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.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a refractory condition characterized by chronic inflammation of the bladder wall, disruption of the urothelial barrier, and neural sensitization. Current therapies, such as oral pentosan polysulfate sodium (PPS) or intravesical hyaluronic acid instillations, offer limited efficacy due to transient effects and an inability to reverse tissue fibrosis. Platelet-rich plasma (PRP), a regenerative medicine approach, has demonstrated significant therapeutic potential in urological disorders through the synergistic actions of its multiple growth factors. This review summarizes the latest advances in PRP therapy for IC/BPS, revealing that the underlying mechanisms primarily involve the release of diverse growth factors, suppression of inflammatory responses, restoration of the urothelial barrier, and modulation of nerve axonal regeneration. Clinically, PRP therapy significantly alleviates symptoms including pelvic/bladder pain, urinary frequency, nocturia episodes, and improves patients'quality of life. Furthermore, it offers advantages such as convenient administration, a favorable safety profile, and strong feasibility, presenting new therapeutic methods and options for the clinical treatment of IC/BPS.

Airway assessment is an important prerequisite for airway management.Difficult airway(DA)is a major challenge in anes-thesia management,and failure to predict DA in advance may lead to serious adverse events such as failed intubation and hypoxemia.Accurate assessment and prediction of possible DA before surgery is of vital importance.Traditional assessment systems rely on the ex-perience of the physician experience for interpretation,with a low sensitivity and difficulties in identifying hidden anatomical abnor-malities.Relying on powerful learning and data analysis capabilities,artificial intelligence(AI)establishes a predictive model for DA by integrating multimodal data on the basis of machine learning and deep learning,thereby improving the efficiency and accuracy of identifying abnormal anatomical structures in the airway,which helps to significantly improve prediction efficiency,develop a targeted regimen,implement effective management,and ensure the safety and quality of anesthesia.This article reviews the research on the ap-plication of AI in predicting DA in recent years.

ObjectiveTo assess the efficiency of a Sophora flavescens Ait (S. flavescens, Ku Shen)-soluble microneedle (SFA-MN) for improving skin lesion symptoms in mice with psoriasis.MethodsSFA-MNs were prepared using a two-mold molding process with 20% w/v polyvinylpyrrolidone and 15% w/v polyvinyl alcohol. The SFA-MNs were assessed for morphology, mechanical properties, in vitro dissolution, identification of components, and skin lesion improvement in imiquimod-induced psoriasis mice.ResultsThe SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis, facilitating efficient drug delivery. Furthermore, they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differentiation 3 and tumor necrosis factor-α. In addition, this system alleviated skin inflammation, splenic swelling, and thymic atrophy in the psoriasis-like mouse model. Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios (m/z) of the secondary fragments N-methylcytisine, 5α, 9α-dihydroxymatrine, sophoramine, matrine, oxysophocarpine, oxymatrine, and kushenol O.ConclusionThe drug delivery strategy combining traditional herbal S. flavescens with soluble microneedle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models, enabling enhanced therapeutic effects compared with the control group.

Objective:To analyze the level of interleukin-36(IL-36) family cytokines in peripheral blood, and explore the regulatory role of recombinant human IL-36α in monocyte function in patients with diabetic kidney disease(DKD).Methods:A total of 41 type 2 diabetes mellitus(T2DM) patients, 36 DKD patients, and 20 controls were consecutively enrolled. Plasma and peripheral blood mononuclear cells(PBMCs) were isolated. Enzyme-linked immunosorbent assay(ELISA) was used to measure plasma levels of IL-36α, IL-36β, IL-36γ, and IL-36 receptor antagonist(IL-36Ra). PBMCs were sorted, and real-time quantitative PCR was performed to detect the mRNA expression of IL-36 receptor subunits in monocytes. Monocytes were stimulated with recombinant IL-36α, and levels of cytotoxic molecules and cytokines in the culture supernatant were measured. Flow cytometry was used to assess the expressions of programmed death receptor-1(PD-1) and cytotoxic T-lymphocyte-associated protein 4(CTLA-4). Co-culture of monocytes with Vero cells was performed to evaluate monocyte cytotoxicity.Results:Plasma levels of IL-36α and IL-36β in the T2DM and DKD groups were significantly higher than those in the control group. The DKD group also showed higher plasma levels of IL-36α compared to the T2DM group( P<0.05). There were no significant differences in IL-36γ and IL-36Ra levels among the three groups( P>0.05). The mRNA expression of IL-36 receptor subunits in monocytes was comparable among the three groups( P>0.05). The DKD group had higher level of tumor necrosis factor-alpha(TNF-α) compared to the control and T2DM groups( P<0.05). The levels of PD-1 and CTLA-4 were lower in the DKD group than those in the control and T2DM groups( P<0.05). The proportion of monocyte-induced Vero cell death was significantly higher in the DKD group compared to the control and T2DM groups( P<0.05). After stimulation with recombinant human IL-36α, monocytes from DKD patients showed a significant increase in the secretion of granzyme B and TNF-α( P<0.05), as well as an increased proportion of monocyte-induced Vero cell death( P=0.024). Conclusion:In DKD patients, elevated IL-36α and granzyme B levels in monocytes enhance monocyte function.

AIM: To investigate the effect of the timing of satisfactory sedation with preoperative oral midazolam on anesthesia induction and recovery in children undergoing adenotonsillectomy. METHODS: A total of 147 children undergoing elective adenotonsillectomy, with ASA physical status orⅡ, aged 2-7 years were selected from November 2022 to June 2023 in the Second Affiliated Hospital of Wenzhou Medical University. The children were orally administered 0.5 mg/kg midazolam in preoperative waiting area and were divided into 10-20 min (rapid onset, M1 group) and 21-30 min (slow onset, M2 group) based on the satisfactory sedation time, or equal volume of sugar pear drink orally (blank control group, C group). Children in all three groups received a general anesthesia method of propofol+fentanyl combined with sevoflurane induction and sevoflurane maintenance. The primary outcome measures were the induction compliance checklist (ICC) score and the pediatric anesthesia emergence delirium (PAED) score in the post-anesthesia care unit (PACU) to assess the occurrence of emergence agitation (EA), and the secondary outcome measures included the parental separation anxiety scale (PSAS), sedation Ramsay score, surgery duration, recovery time, PACU stay time, discharge time, the incidence of perioperative respiratory adverse events (PRAE) and other adverse events in the ward. RESULTS: 147 children were included in the result analysis, with 49 cases in each group. The proportion of perfect induction (ICC=0) were significantly higher in two M groups than that in group C (95.9% vs. 91.8% vs. 61.2%, P=0.001). The maximum and average PAED score in PACU in group M1 showed a significantly higher (6.4±5.0 vs. 4.4 ± 4.1, P=0.029; 5.2 ± 4.5 vs. 3.4 ± 3.6, P=0.030), and the incidence of EA was significantly higher than those in group C (10.2% vs. 30.6%, P=0.022), and increased compared to the group M2 (OR= 0.581, 95%CI 0.231-1.463, P=0.354). There was no statistically significant difference in the maximum and average PAED scores, incidence of EA between group M2 and group C (P>0.05). The Ramsay score and PSAS score in two M groups were higher, PACU stay time and recovery time was longer than those in group C (P<0.05). The pain scores in PACU in group M1 was higher than that of group C (P<0.05). There was no statistically significant difference in the surgical time, discharge time, the incidence of PRAE and other adverse events in the ward among three groups (P>0.05). CONCLUSION: Preoperative oral midazolam can improve the ICC and PSAS scores of children during induction, but it also leads to prolonged recovery time and PACU retention time. The rapid onset of midazolam did not result in better induction and recovery quality, but instead increased the incidence of EA and postoperative pain score.

Objective:To observe the expression of interleukin-35(IL-35) in Hashimoto's thyroiditis(HT) patients, and evaluate its regulatory effect on the balance between regulatory T cells(Treg) and T helper 22(Th22) cells.Methods:Forty-two HT patients and eighteen controls were consecutively enrolled. Plasma and peripheral blood mononuclear cells(PBMC) were isolated. Treg were purified. Plasma IL-35 and IL-22 were detected with enzyme-linked immunosorbent assay. Treg and Th22 percentages were measured using flow cytometry. Real-time quantitative PCR was used to assess mRNA levels of forhead box protein 3(FoxP3) and aryl hydrocarbon receptor(AhR). Treg were stimulated with exogenous IL-35, and were co-cultured with autologous PBMC to induce Treg-to-Th22 phenotypic differentiation, evaluating the effect of IL-35 on Treg function and differentiation.Results:There was imbalance between Treg and Th22 cells in HT group. HT group had reduced Treg percentage, plasma IL-35 and FoxP3 mRNA( P<0.001), while had elevated Th22 percentage and AhR mRNA( P<0.001). There was no significant difference in plasma IL-22 level between two groups( P=0.775). The suppressive capacity of Tregs in the HT group was diminished( P=0.013), and secretion levels of IL-35 and IL-10 were lower than those in the control group( P<0.001). The ability of Tregs in the HT group to differentiate into Th22 cells was increased, with higher levels of CCR4, CCR6, CCR10, AhR mRNA, and IL-22 secretion compared to the control group( P<0.01). IL-35 stimulation induced elevation of Treg percentage, FoxP3 mRNA, and IL-35/IL-10 secretion( P<0.05), but did not affect Th22 percentage, AhR mRNA, or IL-22 secretion( P>0.05). IL-35 stimulation enhanced Treg function in HT group, increasing proliferation inhibition and secretion of IL-35 and IL-10( P<0.05). IL-35 stimulation reduced the differentiation of Treg to Th22 phenotype in HT group, with decreased levels of CCR4, CCR6 CCR10, AhR mRNA, and IL-22 secretion( P<0.05). Conclusion:IL-35 enhances the immunosuppression of Tregs in HT patients and inhibits its differentiation into Th22 cells, thus regulating the balance between Tregs and Th22 cells.

Objective:To understand the epidemiology of rubella and the genetic characteristics of the virus circulating during the period 2021-2022, providing basic scientific data for rubella prevention and control in China.Methods:National rubella incidence data for the period 2021-2022 were obtained from the Infectious Disease Surveillance System module and the Surveillance Report Management module of the China′s Disease Prevention and Control Information System. Positive rubella virus(RuV)isolates were obtained from the National Measles/Rubella Laboratory Network. Two nucleotide (nt) fragments [F1-480 (8 633-9 112 nt) and F2-633 (8 945-9 577 nt)] located in the E1 gene were amplified and determined by reverse transcription polymerase chain reaction (RT-PCR), and the target gene (E1-739) was obtained after collating and splicing. The sequences obtained in this study were used to construct a phylogenetic tree with the reported reference strains for genotype and lineage identification. Additionally, the phylogenetic analysis was performed to assess their genetic relatedness of RuV strains prevalent in China during 2018-2020 from GenBank database.Results:In 2021-2022, the rubella incidence in China was 0.06/100, 000 (2021: 840 cases; 2022: 784 cases), with cases primarily concentrated in the western and southern provinces. Age distribution analysis showed that rubella cases in 2021-2022 was mainly in children under 5 years of age (2021: 34.17%, 287/840; 2022: 42.09%, 330/784), with the highest proportion in children aged 0-2 years. Further analysis of the immunization history of cases revealed that in the 8-23 months age group, a significant proportion of cases had received only one dose of rubella containing vaccine (RCV); cases in the 2-14 years age group were mainly among children who had received two or more doses of RCV; however, cases over 15 years of age were primarily found in individuals who had not received RCV or had unknown immunization history. National virological surveillance data showed that totally 22 RuV virus isolates were obtained, from 6 provinces in China during 2021-2022, which belonged to lineage 1E-L2 (11 strains) and 2B-L2c (11 strains). And these viruses displayed high genetic homology with RuV prevalent from 2018 to 2020.Conclusions:The incidence of rubella in China was maintained at a low level during 2021-2022, and the prevalent RuV strains were lineage 1E-L2 and 2B-L2c.

Operation duration has consistently been regarded as a important factor influencing the outcome of total knee arthroplasty(TKA).Prolonged operation time can give rise to an array of adverse events,ultimately leading to surgical failure,escalated healthcare expenses,and even jeopardizing patient survival.Numerous studies have demonstrated that prolonged operation time is linked with an augmented risk of postoperative complications.Recent investigations have revealed that extended operation duration can heighten the likelihood of postoperative pain,wound dehiscence,anemia and blood transfusion requirements,surgical site infection,sepsis,prolonged hospitalization and readmission rates;impact prosthetic longevity and patient survival rate.