As the number of patients with compromised immune function increases and fungal resistance develops, so does the risk of contracting deadly fungi in humans. Both fungi and humans are eukaryotes, so identifying unique targets for antifungal drug development is difficult. In addition, the existing antifungal drugs are limited by toxicity, drug interaction and drug resistance in practical application, which leads to the increasing incidence and fatal rate of fungal infections. Therefore, it is urgent to develop new antifungal drugs. The semi-synthetic technology using microbial fermentation products from natural sources as lead compounds has become the most used method in structural modification of antifungal drugs due to its advantages of few reaction steps and easy operation. This paper will introduce the current status of natural antifungal drugs in clinical use, as well as the latest progress in the research and development of new semi-synthetic antifungal drugs, and summarize their mechanism of action, structural modifications, advantages and disadvantages, so as to provide reference for the subsequent development of new antifungal drugs.

Objective To evaluate the effectiveness of thermal tomography in breast cancer (BC) screening. Methods We conducted a general population-based BC screening in three regions of Hubei Province (Xiantao, Hongan, and Yangxin Districts). Participants underwent a questionnaire-based interview for baseline data collection. They then received a physical examination, thermal tomography, and ultrasound from doctors and technicians. We compared the efficacies, including sensitivity, specificity, and false-positive rates, of ultrasound and thermal tomography in BC screening. Results A total of 59 712 eligible women were included in this screening program. The BI-RADS 1, 2, 3, 4, and 5 accordance rates between the two screening methods were 0.9549, 0.8047, 0.9037, 0.3352, and 0, respectively. The overall accordance rate was 0.933 1. The kappa consistency results showed that the Cicchetti-Allison and Fleiss-Cohen kappa values were 0.7970 and 0.8583, respectively. Although the two methods had equal sensitivities, specificity was higher in thermal tomography than in ultrasound. The false-positive rate was lower in thermal tomography than in ultrasound. The area under the receiver operating characteristic (ROC) curve of thermal tomography was significantly larger than that of ultrasound. Conclusion The general consistency between thermal tomography and ultrasound in BC screening was high. Thermal tomography outperformed ultrasound in terms of specificity and diagnostic efficiency. Therefore, thermal tomography has a high application value for general population-based BC screening.

AIM: To observe the efficacy of intravitreal Conbercept injection(IVC)in diabetic neovascular glaucoma(NVG).METHODS:Retrospective study. Totally 57 patients(57 eyes)with NVG(stage II)secondary to proliferative diabetic retinopathy(PDR)treated in our hospital were collceted from January 2019 to December 2022. Among them, 30 patients(30 eyes)were treated by IVC and panretinal photocoagulation(PRP)in the observation group, and 27 patients(27 eyes)were treated by PRP in the control group. The best corrected visual acuity(BCVA, LogMAR), intraocular pressure, neovascularization of the iridocorneal angle(NVA), central macular thinkness(CMT)changes and disease progression were analyzed with a follow-up of 2 years.RESULTS: There were no significant differences in baseline characteristics between the two groups(P>0.05). At the last follow-up, the BCVA in the observation group was better than the control group(P<0.05). The intraocular pressure, CMT and progression of NVA in the observation group were less than the control group(all P<0.05). The patients with NVG developed from stage II to stage III in the observation group was less than the control group(P<0.05). In the observation group, the BCVA improved compared with preoperative at 6 mo(P<0.05). In the control group, the BCVA decreased compared with preoperative after 24 mo(P<0.05). Multiple linear regression analysis indicated that NVG progression and intraocular pressure were factors affecting BCVA(LogMAR)changes(β=0.511, 0.014; t=4.461, 2.092; P<0.01, 0.041, respectively). In the observation group, the IOP decreased at 1, 6 and 12 mo compared with preoperative(all P<0.05), while there were no significant differences at 18 and 24 mo compared with preoperative(all P>0.05). In the control group, the intraocular pressure decreased at 6 mo compared with preoperative(P<0.05), while there were no significant differences at 1, 12, 18 and 24 mo compared with preoperative(all P>0.05). There were no significant difference about the types of glaucoma drugs between the observation group and the control group(all P>0.05). There were no infectious endophthalmitis and other complications observed in both groups.CONCLUSION: IVC combined with PRP demonstrates superior efficacy over PRP monotherapy in treating NVG(stage II)secondary to PDR. IVC combined with PRP showed better outcomes in controlling iris neovascularization, slowing visual impairment progression, reducing intraocular pressure, and delaying disease advancement.

AIM: To investigate the protective effect and mechanism of Danlou tablet on retinal ischemia-reperfusion injury(RIRI)in mice.METHODS: A total of 40 ApoE-/- mice were fed with high fat diet for 6 wk, and the RIRI model was established by anterior chamber infusion of pressurized saline. The mice were divided into control group(normal saline for 8 wk), RIRI model group(normal saline for 8 wk), and low-, medium-, and high-dose Danlou tablets groups [1, 2, and 4 g/(kg·d), respectively, for 8 wk]. The morphological changes of retina were observed by hematoxylin-eosin(HE)staining, retinal cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated Nick-End Labeling(TUNEL)staining. The Western-blot assay was used to detect the expression of retinal tissue sample Kelch-like ech-associated protein 1(Keap1), nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), and superoxide dismutase(Sod2)proteins.RESULTS: Compared with the control group, the mouse retina was atrophic with thinning thickness and increasing cell apoptosis, down-regulation of Sod2 protein expression, and up-regulation of Keap1 protein expression in the RIRI model group(all P<0.01). Compared with the RIRI model group, the retinal thickness increased in the medium- and high-dose of Danlou tablets groups(all P<0.01), and the cell apoptosis of retina decreased in the low-, medium- and high-dose of Danlou tablets groups(all P<0.05). There were no significant differences in the expression of Keap1 and HO-1 proteins of mouse retina tissue in the low-dose of Danlou tablets group(P>0.05). The expression of Sod2, Nrf2 and HO-1 proteins up regulated, and the expression of Keap1 protein down regulated in the medium- and high-dose of Danlou tablets groups(all P<0.05).CONCLUSION: Danlou tablet can alleviate RIRI-induced atrophy and thinning of retina and retinal cell apoptosis by regulating Keap1-Nrf2/HO-1 signal pathway and reducing oxidative stress.

Objective To explore the effect of tilianin combined with aerobic training on cognitive function of rats with Alzheimer's disease(AD).Methods Rats were divided into 7 groups:blank group,model group,control group,low dose experimental group,medium dose experimental group,high dose experimental group and combination group,12 rats in each group.The rats in blank group were sham operated,and other groups were AD model rats established by bilateral hippocampal injection of amyloid-beta peptide 1-42(A(31-42).One week after modeling,the rats in control group and combination group were trained on the treadmill,and the rats in other groups were fed quietly.The rats in blank group,model group and control group were given 0.5％carboxymethyl cellulose sodium(CMC)2 mL.The rats in low,medium and high dose experimental groups were given intragastric administration of 5,10 and 20 mg·kg-1·d-1tilianin 2 mL.The rats in combined group were given 20 mg·kg-1·d-1 tilianin 2 mL by gavage.The drug was given for 6 weeks.Cognitive function was evaluated by Morris water maze test.The level of Beta-site APP cleaving enzyme protein 1(BACE1)mRNA in hippocampus was measured by quantitative reverse transcription polymerase chain reaction.The phosphorylation level of nuclear factor-κB(NF-κB)p65 in hippocampus was detected by Western blot.Results The escape latencies of blank group,model group,control group,low dose experimental group,medium dose experimental group,high dose experimental group and combination group were(20.16±2.06),(60.45±6.55),(46.52±2.90),(42.80±3.15),(41.19±2.54),(35.66±2.82)and(28.49±1.97)s;the relative expression of BACE1 mRNA were 1.00±0.06,7.88±0.49,6.02±0.38,4.96±0.57,3.01±0.21,1.98±0.17 and 1.48±0.11;the relative phosphorylation levels of NF-κB p65 were 0.11±0.03,1.46±0.11,0.89±0.10,0.71±0.06,0.37±0.05,0.29±0.02 and 0.15±0.01.Compared between model group and blank group,comparison between low,medium,high dose experimental group and model group,comparison between combination group and high dose experimental group all showed statistically significant differences(all P＜0.05).Conclusion Tilianin combined with aerobic training can improve the cognitive function of AD rats,and its mechanism may be related to the inhibition of inflammation mediated by NF-κB signal pathway.

【Objective】 To investigate the therapeutic effect of Huaier on acute pancreatitis (AP) and its potential mechanism. 【Methods】 A mouse model of cerulean-induced AP was used to verify the therapeutic effect of Huaier in vivo. HE staining and immunohistochemical staining were used to evaluate the histopathological changes of the pancreas, and transmission electron microscopy was used to observe the pyroptosis morphology of the pancreas. In vitro, 266-6 cell line was used as the experimental carrier to verify the protective effect of Huaier on acinar cells. Electron microscopy and Western blotting were used to evaluate the pyroptosis level of acinar cells, and ROS fluorescence probe was used to detect the oxidative stress state of acinar cells. 【Results】 Huaier significantly alleviated the severity of AP in mice. HE staining of pancreas showed that necrosis and inflammatory cell infiltration were reduced, and the level of serum amylase was decreased. Immunohistochemical staining and Western blotting showed that Huaier effectively inhibited the expressions of pyroptosis-related molecules such as NLRP3 and GSDMD in pancreatic tissue. Electron microscopy showed that Huaier could reduce the pyroptosis level of pancreatic acinar cells under inflammatory state. In addition, the level of ROS in acinar cells was significantly reduced after the intervention of Huaier, and ROS-mediated pyroptosis of acinar cells could be effectively inhibited by Huaier. 【Conclusion】 Huaier can effectively reduce the severity of AP by inhibiting ROS-mediated pyroptosis of acinar cells.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Tooth extraction is a common and widely employed therapeutic procedure in oral and maxillofacial surgery.Minimally invasive tooth extraction can reduce both physical and psychological trauma to the patients,and is widely recommended as a first-line clinical treatment.But currently no guidelines or consensus has been available to provide a systematic introduction of minimally invasive tooth extraction to guide the clinical practices.To address this issue,this consensus,based on a comprehensive literature review and clinical experiences of experts,systematically summarizes the indications,target patients,and contraindications of minimally invasive tooth extraction,the overall workflow of this procedure(preoperative preparation,surgical steps,postoperative management,postoperative instructions,medications,and follow-up),and its common postoperative complications to provide a comprehensive guidance for clinical application of this technique.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.