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.

Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.

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.

Objective:To evaluate the efficacy of the combination of acupuncture and meridian acupoint massage based on theory of meridian and tendon for the treatment of elderly patients with lumbar disc herniation (LDH).Methods:A randomized controlled trial study was carried out. Totally 102 elderly patients with LDH qi stagnation and blood stasis syndrome in our hospital from October 2021 to October 2024 were selected as the observation subjects. They were divided into two groups using computer drawing method, with 51 cases in each group. The control group was treated with conventional therapy+meridian acupoint massage, while the observation group was treated with conventional therapy+meridian acupoint massage+ acupuncture based on the theory of meridian and tendon. Both groups received continuous treatment for 4 weeks. TCM syndrome scoring before and after treatment was performed. A lumbar rotation detection training device was used to detect lumbar flexion, extension, flexion, and rotation range of motion; Enzyme immunoassay was used to detect the levels of prostaglandin E 2 (PGE 2), MMP-2, and IL-6; the recovery of lumbar spine function was evaluated using VAS, Oswestry Disability Index (ODI), and Japan Orthopedic Association (JOA) score; adverse reactions during treatment were recorded to assess clinical efficacy. Results:The total effective rate of the observation group was 92.16% (47/51), while that of the control group was 76.47% (39/51), with statistical significance ( χ2=4.74, P=0.029). After treatment, the observation group had lower scores and total scores for lower back pain, lower back stiffness, fatigue, and tongue purple dullness compared to the control group ( t values were 3.83, 4.28, 4.17, 4.85, 5.46, respectively, P<0.01); Lumbar flexion [(82.13 ± 7.91)° vs. (76.32 ± 7.09)°, t=3.91]; posterior extension [(39.15 ± 5.16)° vs. (34.02 ± 5.03)°, t=5.08], bending [(158.14 ± 14.19)° vs. (142.29 ± 13.31)°, t=5.82], the activity of rotation [(39.04 ± 4.79)° vs. (34.82 ± 4.71)°, t=4.49] were higher than those in the control group ( P<0.01), and the plasma levels of PGE 2, MMP-2, and IL-6 were lower than those in the control group ( t values were 4.60, 4.56, and 4.26, respectively, P<0.01); VAS and ODI scores were lower than those in the control group ( t values were 6.52 and 5.33, respectively, P<0.01); the JOA score was higher than that of the control group ( t=4.94, P<0.01). During the treatment period, the incidence of adverse reactions in the observation group was 9.80% (5/51), while in the control group it was 5.88% (3/51), without statistical significance ( χ2=0.54, P=0.461). Conclusion:The combination of acupuncture and meridian acupoint massage based on theory of meridian and tendon can increase lumbar spine mobility, reduce inflammatory factor levels, improve clinical symptoms, enhance efficacy, and have good treatment safety in elderly LDH patients.

Prolonged disorders of consciousness(pDoC)are complex and prolonged conditions that severely impact patient prognosis and remain a clinical treatment challenge.In recent years,neural regulation-based awakening therapies have been widely applied in the assessment and treatment of pDoC patients.Repetitive transcranial magnetic stimulation(rTMS)technology can regulate neural activity and improve patients'consciousness states,demonstrating positive awakening effects for pDoC patients.However,the optimal stimulation parameters and awakening mechanisms of rTMS remain unclear.This article reviews the pathological mechanisms of pDoC,clinical applications of rTMS at different targeting sites and stimulation frequencies,and focuses on exploring how rTMS promotes consciousness recovery through neural mechanisms such as altering neural pathways,reshaping brain networks,promoting synaptic plasticity and neurotransmitter release,regulating neurotrophic factor expression,and modulating cerebral hemodynamics.Based on artificial intelligence,the article also prospects the future clinical research applications of rTMS.

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.

Intracerebral hemorrhage (ICH) is a hemorrhagic cerebrovascular disease with high incidence and mortality. Oxidative stress response plays an important role in the pathological and physiological processes of ICH, and is also a potential effective target for clinical treatment. In this paper, the pathogenesis of oxidative stress after ICH, mechanism of nerve and vascular injury in oxidative stress, and detection and treatment of oxidative stress are reviewed in order to provide references for basic research and clinical practice in ICH.

Objective:To investigate the clinical effect of orbital septal fascia advancement in the correction of mild blepharoptosis.Methods:From December 2016 to January 2020, a total of 77 eyes of 56 patients with mild congenital ptosis who underwent double eyelid surgery were treated. The method of orbital septal fascia advancement was used to correct mild ptosis. Specifically, during double eyelid reconstruction, the orbital septum was opened and the orbital septal fascia about 2 mm in front of the fold was preserved. The posterior lip of the orbital septal fascia was pulled down to the upper part of the tarsal plate, and fixed on the tarsal plate with 3 stitches of 5-0 nylon suture, and appropriate adjustments were made to correct mild ptosis.Results:Patients (56 eyes of 40 cases) were followed up from 6 to 12 months (average 7.4 months), 46 eyes (82.1%) were satisfied with blepharoptosis correction, 8 eyes (14.3%) were basically satisfied with blepharoptosis correction, and 2 eyes (3.6%) were dissatisfied with blepharoptosis correction. 45 eyes (80.4%) were satisfied with blepharoplasty, 7 eyes (12.5%) were basically satisfied with blepharoplasty, and 4 eyes (7.1%) were dissatisfied with blepharoplasty. No double eyelid folds disappeared after surgery, and there were no complications such as incomplete closure, conjunctival prolapse, or exposed keratitis.Conclusions:The correction effect of blepharoptosis is good, and the reconstruction structure is stable with natural appearance, fast recovery and high satisfaction. Therefore, the method can be popularized.

Objective To isolate and culture neural crest cells(NCCs)from lung tissue of mice and to identify the characteristics of the cells in order to provide a new cell model for studying lung injury and injure repair.Methods The mT/mG dual-fluorescence reporter mice and Wnt1-Cre transgenic mice were hybridized,and mT/mG;Wnt1-Cre transgenic mice were screened to obtain enhanced green fluorescent protein(EGFP)permanently labeled NCCs.Cell suspension of mouse lung tissue was prepared by enzymolysis.EGFP+cells(namely NCCs)were har-vested by flow cytometry.Primary culture was performed with DMEM/F12 culture medium optimized in the labora-tory,NCCs was characterized by immunofluorescence microscopy.Then NCCs differentiation was directed by mouse bone marrow mesenchymal stem cells osteogenic induction.Results The mT/mG of EGFP permanently labeled NCCs was successfully obtained by hybridization and high-purity NCCs were isolated from Wnt1-Cre transgenic mice lung tissue.They can be cultured in vitro and with spindle morphology which was,similar to fibroblast adherent proliferation.NCCs expressed the neural crest stem cell marker Sox10 and induced to differentiate into osteoblasts.Conclusions NCCs isolated and cultured from lung tissue of mT/mG;Wnt1-Cre transgenic mice show stable prolif-eration and have the characteristics of neural crest stem cells,which may function as a potential cell model for re-search on lung tissue injury and the mechanism of repair.