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 analyze the characteristics and risk factors associated with postoperative deep vein thrombosis(DVT)of the lower extremities in patients undergoing surgery for lumbar degenerative diseases.Methods A retrospective analysis was conducted on clinical data from 298 patients who were hospitalized for lumbar degenerative diseases and underwent lumbar spine surgery treatment in the First Affiliated Hospital of Nanchang University from October 1,2022 to April 15,2023.Patients were divided into DVT group(n=71)and non-DVT group(n=227)according to whether DVT of the lower limbs occurred within 1 week postoperatively.The incidence and distribution characteristics of postoperative DVT were analyzed.Univariate and binary logistic regression analyses were performed to identify risk factors for DVT,and receiver operating characteristic(ROC)curves were used to determine cut-off values for relevant risk factors.Results A total of 298 patients were included,among whom 159 were males(53.4%)and 139 were females(46.6%),with an average age of(64.5±9.8)years.DVT occurred in 71 patients,and the incidence of lower extremity DVT was 23.8%.In the DVT group,there were 49 cases(69.0%)of intermuscular vein thrombosis,and 22 cases of other types of thrombosis(7 cases of peroneal vein thrombosis,4 cases of posterior tibial vein thrombosis,3 cases of common femoral vein thrombosis,1 case of anterior tibial vein thrombosis,and 7 cases of multiple thrombosis);58 cases(81.7%)had DVT in one lower extremity,and 13 cases(18.3%)had DVT in both lower extremities.Univariate analysis results showed that age,body mass index(BMI),length of hospital stay,history of hypertension,operative time,and intraoperative blood loss were associated with the occurrence of lower extremity DVT after surgery for lumbar degenerative diseases(P<0.05).Binary logistic regression analysis results indicated that older age(OR=1.079,P<0.01),higher BMI(OR=1.130,P=0.01),history of hypertension(OR=2.992,P<0.01),and larger intraoperative blood loss(OR=1.002,P=0.03)were independent risk factors for the occurrence of lower extremity DVT.ROC curve analysis demonstrated that patients with age>58.5 years,BMI>24.01 kg/m2,history of hypertension,and intraoperative blood loss>550 ml had a significantly increased risk of postoperative lower limb DVT.Conclusions The incidence of lower extremity DVT after surgery for lumbar degenerative disease is high,and intermuscular venous thrombosis is more common.Older age,higher BMI,history of hypertension,and larger intraoperative blood loss are independent risk factors for the occurrence of lower extremity DVT after surgery.

Objective To summarize the clinical features,treatment and prognosis of patients with primary central nervous system lymphoma(PCNSL)with clonal bone marrow B cells,and to explore the influence on clinical diagnosis and treatment.Methods PCNSL patients with clonal bone marrow B cells diagnosed by flow cytometry between Jan 2020 and Jul 2023 at Huashan Hospital of Fudan University were enrolled.The auxiliary examination data of these patients were collected,including complete blood count,routine biochemistry,bone marrow aspiration and biopsy,contrast-enhanced brain MRI,and whole-body PET-CT.Kaplan-Meier was used to draw the survival curve,and relevant literature was reviewed.Results A total of 223 newly diagnosed PCNSL patients were included,187 of whom completed bone marrow puncture and biopsy evaluation.We found clonal bone marrow B cells in 16 of 187 cases(8.56%)by flow cytometry.2 patients showed B lymphoma involving the bone marrow.All patients received a high-dose methotrexate based chemotherapy.The median progression free survival(PFS)of 16 patients with clonal bone marrow B cells was 11.1 months,and the median PFS of 171 patients with normal bone marrow was 12.6 months.There was no significant difference in the PFS between the two groups.Conclusion PCNSL with clonal bone marrow B cells had no specific clinical features,but bone marrow flow cytometry showed clonal B cells.High-dose methotrexate treatment regimen is effective.There was no significant difference in PFS for PCNSL patients with clonal B cells and normal findings in bone marrow.Clonal B cells in bone marrow may be caused by monoclonal B-cell lymphocytosis(MBL),lymphoma involves the bone marrow and the presence of common precursor cells.Bone marrow examination should be performed in the initial evaluation of suspected PCNSL.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To establish a rapid screening and analysis method for etomidate and its ana-logues using a portable mass spectrometer equipped with a thermal desorption-atmospheric pressure chemical ionization source-linear ion trap.Methods A 10 μL aliquot of a standard solution at a con-centration of 1 μg/mL was taken,and after the solvent evaporated,the sample was inserted into the in-let of the portable mass spectrometer for detection.By adjusting the collision-induced dissociation pa-rameters,the molecular ion peak and fragment ion peak information of the standard were obtained and used to establish a reference database.In addition,the method was applied to 29 seized liquid and plant samples.Results A screening system for etomidate and its analogues was established based on the portable mass spectrometer and the corresponding mass spectrometry library.The system enables qualitative screening analysis by identifying primary protonated molecular ions and secondary product ions of etomidate and its analogues.The limits of detection for etomidate and its 12 analogues ranged from 0.1 to 10 μg/mL.Etomidate and its analogues were detected in all 29 liquid and plant samples.However,this method could not distinguish between isomeric imidazole esters,such as isopropoxate and propoxate.Additionally,when testing 2-SH-etomidate,there was a false positive for the detection of etomidate.Conclusion This study established a rapid screening method for etomidate and its ana-logues using a portable mass spectrometer.The method combines the high sensitivity of mass spectrome-try with the on-site applicability of portable devices,significantly improving detection efficiency and meeting the on-site detection needs of etomidate and its analogues.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To explore the application value of integrated Chinese and western medicine in the treatment of sepsis-induced coagulopathy (SIC) induced by bacterial pneumonia sepsis.Methods:A total of 60 inpatients with bacterial pneumonia and sepsis admitted to the Dongzhimen Hospital of Beijing University of Chinese Medicine from October 2023 to June 2024 were collected in a cross-sectional study. Serum samples were collected, and immune indexes, coagulation function and some laboratory test results of the patients were detected or recorded. Sepsis Associated Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score were evaluated.Results:Among the 60 patients, 71.7%( n=43) were associated with coagulation disorder, 65%( n=39) showed hemorrhagic SIC; A total of 37 patients (61.7%) were treated with integrated traditional Chinese and western medicine, and 23 patients (38.3%) were treated with Western medicine. The main types of syndrome differentiation were toxic-heat syndrome ( n=48, 80.0%) and blood-stasis syndrome ( n=11, 18.3%). Serum human monocyte chemoattractant protein-1 (MCP-1) and platelet count (PLT) in patients with blood stasis syndrome were significantly lower than those in toxic-heat syndrome (all P<0.05). In patients with bacterial pneumonia sepsis, the total score of syndrome of excess of fu-viscera (Fu-shi-zheng) was positively correlated with programmed death ligand-1 (PD-L1) ( r=0.293, P=0.023) and tumor necrosis factor-α (TNF-α) ( r=0.436, P=0.001). The total score of toxin-heat syndrome ( r=0.323, P=0.016) and excess of fu-viscera syndrome ( r=0.354, P=0.008) were positively correlated with prothrombin time (PT). PD-1 was positively correlated with SOFA score ( r=0.343, P=0.007) and APACHE Ⅱ score ( r=0.354, P=0.006). The PD-1 level and SOFA and APACHE Ⅱ scores of the patients treated with integrated Chinese and western medicine were significantly lower than those treated with Western medicine alone (all P<0.05). Conclusions:The combined intervention of traditional Chinese medicine and Western medicine based on " Fuzheng Touxie Jiedu (The method of strengthening the body and removing the toxin)" has strong clinical guiding significance, and can effectively improve the immune function and prognosis of bacterial pneumonia SIC.

Objective:To explore the application value of integrated Chinese and western medicine in the treatment of sepsis-induced coagulopathy (SIC) induced by bacterial pneumonia sepsis.Methods:A total of 60 inpatients with bacterial pneumonia and sepsis admitted to the Dongzhimen Hospital of Beijing University of Chinese Medicine from October 2023 to June 2024 were collected in a cross-sectional study. Serum samples were collected, and immune indexes, coagulation function and some laboratory test results of the patients were detected or recorded. Sepsis Associated Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score were evaluated.Results:Among the 60 patients, 71.7%( n=43) were associated with coagulation disorder, 65%( n=39) showed hemorrhagic SIC; A total of 37 patients (61.7%) were treated with integrated traditional Chinese and western medicine, and 23 patients (38.3%) were treated with Western medicine. The main types of syndrome differentiation were toxic-heat syndrome ( n=48, 80.0%) and blood-stasis syndrome ( n=11, 18.3%). Serum human monocyte chemoattractant protein-1 (MCP-1) and platelet count (PLT) in patients with blood stasis syndrome were significantly lower than those in toxic-heat syndrome (all P<0.05). In patients with bacterial pneumonia sepsis, the total score of syndrome of excess of fu-viscera (Fu-shi-zheng) was positively correlated with programmed death ligand-1 (PD-L1) ( r=0.293, P=0.023) and tumor necrosis factor-α (TNF-α) ( r=0.436, P=0.001). The total score of toxin-heat syndrome ( r=0.323, P=0.016) and excess of fu-viscera syndrome ( r=0.354, P=0.008) were positively correlated with prothrombin time (PT). PD-1 was positively correlated with SOFA score ( r=0.343, P=0.007) and APACHE Ⅱ score ( r=0.354, P=0.006). The PD-1 level and SOFA and APACHE Ⅱ scores of the patients treated with integrated Chinese and western medicine were significantly lower than those treated with Western medicine alone (all P<0.05). Conclusions:The combined intervention of traditional Chinese medicine and Western medicine based on " Fuzheng Touxie Jiedu (The method of strengthening the body and removing the toxin)" has strong clinical guiding significance, and can effectively improve the immune function and prognosis of bacterial pneumonia SIC.

Aim To investigate the role and mecha-nism of allopurinol(ALLO)in restoring the abnormal metabolism of kynurenine(Kyn)mediated by trypto-phan-2,3-dioxygenase 2(TDO2)to ameliorate ulcera-tive colitis(UC)in mice,and to provide experimental basis for the treatment of UC by ALLO.Methods A dextran sodium sulfate(DSS)-induced mouse UC mod-el was established,and the mice were randomly divided into the control group,the model group,the ALLO low,medium and high-dose groups(10,20,and 40 mg·kg-1),and the positive-significant salazosulfapyridine(SASP)(200 mg·kg-1)group.The body mass and disease activity index(DAI)scores of mice were re-corded;HE staining was performed to observe the de-gree of pathological damage in colon tissue;Western blot was performed to detect TDO2 protein expression in colon tissue;flow cytometry was performed to detect changes in the proportion of macrophages in spleen and mesenteric lymph nodes;ELISA was employed to de-tect the levels of TNF-α,IL-1β and IL-6 pro-inflamma-tory cytokines in the supernatant of colon tissue homog-enate;high performance liquid chromatography(HPLC)was used to detect the levels of tryptophan(Trp)and Kyn in the supernatant of colon tissue ho-mogenate.Results Compared with the model group,ALLO administration significantly ameliorated colonic histopathological injury in UC mice,decreased the pro-portion of macrophages in spleen and mesenteric lymph nodes,down-regulated the levels of TNF-α,IL-1 β,and IL-6 pro-inflammatory factors in serum of homogenate of colonic tissues,and inhibited the activity(Kyn/Trp ratio)and expression of TDO2 in colonic tissues.Con-clusion ALLO improves disease manifestations in mice with ulcerative colitis,which may be related to its restoration of abnormal Kyn metabolism.