Precancerous lesions of gastric cancer （PLGC） are a group of pathological changes caused by abnormalities in the structure， morphology， and differentiation of gastric mucosal epithelial cells. Since the early symptoms are hidden and non-specific， PLGC is not easy to be diagnosed and it has often developed into intermediate or advanced gastric cancer once being diagnosed and missed the best time for treatment. Accordingly， the incidence of this disease is increasing year by year， which lifts a heavy burden on the patients. The pathogenesis of PLGC is complex， involving inflammatory microenvironment， bile reflux， glycolysis， autophagy， and apoptosis. Currently， PLGC is mainly treated with anti-inflammatory and endoscopic therapies， which are difficult to curb the development of PLGC. Therefore， seeking a safe and effective therapy is an important topic of modern research. Traditional Chinese medicine （TCM）， characterized by treatment based on syndrome differentiation and a holistic view， exerts effects via multiple pathways， mechanisms， and targets. Recent studies have confirmed that TCM can regulate the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）， Wnt/β-catenin， Sonic Hedgehog， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， hypoxia-inducible factor-1α （HIF-1α）， neurogenic locus notch homolog protein （Notch）， nuclear factor E₂-related factor 2 （Nrf2） and other signaling pathways. By targeting these pathways， TCM can inhibit aerobic glycolysis， reduce oxidative stress， repair the inflammatory microenvironment， regulate cellular autophagy， and promote vascular normalization， thereby delaying or reversing PLGC. However， few researchers have systematically summarized the TCM regulation of PLGC-associated pathways. By reviewing the relevant articles at home and abroad， this paper summarized the roles of the above signaling pathways in the development of PLGC and the research progress in the regulation of signaling pathways by TCM in the treatment of PLGC， with a view to providing a new theoretical basis for the clinical research on PLGC and the drug development for this disease.

Objective To assess the efficacy and safety of Tiaozhou Ziyin(TZZY)recipe for treatment of premature ovarian insufficiency(POI)and explore the possible mechanisms.Methods We used bioinformatics analyses and network pharmacology to identify the main active ingredients in TZZY recipe and their core targets,which were verified by Western blotting.We tested the efficacy and safety of the recipe in 60 POI patients,who were randomized into control group(n=30)with Femoston treatment and TZZY group(n=30)with additional TZZY recipe treatment for 3 menstrual cycles.Results The core active ingredients of TZZY recipe included kaempferol,β-sitosterol,luteolin,and quercetin.The core targets included SRC,TP53,STAT3,PIK3CA,and MAPK3,which were involved in positive regulation of cell movement and protein phosphorylation,the cancer pathways and the PI3K-Akt signaling pathway.Molecular docking showed that the core active ingredients had good binding ability with the core targets.In female rat models of POI,TZZY recipe treatment significantly up-regulated ovarian expressions of p-PI3K and p-Akt proteins.In the clinical trial,treatment with Femoston and Femoston plus TZZY recipe both significantly increased E2 levels and reduced FSH and LH levels and Kupperman scores of the patients,and the combined treatment produced significantly stronger effects.Both treatments increased the number of antral follicles of the patients,but the combined treatment also significantly increased the levels of AMH.Conclusion The therapeutic mechanism of TZZY recipe for POI involves multiple active ingredients,multiple therapeutic targets and multiple pathways,and activating the PI3K/Akt pathway is one of its main mechanisms of action,to improve ovarian reserve function,alleviate clinical symptoms,and enhance clinical efficacy in POI patients.

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".

Renal injury is one of the common ad-verse reactions in the clinical application of chemo-therapy drugs,which is the main reason why the chemotherapy can not be carried out in the whole cycle.The pathological mechanism of chemothera-py-induced renal injury is very complicated,mainly involving oxidative stress,inflammatory response,apoptosis,mitochondrial dysfunction,and regula-tion of transporters,causing pathological damage to renal tubules or glomeruli.At present,there is no specific pharmacological intervention for the treatment of chemotherapy-induced renal injury.As a treasure of traditional Chinese medicine,tradi-tional Chinese medicine has the advantages of overall regulation,multi-targeting,small adverse re-actions and no obvious drug dependence in the prevention and treatment of chemotherapy-in-duced renal injury.In recent years,there have been more and more studies on the intervention of che-motherapy-induced renal injury by multi-compo-nent and multi-directional intervention of active components,extracts and compounds of tradition-al Chinese medicine,and some progress has been made.A large number of studies have shown that the potential mechanisms of traditional Chinese medicine in preventing and treating renal injury in-duced by chemotherapy include inhibiting oxida-tive stress,reducing inflammatory response and in-hibiting apoptosis.Although there are many stud-ies on the mechanism of action of traditional Chi-nese medicine in the treatment of chemotherapy-induced renal injury,there is still a lack of systemat-ic review.Based on this,this paper summarizes the mechanism of renal injury induced by chemothera-py and the intervention of traditional Chinese medi-cine,so as to provide theoretical support for its clinical treatment and new drug innovation.

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.

BACKGROUND:The level of peripheral erythrocytes in rats is significantly increased under hypoxia exposure,and the proliferation of nucleated erythrocytes in the bone marrow may be one of the direct causes of the increase in peripheral erythrocytes.Previous studies have focused on the effects of factors such as erythropoietin and hypoxia-inducible factor,but little research has been done on related factors such as inflammation and immunity.OBJECTIVE:To study the expression of interleukin-18 in bone marrow nucleated erythrocytes,bone marrow supernatant and peripheral blood of rats after hypoxia exposure,and to explore the possible role of interleukin-18 in the pathogenesis of chronic mountain sickness.METHODS:Sixteen healthy male SD rats were randomly divided into two groups:the experimental group was kept in a hypobaric oxygen chamber at a simulated altitude of 5 000 m for 28 days,and the control group was kept in a laboratory at an altitude of 2 260 m for 28 days.The blood routine tests of the two groups of rats were performed.The proportion of CD71+nucleated erythrocytes in the bone marrow of the two groups of rats was determined by flow cytometry.The expressions of interleukin 18 mRNA and protein in CD71+nucleated erythrocytes in the bone marrow of the two groups of rats were determined by RT-qPCR and western blot assay.The expressions of interleukin 18 protein in the sternum of the two groups of rats were determined by immunofluorescence.The levels of interleukin 18 in the peripheral blood and bone marrow supernatant of the two groups of rats were determined by ELISA.RESULTS AND CONCLUSION:(1)The indexes of erythrocyte count,hemoglobin,hematocrit,and mean hemoglobin content in peripheral blood of the experimental group were higher than those of the control group(P＜0.05).(2)The proportion in bone marrow CD71+erythroblasts was significantly higher in the experimental group than that in the control group(P＜0.05).(3)RT-qPCR results showed that the expression of interleukin 18 mRNA in CD71+nucleated erythrocytes in the bone marrow of rats in the experimental group was significantly higher than that in the control group(P＜0.05).(4)Western blot assay results showed that the expression of interleukin 18 protein in CD71+nucleated erythrocytes in the bone marrow of rats in the experimental group was significantly higher than that in the control group(P＜0.05).(5)The immunofluorescence results showed that the expression of interleukin 18 protein in the sternum of rats in the experimental group was significantly higher than that in the control group(P＜0.05).(6)ELISA results exhibited that the level of interleukin 18 in the serum of rats of the experimental group was higher than that in the control group(P＜0.05),but the level of interleukin 18 in the bone marrow supernatant of rats in the experimental group was lower than that in the control group(P＜0.05).The results indicate that the increased expression of interleukin 18 in bone marrow CD71+erythroblasts and peripheral blood of rats under hypobaric hypoxia may be involved in the proliferation of erythroblasts in bone marrow.

Objective:To evaluate the predictive efficacy of different comorbidity indices for hospitalization due to acute exacerbations in chronic obstructive pulmonary disease (COPD) patients with comorbidities (CO-COPD).Methods:This retrospective cohort study included 259 stable COPD patients with comorbidities from Beijing Tongren Hospital, Capital Medical University, between October 2021 and September 2023, all with ≥1-year follow-up. Patients were categorized into hospitalized ( n=75) and non-hospitalized ( n=184) groups based on acute exacerbation events. Clinical characteristics, comorbidities, and comorbidity indices, including Charlson Comorbidity Index (CCI), COPD-specific Comorbidity Test (COTE), and comorbidities in chronic obstructive lung disease index (COMCOLD) were compared between two goups. Risk facors of hospitalization due to acute exacerbations were analyzed by Cox regression. Modified indices were developed by incorporating additional respiratory comorbidities (asthma, bronchiectasis, lung cancer) weighted by hazard ratios (HRs) from Cox reguression. The predictive performance of different comorbidity indices for hospitalization was assessed by receiver operating characteristic (ROC) curves. Results:Hospitalized patients exhibited lower BMI, FEV 1% predicted, and FEV 1/FVC (all P<0.05), alongside higher modified British Medical Research Coucil (mMRC) scores and COPD assessment test (CAT) scores, eosinophil counts, and Global Initiative for Chronic Obstructive Lung Disease, (GOLD)severity ( t=3.73, Z=-3.43, Z=-2.43, Z=-11.10, Z=-11.32, Z=-1.80, χ2=17.62, all P<0.05); and also higher use rates of inhaled corticosteroid (ICS) and systemic oral corticosteroid (OCS) ( χ2=5.48, 7.15, all P<0.05). The comorbidities of asthma, bronchiectasis, lung cancer, hypertension, coronary atherosclerotic heart disease, anxiety and depression in hospitalized group were significantly higher ( χ2=22.49, 18.30, 15.63, 5.10, 4.68, 7.46, 5.16, all P<0.05), along with the increased CCI and COTE index ( P<0.05). Comorbid asthma, bronchiectasis, and lung cancer were independent risk factors for hospitalization ( HR=1.841, 2.924, and 2.076, respectively; all P<0.05). Original CCI and COTE showed moderate predictive value ( AUC=0.609 and 0.655), while modified CCI, COTE, and COMCOLD demonstrated improved performance ( AUC=0.730, 0.760, and 0.713, respectively). At optimal cutoffs (modified CCI>3.5, COTE>4.5, COMCOLD>6.5), sensitivities were 61.3%, 76.0%, and 58.7%, with specificities of 70.1%, 61.4%, and 72.3%. Age-stratified analysis revealed enhanced predictive utility of modified indices across age groups. Conclusions:CCI, COTE, and COMCOLD provide modest predictive value for hospitalization in CO-COPD. Modified indices incorporating respiratory comorbidities significantly improve risk stratification, offering clinical utility for identifying high-risk patients in primary care settings.

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.

OBJECTIVES: To assess the efficacy and safety of Tiaozhou Ziyin (TZZY) recipe for treatment of premature ovarian insufficiency (POI) and explore the possible mechanisms. METHODS: We used bioinformatics analyses and network pharmacology to identify the main active ingredients in TZZY recipe and their core targets, which were verified by Western blotting. We tested the efficacy and safety of the recipe in 60 POI patients, who were randomized into control group (n=30) with Femoston treatment and TZZY group (n=30) with additional TZZY recipe treatment for 3 menstrual cycles. RESULTS: The core active ingredients of TZZY recipe included kaempferol, β-sitosterol, luteolin, and quercetin. The core targets included SRC, TP53, STAT3, PIK3CA, and MAPK3, which were involved in positive regulation of cell movement and protein phosphorylation, the cancer pathways and the PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had good binding ability with the core targets. In female rat models of POI, TZZY recipe treatment significantly up-regulated ovarian expressions of p-PI3K and p-Akt proteins. In the clinical trial, treatment with Femoston and Femoston plus TZZY recipe both significantly increased E₂ levels and reduced FSH and LH levels and Kupperman scores of the patients, and the combined treatment produced significantly stronger effects. Both treatments increased the number of antral follicles of the patients, but the combined treatment also significantly increased the levels of AMH. CONCLUSIONS The therapeutic mechanism of TZZY recipe for POI involves multiple active ingredients, multiple therapeutic targets and multiple pathways, and activating the PI3K /Akt pathway is one of its main mechanisms of action, to improve ovarian reserve function, alleviate clinical symptoms, and enhance clinical efficacy in POI patients.
Female ; Primary Ovarian Insufficiency/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Rats ; Molecular Docking Simulation ; Signal Transduction ; Sitosterols/therapeutic use* ; Kaempferols/therapeutic use*