults: a secondary analysis of a nationwide cohort.

AIMS: To evaluate the type 2 diabetes mellitus (T2DM) risk of individuals with different types of dyslipidaemia and compare the predictive value of distinct lipid parameters in predicting T2DM. METHODS: We conducted a secondary analysis of data from the China Health and Retirement Longitudinal Study (CHARLS). 17 708 individuals over 45 years old were interviewed, and 11 847 blood samples were collected at the baseline survey (2011-2012). Outcome of T2DM was confirmed during two follow-up surveys (2013-2014 and 2015-2016). The HRs and 95% CI of T2DM associated with dyslipidaemia were estimated by Cox proportional hazards regressions model. The discriminatory value of eight lipid parameters were compared by the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: A total of 7329 participants were enrolled in our analysis; during the mean follow-up time of 3.4 years, 387 (5.28%) participants developed new-onset diabetes. Compared with participants in normal lipid levels, the T2DM risk of those with hypercholesterolaemia, hypertriglyceridaemia and low high-density lipoprotein cholesterol (HDL-C) were significantly increased (HRs (95% CI) were 1.48 (1.11 to 1.96), 1.92 (1.49 to 2.46) and 1.67 (1.35 to 2.07), respectively). The AUCs of non-HDL-C (0.685, 95% CI 0.659 to 0.711), triglyceride (TG) (0.684, 95% CI 0.658 to 0.710), total cholesterol (TC)/HDL-C (0.685, 95% CI 0.659 to 0.712) and TG/HDL-C (0.680, 95% CI 0.654 to 0.706) were significantly (p<0.005) larger than that of other lipid parameters. CONCLUSION: Middle-aged and elderly adults with hypertriglyceridaemia, hypercholesterolaemia and low HDL-C were at higher risk for developing diabetes. Non-HDL-C, TG, TC/HDL and TG/HDL have greater performance than other lipid parameters in predicting T2DM incidence.

Identification of the optimal points for the acupuncture treatment of neck pain in China: protocol for a multicenter, matched, case-control study.

INTRODUCTION: Neck pain (NP) is a common condition that can be effectively treated by acupuncture. However, several treatment point prescriptions (ie, local acupoints, distal acupoints, and sensitised acupoints) may be used. The present study aims to identify the types of sensitisation and the distribution of sensitised points in patients with NP, to analyse the cut-off values and sensitisation rate for acupoint sensitisation, and to summarise the dominant forms of optimally sensitised points. This information will be helpful when choosing the optimal points to treat NP. METHODS AND ANALYSIS: This multicentre, matched, case-control study will enrol 224 patients with NP, and 224 age-matched and sex-matched healthy participants as controls. Body surface temperature, mechanical pain threshold, pressure pain threshold and skin resistance will be assessed at the 15 acupoints most frequently used to treat NP, and at the five body regions in which pain occurs most frequently. Hypothesis testing will be used to compare the differences in variables between cases and controls. In addition, receiver operating characteristic curve analysis will be used to explore the cut-off values of the sensitive states of heat, pain and electrical resistance, which indicate sensitisation of the acupoint. The optimal points will be comprehensively determined by the acupoint sensitisation rate and OR. ETHICS AND DISSEMINATION: Ethical approval of this study has been granted by the Research Ethical Committee of the Teaching Hospital of Chengdu University of Traditional Chinese Medicine (ID: 2018 KL-016). The outcomes of the study will be disseminated through peer-reviewed publications. TRIAL REGISTRATION: ChiCTR1800016220.