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.

Objective Based on the general belief that the tongue characteristics of blood stasis constitution is"purple tongue,tortuous sublingual vessels",this study systematically summarized blood stasis tongue characteristics using artificial intelligence image processing combined with expert evaluation.Methods A physical questionnaire survey was conducted on 1275 college students,and 100 cases were randomly selected from the blood stasis constitution group and the mild constitution group.After collecting the tongue images,Unet,OpenCV,YOLOv5 and YOLOv8 algorithms combined with expert evaluation method were used to extract and analyze the tongue features of the two groups.By comparing the differences of tongue image characteristics between the blood stasis constitution group and the mild constitution group,the tongue characteristics of blood stasis constitution were systematically summarized.Results Compared with the mild constitution group,the proportion of light dark tongue and light purple tongue in the blood stasis constitution group was significantly higher(P＜0.05).The I value,L value and a value of the tongue area 1 in the blood stasis constitution group were significantly larger(P＜0.01,P＜0.05).The S value and a value of area 2 and area 3 were significantly larger(P＜0.05),and the I value,L value,a value and b value of area 5 were significantly smaller(P＜0.01,P＜0.05).Compared with the mild constitution group,the proportion of tooth marks tongue in the blood stasis constitution group was significantly higher(P＜0.01),the proportion of cracked tongue in the blood stasis constitution group was significantly larger(P＜0.05),and the number of tooth marks,crack area,relative height of crack and relative width of crack in the blood stasis constitution group were significantly larger(P＜0.01,P＜0.05).Compared with the mild constitution group,the I value,L value,a value and b value of tongue coating area 1 in the blood stasis constitution group were significantly larger(P＜0.01,P＜0.05),the I value,L value,S value,a value and b value of tongue coating area 2 were significantly larger(P＜0.01,P＜0.05),the I value,S value,a value and b value of tongue coating area 3 were significantly larger(P＜0.01,P＜0.05),the b value of tongue coating area 4 was significantly larger(P＜0.05),the S value,a value and b value of tongue coating area 5 were significantly larger(P＜0.01,P＜0.05).The proportion of thick tongue coating and greasy tongue coating in the blood stasis group was significantly higher than that in the gentleness group(P＜0.05).Compared with the mild constitution group,the proportion of tortuous,thickened and nodular sublingual collaterals in the blood stasis constitution group was significantly larger(P＜0.01,P＜0.05).The a value,I value,S value,b value and relative width of sublingual collaterals in the blood stasis constitution group were significantly larger(P＜0.01,P＜0.05).Conclusion On the basis of the general belief that the characteristics of blood stasis constitution tongue are dark purple tongue and dark purple sublingual collaterals/varicose veins/thickening,blood stasis constitution people also have new tongue characteristics,such as redder tips and edges,more teeth marks and fissures,thicker and greasier coatings,and yellow fur.These findings offer new insights for"to identify the constitution of traditional Chinese medicine and prevent diseases by observing the tongue manifestation".

Objective:To develop the Symptom Assessment Scale for Patients Undergoing Bladder Irrigation Chemotherapy and evaluate its reliability and validity.Methods:Based on the theory of unpleasant symptoms, a preliminary version of the Symptom Assessment Scale for Patients Undergoing Bladder Irrigation Chemotherapy was developed through literature analysis, semi-structured interviews, and the Delphi method. After revising certain items in the pre-survey, convenience sampling was used to select patients who underwent bladder instillation chemotherapy in the Department of Urology Surgery of three ClassⅢ Grade A hospitals in Yunnan Province from January to July 2024 as research subjects to test the reliability and validity of the scale.Results:A total of 168 questionnaires were distributed, and 162 valid questionnaires were collected, with a valid response rate of 96.429% (162/168). The Symptom Assessment Scale for Patients Undergoing Bladder Irrigation Chemotherapy covered two areas of symptom severity and symptom distress, comprising five dimensions and 27 items. The Cronbach's α coefficient for the total scale was 0.953, and the split-half reliability coefficient was 0.806. Exploratory factor analysis revealed that the four common factors for symptom severity contributed to 73.196% of the cumulative variance, while the single common factor for symptom distress accounted for 68.285% of the cumulative variance. Confirmatory factor analysis revealed that all indicators met the fit criteria, indicating that the model possessed good goodness-of-fit. The content validity index at the scale level was 0.940, while the content validity index at the item level ranged from 0.833 to 1.000.Conclusions:The Symptom Assessment Scale for Patients Undergoing Bladder Irrigation Chemotherapy developed in this study demonstrates good reliability and validity, and is suitable for evaluating symptoms in patients undergoing bladder infusion chemotherapy.

BACKGROUND:Ovarian tissue vitrification cryopreservation is one of the important methods for preserving fertility.Tanshinone ⅡA has various pharmacological activities,including anti-oxidation,inhibition of inflammatory response,and reduction of apoptosis,but its role as an additive for vitrification cryoprotection of ovarian tissue is still unclear.OBJECTIVE:To explore the protective effect of tanshinone ⅡA on vitrification cryopreservation of mouse ovarian tissue.METHODS:Twenty-five 6-week-old female KM mice were randomly selected and their ovarian tissues were randomly divided into five groups,with 10 ovaries per group.The fresh group was not cryopreserved.The frozen control group used vitrification cryoprotectant.The 0.5,2.5,and 5 μmol/L tanshinone ⅡA groups used vitrification cryoprotectant containing 0.5,2.5,and 5 μmol/L tanshinone ⅡA,respectively,and were cryopreserved in liquid nitrogen.After 3 days of storage,the cryopreserved tubes were taken out and thawed.The ovarian tissue and follicle morphology of each group were observed by hematoxylin-eosin staining,and the normal follicle morphology and survival rate were analyzed.The levels of superoxide dismutase,catalase,malondialdehyde,tumor necrosis factor-α,interleukin-1β,and interleukin-17 in the ovary were detected by enzyme-linked immunosorbent assay.RT-qPCR and western blot assay were used to detect the mRNA and protein expressions of nuclear factor E2-related factor 2(Nrf2)and heme oxygenase 1(HO-1)in the mouse ovary.RESULTS AND CONCLUSION:(1)Compared with the fresh group,the frozen control group had abnormal morphology of follicles at all levels in the ovary,decreased follicle survival rate(P＜0.05),decreased superoxide dismutase and catalase activities(P＜0.05);the levels of malondialdehyde,and tumor necrosis factor α,interleukin 1β,and interleukin 17 were all increased(P＜0.05),and the mRNA and protein expressions of Nrf2 and HO-1 were decreased(P＜0.05).(2)Compared with the frozen control group,different concentrations of tanshinone ⅡA could improve the morphology of follicles at all levels in the ovary,increase the survival rate of follicles,enhance the activities of superoxide dismutase and catalase,and reduce the levels of malondialdehyde,tumor necrosis factor α,interleukin 1β,and interleukin 17,increased the mRNA and protein expression of Nrf2 and HO-1 in a concentration-dependent manner,with 5 μmol/L tanshinone ⅡA having the most significant effect.(3)The results show that tanshinone ⅡA may reduce the oxidative stress level and inflammatory response of mouse ovarian tissue by mediating the Nrf2/HO-1 signaling pathway,thereby alleviating the reproductive damage caused by vitrification cryopreservation of mouse ovaries.

BACKGROUND:The biomechanical analysis of scoliosis cases is limited,with only independent analysis focusing on the spine or lower limbs,thus lacking a comprehensive evaluation of the multidimensional body.As a result,it becomes challenging to reflect the movement relationship between the trunk and lower limbs during daily activities,which hinders comprehensive clinical treatment guidance. OBJECTIVE:To explore the relationship between different segments of the spine and the kinematics/kinetics of the lower limbs during gait activities by measuring spinal kinematics in scoliosis patients,to provide a comprehensive and multi-level assessment of the biomechanical differences between scoliosis patients and the normal population,consequently offering evidence-based guidance for the prevention and treatment of scoliosis. METHODS:A cross-sectional study was conducted from July 2020 to June 2021 at the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine in Fuzhou University City.A total of 28 scoliosis patients and 28 normal individuals in the same age group were included.Three-dimensional motion capture system was used to capture gait kinematic data at a sampling frequency of 100 Hz.Two force plates(AMTI 400600,sampling frequency 1 500 Hz)were embedded in a 10-meter-long 2.4-meter-wide level ground walkway(with an effective data collection length of 4 m)to collect kinetic data.The differences in spatial-temporal parameters,kinematics,and kinetics of gait between the two groups were compared.Immediately after inclusion,all subjects underwent full spinal X-ray measurements to compare the differences between the scoliosis and normal groups. RESULTS AND CONCLUSION:(1)Patients with scoliosis exhibited reduced relative rotational range of motion between the shoulder and trunk,as well as between the thorax and pelvis,compared to the normal group(P<0.05).However,the rotational range of motion in the pelvis was larger in patients with scoliosis compared to the normal group(P<0.05).(2)Patients with scoliosis showed decreased range of motion in the hip and knee joints,as well as reduced peak torque in hip joint flexion and extension,and lower peak values of ground reaction forces in the concave and convex directions,in comparison to the normal group(P<0.05).(3)Patients with scoliosis demonstrated greater asymmetry indices in knee joint range of motion,relative rotational range of motion between the shoulder and trunk,and between the thorax and pelvis,when compared to the normal group(P<0.05).(4)These findings illustrate a rigid movement pattern among the shoulder,thorax,and pelvis in patients with scoliosis during level walking.There is a reduction in range of motion in the hip and knee joints,as well as decreased peak torque values in hip joint flexion and extension,and ground reaction forces in the concave and convex directions.These characteristics can serve as foundational elements for assessing rehabilitation and developing treatment plans.

BACKGROUND: Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing. METHODS: Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen's kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS. RESULTS: A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS. CONCLUSION ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Circulating Tumor DNA/blood* ; High-Throughput Nucleotide Sequencing/methods* ; Female ; Male ; Lung Neoplasms/pathology* ; Middle Aged ; Mutation/genetics* ; Aged ; Adult ; Aged, 80 and over

Magnolol, a compound extracted from Magnolia officinalis, demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases. Its biological activities encompass anti-inflammatory, antioxidant, anticoagulant, and anti-diabetic effects. Growth/differentiation factor-15 (GDF-15), a member of the transforming growth factor β superfamily, is considered a potential therapeutic target for metabolic disorders. This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism. The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo, and determined the involvement of endoplasmic reticulum (ER) stress signaling in this process. Luciferase reporter assays, chromatin immunoprecipitation, and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4 (ATF4), CCAAT enhancer binding protein γ (CEBPG), and CCCTC-binding factor (CTCF). The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene, as well as the influence of single nucleotide polymorphisms (SNPs) on magnolol and ATF4-induced transcription activity. Results demonstrated that magnolol triggers GDF-15 production in endothelial cells (ECs), hepatoma cell line G2 (HepG2) and hepatoma cell line 3B (Hep3B) cell lines, and primary mouse hepatocytes. The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene. SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15. In high-fat diet ApoE^-/- mice, administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15. These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity, indicating its potential as a drug for the treatment of metabolic disorders.
Lignans/pharmacology* ; Growth Differentiation Factor 15/metabolism* ; Animals ; Biphenyl Compounds/pharmacology* ; Endoplasmic Reticulum Stress/drug effects* ; Activating Transcription Factor 4/genetics* ; Mice ; Humans ; Male ; Magnolia/chemistry* ; CCAAT-Enhancer-Binding Proteins/genetics* ; Mice, Inbred C57BL

Objective To establish a quality control method for Bletilla compound spleen-tonifying Traditional Chinese Medicine(TCM). Methods The content of gallic acid was determined by HPLC. Atractylodes macrocephala Koidz, Codonopsis pilosula Nannf and Pulsatillae Radix were identified by TLC. Results The identification and determination methods showed good specificity. Gallic acid displayed good linearity within the range of 3.6-179.8 µg/ml （r=0.999 9）. The average recovery was 101.12% （RSD 0.98%）. Conclusion The TLC and HPLC could be used as quality control method for Bletilla compound spleen-tonifying TCM.

Objective:To evaluate the safety and efficacy of laparoscopes adhesiolysis in the treatment of adhesive intestinal obstruction.Methods:A retrospective analysis was conducted on the clinical data of 30 patients with adhesive intestinal obstruction who underwent laparoscopes adhesiolysis at the First Affiliated Hospital, Zhejiang University School of Medicine between January 2021 and December 2024. The demographics, surgical parameters and postoperative complications were recorded.Results:Among the 30 patients, 16 were male and 14 were female, with age of (55.93 ± 13.83) years. A history of abdominal surgery was present in 25 patients (83.3%). Of the surgeries, 4 cases (13.3%) were performed as emergency procedures and 26 cases (86.7%) were elective. The operative time was (125.57 ± 48.25) min, and intraoperative blood loss was (26.17 ± 16.90) ml. The time to first flatus was (3.30 ± 1.95) d, the time to first oral intake was 4.00 (3.00, 5.00) d, the hospital stay was (24.23 ± 17.97) d, and the postoperative hospital stay was 11.50 (6.75, 18.75) d. The incision pain score 0 score was in 8 cases (26.7%), 1 score in 5 cases (16.7%), 2 scores in 10 cases (33.3%), 3 scores in 3 cases (10.0%), 4 scores in 3 cases (10.0%), and 5 scores in 1 case (3.3%). One case developed a postoperative wound infection. The patients were followed up for 1 year, 1 patient experienced recurrent incomplete intestinal obstruction due to widespread peritoneal metastasis from gastric cancer.Conclusions:Laparoscopes adhesiolysis is a safe and effective treatment for adhesive intestinal obstruction, offering advantages in terms of postoperative recovery and low complication rates. The continued use of minimally invasive techniques is recommended in the management of this condition.

Objective:To analyze the relationship between 24-hour urinary calcium (24 h UCa) level and the risk of end-stage kidney disease (ESKD), cardiovascular disease (CVD), and all-cause mortality.Methods:In the Chinese Cohort Study of Chronic Kidney Disease, we examined 3 375 patients aged 18-74 years with CKD stages 1-4. Kaplan-Meier survival and Cox proportional hazard regression models were used to test a time-to-event association between levels of 24 h UCa and incidence of ESKD, CVD, and all-cause mortality.Results:During a follow-up of 4.17 (3.37, 5.20) years, 179, 145, 104 and 38 ESKD events occurred in <0.60, 0.60-, 1.20-, ≥2.32 mmol 24 h UCa groups. Higher levels of 24 h UCa (1.20-,≥2.32 mmol) were independently associated with a lower incidence of ESKD events in patients with CKD, with HR (95% CI) of 0.71 (0.54-0.93) and 0.43 (0.29-0.64), respectively. No significant associations with CVD and all-cause mortality endpoints were detected. Conclusion:Among patients with CKD, levels of 24 h UCa displayed an association with the risk of ESKD among patients with CKD stages 1-4.