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 investigate the impact of Netupitant and palonosetron hydrochloride capsules （NEPA） on the pharmacokinetics of Paclitaxel for injection （albumin bound） （i. e. albumin-bound paclitaxel） under different intestinal microenvironment conditions. METHODS Male SD rats were divided into a normal group and a model group （n＝16）. Rats in the model group were intragastrically administered vancomycin solution to establish an intestinal disorder model. The next day after modeling， intestinal microbiota diversity was analyzed， and the mRNA expressions of cytochrome P450 3A1 （CYP3A1） and CYP2C11 in small intestine and liver tissues as well as those protein expressions in liver tissue were measured. Male SD rats were grouped as described above （n＝16）. The normal group was subdivided into the TP chemotherapy group （TP-1 group） and the TP chemotherapy+NEPA group （TP+NEPA-1 group）； the model group was subdivided into the TP chemotherapy group （TP-2 group） and the TP chemotherapy+NEPA group （TP+NEPA-2 group） （n＝8）. Rats in the TP+NEPA-1 and TP+NEPA-2 groups received a single intragastric dose of NEPA suspension （25.8 mg/kg， calculated by netupitant）. One hour later， all four groups received a single tail vein injection of albumin-bound paclitaxel and cisplatin. Blood samples were collected at different time points after the last administration. Using azithromycin as the internal standard， plasma paclitaxel concentrations were determined by liquid chromatography-tandem mass spectrometry. The main pharmacokinetic parameters were calculated using DAS 2.0 software and compared between groups. RESULTS Compared with the normal group， the model group showed significantly decreased Chao1 and Shannon indexes （P＜0.05）， significant alterations in microbiota composition and relative abundance， and significantly downregulated expressions of CYP3A1 mRNA in liver tissue and CYP2C11 mRNA in both small intestine and liver tissues （P＜0.05）. Compared with the TP-1 group， the AUC0－t， AUC0－∞， MRT0－t of paclitaxel in the TP-2 group， the cmax， AUC0－t， AUC0－∞ of paclitaxel in the TP+NEPA-1 group and TP+NEPA-2 group were significantly increased or prolonged； CL of paclitaxel in the TP-2 group， Vd and CL of paclitaxel in the TP+NEPA-1 group and the TP+NEPA-2 group were significantly decreased or shortened （P＜0.05）. Compared with the TP-2 group， cmax of paclitaxel in the TP+NEPA-2 group was significantly increased， and Vd and MRT0－t were significantly decreased or shortened （P＜0.05）. CONCLUSIONS Intestinal microbiota disorder affects the mRNA expressions of CYP3A1 and CYP2C11， leading to decreased clearance and increased systemic exposure of paclitaxel. Concomitant administration of NEPA under normal intestinal microbiota condition increases paclitaxel exposure. However， under conditions of intestinal microbiota disorder， concomitant administration of NEPA has a limited impact on paclitaxel systemic exposure.

Objective: To create a prediction model for stroke risk among middle-aged and elderly populations, so as to provide a basis for early identification of high-risk population for stroke. Methods: From October to December 2023, residents aged ≥45 years in Chongchuan District, Nantong City, Jiangsu Province were selected using a multi-stage stratified random sampling method. The demographic information, life behavior, and chronic disease data were collected through a questionnaire survey. The standardized prevalence of stroke was calculated using data from the seventh National Population Census. The subjects were randomly divided into the training set and the internal validation set according to the ratio of 8∶2. The basic demographic information, life behavior, and chronic diseases of residents aged ≥45 years in Rugao City were collected from July to August 2023 as the external validation set. Predictive factors were selected using multivariable logistic regression model, and a nomogram for stroke among residents aged ≥45 years was established. The prediction effect was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and Hosmer-Lemeshow goodness of fit test. Results: A total of 6 290 residents aged ≥45 years were included, including 2 975 males (47.30%) and 3 315 females (52.70%). The average age was (61.90±10.20) years. The prevalence of stroke was 3.80%, and the standardized prevalence was 3.36%. The multivariable logistic regression showed that age, smoking, hypertension, and hyperlipidemia were predictors of stroke risk among residents aged ≥45 years, and the prediction model was ln[p/(1-p)]=-4.619+0.046×age+0.383×smoking+0.887×hypertension+0.678×hyperlipidemia. The AUC values of the training set, internal validation set, and external validation set were 0.748, 0.755, and 0.738, respectively. The consistency indexes were 0.748, 0.755, and 0.738, respectively. The Hosmer-Lemeshow goodness of fit test showed a good fitting effect (P>0.05). Conclusion The prediction model based on age, smoking, hypertension, and hyperlipidemia has good discrimination and calibration, and can be used to predict the risk of stroke among middle-aged and elderly populations aged ≥45 years.

Objective: To investigate trends in incidence and mortality of colorectal cancer in Nantong City, Jiangsu Province from 2013 to 2022. Methods: Data on incidence and mortality of colorectal cancer from 2013 to 2022 in Nantong City were collected through the Nantong City cancer registry. The crude incidence, crude mortality, average age at onset, and average age at death of colorectal cancer were calculated. Chinese population-standardized incidence, Chinese population-standardized mortality, Chinese population-standardized average age at onset and Chinese population-standardized average age at death were calculated using the age structure of the standard population from the Fifth National Population Census in 2000. Trends in incidence and mortality of lung cancer from 2013 to 2022 were evaluated using average annual percent change (AAPC). Trends in the Chinese population-standardized average age at onset and Chinese population-standardized average age at death of lung cancer from 2013 to 2022 were evaluated using the linear regression model. Results: From 2013 to 2022, the crude incidence and Chinese population-standardized incidence of colorectal cancer in Nantong City increased from 33.63/105 and 16.05/105 to 53.82/105 and 19.62/105, respectively, showing upward trends (AAPC=5.665% and 2.467%, both P<0.05). The crude mortality increased from 15.99/105 in 2013 to 25.65/105 in 2022, also showing an upward trend (AAPC=5.514%, P<0.05), while no statistically significant trend was found in the Chinese population-standardized mortality (P>0.05). The Chinese population-standardized incidence of colorectal cancer showed upward trends in both males and females (AAPC=2.666% and 1.790%, both P<0.05). The Chinese population-standardized mortality showed an upward trend in males (AAPC=1.966%, P<0.05), but no statistically significant trend was found in females (P>0.05). The crude incidence of colorectal cancer in the groups aged 40-<50 years, 50-<60 years, 60-<70 years, 70-<80 years, and ≥80 years showed upward trends (AAPC=4.045%, 2.833%, 2.300%, 1.948%, and 1.775%, all P<0.05), and the crude mortality in the group aged ≥80 years showed an upward trend (AAPC=3.240%, P<0.05). The average age at onset of colorectal cancer increased at an annual average of 0.156 years (P<0.05), while the trend in the Chinese population-standardized average age at onset was not statistically significant (P>0.05). The average age at death and the Chinese population-standardized average age at death increased at an annual average of 0.325 and 0.153 years, respectively (both P<0.05). Conclusions From 2013 to 2022, both the crude incidence and mortality of colorectal cancer in Nantong City showed upward trends. Males and individuals aged ≥40 years faced a higher risk of both incidence and mortality. It is recommended to implement comprehensive prevention and control measures targeting these high-risk populations to reduce the burden of colorectal cancer.

The pathogenesis of Alzheimer's disease(AD)is complex and unclear.Existing drugs can only alleviate its symp-toms,and there is an urgent need to develop effective therapeutic drugs.As the representative drugs of tonic and enlightening medicine,ginseng and acorus calamus have pharmacological effects to improve memory,improve learning ability and reduce cognitive impairment,which are commonly used in Chinese med-icine for the treatment of dementia.The combination of ginseng and acorus calamus can further promote the active ingredients in-to brain to exert their medicinal effects,and delay the process of AD through anti-inflammatory,anti-oxidative stress,modulation of neuronal-synaptic plasticity and other multiple pathways,with multi-level,multi-system and multi-target action characteristics.This paper attempts to summarize the existing research results and lay the foundation for further exploring the synergistic mech-anism of action of ginseng-acorus calamus combination and the dose-effect relationship of the combination,so as to provide a sci-entific basis for the development of innovative Chinese medicines for the prevention and treatment of AD.

Exosomes represent a class of nanoscale extracellular vesicles that facilitate the exchange of genetic information among various cells.Alzheimer's disease(AD)stands as a progressive neurodegenerative disorder characterized by its subtle and advan-cing onset,representing the foremost form of dementia lacking effective therapeutic interventions.Notably,investigations have illuminated the involvement of exosomes in the pathogenesis of AD,attributing diagnostic and therapeutic significance to their role,particularly concerning exosomal microRNAs(miRNA).The miRNAs carried by exosomes serve as potential biomarkers for AD,while also exhibiting potential benefits in ameliorating cognitive dysfunction in individuals afflicted by AD.This article aims to comprehensively review the origins of exosomes(encom-passing both mesenchymal cell-derived exosomes and brain-de-rived exosomes)and their potential as therapeutic agents targe-ting AD.

Objective:To analyze the clinical and imaging features of patients with COVID-19-related osmotic demyelination syndrome (ODS).Methods:COVID-19-related ODS cases diagnosed in the Department of Neurology, Peking Union Medical College Hospital from January 2020 to September 2023 were retrospectively reviewed. And their past medical history, possible triggers, clinical manifestations, imaging manifestations, treatment and prognosis were summarized.Results:A total of 5 patients with COVID-19-related ODS were included. Electrolyte disturbances acted as an inducement of ODS in all patients (5/5),4 of whom with hyponatremia. Four of 5 patients first presented with disturbance of consciousness, followed by predominant dystonia. Imaging of all patients (5/5) showed isolated extrapontine myelinolysis (EPM). With the prolongation of the course of disease, such signal intensity could return to normal, and lesions showed atrophic changes in some patients. The patients′ clinical symptoms were partly relieved within a few days to a few months after treatment.Conclusions:COVID-19-related ODS is mostly associated with hyponatremia, and EPM is more common. COVID-19 should be considered as a risk factor for ODS.

Objective To investigate the correlation of human epididymis protein 4(HE4)with proteinuria in patients with type 2 diabetes mellitus(T2DM).Methods A total of 147 T2DM patients from January 2020 to July 2023 in Jiujiang NO.l People's Hospital were enrolled in observation group.According to the severity of proteinuria,observation group was divided into three groups:Normal albuminuria group(101 cases),microalbuminuria group(25 cases),and massive albuminuria group(21 cases).50 healthy examinees with gender and age matching during the same period were selected as control group.HE4 levels and clinical indicators in each group were compared and analyzed.Correlation between HE4 and proteinuria was analyzed by using univariate and multivariate linear regression.Results The correlation network diagram reveals that HE4 functions was a pivotal node linking serum albumin,urinary microalbumin,urinary microalbumin-to-creatinine ratio(UACR),and renal function biomarkers.Compared to control group,HE4 levels significantly elevated in observation group(P＜0.01).Both univariate and multivariate linear regression analysis demonstrate a positive correlation between HE4 and UACR.Logistic regression analysis shew that after adjusting for confounding factors including age,gender,estimated glomerular filtration rate(eGFR),albumin(ALB),blood urea nitrogen(BUN),serum creatinine(SCr),uric acid(UA),lactate dehydrogenase(LDH)etc.elevated HE4 levels was a risk factor for proteinuria(OR=1.110,95％CI:1.005-1.226).Conclusion Elevated HE4 levels in patients with T2DM is positivly correlated with UACR.Increase its level increases the risk of proteinuria in T2DM patients.

Objective To investigate the efficacy and safety of intravenous thrombolysis with low-dose and standard-dose recombinant tissue plasminogen activator(rt-PA)in the elderly patients(aged over 80 years)with acute ischemic stroke(AIS).Methods A total of 201 elderly patients with AIS treated at Tianjin Fourth Central Hospital from February 2019 to February 2023 were prospectively included and randomly assigned to the rt-PA low-dose group(n=93,0.6 mg/kg)and rt-PA standard-dose group(n=108,0.9 mg/kg).The incidence of intra-cranial hemorrhage,symptomatic intracranial hemorrhage,fatal intracranial hemorrhage,neurologic deterioration within 7 days and mortality within 90 days were observed to evaluate the safety.The neurologic improvement rate and good prognosis rate at 90 days were used to evaluate the effectiveness.A stratified analysis of 90-day outcomes was performed based on stroke severity and age.Results The incidence of intracranial hemorrhage,symptomatic intracranial hemorrhage and fatal intracranial hemorrhage within 7 days in rt-PA low-dose group was lower than that in rt-PA standard-dose group(P＜0.05).There were no statistically significant differences between the two groups concerning the residual safety index and the effectiveness index.The 90-day good prognosis rate of moderate stroke sub-group and of≥90 years of age sub-group in rt-PA low-dose group were both higher than that of rt-PA standard-dose group(P＜0.05).Conclusions For AIS patients with moderate stroke and aged over 90 years,intravenous thrombolytic therapy with rt-PA 0.6 mg/kg is recommended.

[Purpose]To analyze the incidence and mortality trends,and survival of gallbladder cancer in Nantong City of Jiangsu Province from 2013 to 2017.[Methods]The gallbladder cancer incidence and mortality data from 2013 to 2017 were collected from Nantong cancer registries.The crude incidence/mortality rates,age-standardized incidence/mortality rates by Chinese and world standard population(ASIRC/ASMRC,ASIRW/ASMRW)were calculated by sex,age and regions(urban and rural).Joinpoint software was used to analyze the incidence and mortality trends of gallbladder cancer.The observed survival rate and relative survival rate were calculated by using life table method and Ederer Ⅱ method.[Results]From 2013 to 2017,the gallbladder cancer crude incidence and mortality rates were 6.36/105 and 4.91/105,ASIRC and ASMRC were 2.62/105 and 1.94/105,respectively.The crude incidence and mortality,and ASMRC showed an upwards trend(all P＜0.05).The ASIRC for men and women was 2.43/105 and 2.83/105,the ASMRC for men and women was 1.74/105 and 2.16/105,respectively.ASIRC and ASMRC in women were higher than those in men.The ASIRC in urban and rural areas was 2.40/105 and 2.69/105,and the ASMRC was 1.61/105 and 2.05/105,respectively.ASIRC and ASMRC in rural areas were higher than those in urban areas.The average age of onset was 70.33 years old and the average age of death was 71.86 years old.The 5-year observed survival rate was 12.90％,and the 5-year relative survival rate was 14.47％.Both the 5-year observed survival rate and relative survival rate showed an upwards trend(both P＜0.05).[Conclusion]The incidence and mortality rates of gall-bladder cancer in Nantong City are relatively high and the survival rate is generally low.It is sug-gested that targeted prevention and control measures of gallbladder cancer in Nantong City should be strengthened,particularly in rural areas and for middle-aged and elderly women.