Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs. Nevertheless, the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance, thereby substantially restricting their therapeutic utility. Consequently, there is an imperative need to expedite the discovery of novel antifungal agents. This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation. These emerging compounds exhibit unique benefits concerning their modes of action, antimicrobial spectra, and pharmacokinetic characteristics, potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens. It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.

Background Occupational stress has emerged as a critical public health concern affecting the physical and mental well-being of workers in the manufacturing sector. However, researchers typically evaluate its core driver—cumulative fatigue—using a crude binary “present/absent” variable, thereby overlooking the high-dimensional complexity and heterogeneity inherent in fatigue characteristics. This oversimplification constrains both the precision and predictive performance of occupational stress risk assessment model. Objective Leveraging a data-driven approach, to survey data on cumulative fatigue among manufacturing employees, and then use this new classification to develop and validate an occupational stress prediction model, with an ultimate aim of enhancing the accuracy and effectiveness of occupational stress assessment. Methods A set of cross-sectional survey data on 3871 manufacturing employees in 2021 were derived from the “Long working hours exposure and its adverse health effect risk assessment” program of the National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention. Occupational stress was assessed using the Core Occupational Stress Measurement Scale, while cumulative fatigue was evaluated via the Worker’s Self-Diagnostic Questionnaire for Fatigue Accumulation. Boruta method was applied to screen core variables from 20 occupational stress influencing factors. Dimensionality reduction of cumulative fatigue features was performed using a Bayesian sparse autoencoder (BASE), followed by comparison and application of clustering methods to achieve multi-class classification of the reduced features. Six machine learning classification models were then selected including logistic regression, support vector machine, decision tree, random forest, adaptive boosting, and lightweight gradient boosting machine (LightGBM) to construct and compare two occupational stress prediction models involving cumulative fatigue combined with ten other core variables: one utilizing the original binary cumulative fatigue label as a core variable, and another employing the novel fatigue classification proposed herein as a core variable. Results The positive rate of occupational stress among the manufacturing employees was 38.9%. The Boruta method identified 11 core variables of occupational stress: depressive symptoms, cumulative fatigue, age, length of service, tenure in current position, average weekly working hours, average daily overtime hours, average monthly income, low levels of exercise, life satisfaction, and sleep quality. The BSAE reduced the original cumulative fatigue factors to 12 dimensions, while the K-means clustering grouped the reduced fatigue features into three categories: no fatigue, moderate fatigue, and sever fatigue. Six occupational stress prediction models were constructed using the three-category labels of cumulative fatigue and ten additional factors. The results indicated that the LightGBM model performed best, achieving an area under the curve (AUC) of 0.78, an accuracy of 0.77, and an F1 score of 0.72. Compared with the model incorporating the traditional binary labels for cumulative fatigue, the best prediction AUC (0.72), accuracy (0.66), and F1 score (0.65) improved by 6%, 11%, and 7%, respectively. Conclusion Cumulative fatigue is a significant predictor of occupational stress among manufacturing employees. Applying data dimensionality reduction combined with three-class cluster analysis to characterize cumulative fatigue improves the performance of occupational stress prediction models. From a data-driven perspective, machine learning methods demonstrate strengths in processing complex datasets, capturing nonlinear relationships, and generating predictions based on key variables. This study therefore confirms that refined processing of core factors substantially enhances the predictive capability of machine learning models in assessing occupational stress risk in the manufacturing workforce.

This study was designed to investigate the effect of silencing microtubule-affinity regulating kinase 4(MARK4)on the apoptosis,inflammatory cytokine release and intestinal barrier protein expression of FHC cells in a lipopolysaccharide(LPS)-induced ulcerative colitis(UC)model,and the underlying molecular mechanisms.Western blot analysis was used to measure the expression levels of MARK4 and apoptosis-related factors including Caspase-1,NLRP3,and GSDMD in colon tissues from both UC patients and healthy individuals,as well as in LPS-induced FHC cell inflammation model.FHC cells was transfected with shRNA to silence MARK4.In control(normal FHC cells),LPS(LPS-stimulated FHC cells),and MARK4-silenced+LPS(shRNA-and LPS-treated FHC cells)groups,the expression levels of Caspase-1,NLRP3,GSDMD,intestinal barrier proteins,and NF-κB pathway-related proteins were assessed by Western blotting.ELISA and RT-qPCR were used to measure the expression levels of inflammatory cytokines IL-1β,IL-6,and TNF-α;flow cytometry was utilized to assess apoptosis.Data showed that both in UC patient colon tissues and the in vitro LPS-induced FHC cell UC inflammation model,there was a significant increase in the expression of MARK4 and apoptosis-related proteins including NLRP3,Caspase-1,and GSDMD.Silencing MARK4 inhibited the expression of these apoptosis-related proteins and downregulated the inflammatory cytokines IL-1β,IL-6,and TNF-α in LPS-induced FHC cells.Silencing MARK4 also reduced apoptosis,increased the expression of intestinal barrier proteins ZO-1,Occludin,and upregulated Claudin2.Gene Set Enrichment Analysis(GSEA)indicated a positive correlation between MARK4 and the NF-κB signaling pathway.Furthermore,silencing of MARK4 inhibited the expression levels of p-P65 and p-IKKα in the NF-κB pathway.In conclusion,MARK4 is significantly upregulated in UC tissues and cells.Silencing MARK4 inhibits the activation of the NF-κB signaling pathway,thereby inhibiting the apoptosis and inflammatory factor expression of UC cells.Thus,MARK4 could be a potential therapeutic target for UC patients.

Objective To explore the efficacy and safety of lung recruitment maneuver(LRM)on postoperative hypoxemia in patients with acute type A aortic dissection(ATAAD).Methods A total of 56 ATAAD patients with postoperative hypoxemia in the First Affiliated Hospital of Guangxi Medical University from November 2019 to May 2022 were selected and randomly divided into LRM group(n=36)and conventional treatment group(n=20).Patients in conventional treatment group received routine mechanical ventilation on the basis of lung protective ventilation.The patients in LRM group were treated with incremental positive end expiratory pressure(PEEP).Arterial blood gas analysis,respiratory parameters,hemodynamics parameters and serum interleukin(IL)-6 and IL-10 levels were compared between two groups before and after treatment.Results At 12h and 24h after treatment,arterial partial pressure of oxygen(PaO2),oxygenation index(OI),static compliance(Cstat)and dynamic compliance(Cdyn)in two groups were significantly higher than before treatment,the alveolar-arterial gradient of oxygen[PO2(A-a)],respiratory index(RI),peak inspiratory pressure(Ppeak)and plateau pressure(Pplat)were significantly lower than before treatment(P<0.05).PaO2,OI,Cstat and Cdyn in LRM group were significantly higher than those in conventional treatment group,PO2(A-a),RI,Ppeak and Pplat were significantly lower than those in conventional treatment group(P<0.05).Systolic blood pressure and mean arterial pressure decreased and central venous pressure increased during pulmonary reexpansion in LRM group(P<0.05),and all patients returned to baseline level after pulmonary reexpansion.At 12h after treatment,serum IL-6 and IL-10 levels in both groups were significantly lower than before treatment(P<0.05).Conclusion Incremental PEEP can improve oxygenation and lung compliance in patients with hypoxemia after ATAAD surgery,but it has transient effects on hemodynamics,and should be closely monitored during treatment.

【Objective】 To clarify the concept of health literacy among children and adolescents with accidental injuries through literature review and analysis. 【Methods】 A systematic search was conducted across multiple databases, including China National Knowledge Infrastructure, Wanfang database, VIP database, China Biomedical literature database, PubMed, CINAHL, and PscyINFO database. The literature was analyzed using Rodgers′ evolutionary concept analysis method. 【Results】 A total of 56 articles were included. The health literacy of children and adolescents with accidental injuries comprised three conceptual attributes:cognition, emotion and behavior. The influencing factors included children′s demographic factors, family and school related factors and social related factors. The result can be beneficial to reduce the occurrence of injury events, save family economic expenditure and alleviate the burden on social medical resources. However, there is currently a lack of specific measurement tools for assessing health literacy in this population, as the existing evaluation items are drawn from general health literacy scales. 【Conclusions】 The concept of health literacy among children and adolescents with accidental injuries is multifaceted and evolving. Future research should focus on exploring the characteristics of health literacy among children and adolescents of different ages and regions from their own perspectives. Additionally, efforts should be made to refine the concept and develop specialized measurement tools to facilitate further studies in this area.

With the decline in male fertility in recent years, infertility has become an urgent global problem to be solved. Existing evidence shows that gut microbiota has an important impact on male reproductive health, and gut microbiota disorder can affect spermatogenesis by inducing inflammation, metabolic disorder and endocrine disruption. This paper systematically reviews the relevant research progress in this field, focusing on the impact of gut microbiota disorder on male reproductive ability from the aspects of gut microbiota and spermatogenesis, gut microbiota and sex hormone metabolism, effects of fecal microbiota transplantation and dietary regulation on male reproductive function, and discusses the future research directions of gut micro-biota and male infertility.

Premature ejaculation (PE) is the most common male sexual dysfunction with a high incidence, which seriously affects the relationship between a husband and wife and family harmony. Drug therapy is a first-line treatment for PE patients with premature ejaculation, and has achieved good efficacy, but the clinically available drugs are single and the abandonment rate is high. Coupled with the ineffective treatment of some patients, new drug research and development is imminent. This paper systematically reviews the current status of drug treatment for premature ejaculation, focusing on the research and development of new drugs and research progress in order to provide a reference for clinicians.

Chinese medicinal materials are the basis for the inheritance and development of traditional Chinese medicine,as well as strategic resources related to the national economy and people's livelihood.In 2015,12 departments,including the Ministry of Industry and Information Technology,and the State Administration of Traditional Chinese Medicine,jointly formulated the Plan for the Protection and Development of Traditional Chinese Medicine(2015-2020)(hereinafter referred to as the Plan),focusing on seven major construction tasks for the protection and development of traditional Chinese medicine.Through the summary and evaluation of the Plan,it can be seen that the overall development goals and 7 specific indicators have been achieved by 2020.It has been focused on solving the problems of the loss and depletion of some wild Chinese medicinal materials resources and the shortage of Chinese medicinal materials supply.Promoting to alleviate the problems,including the abuse of chemical fertilizers,pesticides,and growth regulators.The extensive production and management of Chinese medicinal materials,as well as the poor exchange of supply and demand information were effectively improved.On the whole,the development and protection of Chinese medicinal materials were promoted.Moreover,the dependence on wild Chinese medicinal materials was reduced through scientific development of Chinese medicinal materials production.And the sustainable development of the Chinese medicinal materials industry was coordinated with the protection of the ecological environment.However,there were still some problems and deficiencies,such as a lack of accurate information guidance,an incomplete price formation mechanism,and an incomplete whole-process traceability system of Chinese medicinal materials.It is suggested that during the 14th Five-Year Plan period,we should continuously strengthen the protection and sustainable development of traditional Chinese medicine resources,and build a new development pattern for traditional Chinese medicine industry based on the new development concept and requirement.

Objective To explore the characteristics of opportunistic infections(OIs)in HIV-infected indi-viduals with suboptimal immune reconstitution after ART treatment so as to provide a reference for preventing and managing HIV infections.Methods The clinical data including opportunistic infections specifically were acquired from 112 HIV-infected individuals with suboptimal immune reconstitution from the outpatient department of Wuming Hospital,Guangxi Medical University.The impact of baseline CD4+T lymphocyte counts on the incidence,type,and mixed infection rates of the opportunistic infections were analyzed.Results The opportunistic infection rate among the 112 HIV-infected individuals with suboptimal immune reconstitution was 42.86%,among which fungal infections were the most commonly seen.The opportunistic infection rate of the patients with a baseline of CD4+T lymphocyte counts≤50/μL was significantly higher than that of the patients with a baseline of CD4+T lymphocyte counts>50/μL,and there was no significant difference in the type of opportunistic infections as well as the rate of mixed infections.Conclusion HIV-infected people with suboptimal immune reconstitution in Guangxi are susceptible to HIV OIs.Among them,the group with a baseline CD4+ T lymphocyte counts≤50/μL has a higher rate of OIs,mainly fungal infections.

Ginger moxibustion has the effect of regulating zang-fu organs and activating qi and blood circulation. When used, ginger paste is required to be close to human skin. Currently, the ginger box used clinically in the hospital can't meet the requirement of large area fitting human skin, and the efficacy of ginger moxibustion is significantly reduced. In this study, a flexible ginger paste box was proposed, which was composed of flexible components polydimethylsiloxane (PDMS), spring and wire netting. The large flexibility of the structure made it fit well with human skin. Finite element method was used to study the fitting degree between ginger paste box and waist soft tissue. Finite element models of flexible ginger paste box and waist soft tissue were established based on Hypermesh and Abaqus software. The equivalent contact area between the flexible ginger paste box and waist was obtained by numerical simulation under different PDMS unilateral thickness, spring wire diameter, wire netting diameter and ginger paste layer thickness. The four parameters were taken as the influencing factors, and the equivalent contact area was taken as the optimization objective. The typical value analysis and variance analysis of S/N were performed by Taguchi method, and the results showed that among the four influencing factors, the wire netting diameter had the largest influence on equivalent contact area and its contribution rate reached 41.98%. The contribution rates of PDMS unilateral thickness, spring wire diameter and ginger paste layer thickness reached 36.48%, 13.97% and 6.50%, respectively. The optimized PDMS unilateral thickness, spring wire diameter, wire netting diameter and ginger paste layer thickness were 1.5, 0.4, 0.15, 35 mm, respectively, and the equivalent contact area was 95.60 cm ². The optimized flexible ginger paste box with great fitting performance can improve the effect of ginger moxibustion.
Acupuncture Points ; Finite Element Analysis ; Ginger/chemistry* ; Humans ; Moxibustion/methods* ; Skin