Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by profound metabolic dysregulation and hepatic inflammation and represents a major global health burden with limited effective therapeutic options. Increasing evidence suggests that improving mitochondrial function and enhancing mitophagy may offer promising strategies for MASH treatment. Ginsenoside Rg1 (G-Rg1) has been reported to exert potent anti-inflammatory and antioxidant effects; however, its precise molecular mechanisms and targets in MASH remain unclear. In this study, we investigated whether G-Rg1 ameliorates diet-induced MASH by promoting mitophagy and sought to identify its direct molecular target. Mice treated with G-Rg1 were evaluated using histological, biochemical, and indirect calorimetric analyses to assess hepatic steatosis, fibrosis, inflammation, and energy metabolism. Transcriptomic profiling and transmission electron microscopy revealed enhanced mitophagy and improved mitochondrial ultrastructure following G-Rg1 treatment. Virtual screening and molecular docking identified glutaminase 2 (GLS2) as a potential target of G-Rg1, which was subsequently confirmed by drug affinity-responsive target stability, cellular thermal shift, and binding assays. Mechanistically, G-Rg1 activated the GLS2/PINK1/Parkin pathway, leading to increased mitophagy, reduced hepatocellular lipid accumulation, restoration of mitochondrial function, and attenuation of oxidative stress. Notably, GLS2 overexpression recapitulated the protective effects of G-Rg1 both in vitro and in vivo. Collectively, these findings demonstrate that G-Rg1 alleviates MASH by targeting GLS2 to activate PINK1/Parkin-mediated mitophagy, highlighting GLS2-regulated mitophagy as a potential therapeutic target for MASH.

[This corrects the article DOI: 10.3389/fimmu.2023.1204338.].

BACKGROUND:Previous research indicated that physicians possess limited knowledge of the diagnosis and treatment of invasive fungal disease (IFD). OBJECTIVE:This study aimed to assess the efficacy of training via video or PDF formats in increasing physicians' knowledge of IFD. METHODS:This was a multicentre, cluster-randomised controlled trial involving 18 tertiary hospitals in China. Physicians specialising in IFD clinical diagnosis and treatment from four departments were randomised 1:1 into a video training group or PDF training group, and questionnaires were completed before and after training. The primary outcome was the change in total questionnaire score before and after training. RESULTS:Of the 294 participants, 146 were assigned to the video group and 148 to the PDF group. Engagement with the training materials was observed among 127 participants from the video group and 135 from the PDF group. In the per-protocol set (PPS), post-training score improvements for total scores (p = 0.008), invasive candidiasis scores (p < 0.001), and invasive aspergillosis scores (p = 0.044) in the video group were significantly greater than those in the PDF group. Overall, 161 (61.5%) physicians in the PPS exhibited enhanced total scores post-training, with the video group outperforming the PDF group (70.9% vs. 52.6%, p = 0.002). The findings in the FAS were largely consistent with those observed in the PPS. CONCLUSION:Both video and PDF training modules are appealing to physicians. Further, the video training module displayed superior efficacy in improving physicians' knowledge of IFD.

Functional cure of chronic hepatitis B virus (HBV) infection remains a significant challenge, making viral-entry-blocking antibodies a promising antiviral strategy. Here, we developed a structure-guided computational workflow for affinity-enhancing candidate mutations at the interface between the humanized neutralizing antibody HzKR127 and the HBV preS1 peptide epitope. Based on the crystal structure of the HzKR127–preS1 complex, we performed single-site saturation mutagenesis across the paratope, evaluating variants with a consensus effect score integrated from seven computational models. Benchmarking against published alanine scanning data showed that our consensus score effectively identified major-affinity-loss residues, achieving ROC AUC values of 0.81 and 0.84 for residue-level and site-level predictions, respectively. Mutational profiling revealed distinct asymmetric mutational responses, with broad intolerance on the preS1 side and localized favorable substitutions within antibody CDRs. Multilevel prioritization identified 26 antibody-side candidates, 17 of which showed improved HADDOCK refinement scores compared to the wild type. In particular, the H:D97W/F/Y substitutions presented the strongest structural rationale for enhancing improved interfacial packing through aromatic hydrophobic contacts with preS1 Phe10. These findings provide a prioritized list of candidates for experimental validation and a practical framework for the rational optimization of antibodies targeting functionally constrained viral epitopes.

Background Metabolic dysfunction-associated fatty liver disease (MAFLD) imposes a significant global health burden, and safe and effective treatments are still lacking. Ginsenoside Rg1 (Rg1), a key bioactive compound extracted from ginseng, can effectively alleviate liver injury associated with MAFLD, but the specific molecular mechanism remains unclear. Objective This study aims to investigate the therapeutic effects of Rg1 on MAFLD and elucidate its underlying mechanisms. Methods A mouse model of MAFLD was established using the methionine-choline-deficient(MCD) diet, and Rg1 was given intragastrically for 4 consecutive weeks. The effects of Rg1 on MAFLD were investigated in vitro by cultivating HepG2 cells with free fatty acids (FFA). We used commercial assay kits, histopathological staining, transmission electron microscopy (TEM), immunofluorescence (IF), polymerase chain reaction (PCR), and Western blotting (WB) to assess parameters related to inflammation, oxidative stress, and ferroptosis in liver tissue and HepG2 cells. Molecular docking and the Nrf2 inhibitor (ML385) were used to validate the potential mechanisms underlying the hepatoprotective effects of Rg1. Results Rg1 treatment dramatically reduced hepatic Fe 2+ , oxidative stress, and inflammatory factor levels. In vitro experiments revealed that Rg1 reduced iron, MDA, and ROS levels, while upregulating SLC7A11 and GPX4 to inhibit oxidative stress and ferroptosis. These results suggest that Rg1 exerts antioxidant and anti-ferroptotic effects by activating the Nrf2/GPX4 signaling pathway. Conclusion Rg1 is a natural bioactive compound with potential therapeutic applications for MAFLD; it inhibits hepatic ferroptosis, reduces oxidative stress, and alleviates MAFLD by activating the Nrf2/GPX4 pathway.

In recent years, some cases of severe visceral leishmaniasis (VL) in immunocompetent adults have gradually been reported. Hemophagocytic lymphohistiocytosis (HLH) and intestinal hemorrhage are two rare complications in patients with VL. Without treatment, the mortality rate of such patients is extremely high. We report a case of a 31-year-old immunocompetent male who initially presented with fever of unknown origin (FUO), later developed HLH and experienced multiple episodes of life-threatening intestinal hemorrhage. The diagnosis of visceral leishmaniasis was confirmed through metagenomic next-generation sequencing (mNGS). The patient was successfully treated with amphotericin B deoxycholate (AmB-D) and supportive care. During the two-year follow-up period, no new complications were found. This case highlights the value of mNGS in the diagnosis of complex infectious diseases and emphasizes the clinical significance of the multidisciplinary collaborative model for patients with VL and complex complications. It can provide a reference for the early diagnosis and comprehensive treatment of severe VL.

The study aims were to present in vitro susceptibilities of clinical isolates from Gram-negative bacteria bloodstream infections (GNBSI) collected in China. GNBSI isolates were collected from 18 tertiary hospitals in 7 regions of China from 2018 to 2020. Minimum inhibitory concentrations were assessed using a Trek Diagnostic System. Susceptibility was determined using CLSI broth microdilution, and breakpoints were interpreted using CLSI M100 (2021). A total of 1,815 GNBSI strains were collected, with E. coli (42.4%) and Klebsiella pneumoniae (28.6%) being the most prevalent species, followed by P. aeruginosa (6.7%). Susceptibility analyses revealed low susceptibilities (<40%) of ESBL-producing E. coli and K. pneumonia to third-/fourth-generation cephalosporins, monobactamases, and fluoroquinolones. High susceptibilities to colistin (95.0%) and amikacin (81.3%) were found for K. pneumoniae , while Acinetobacter baumannii exhibited a high susceptibility (99.2%) to colistin but a low susceptibility to other antimicrobials (<27.5%). Isolates from ICUs displayed lower drug susceptibility rates of K. pneumoniae and A. baumannii than isolates from non-ICUs (all P < 0.05). Carbapenem-resistant and ESBL-producing K. pneumoniae detection was different across regions (both P < 0.05). E. coli and K. pneumoniae were major contributors to GNBSI, while A. baumannii exhibited severe drug resistance in isolates obtained from ICU departments.

Background Vancomycin-resistant Enterococcus faecium (VREfm) and Enterococcus faecalis (VREfs) are major antimicrobial resistance threats. Previous assessments rarely distinguished species, limiting understanding of their epidemiology and control. To address this gap, we analysed trends from 1990 to 2021 and projected the burden through 2050 in order to assess the global burden, inequalities, and future patterns of VREfm and VREfs. Methods We analysed deaths and disability-adjusted life years (DALYs) from Measuring Infectious Causes and Resistance Outcomes for Burden Estimation (MICROBE) across 204 countries from 1990 to 2021. Temporal trends were assessed using estimated annual percentage change (EAPC). Associations with the socio-demographic index (SDI), health inequalities, and decomposition of burden changes were examined. Future trends to 2050 were projected using a Bayesian age–period–cohort (BAPC) model. Results In 2021, 11,021 deaths and 353,634 DALYs were attributable to VREfm worldwide, compared with 2,991 deaths and 82,025 DALYs attributable to VREfs. Since 1990, VREfm has increased mainly in higher-SDI regions, whereas VREfs has decreased in lower-SDI settings. Based on the BAPC model, VREfm burden is projected to continue rising across all indicators by 2050, while VREfs shows a sustained decline. Conclusions This study demonstrates divergent species-specific trends, with an increasing burden of VREfm and a decline in VREfs. VREfm is concentrated in middle- to high-SDI regions, while VREfs is in lower-SDI regions. For both species, burden peaks in young children and older adults. These divergent patterns necessitate tailored strategies that prioritise young children and older adults, with a focus on hospital infection control and antimicrobial stewardship for VREfm in higher-SDI regions, and on community prevention and One Health approaches for VREfs in lower-SDI regions.

Ginsenoside Rg1 (G-Rg1), a traditional Chinese medicine, alleviates metabolic dysfunction-associated steatotic liver disease (MASLD). However, the mechanism by which G-Rg1 improves metabolic disorders in MASLD by regulating the gut microbiota remains ambiguous‌. We constructed a diet-induced murine MASLD model and employed 16S rRNA sequencing and non-targeted metabolomic analysis to ‌investigate the mechanism of G-Rg1 in treating MASLD, focusing on its regulatory effect on the gut microbiota. Our results revealed that G-Rg1 significantly increased the 5-hydroxyindoleacetic acid levels and activated the aryl hydrocarbon receptor (AHR) by enhancing intestinal permeability, modulating the gut microbiota composition, and influencing tryptophan metabolism. Therefore, G-Rg1 improved immune function and reduced liver inflammation and lipid deposition in the MASLD mouse model. In contrast, the effect of G-Rg1 was impaired upon removal of the gut microbiota. Furthermore, fecal microbiota transplantation in G-Rg1-treated mice improved MASLD. These finding s suggest that regulating the gut microbiota may play an important role in G-Rg1's ability to protect against MASLD. G-Rg1 may exert its anti-MASLD effects through the gut microbiota, tryptophan metabolism, AHR activation, and interleukin-22 signaling, offering a novel approach for G-Rg1-mediated MASLD treatment.

BackgroundBloodstream infection (BSI) exhibits elevated mortality, particularly among elderly patients manifesting atypical symptoms. Although blood culture (BC) remains the diagnostic gold standard, its limited sensitivity and prolonged turnaround time impede early detection. Droplet digital polymerase chain reaction (ddPCR), a novel pathogen detection method with superior sensitivity and rapid results, demonstrates significant diagnostic and prognostic for BSI. However, heightened sensitivity may increase false positive rates, with elderly patients particularly susceptible to specimen contamination and transient bacteremia.MethodsThis retrospective study employed clinical judgment as the diagnostic reference. Patients were stratified into BSI and non-BSI groups, with data collected on ddPCR and BC results, imaging and laboratory findings, medication response, and discharge outcomes. The diagnostic accuracy and antibiotic guidance efficacy of ddPCR and BC were compared, and the clinical utility of ddPCR was evaluated for prognostic assessment and false positive identification.ResultsThe analysis encompassed 355 episodes from 280 elderly patients with suspected BSI. ddPCR demonstrated significantly higher detection rates compared to BC in BSI group (59.33% versus 20.57%). Combined implementation increased detection to 65.07%. Regardless of clinical judgment (59.61% versus 20.57%) or alternative microbiological tests (90.63% versus 7.14%) served as the reference standards, ddPCR exhibited superior sensitivity to BC. No significant differences emerged in antibiotic adjustment rates or therapeutic efficacy between ddPCR and BC. Elevated microbial species diversity correlated with unfavorable discharge outcomes (P<0.001, OR=2.122). Multiple follow-up ddPCR monitoring revealed progressive increases in the number of species and the copies of some (or all) species among patients with poor outcomes, contrasting with decreasing trends in those with favorable outcomes. When detecting Streptococcus, coagulase-negative Staphylococci (CoNS), Acinetobacter baumannii complex, and Candida, diagnostic thresholds of 132.55, 182.70/262.24, and 174.78 copies/mL, respectively, were established to help differentiate false-positive results.ConclusionThe combination of ddPCR with BC improves BSI diagnosis in elderly patients and facilitates antibiotic treatment optimization. Moreover, ddPCR demonstrates potential for prognostic evaluation and false-positive discrimination. Nevertheless, these findings require further validation through large-scale prospective studies employing predefined clinical criteria.

Predicting the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is critical for early intervention. Towards this end, various deep learning models have been applied in this domain, typically relying on structural magnetic resonance imaging (sMRI) data from a single time point whereas neglecting the dynamic changes in brain structure over time. Current longitudinal studies inadequately explore disease evolution dynamics and are burdened by high computational complexity. This paper introduces a novel lightweight 3D convolutional neural network specifically designed to capture the evolution of brain diseases for modeling the progression of MCI. First, a longitudinal lesion feature selection strategy is proposed to extract core features from temporal data, facilitating the detection of subtle differences in brain structure between two time points. Next, to refine the model for a more concentrated emphasis on lesion features, a disease trend attention mechanism is introduced to learn the dependencies between overall disease trends and local variation features. Finally, disease prediction visualization techniques are employed to improve the interpretability of the final predictions. Extensive experiments demonstrate that the proposed model achieves state-of-the-art performance in terms of area under the curve (AUC), accuracy, specificity, precision, and F1 score. This study confirms the efficacy of our early diagnostic method, utilizing only two follow-up sMRI scans to predict the disease status of MCI patients 24 months later with an AUC of 79.03%.

Following the publication of the above article, the authors drew to the attention of the Editorial Office that, after having reviewed all the figures and the data of their drawing software, they discovered that the pictures in the 'Control' and 'DEX' groups of Fig. 4D on p. 904 had been incorrectly imported into Fig. 6 on p. 905 when assembling this figure, effectively replacing the original and correctly placed images in Fig. 6D and E. The original (and correct) version of Fig. 6 is shown on the next page. All the authors agree with the publication of this Corrigendum, and express their gratitude to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 41: 899‑907, 2018; DOI: 10.3892/ijmm.2017.3297].

Acute genital ulcers (AGU) have been associated with various pathogens, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV). However, cases of AGU associated with coronavirus disease 2019 (COVID-19) are rare, and this disease significantly impairs human quality of life. In this case, we report a 37-year-old woman who presented with a five-day history of a painful genital ulcer and fever. A month earlier, she had experienced a COVID-19 infection that resolved without medical therapy. Physical examination revealed that multiple asymmetric ulcers presented on labia minora covered with whitish exudates. The patient, without any high-risk sexual behavior, or a personal or family history of autoimmune disorders or inflammatory bowel disease, was diagnosed with COVID-19-related AGU after ruling out other infectious and immune diseases. Following a two-week treatment of oral prednisone, her vulvar edema, ulcers, and fever improved significantly. This case suggests that AGU may be triggered by a COVID-19 infection.

The escalating incidence of infective endocarditis (IE) caused by aminoglycoside-resistant Enterococcus is a growing concern for clinicians. This issue is particularly pronounced in elderly patients, who face an elevated risk of renal damage during antibiotic treatment, thereby limiting available pharmacological options. Furthermore, elderly patients often present with multiple comorbidities, leading to heightened mortality rates. In this article, we present a case involving an elderly male patient who sought medical attention on two separate occasions due to inflammation of the lower extremities and lumbosacral pain. Subsequent diagnosis revealed infective endocarditis (IE) caused by high-level gentamicin-resistant Enterococcus faecalis through blood culture and echocardiography. The patient also experienced peripheral and cerebral arterial embolism, secondary spine infection, and subsequent heart failure, highlighting the severity of the clinical situation. Following an initial 10-day course of vancomycin and ceftriaxone therapy, the patient developed renal impairment, necessitating a switch to bactericidal therapy with ampicillin in combination with ceftriaxone. Additionally, aortic valve replacement was performed during this period. Ultimately, the patient achieved clinical remission. This case underscores the critical importance of prompt and accurate diagnosis, appropriate antibiotic selection, and timely surgical intervention in enhancing the prognosis of elderly patients with IE.

Background China Against Drug Resistance (CARE) project was launched for improving antimicrobial use and infection control in Chinese hospitals. The first step was developing a Point Prevalence Survey (PPS) tool for assessing at patient bedside risk factors and rates of hospital acquired infections (HAIs) and quality indicators of antimicrobial usage and testing its workability. Methods After a pilot phase (2016), the CARE PPS tool was deployed in 2018-9 in eight large Chinese hospitals. Each hospital selected 3-5 adult departments (intensive care, surgery, medicine). The questionnaire in English and Chinese, on paper and tablet computer, was filled out directly at the patient's bedside by local infection control teams, microbiologists, pharmacists and clinicians. Results The number of patients visited per day and per investigator team increased from 20-30 during the pilot phase in the first hospital to 40-50 in the eight other hospitals. The main characteristics of the 1,170 patients included (ICU 138, medicine 430, surgery 602) were: median age 60 years; Mac Cabe score 1 74.7%; catheters: central vascular 14.3%, peripheral vascular 50.9%, urinary 19.8%; surgery during stay 31.8%. HAIs prevalence was 6.3% (mainly respiratory tract, surgical-site; main bacteria: Acinetobacter, Pseudomonas, Klebsiella ). 54.4% of the patients were receiving antimicrobials for therapeutical use (≈3/4 single drug): from 36% in surgery to 78.3% in ICU, mostly large spectrum beta-lactams. Examination of patient records at the bedside found the reason for the treatment (53%), treatments based on microbiological results (9.3%), and prescription reassessment (30.7%). Conclusion The study showed that antimicrobial policy and HAI prevention could be improved by using Care-PPS in Chinese hospitals. Although obtained on a limited number of patients, the results demonstrated that there is room for improvement in antimicrobial policy and HAI prevention in the participating hospitals.

Streptococcus pyogenes, also known as Group A Streptococcus (GAS), can cause severe invasive diseases with high fatality rates. We report a case of necrotizing fasciitis and myositis complicated by Streptococcal Toxic Shock-Like Syndrome (STSS) caused by the invasive emm 22/ST46 strain of Streptococcus pyogenes in China. A previously healthy 57-year-old Chinese Canadian man presented with right calf pain and ulceration following a hike in the Gobi Desert, which progressed to unconsciousness and severe infection. Despite initial treatment, his condition deteriorated, leading to his transfer to our intensive care unit. Metagenomic Next-Generation Sequencing identified Streptococcus pyogenes, and antimicrobial susceptibility testing revealed resistance to erythromycin, tetracycline, and clindamycin. Despite broad-spectrum antimicrobial therapy, debridement, and supportive measures, the patient's condition necessitated amputation of the right lower limb. He recovered and was discharged from the hospital on Day 43. Whole-genome sequencing of the isolate identified 15 multiple virulence factors. Phylogenetic analysis revealed that the closest relative of the isolate was a strain identified in China. This case underscores the importance of early recognition and treatment of invasive GAS infections to prevent severe outcomes, and we should pay attention to invasive emm 22/ST46 GAS infections in China.

Recent studies have found that lipid levels in patients with chronic hepatitis B (CHB) may change during antiviral therapy. To assess the effects of first-line nucleot(s)ide analogues (NAs) on lipid profiles in patients with CHB using network meta-analysis. Seven electronic databases (PubMed, Embase, Cochrane Library, and four Chinese databases) were searched for cohort studies on the effect of NA on lipids in patients with CHB up to August 1, 2023. The changes of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were taken as outcomes. The mean difference (MD) of continuous variables and 95

老年医学专科医师规范化培训对于提高老年科医师的整体水平以应对当今社会深度老龄化现状发挥着重要的作用.现代老年医学重点关注老年人的整体健康状态以及对其提供连续性医疗服务.文章根据上述老年医学理念,鉴于我国当前老年医学专科医师规范化培训的现状,结合老年专科医师应具备的基本素养和临床技能掌握如衰老的发病机制、老年疾病的精准诊治技术、老年综合征及老年综合评估技术、安全转诊及安宁疗护技能等,主要从改善各阶段医学生的老年医学教育现状、改善当前个体化老年医疗模式为"生物-心理-社会-环境"的现代医学模式、提高培训师资水平及提高老年医学专科医师的基础和临床研究素养等方面,探讨了老年医学专科医师规范化培训的对策.笔者建议将现代老年医学理念融入贯穿到老年医学专科医师培养过程中,为老年医学人才培养和专科医师规范化培训体系的建立提供参考.

China is an epidemic area of hepatitis E, and the serum prevalence data is very important for formulating prevention and control strategies. However, almost all related research in the past decade are cross‐sectional studies. In this study, we analyzed the serological data from 2012 to 2021 in Chongqing for 10 consecutive years. We found that the positive rate of hepatitis E IgG antibody increased gradually, from 1.61% in January 2012 to 50.63% in December 2021. The autoregressive integrated moving average model was used to predict the trend, and it was found that it will continue to show an upward trend in the recent future. In contrast, the positive rate of IgM and clinical incidence of hepatitis E showed a relatively stable trend. Although the positive rate of antibodies gradually increased with age, there was no significant difference in the age distribution of the subjects each year. Therefore, these results suggest that the accumulated infection of hepatitis E in Chongqing may be gradually increasing, but the clinical incidence rate remains unchanged, which provides a new concern for formulating prevention and control strategies.

Ginsenoside Rg1 (GRg1), a key bioactive component of medicinal herbs, has shown beneficial effects on non-alcoholic fatty liver disease (NAFLD) and numerous other conditions. Nevertheless, the specific targets that are actively involved and the potential mechanisms underlying NAFLD treatment remain unclear. This study aimed to elucidate the therapeutic effects and mechanism of GRg1 in alleviating NAFLD using a combined approach of network pharmacology and molecular biology validation. The analysis yielded 294 targets for GRg1 and 1293 associated with NAFLD, resulting in 89 overlapping targets. Through protein-protein interactions (PPI) network topology analysis, 10 key targets were identified. Upon evaluating the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis, GRg1 may exert therapeutic effects on NAFLD by negatively regulating the apoptotic process, insulin and endocrine resistance, the AGE-RAGE signaling pathway in diabetic complications, and the Estrogen, PI3K/Akt, and MAPK pathways. The three differential gene targets for Akt1, EGFR, and IGF1 were identified through the compound-target network in conjunction with the aforementioned methods. The molecular docking and molecular dynamics (MD) simulations showed that AKT1 and EGFR had a strong binding affinity with GRg1. Overall, our findings point to a novel therapeutic strategy involving NAFLD, with further in vivo and in vitro studies promising to deepen our comprehension and validate its potential advantages.Communicated by Ramaswamy H. Sarma.