Objective:To explore the effects of holmium laser enucleation of the prostate with early complete transection of the urethral mucosa at the tip of the prostate on urinary control function and sexual function in patients with benign prostatic hyperplasia (BPH).Methods:Eighty patients with BPH who underwent holmium laser enucleation of the prostate in the Affiliated Hospital of Yan′an University from January 2019 to January 2023 were collected as the research subjects. The patients were divided into the observation group and the control group by the random number table method, with 40 cases in each group. The observation group underwent early holmium laser enucleation of the prostate with early complete transection of the urethral mucosa at the tip of the prostate, while the control group underwent conventional holmium laser prostatectomy. The general conditions, urinary control function and sexual function of the two groups of patients after the operation were compared. The adverse ejaculation conditions 6 months after the operation were recorded.Results:There was no statistically significant difference in age and prostate volume between the two groups of patients (all P>0.05). The operation time, intraoperative blood loss, postoperative indwelling urinary catheter time and postoperative hospital stay in the observation group were significantly less than those in the control group (all P<0.05). The International Prostate Symptom Scale (IPSS) score, Quality of Life (QOL) score, the maximum flow rate (Qmax), and post void residual (PVR) in the bladder of the two groups of patients 6 months after the operation were compared with those before the operation, and the differences were statistically significant (all P<0.05), while there were no statistically significant differences between the groups (all P>0.05). There were no statistically significant differences in the International Index of Erectile Function (IIEF-5) scores and Erection Hardness Grading Scale (EHGS) grades of the two groups of patients 6 months after surgery compared with those before surgery (all P>0.05), and there were also no statistically significant differences between the groups (all P>0.05). There was no statistically significant difference in the ejaculation function score and ejaculation distress score 6 months after the operation in the observation group compared with those before the operation (all P>0.05), while in the control group, the ejaculation function score 6 months after the operation was lower than that before the operation, and the ejaculation distress score was higher than that before the operation (all P<0.05). The ejaculation function score and ejaculation distress score of the observation group 6 months after the operation were significantly better than those of the control group (all P<0.05). The incidences of retrograde ejaculation and reduced semen volume 6 months after the operation in the observation group were both lower than those in the control group (all P<0.05). There was no statistically significant difference in the incidence of rapid ejaculation, ejaculation pain, hematospermia, etc. between the two groups of patients 6 months after the operation (all P>0.05). Conclusions:In holmium laser enucleation of the prostate, early complete transection of the urethral mucosa at the tip of the prostate has an improving effect on urinary control function and sexual function in patients with BPH, and increases the confidence in postoperative life and satisfaction with orgasm of BPH patients.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective:To explore the effects of holmium laser enucleation of the prostate with early complete transection of the urethral mucosa at the tip of the prostate on urinary control function and sexual function in patients with benign prostatic hyperplasia (BPH).Methods:Eighty patients with BPH who underwent holmium laser enucleation of the prostate in the Affiliated Hospital of Yan′an University from January 2019 to January 2023 were collected as the research subjects. The patients were divided into the observation group and the control group by the random number table method, with 40 cases in each group. The observation group underwent early holmium laser enucleation of the prostate with early complete transection of the urethral mucosa at the tip of the prostate, while the control group underwent conventional holmium laser prostatectomy. The general conditions, urinary control function and sexual function of the two groups of patients after the operation were compared. The adverse ejaculation conditions 6 months after the operation were recorded.Results:There was no statistically significant difference in age and prostate volume between the two groups of patients (all P>0.05). The operation time, intraoperative blood loss, postoperative indwelling urinary catheter time and postoperative hospital stay in the observation group were significantly less than those in the control group (all P<0.05). The International Prostate Symptom Scale (IPSS) score, Quality of Life (QOL) score, the maximum flow rate (Qmax), and post void residual (PVR) in the bladder of the two groups of patients 6 months after the operation were compared with those before the operation, and the differences were statistically significant (all P<0.05), while there were no statistically significant differences between the groups (all P>0.05). There were no statistically significant differences in the International Index of Erectile Function (IIEF-5) scores and Erection Hardness Grading Scale (EHGS) grades of the two groups of patients 6 months after surgery compared with those before surgery (all P>0.05), and there were also no statistically significant differences between the groups (all P>0.05). There was no statistically significant difference in the ejaculation function score and ejaculation distress score 6 months after the operation in the observation group compared with those before the operation (all P>0.05), while in the control group, the ejaculation function score 6 months after the operation was lower than that before the operation, and the ejaculation distress score was higher than that before the operation (all P<0.05). The ejaculation function score and ejaculation distress score of the observation group 6 months after the operation were significantly better than those of the control group (all P<0.05). The incidences of retrograde ejaculation and reduced semen volume 6 months after the operation in the observation group were both lower than those in the control group (all P<0.05). There was no statistically significant difference in the incidence of rapid ejaculation, ejaculation pain, hematospermia, etc. between the two groups of patients 6 months after the operation (all P>0.05). Conclusions:In holmium laser enucleation of the prostate, early complete transection of the urethral mucosa at the tip of the prostate has an improving effect on urinary control function and sexual function in patients with BPH, and increases the confidence in postoperative life and satisfaction with orgasm of BPH patients.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To investigate the incidence and types of patient-ventilator asynchrony(PVA)in mechanically ventilated patients within the intensive care unit(ICU),and to identify associated high-risk factors,thereby providing a basis for reducing PVA,enhancing mechanical ventilation efficiency,and refining ventilation strategies.Methods A prospective observational study was conducted among patients admitted to the general ICU of the Affiliated Hospital of Guizhou Medical University from October to December 2024 who were receiving mechanical ventilation.Inclusion criteria were as follows:age ≥18 years and mechanical ventilation duration ≥12 hours.Exclusion criteria included complete controlled mechanical ventilation,palliative care or do-not-resuscitate status,and lack of informed consent.Senior respiratory therapists performed daily bedside observations of ventilator waveforms for 10～15 minutes between 08:00 and 12:00.PVA was diagnosed based on pressure-time and flow-time waveforms,with the types of PVA being recorded.Demographic and clinical data,including age,sex,body mass index(BMI),primary diagnosis,comorbidities,APACHEⅡ score at ICU admission,blood gas analysis,ventila-tion mode and parameters,analgesia and sedation status,duration of mechanical ventilation,and length of ICU stay,were collected.The incidence and types of PVA during the observation period were analyzed.Univariate and multivariate logistic regression analyses were performed to identify high-risk factors for PVA.Clinical outcomes were compared between patients with and without PVA.Results A total of 105 patients and 453 episodes of assisted mechanical ventilation waveforms were analyzed.Among these,60.95％(64/105)experienced at least one episode of PVA.Of the 453 ventilation waveforms assessed,35.76％(162/453)demonstrated PVA.The types of PVA,ranked by incidence,were as follows:cycling mismatch(12.58％,57/453),double triggering(11.92％,54/453),ineffective triggering(9.49％,43/453),flow starvation(5.30％,24/453),and exhalation flow limitation(1.77％,8/453).The incidence of PVA varied significantly across different ventilation modes:45.7％in volume-assist/control ventilation(V-A/C),38.1％in pressure-assist/control ventilation(P-A/C),42.9％in synchronized intermittent mandatory ventilation(SIMV),and 16.7％in pressure support ventilation(PSV)(P<0.001).Multi-variate logistic regression analysis revealed that the mechanical ventilation mode[reference:PSV;V-A/C:OR=4.687,95％CI:2.140～10.263,P<0.001;P-A/C:OR=2.922,95％CI:1.489～5.734,P=0.002;SIMV:OR=4.682,95％CI:1.758～12.466,P=0.002]and actual respiratory rate(OR=1.07,95％CI:1.016～1.127,P=0.011)were significant high-risk factors for PVA.Patients with PVA had a significantly longer duration of mechanical ventilation[8.21(5.35,13.91)days vs.3.00(1.96,5.71)days,P<0.001]compared to those without PVA.Conclusions PVA is commonly observed in ICU patients receiving assisted invasive mechanical ventilation,with cycling mismatch,double triggering,and ineffective triggering being the most prevalent types.The incidence of PVA tends to be lower when using the PSV mode.Clinically,real-time monitoring of patient-ventilator synchrony via ventilator waveforms,along with the optimization of ventilator modes and parameters,should be employed to minimize the occurrence of PVA and enhance the efficiency of mechanical ventilation.

Objective:To compare the safety and efficacy of 3D-printed porous bioceramic artificial bone and artificial bone substitutes in the treatment of limb bone defects.Methods:A total of 220 patients with post-traumatic limb bone defects admitted to Xijing Hospital Affiliated to Air Force Medical University of the Chinese People's Liberation Army (34 cases), the Third Hospital of Hebei Medical University (60 cases), Xi'an Honghui Hospital (28 cases), the Third Hospital of Southern Medical University (18 cases), Changsha Third Hospital (28 cases), Foshan Traditional Chinese Medicine Hospital (16 cases), Foshan Fuxing Chancheng Hospital (12 cases), and Henan Provincial Orthopaedic Hospital (24 cases) from May 2022 to October 2023 were included as research subjects. According to the manufacturing method of the bone graft material, the subjects were randomly divided into the 3D printed porous bioceramic artificial bone group (3D printing group) and the artificial bone substitute group (non-3D printing group) at a ratio of 1:1 by the envelope method. Adverse events that might be related to the surgery were selected through correlation evaluation and classified as abnormal laboratory indicators, systemic or other site symptoms and abnormalities, and local symptoms and abnormalities of the affected limb. The safety of the two groups was compared. The bone graft fusion rate, bone defect repair and healing rate, and short form 12 (SF-12) score of the two groups were calculated to evaluate the postoperative recovery.Results:Thirty-two cases were excluded (4 cases refused to use their data after reconsideration, 7 cases were not used after preoperative assessment, and 21 cases exceeded the standard for body mass index and laboratory indicators upon re-examination). A total of 188 cases were randomly divided into the 3D printing group and the non-3D printing group according to the random method, with 94 cases in each group. Among them, 11 cases in the 3D printing group and 9 cases in the non-3D printing group dropped out due to loss to follow-up. Finally, 168 cases completed the follow-up, including 83 cases in the 3D printing group and 85 cases in the non-3D printing group. In the 3D printing group, there were 53 males and 30 females, with an average age of 47.9±12.7 years; in the non-3D printing group, there were 53 males and 32 females, with an average age of 48.6±12.9 years. A total of 51 cases in the two groups experienced adverse events related to the surgery, including 13 cases of abnormal laboratory indicators (5 cases in the 3D printing group and 8 cases in the non-3D printing group), 15 cases of systemic or other site symptoms and abnormalities (9 cases in the 3D printing group and 6 cases in the non-3D printing group), and 23 cases of local symptoms and abnormalities of the affected limb (13 cases in the 3D printing group and 10 cases in the non-3D printing group). There was no statistically significant difference in the incidence of adverse events between the two groups ( P>0.05). The bone graft fusion rates of the 3D printing group and the non-3D printing group at 6 months after surgery were 99%(82/83) and 99%(84/85), respectively, and the bone defect repair and healing rates were 89%(74/83) and 89%(76/85), respectively. At the time of 12 months after surgery, the bone graft fusion rates were 99%(82/83) and 99%(84/85), respectively, and the bone defect repair and healing rates were 94%(78/83) and 92%(78/85), respectively. There was no statistically significant difference in the bone graft fusion rate and bone defect repair and healing rate between the two groups ( P>0.05). The SF-12 scores during the screening period were 27.82±2.96 points and 27.22±4.23 points in the 3D printing group and the non-3D printing group, respectively, and at 3 months after surgery were 28.08±3.13 points and 27.64±3.16 points, at 6 months after surgery were 29.42±3.10 points and 28.55±3.45 points, and at 12 months after surgery were 29.78±2.80 points and 29.58±2.94 points, respectively. There was no statistically significant difference between the groups ( P>0.05). Both groups of surgeries were successfully completed without any serious surgical or bone graft-related complications. Conclusion:The safety and efficacy of 3D-printed porous bioceramic artificial bone in the treatment of limb bone defects are not significantly different from those of currently clinically applied artificial bone substitutes.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

The rupture of carotid vulnerable plaques is the core pathological basis for major cardiovascular and cerebrovascular events. However， the insufficient alignment between existing animal models and the clinical disease and syndrome characteristics of traditional Chinese and western medicine has limited research progress. In this study， biomedical databases in China and abroad were systematically searched， and the modeling mechanisms and evaluation systems of carotid vulnerable plaque animal models were systematically assessed based on diagnostic criteria of both traditional Chinese and western medicine. Analysis of the clinical correspondence indicated that existing animal models can be categorized into four types： simple high-fat diet， surgical induction combined with high-fat feeding， genetic engineering combined with high-fat feeding， and drug induction combined with high-fat feeding. Among these， the compound strategy of surgical induction combined with high-fat feeding has become the current mainstream approach， showing good concordance with western medicine. The study found that the double balloon injury rabbit model and the ApoE^-/- mouse carotid artery tandem constriction combined with high-fat feeding model demonstrated a high degree of clinical correspondence with both traditional Chinese and western medicine in terms of vulnerable plaque imaging and pathological features. Nevertheless， existing models still face significant technical limitations in faithfully simulating plaque pathology and in translating findings to clinical applications. To address these challenges， integrating complex comorbidity mechanism construction， multimodal dynamic mechanism monitoring， and collaborative evaluation systems of traditional Chinese and western medicine could enable the development of highly concordant carotid vulnerable plaque disease-syndrome combination animal models. Such models would provide a reproducible experimental platform for targeted drug development to regulate plaque stability and for individualized precision treatment， as well as a theoretical basis for innovation in clinical diagnostic and therapeutic strategies.

The safety of traditional Chinese medicine(TCM) has always been taken very seriously, and rich and valuable theories and experiences have been developed to ensure the safe and precise use of TCM in clinical practices. In recent years, the cognitive theory of toxicity of TCM, has undergone a profound change. TCM is characterized by the existence of intrinsic toxicity, idiosyncratic toxicity, and indirect toxicity related to organic factors. Therefore, the traditional theories and experiences of TCM, which focus on the prevention and control of intrinsic toxicity, fail to be used for the development of risk prevention and control countermeasures for newly discovered TCM with idiosyncratic toxicity and indirect toxicity. Accordingly, based on the toxicity classification and mechanism characteristics of TCM, this paper proposed a new strategy and method in TCM compatibility for detoxification based on componenttarget-effect interaction. The strategy based on component-target-effect interaction is to carry out TCM compatibility for detoxification by blocking the occurrence of drug-mediated damage and promoting damage repair through component interactions, target interactions,and/or effect interactions. Based on this theory, the paper established a strategy for TCM compatibility that aligned with the cognitive theory of toxicity of TCM, so as to achieve safe and precise use of TCM in clinical practices. The strategy based on component-targeteffect interaction has been exemplarily applied to the development of countermeasures to reduce the toxicity of TCM, including Polygonum Multiflorum, Epimedii Folium, and Psoraleae Fructus, and a new mechanism of Glycyrrhizae Radix et Rhizoma to " harmonize various medicines and detoxify myriad poisons" was illustrated, providing a scientific basis for the safe and precise use of TCM in clinical practice. This paper explained the scientific connotation, application forms, and application examples of componenttarget-effect interaction, aiming to provide a theoretical and methodological basis for guaranteeing the precise use of TCM in clinical practice and innovate the theories and methods of TCM compatibility for detoxification.
Drugs, Chinese Herbal/chemistry* ; Humans ; Medicine, Chinese Traditional/methods* ; Animals ; Drug-Related Side Effects and Adverse Reactions/prevention & control*