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.

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 explore the factors influencing erectile dysfunction (ED) in male patients after renal transplantation, so as to provide basis for the prevention and treatment of this disease. 【Methods】 Kidney transplant recipients followed up in the Kidney Transplant Clinic of Xijing Hospital during Sep.1, 2022 and May 1, 2023 were selected as the study objects.Questionnaires were distributed, and the erectile function was measured with Sexual Health Inventory for Men (SHIM).Factors associated with ED were analyzed with multivariate logistic regression. 【Results】 A total of 300 questionnaires were distributed, and 276 valid ones were collected, including 182 cases (65.9%) suffering from ED of varying degrees.Multivariate logistic regression analysis showed that age [(<30 years/>50 years, OR: 0.120, 95%CI: 0.033-0.405, P<0.001), (30-40 years/>50 years, OR: 0.223, 95%CI: 0.102-0.463, P<0.001), (>40-50 years/>50 years, OR: 0.320, 95%CI: 0.139-0.719, P<0.01)], level of International Prostate Symptom Score (IPSS) (OR: 1.95, 95%CI: 1.211-3.248, P<0.01), International Prostate Symptom Score-Quality of Life item (IPSS-QoL) (OR: 1.482, 95%CI: 1.201-1.854, P<0.01), and income [(≥10 000 Yuan/<3 000 Yuan, OR: 0.156, 95%CI: 0.053-0.429, P<0.001), (5 000-<10 000 Yuan/<3 000 Yuan, OR: 0.418, 95%CI: 0.199-0.864, P<0.05), (≥10 000 Yuan/3 000-<5 000 Yuan, OR: 0.205, 95%CI: 0.069-0.573, P<0.01)] were independent and significant factors of ED. 【Conclusion】 The prevalence of ED in renal transplantation recipients is high.Age, income, IPSS and IPSS-QoL are the influencing factors.ED after renal transplantation is not only determined by physical and functional factors, but also closely related to social and psychological factors.

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.

Tbx18,Wt1,and Tcf21 have been identified as epicardial markers during the early embryonic stage.However,the gene markers of mature epicardial cells remain unclear.Single-cell transcriptomic analysis was performed with the Seurat,Monocle,and CellphoneDB packages in R software with standard pro-cedures.Spatial transcriptomics was performed on chilled Visium Tissue Optimization Slides(10x Genomics)and Visium Spatial Gene Expression Slides(10x Genomics).Spatial transcriptomics analysis was performed with Space Ranger software and R software.Immunofluorescence,whole-mount RNA in situ hybridization and X-gal staining were performed to validate the analysis results.Spatial transcriptomics analysis revealed distinct transcriptional profiles and functions between epicardial tissue and non-epicardial tissue.Several gene markers specific to postnatal epicardial tissue were identified,including Msln,C3,Efemp1,and Upk3b.Single-cell transcriptomic analysis revealed that cardiac cells from wildtype mouse hearts(from embryonic day 9.5 to postnatal day 9)could be categorized into six major cell types,which included epicardial cells.Throughout epicardial development,Wt1,Tbx18,and Upk3b were consistently expressed,whereas genes including Msln,C3,and Efemp1 exhibited increased expression during the mature stages of development.Pseudotime analysis further revealed two epicardial cell fates during maturation.Moreover,Upk3b,Msln,Efemp1,and C3 positive epicardial cells were enriched in extracellular matrix signaling.Our results suggested Upk3b,Efemp1,Msln,C3,and other genes were mature epicardium markers.Extracellular matrix signaling was found to play a critical role in the mature epicardium,thus suggesting potential therapeutic targets for heart regeneration in future clinical practice.

【Objective】 To analyze the correlation between the expressions of CD10,CA9 and CD133 and the prognosis of patients with metastatic renal clear cell carcinoma (mccRCC) treated with sorafenib or sunitinib. 【Methods】 A total of 80 mccRCC patients who received sorafenib or sunitinib as first-line therapy were retrospectively enrolled. Immunohistochemical staining (IHC) was performed for CD10,CA9 and CD133 in tumor tissue samples to analyze the correlation between the expression of each marker and clinicopathologic variables. Univariate and multivariate Cox proportional risk models were used to analyze prognostic factors of progression free survival (PFS) and overall survival (OS),and Kaplan-Meier survival analysis was performed for CA9 expression and PFS,OS in the treatment subgroups. 【Results】 Altogether 37 patients (46.25%) had PFS,and the median PFS (mPFS) was 24.9 months (95%CI:16.5-33.2 months),while 55 patients (68.75%) died and the median OS (mOS) was 44.2 months (95%CI:14.6-73.7). Low expression of CD10 was correlated with high Fuhrman grade (χ²=6.241,P=0.012),lymph node metastasis (χ²=5.952,P=0.015),and the number of metastatic organs ≥2 (χ²=8.205,P=0.004). Univariate analysis showed that Fuhrman grade,number of metastatic organs and lymph node metastasis were the prognostic factors of PFS (P<0.05),while the number of metastatic organs,lymph node metastasis and CA9 expression were the prognostic factors of OS (P<0.05). Multivariate analysis showed that Fuhrman grade was an independent factor of PFS (HR=2.457,95%CI:1.126-5.365,P=0.024),and the number of metastatic organs was an independent prognostic factor of OS (HR=1.857,95%CI:1.048-3.290,P=0.034). Survival analysis in subgroups showed that high CA9 expression in the sorafenib group was associated with longer OS (HR=0.401,95%CI:0.204-0.787,P=0.008). 【Conclusion】 Low expression of CA9 is an non-independent risk factor for OS,while CD10 and CD133 cannot be used as prognostic factors for mccRCC patients. Since mccRCC patients with low CA9 expression have less survival benefit from sorafenib and sunitinib,they can choose target therapy combined with immunotherapy or dual immunotherapy according to the guidelines to improve prognosis.

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.

Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is a rare tumor. At present, there are still many disputes in its epidemiology, pathogenesis, selection of diagnostic methods, treatment and prognosis. Asbestos exposure, ionizing radiation and chromosome abnormalities are the risk factors of MMTVT. Immunohistochemistry, ultrasonography and electron microscope can be used for the diagnosis and aggressive surgery is the main treatment method. The development of endoscopic surgery, multi-disciplinary treatment (MDT), tumor targeted therapy and immunotherapy will bring more benefits to MMTVT patients.

BACKGROUND: Ovarian cancer is one of the most widespread malignant diseases of the female reproductive system worldwide. The plurality of ovarian cancer is diagnosed with metastasis in the abdominal cavity. Epithelial-mesenchymal transition (EMT) exerts a vital role in tumor cell metastasis. However, it remains unclear whether long non-coding RNA (lncRNA) are implicated in EMT and influence ovarian cancer cell invasion and metastasis. This study was designed to investigate the impacts of lncRNA AC005224.4 on ovarian cancer. METHODS: LncRNA AC005224.4, miR-140-3p, and snail family transcriptional repressor 2 ( SNAI2 ) expression levels in ovarian cancer and normal ovarian tissues were determined using real-time quantitative polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) and Transwell (migration and invasion) assays were conducted to measure SKOV3 and CAOV-3 cell proliferation and metastasis. E-cadherin, N-cadherin, Snail, and Vimentin contents were detected using Western blot. Nude mouse xenograft assay was utilized to validate AC005224.4 effects in vivo . Dual-luciferase reporter gene assay confirmed the targeted relationship between miR-140-3p and AC005224.4 or SNAI2 . RESULTS: AC005224.4 and SNAI2 upregulation and miR-140-3p downregulation were observed in ovarian cancer tissues and cells. Silencing of AC005224.4 observably moderated SKOV3 and CAOV-3 cell proliferation, migration, invasion, and EMT process in vitro and impaired the tumorigenesis in vivo . miR-140-3p was a target of AC005224.4 and its reduced expression level was mediated by AC005224.4. miR-140-3p mimics decreased the proliferation, migration, and invasion of ovarian cancer cells. SNAI2 was identified as a novel target of miR-140-3p and its expression level was promoted by either AC005224.4 overexpression or miR-140-3p knockdown. Overexpression of SNAI2 also facilitated ovarian cancer cell viability and metastasis. CONCLUSION AC005224.4 was confirmed as an oncogene via sponging miR-140-3p and promoted SNAI2 expression, contributing to better understanding of ovarian cancer pathogenesis and shedding light on exploiting the novel lncRNA-directed therapy against ovarian cancer.
Animals ; Mice ; Humans ; Female ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Ovarian Neoplasms/metabolism* ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition/genetics* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic/genetics* ; Snail Family Transcription Factors/metabolism*