ObjectiveTo establish a regional risk assessment system for hospital-acquired infections in neurosurgery department of general hospital, and to evaluate its prevention and control effectiveness. MethodsFailure mode and effect analysis (FMEA) was used to identify the core risk factors for infections in neurosurgery department. The risk priority number (RPN) of each risk factor was calculated to determine the priority intervention targets. Targeted interventions were developed and continuously refined through the plan-do-check-act (PDCA) cycles. Data from January to June 2023 (control group) and July to December 2023 (intervention group) were collected to compare the differences in environmental hygiene monitoring qualification rate, incidence rate of hospital-acquired infections among inpatients, and detection rate of bacterial antimicrobial resistance. ResultsHigh-risk factors for hospital-acquired infections in neurosurgery department included patient-related risk factors, inadequate implementation of isolation measures for special infections, and poor compliance with surgical site infection (SSI) prevention protocols. After intervention, the environmental hygiene qualification rate significantly increased from 81.55% to 100.00% (χ²=120.49, P<0.001). The overall hospital-acquired infection rate among inpatients decreased from 2.62% to 2.45%, the infection rate of per case declined from 3.12% to 2.84%, and the detection rate of multidrug-resistant organism infections reduced from 43.72% to 36.79%. Additionally, antimicrobial utilization rate decreased from 48.75% to 42.53% (χ²=34.09, P<0.001). ConclusionThe FMEA-based risk assessment system can effectively identify critical infection risks in neurosurgery department, and targeted interventions can significantly improve infection prevention and control performance.

Objective To investigate the antibacterial activity of the antifungal peptide Mt6-21DLeu derived from Musca domestica against Acinetobacter baumannii (AB) and unravel its underlying mechanisms, so as to provide insights into development of novel agents against AB. Methods The minimum inhibitory concentrations (MICs) of Mt6-21DLeu, M. domestica-derived antifungal peptide-1 (MAF-1A), and polymyxin B were determined against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and AB using the broth microdilution assay, and the antibacterial activity of Mt6-21DLeu and polymyxin B was dynamically assessed against AB over 24 hours with time-kill curves. The inhibitory effects of Mt6-21DLeu and polymyxin B on biofilm formation in AB at concentrations of 1/4 × MIC, 1/2 × MIC and MIC, and the eradication effects of Mt6-21DLeu and polymyxin B on mature biofilms in AB at concentrations of MIC, 2 × MIC, and 4 × MIC were evaluated using crystal violet staining. Structural changes in the cell membrane of AB were observed 3 hours post-exposure to Mt6-21DLeu at concentrations of MIC and 2 × MIC using scanning electron microscopy, and alterations in the cell membrane permeability of AB were analyzed 3 hours post-treatment with Mt6-21DLeu at concentrations of MIC and 2 × MIC by means of fluorescence microscopy and propidium iodide (PI) staining. Intracellular reactive oxygen species (ROS) levels in AB were measured 3 hours post-treatment with Mt6-21DLeu at concentrations of MIC, 2 × MIC, and 4 × MIC using flow cytometry. The survival of Caenorhabditis elegans exposed to Mt6-21DLeu at concentrations of MIC, 2 × MIC, and 4 × MIC was monitored for 7 consecutive days, and survival curves were plotted to evaluate the in vivo toxicity of Mt6-21DLeu. In addition, C. elegans infected with AB and treated with Mt6-21DLeu at a concentration of 4 × MIC served as the treatment group, and uninfected C. elegans served as the control group, while infected but untreated C. elegans served as the infection group. The in vivo antibacterial efficacy of Mt6-21DLeu at a concentration of 4 × MIC was evaluated by comparing the survival curves and bacterial load among the three groups. Results The MICs of MAF-1A were all >128 μg/mL against S. aureus, B. subtilis, E. coli, K. pneumoniae, P. aeruginosa, and AB. In contrast, the MICs of Mt6-21DLeu were >128, 32, 8, 8, 16, and 4 μg/mL against these strains, respectively, and the MIC of Mt6-21DLeu against AB was close to that of polymyxin B (2 μg/mL). Time-kill curve analysis showed that both Mt6-21DLeu at concentrations of MIC and 2 × MIC and polymyxin B at a concentration of MIC inhibited AB growth over the 24-hour study period. The biofilm biomass in AB was (52.38 ± 6.92)%, (40.88 ± 9.17)% and (14.77 ± 6.00)% post-exposure with Mt6-21DLeu at concentrations of 1/4 × MIC, 1/2 × MIC and MIC, (61.58 ± 7.35)%, (47.42 ± 5.51)% and (20.85 ± 10.48)% post-treatment with polymyxin B at concentrations of 1/4 × MIC, 1/2 × MIC and MIC, and (100.00 ± 15.92)% in the control group (only bacterial suspension), respectively (F = 68.38, P < 0.001), and pairwise comparisons indicated that Mt6-21DLeu and polymyxin B at all concentrations significantly inhibited biofilm formation as compared to the control group (all P values < 0.001). The mature biofilm biomass in AB was (73.44 ± 11.41)%, (72.56 ± 13.08)% and (49.65 ± 9.23)% post-exposure to Mt6-21DLeu at concentrations of MIC, 2 × MIC, and 4 × MIC, (84.38 ± 8.60)%, (72.31 ± 9.63)% and (58.85 ± 4.96)% post-treatment with polymyxin B at concentrations of MIC, 2 × MIC, and 4 × MIC, and (100.00 ± 6.36)% in the control group (F = 35.63, P < 0.001), and pairwise comparisons revealed that Mt6-21DLeu at all concentrations significantly eradicated biofilm biomass (all P values < 0.05); however, polymyxin B showed no clear-cut eradication effect at a concentration of MIC (P > 0.05). Scanning electron microscopy revealed pore formation and content leakage in the cell membrane of AB 3 hours post-treatment with Mt6-21DLeu at concentrations of MIC and 2 × MIC. Fluorescence microscopy showed that the proportions of PI-stained AB were (24.79 ± 11.51)% and (68.44 ± 15.80)% post-treatment with Mt6-21DLeu at concentrations of MIC and 2 × MIC, and (0.96 ± 0.94)% in the phosphate-buffered saline (PBS) treatment group (F = 105.90, P < 0.001), with the highest proportion of PI-stained AB seen post-treatment with Mt6-21DLeu at a concentration of 2 × MIC (P < 0.05). Flow cytometry revealed that the relative intracellular ROS levels in AB were (652.00 ± 141.90), (694.33 ± 14.19), and (974.33 ± 160.02) 3 hours post-treatment with Mt6-21DLeu at concentrations of MIC, 2 × MIC and 4 × MIC, and (403.67 ± 86.56) in the PBS treatment group, respectively (F = 12.27, P < 0.05), with the highest intracellular ROS level measured following treatment with Mt6-21DLeu at a concentration of 4 × MIC (P < 0.05). Survival curve analysis revealed that Mt6-21DLeu posed no impact on C. elegans survival at concentrations of MIC (χ² = 0.02, P > 0.05), 2 × MIC (χ² = 0.06, P > 0.05) or 4 × MIC (χ² = 0.16, P > 0.05), and there was a significant difference in the survival period of C. elegans among the control group, the infection group, and the treatment group (χ² = 82.66, P < 0.05), with a significantly longer survival period in the treatment group than in the infection group (χ² = 45.00, P < 0.05). In addition, the log-transformed bacterial colony counts in C. elegans were (0.00 ± 0.00), (5.46 ± 0.03), and (3.91 ± 0.47) CFU/mL in the control group, the infection group, and the treatment group, respectively (F = 324.80, P < 0.001), and the log-transformed bacterial colony counts in C. elegans were significantly lower in the treatment group than in the infection group (P < 0.05). Conclusions Mt6-21DLeu exerts potent antibacterial effects through disrupting the cell membrane integrity of AB and promoting intracellular ROS accumulation in AB, and exhibits promising potential for treatment of AB infections both in vivo and in vitro, which may serve as a candidate drug molecule against multidrug-resistant AB infections.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

BACKGROUND: Pulmonary arterial hypertension (PAH) presents a significant health burden in Asia and remains a critical challenge. This study aims to delineate the PAH burden in Asia from 1990 to 2021. METHODS: Using the latest data from the Global Burden of Disease 2021, we evaluated and analyzed the distributions and patterns of PAH disease burden among various age groups, sexes, regions, and countries in Asia. Additionally, we examined the associations between PAH disease burden and key health system indicators, including the socio-demographic index (SDI) and the universal health coverage (UHC) index. RESULTS: In 2021, there were 25,989 new PAH cases, 103,382 existing cases, 13,909 PAH-associated deaths, and 385,755 DALYs attributed to PAH in Asia, which accounted for approximately 60% of global PAH cases. The age-standardized rates (ASRs) for prevalence and deaths were 2.05 (95% uncertainty interval [UI]: 1.66-2.52) per 100,000 population and 0.31 (95% UI: 0.23-0.38) per 100,000 population, respectively. From 1990 to 2021, Asia reported the lowest ASRs for PAH prevalence but the highest ASRs for deaths compared to other continents. While the ASRs for prevalence increased slightly, ASRs for mortality and DALYs decreased over time. This increasing burden of PAH was primarily driven by population growth and aging. The burden was especially pronounced among individuals aged ≥60 years and <9 years, who collectively accounted for the majority of deaths and DALYs. Moreover, higher SDI and UHC levels were linked to reduced incidence, but higher prevalence rates. CONCLUSIONS Although progress has been made in reducing PAH-related mortality and DALYs, the disease continues to impose a substantial burden in Asia, particularly among older adults and young children. Region-specific health policies should focus on improving early diagnosis, expanding access to treatment, and effectively addressing the growing PAH burden in the region.
Humans ; Global Burden of Disease ; Male ; Female ; Middle Aged ; Adult ; Asia/epidemiology* ; Prevalence ; Aged ; Pulmonary Arterial Hypertension/mortality* ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Hypertension, Pulmonary/epidemiology*

This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals ; Endoplasmic Reticulum Stress/drug effects* ; Diabetic Nephropathies/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Inflammasomes/drug effects* ; Male ; Kidney/pathology* ; Endoplasmic Reticulum Chaperone BiP ; Humans ; Interleukin-18/genetics* ; Mice, Inbred C57BL

OBJECTIVES: To analyze the early clinical outcomes of the Xcor^TM transcatheter aortic valve replacement (TAVR) system in treating severe aortic stenosis. This study has been registered at Chinese Clinical Trial Registry (ChiCTR2200065593). METHODS: This single-arm, prospective clinical trial enrolled patients with severe aortic stenosis treated with the Xcor^TM TAVR system at the Section of Heart Valve & Coronary Artery Surgery, Guangdong Provincial People's Hospital. Perioperative and follow-up parameters were compared to evaluate differences in hemodynamic outcomes. All-cause mortality, aortic regurgitation, paravalvular leakage, cerebrovascular events, and reoperation were analyzed. RESULTS: Thirty-two patients with severe aortic stenosis were included (20 males, 12 females), with (70.9±4.3) years old and a Society of Thoracic Surgeons (STS) score of 6.45% (6.07%, 7.28%). Notably, 87.5% of patients had New York Heart Association (NYHA) class≥Ⅲ. All patients underwent successful Xcor^TM bioprosthesis implantation, achieving an immediate technical success rate of 100.0% and device success rate of 96.9%. Mean aortic valve gradient decreased from (55.21±23.17) mmHg (1 mmHg=0.133 kPa) to (8.45±5.30) mmHg, peak aortic jet velocity decreased from (4.66±0.85) m/s to (1.99±0.48) m/s, aortic valve area increased from (0.66±0.21) cm² to (2.09±0.67) cm² (all P<0.01). Intraoperative ventricular fibrillation occurred in one patient, while one case exhibited moderate prosthetic valve regurgitation and paravalvular leakage post-procedure. At 12-month follow-up, sustained improvements were observed in cardiac function, left ventricular ejection fraction, hemodynamic parameters, and SF-12 quality-of-life scores (all P<0.01). All-cause mortality was 12.5% (4/32), with 13.8% (4/29) developing moderate paravalvular leakage. CONCLUSIONS The Xcor^TM TAVR system demonstrated favorable early outcomes in severe aortic stenosis patients, significantly improving symptoms and hemodynamics while exhibiting excellent performance in preventing malignant arrhythmias and coronary obstruction.
Humans ; Male ; Female ; Aortic Valve Stenosis/surgery* ; Transcatheter Aortic Valve Replacement/methods* ; Aged ; Follow-Up Studies ; Prospective Studies ; Treatment Outcome ; Aged, 80 and over ; Heart Valve Prosthesis ; Middle Aged

Abuse of amphetamine-based stimulants is a primary public health concern. Recent studies have underscored a troubling escalation in the inappropriate use of prescription amphetamine-based stimulants. However, the neurophysiological mechanisms underlying the impact of acute methamphetamine exposure (AME) on sleep homeostasis remain to be explored. This study employed non-human primates and electroencephalogram (EEG) sleep staging to evaluate the influence of AME on neural oscillations. The primary focus was on alterations in spindles, delta oscillations, and slow oscillations (SOs) and their interactions as conduits through which AME influences sleep stability. AME predominantly diminishes sleep-spindle waves in the non-rapid eye movement 2 (NREM2) stage, and impacts SOs and delta waves differentially. Furthermore, the competitive relationships between SO/delta waves nesting with sleep spindles were selectively strengthened by methamphetamine. Complexity analysis also revealed that the SO-nested spindles had lost their ability to maintain sleep depth and stability. In summary, this finding could be one of the intrinsic electrophysiological mechanisms by which AME disrupted sleep homeostasis.
Animals ; Methamphetamine ; Electroencephalography ; Male ; Sleep/drug effects* ; Central Nervous System Stimulants ; Delta Rhythm/drug effects* ; Sleep Stages/drug effects*

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*