Fungal infections have emerged as a critical public health issue endangering human health. However, the existing arsenal of antifungal agents is limited in diversity and is commonly plagued by drawbacks including narrow antimicrobial spectrums and the frequent emergence of drug resistance, which severely compromises the efficacy of clinical treatments. Pathogenic fungi can develop extensive adaptability to currently available drugs through multiple mechanisms, which are mainly manifested in three aspects: drug resistance, tolerance and persistence. The molecular mechanisms and regulatory pathways underlying drug resistance, tolerance and persistence in pathogenic fungi were systematically summarized in this review, and the counteractive strategies such as combination therapy and the development of novel antifungal agents were further discussed, which aimed to provide theoretical basis and practical reference for the precision treatment of fungal infections.

ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome （IBS-C） by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine （5-HT）， vasoactive intestinal peptide （VIP）， and substance P （SP）. MethodsA randomized controlled design was adopted， and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups （36 cases）.The observation group received Sanren Runchang formula granules twice daily， and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale （IBS-SSS）， IBS Quality of Life Scale （IBS-QOL）， and Bristol Stool Form Scale （BSFS） were used to assess clinical symptoms， and bowel movement frequency was recorded. The Self-Rating Anxiety Scale （SAS） and Self-Rating Depression Scale （SDS） were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT， VIP， and SP. ResultsThe total response rate in the observation group was 91.67% （33/36）， which was higher than that （77.78%， 28/36） in the control group （χ²=4.50， P<0.05）. After treatment， both groups showed increased defecation frequency and BSFS scores， decreased IBS-SSS total score， abdominal pain and bloating scores， IBS-QOL health anxiety， anxiety， food avoidance， and behavioral disorders scores， SAS and SDS scores， serum 5-HT and VIP levels， and increased SP levels （P<0.05， P<0.01）. Moreover， the observation group showed more significant changes in the indicators above than the control group （P<0.05， P<0.01）. The SP level showed no significant difference between the two groups. During the 4-week follow-up， the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group， and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients， with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP， suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However， its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.

ObjectiveTo establish and evaluate a hyperuricemia （HUA） mouse model with the damp-turbidity internal accumulation syndrome. MethodsThirty-six C57BL/6J mice were randomly divided into control group， chemically induced model group （Model）， and model combined with high-fat and fatigue group （Model+HF）. Twenty-four uricase gene knockout （UOX^-/-） mice were randomly divided into UOX^-/- group and UOX^-/-+HF group， with 12 mice in each group. The Model group and the Model+HF group established the HUA model by intragastric administration of potassium oxyazinate combined with adenine. The Model+HF group and the UOX^-/-+HF group adopted a high-fat diet combined with weight-bearing exhaustive swimming to establish the HUA model with the damp-turbidity internal accumulation syndrome. On day 1， 7， 14， 21， and 28 after modeling， the damp-turbidity internal accumulation syndrome score of each group was evaluated. On day 1 and day 28， a weight-bearing swimming exhaustion test was performed， and the exhaustive swimming time was recorded. On day 28， liver and kidney indexes were calculated， and hematoxylin-eosin （HE） staining was used to observe histopathological changes in liver and kidney tissues. Serum levels of uric acid （UA）， xanthine dehydrogenase （XDH）， xanthine oxidase （XOD） and urea nitrogen （BUN） were detected through biochemical assays. ELISA was used to detect serum levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. Immunohistochemistry was used to detect the protein expression of organic anion transporter 1 （OAT1） and glucose transporter 9 （GLUT9） in renal tissues. Quantitative real-time PCR （qRT-PCR） was used to detect the mRNA expressions of adenosine triphosphate binding transporter G2 （ABCG2）， hypoxia-inducible factor-1α （HIF-1α）， urate anion transporter 1 （URAT1）， and GLUT9 in renal tissues. ResultsOn day 14 of modeling， the damp-turbidity internal accumulation syndrome scores of mice in the Model+HF group and the UOX^-/-+HF group were elevated compared with the control group（P＜0.05）； on day 28， the scores significantly increased， and the exhaustive swimming time was shortened （P＜0.01）， indicating successful establishment of the damp-turbidity internal accumulation syndrome model. Compared with the control group， all other groups exhibited increased kidney index， serum levels of UA， XDH， XOD， BUN， TNF-α， and IL-1β， elevated renal mRNA expression of HIF-1α， URAT1， OAT1， and GLUT9， and decreased renal ABCG2 mRNA expression （P＜0.01 or P＜0.05）. Significant pathological damage in the kidney was observed in the Model+HF group and the UOX^-/-+HF group compared to the Model group and the UOX^-/- group， with decreased serum UA and increased BUN and TNF-α levels （P＜0.05 or P＜0.01）， as well as increased expression of OAT1 and GLUT9 in the renal tissue. ConclusionBoth chemical induction and gene knockout， combined with a high-fat diet and weight-bearing exhaustive swimming， can successfully establish mouse models of HUA with damp-turbidity internal accumulation syndrome. Chemical induction is simple to operate and cost-effective， suitable for short-term drug screening， while UOX gene knockout induces spontaneous elevation of serum uric acid levels without drug administration， which may better mimick human metabolic characteristics.

ObjectiveTo establish and evaluate a hyperuricemia （HUA） mouse model with the damp-turbidity internal accumulation syndrome. MethodsThirty-six C57BL/6J mice were randomly divided into control group， chemically induced model group （Model）， and model combined with high-fat and fatigue group （Model+HF）. Twenty-four uricase gene knockout （UOX^-/-） mice were randomly divided into UOX^-/- group and UOX^-/-+HF group， with 12 mice in each group. The Model group and the Model+HF group established the HUA model by intragastric administration of potassium oxyazinate combined with adenine. The Model+HF group and the UOX^-/-+HF group adopted a high-fat diet combined with weight-bearing exhaustive swimming to establish the HUA model with the damp-turbidity internal accumulation syndrome. On day 1， 7， 14， 21， and 28 after modeling， the damp-turbidity internal accumulation syndrome score of each group was evaluated. On day 1 and day 28， a weight-bearing swimming exhaustion test was performed， and the exhaustive swimming time was recorded. On day 28， liver and kidney indexes were calculated， and hematoxylin-eosin （HE） staining was used to observe histopathological changes in liver and kidney tissues. Serum levels of uric acid （UA）， xanthine dehydrogenase （XDH）， xanthine oxidase （XOD） and urea nitrogen （BUN） were detected through biochemical assays. ELISA was used to detect serum levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. Immunohistochemistry was used to detect the protein expression of organic anion transporter 1 （OAT1） and glucose transporter 9 （GLUT9） in renal tissues. Quantitative real-time PCR （qRT-PCR） was used to detect the mRNA expressions of adenosine triphosphate binding transporter G2 （ABCG2）， hypoxia-inducible factor-1α （HIF-1α）， urate anion transporter 1 （URAT1）， and GLUT9 in renal tissues. ResultsOn day 14 of modeling， the damp-turbidity internal accumulation syndrome scores of mice in the Model+HF group and the UOX^-/-+HF group were elevated compared with the control group（P＜0.05）； on day 28， the scores significantly increased， and the exhaustive swimming time was shortened （P＜0.01）， indicating successful establishment of the damp-turbidity internal accumulation syndrome model. Compared with the control group， all other groups exhibited increased kidney index， serum levels of UA， XDH， XOD， BUN， TNF-α， and IL-1β， elevated renal mRNA expression of HIF-1α， URAT1， OAT1， and GLUT9， and decreased renal ABCG2 mRNA expression （P＜0.01 or P＜0.05）. Significant pathological damage in the kidney was observed in the Model+HF group and the UOX^-/-+HF group compared to the Model group and the UOX^-/- group， with decreased serum UA and increased BUN and TNF-α levels （P＜0.05 or P＜0.01）， as well as increased expression of OAT1 and GLUT9 in the renal tissue. ConclusionBoth chemical induction and gene knockout， combined with a high-fat diet and weight-bearing exhaustive swimming， can successfully establish mouse models of HUA with damp-turbidity internal accumulation syndrome. Chemical induction is simple to operate and cost-effective， suitable for short-term drug screening， while UOX gene knockout induces spontaneous elevation of serum uric acid levels without drug administration， which may better mimick human metabolic characteristics.

Objective To develop and validate a machine learning model based on preoperative clinical characteristics, laboratory indices, and radiological features for the non-invasive prediction of spread through air spaces (STAS) in patients with early-stage lung adenocarcinoma. Methods Preoperative data from patients with early-stage lung adenocarcinoma who underwent surgical resection at Northern Jiangsu People's Hospital between January 2020 and August 2025 were retrospectively collected. The data included clinical characteristics, laboratory indices, and radiological features. Patients were divided into a STAS-positive and a STAS-negative group based on postoperative pathological findings. The dataset was randomly split into a training set and a testing set at a 7 : 3 ratio. Feature variables were selected using the maximum relevance and minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator (LASSO) regression. Five machine learning models were constructed: logistic regression (LR), random forest (RF), support vector machine (SVM), light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). The shapley additive explanations (SHAP) method was employed to interpret the optimal prediction model. Results A total of 377 patients were included, comprising 177 (46.9%) males and 200 (53.1%) females, with a mean age of (63.31±9.73) years. There were 261 patients in the training set and 116 patients in the testing set. In the training set, statistically significant differences were observed between the STAS-positive group (n=130) and STAS-negative group (n=131) across multiple features, including age, sex, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), clinical T stage, and maximum solid component diameter (P<0.05). A final set of 10 feature variables was selected by combining mRMR and LASSO regression, and five machine learning models (LR, RF, SVM, LightGBM, XGBoost) were developed. The XGBoost model demonstrated optimal performance in both the training and testing sets, achieving AUCs of 0.947 [95%CI (0.920, 0.975)] and 0.943 [95%CI (0.894, 0.993)], respectively. DCA indicated that the XGBoost model provided a high net clinical benefit across a wide range of threshold probabilities. SHAP analysis revealed that the vessel convergence sign, clinical T stage, age, consolidation-to-tumor ratio (CTR), and MLR were the features with the highest contributions to STAS prediction. Conclusion The XGBoost model effectively predicts preoperative STAS status in early-stage lung adenocarcinoma, exhibiting excellent discriminative performance and good clinical interpretability. Key predictors such as the vessel convergence sign, clinical T stage, age and CTR provide a crucial reference for preoperative risk assessment and the individualized selection of surgical strategies, ultimately benefiting patients.

The Huangdi Neijing proposes the " using bitter herbs to nourish or purge" theory to guide clinical prescription and formulation of herbal remedies based on the physiological characteristics and functions of the five zang viscera, along with the properties and flavors of medicinal herbs. This study explored diabetic kidney disease pathogenesis and treatment based on the " using bitter herbs to nourish or purge" theory. Kidney dryness is a key pathological factor in diabetic kidney disease, and the disharmony of kidney dryness is an essential aspect of its pathogenesis. Strengthening is the primary therapeutic principle, and kidney dryness is a persistent factor throughout the occurrence and progression of diabetic kidney disease. In the early stage, the pathogenesis involves heat-consuming qi and injuring yin, leading to kidney dryness. In the middle stage, the pathogenesis manifests as qi deficiency and blood stasis in the collaterals, resulting in turbidity owing to kidney dryness. In the late stage, the pathogenesis involves yin and yang deficiency, with kidney dryness and disharmony. This study proposes the staging-based treatment based on the " need for firmness" characteristic of the kidney. The aim is to provide new insights for clinical diagnosis and treatment in traditional Chinese medicine by rationally using pungent, bitter, and salty medicinal herbs to nourish and moisturize the kidney. This approach seeks to promote precise syndrome differentiation and personalized treatment for different stages of diabetic kidney disease, thereby enhancing clinical efficacy.

Objective To explore the impact of the number of negative lymph node resections on the overall survival and recurrence rate of patients with ovarian cancer.Methods A retrospective selection was made of 150 ovarian cancer patients admitted to our hospital from October 2021 to October 2023 as the research subjects.According to the standard of the number of negative lymph nodes removed,they were divided into three groups:T1 group(≤17),T2 group(18～27),and T3 group(≥28).Clinical characteristics and surgical indicators were collected,and the recurrence and survival situations were analyzed.Results The clinical characteristic analysis results showed that there were no statistically significant differences among the three groups in terms of age,meno-pausal status,BMI,CCI,family history of tumors,etc.(P>0.05).There were no significant differences in surgi-cal methods,residual lesion size,postoperative complications among the three groups(P>0.05).In terms of operation time,T1 group0.05),but with the increase in the number of lymph node resections(from T1 group to T3 group),the recurrence rate showed a statistically significant downward trend(P<0.05).Cox regression analysis showed that the univariate analysis indicated that for each additional negative lymph node,the risk of death decreased by 4.7%(HR=0.953,P<0.05);the multivariate analysis(after adjusting for confounding factors)showed that the risk decreased by 5.8%(HR=0.942,P<0.05).Restricted cubic spline(RCS)analysis confirmed a significant linear association between the two(P<0.05).With 5 lymph nodes as the reference,the risk ratios for 10,20,and 30 resections were 1.003,0.760,and 0.317,respectively,and the trend showed that the risk of death contin-ued to decrease as the number of lymph nodes increased.Multivariate Cox analysis showed that the risk of death in T3 group was 68%lower than that in T1 group(P<0.05),the risk in FIGO stage Ⅲ was 3.11 times higher(P<0.05),and the risk in high-grade tumors was 2.80 times higher(P<0.05).Conclusions The number of nega-tive lymph nodes removed in patients with ovarian cancer is linearly correlated with prognosis.The more lymph nodes removed,the lower the risk of death for the patients.Adequate lymph node removal should be an important part of the surgical treatment for ovarian cancer.

Hedysari radix is the characteristic chi-nese medicine of Gansu Province,with"MiCang Hedysari radix"as the best.Modern pharmacologi-cal research has shown that it has polysaccharides and flavonoids,which have good anti-tumor effects and can inhibit the occurrence and development of various cancers,such as lung cancer,liver cancer,and breast cancer.Cancer is ranked as the second leading cause of death in the world,and the mor-bidity and mortality rates are increasing year by year,seriously affecting the quality of life.At pres-ent,with the modernization of Traditional Chinese Medicine(TCM),there has been a significant break-through in the treatment of malignant tumors with TCM.Based on this,by collating the relevant litera-ture at home and abroad in recent years,the anti-tumor effects and mechanisms of Hedysari radix and its active ingredients are summarized to pro-vide a scientific basis for the study of elucidating the material basis of the anti-tumor effects of He-dysari radix and to promote the development of the Hedysari radix industry.

Cardiovascular diseases(CVD)are chronic disease with high morbidity and mortality in the world.Pinellia ternatais a traditional Chi-nese medicinal herb and has the effects on drying dampness,resolving phlegm,lowering symptoms,stopping vomiting and relieving swelling.In recent years,researches showed that Pinellia ternataand its active ingredients(β-sitosterol,baicalin,baica-lein,quercetin)had significant effects in the treat-ment of cardiovascular diseases.This review sum-marized and analyzed the role and mechanism of Pinellia ternata and its active ingredients in cardio-vascular diseases,which provided a theoretical ba-sis for its clinical application.

Background and purpose:Breast cancer stem cells play an important role in the occurrence and development of cancer.The high mortality of breast cancer patients is closely related to the recurrence and metastasis of cancer.However,the self-renewal and differentiation ability of breast cancer stem cells can lead to chemotherapy resistance,thus affecting the recurrence and metastasis of cancer.This study aimed to explore the impact of miR-193a-3p on the migration and invasion of breast cancer stem cells by targeting the tripartite motif-containing protein 14(TRIM14).Methods:Human breast cancer cell T47D was randomly assigned into control group,NC mimics group(transfected with NC mimics),miR-193a-3p mimics group(transfected with miR-193a-3p mimics),miR-193a-3p mimics+pcDNA-NC group(transfected with miR-193a-3p mimics+pcDNA-NC)and miR-193a-3p mimics+pcDNA-TRIM14 group(transfected with miR-193a-3p mimics+pcDNA-TRIM14).Separation of stem cells using flow cytometry and detection of cell spheroidization ability were carried out.Cell counting kit-8(CCK-8)experiment was used to detect cell proliferation.Transwell experiment was used to measure cell migration and invasion.Flow cytometry was used to detect cell apoptotic rate.Western blot was used to detect the expressions of cyclin D1,matrix metalloproteinase-2(MMP-2),Bcl-2-associated X protein(Bax),and TRIM14 protein in cells.Dual luciferase assay was used to detect the interaction between miR-193a-3p and TRIM14.Results:T47D stem cells had the ability to form spheroids,and with increasing time,the spheroid volume of T47D stem cells gradually increased.Compared with the Control group and NC mimics group,the miR-193a-3p mimics group showed increased miR-193a-3p expression,apoptotic rate,and Bax protein expression(P＜0.05),and decreased TRIM14 mRNA and protein expression,survival rate,clone number,migration number,invasion number,cyclin D1 and MMP-2(P＜0.05).Compared with the miR-193a-3p mimics group and the miR-193a-3p mimics+pcDNA NC group,the miR-193a-3p mimics+pcDNA-TRIM14 group showed decreased cell apoptosis rate and Bax protein(P＜0.05),and increased TRIM14 mRNA and protein expression,survival rate,clone number,migration number,invasion number,cyclin D1 and MMP-2(P＜0.05).There were multiple binding sites between miR-193a-3p and TRIM14.Compared with the miR-NC+TRIM14-WT group,the miR-193a-3p mimics+TRIM14-WT group showed a prominent decrease in dual luciferase activity(P＜0.05).Conclusion:MiR-193a-3p may inhibit the migration and invasion of breast cancer stem cells through inhibiting TRIM14.