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.

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*

Objective:To explore the clinical characteristics of 1q21.1 microdeletion by using single nucleotide polymorphism microarrays (SNP array).Methods:Eighteen cases of 1q21.1 microdeletion syndrome diagnosed at the Longgang District Maternal and Child Health Care Hospital of Shenzhen City from June 2017 to December 2022 were selected as the study subjects. Clinical data of the patients were collected. Results of chromosomal karyotyping and SNP assay were retrospectively analyzed.Results:Among the 18 cases with 1q21.1 microdeletions, 13 had a deletion between BP3 and BP4, 4 had a deletion between BP1/BP2 and BP4, whilst 1 had a proximal 1q21.1 deletion (between BP2 and BP3) involving the Thrombocytopenia-absent radius (TAR) region. The deletions had spanned from 360 kb to 3.9 Mb, which encompassed the GJA5, GJA8, CHD1L, RBM8AB and other morbid genes. In three families, the proband child has inherited the same 1q21.1 microdeletion from their parents, whose clinical phenotype was normal or slightly abnormal. The clinical phenotypes of 1q21.1 microdeletion had included cognitive or behavioral deficits in 9 cases (9/18, 50.0%), growth retardation in 8 cases (8/18, 44.4%), craniofacial deformities in 7 cases (7/18, 38.8%), cardiovascular malformations in 5 cases (5/18, 27.8%), and microcephaly in 3 cases (3/18, 16.7%). Conclusion:1q21.1 microdeletion syndrome has incomplete penetrance and varied expression such as intellectual impairment, growth and development delay, and microcephaly, with a wide range of non-specific phenotypes.

Objective To investigate the correlations of serum Aβ1-42,P-Tau181,and Hcy levels with sleep disorders in patients with Parkinson's disease(PD).Methods A total of 80 PD patients were divided into a normal sleep group(＜7 points)and a sleep disorder group(≥7 points)based on the evaluations with Pittsburgh Sleep Quality Index(PSQI).Univariate and multivariate logistic regression analyses were performed to investigate the correlations between the levels of serum A β1-42,P-Tau181,and Hcy levels and sleep disorders.Receiver operating characteristic(ROC)curves were used to analyze the efficacy parameters of different indicators in pre-dicting sleep disorders in those patients.Results Univariate and multivariate logistic regression analyses showed that serum Aβ1-42 and Hcy were protective and independent risk factors for sleep disorders in the PD patients,respectively(P＜0.05).The predictive AUCs of serum Aβ1-42 and Hcy levels for sleep disorders in the PD patients were 0.757(95%CI:0.652～0.861)and 0.796(95%CI:0.688～0.905),respectively.Conclusion The levels of serum Aβ1-42 and Hcy in PD patients are closely related to sleep disorders.Therefore,they can be used as predic-tive factors for clinical diagnosis of PD with sleep disorders.

Objective:To explore the gene microarray of patients with ankylosing spondylitis in GEO database by using various bioinformatics methods, and to explore the possible targets and mechanisms of action.Methods:The GEO database was searched with "ankylosing spondylitis" the keyword, and the expression profile of genes related to AS was selected as the research object. Standard difference analysis, weighted co-expression analysis and gene set enrichment analysis were conducted to construct the disease set. GO and KEGG enrichment analysis were performed on the disease sets. The NCC algorithm identifies the first five key genes. THP-1 cells were implanted into RPMI-1640 culture medium containing 10% fetal bovine serum to multiply and construct the cell model of AS in vitro. The expression levels of 5 key genes were detected by qRT-PCR and Western blot. The experimental measurement data were expressed as mean± standard deviation, and the t test was used in comparison between the two groups. Results:One thousand six hundred and sixty seven disease genes were analyzed, functional annotation was mainly concentrated in 689 molecular components of cytoplasmic ribosomes, ribosomal subunits, ribosomes, cytoplasmic large ribosomal subunits, the structural composition of ribosomal REDOX enzyme activity, 1 002 molecular functions of NADH dehydrogenase activity, NADH dehydrogenase activity, and 5 764 molecular processes of mRNA catabolism and RNA catabolism The physical process involved 1 002 signaling pathways involved in Alzheimer′s disease, Prion disease, Parkinson′s disease, and the first 5 key genes were identified as RPS11, RPL4, RPL37A, RPS23, and RPS9. The experimental results were obtained by t test. The results showed that TNF-α mRNA ( t=5.59, P=0.001) and protein ( t=20.14, P<0.001) were significantly increased, indicating that LPS had induced inflammatory response in THP-1 cells, while RPL37AmRNA ( t=5.87, P=0.001), RPS11 mRNA ( t=3.88, P=0.008), RPS23 mRNA ( t=2.64, P=0.038), RPL37A protein ( t=3.18, P=0.030), RPS11 protein ( t=11.26, P<0.001), RPS23 protein ( t=5.64, P<0.001), increased, while RPS9 mRNA ( t=3.16, P=0.020), RPL4 mRNA ( t=2.54, P=0.044), RPS9 protein ( t=5.85, P<0.001) and RPL4 ( t=2.93, P=0.040) protein expressions decreased. RPL23 stimulated the joint synovial tissue to produce effect-T lymphocytes and release a large number of IL-2 and other inflammatory cytokines. RPS9 acts on the early stages of ribosomogenesis, and knocking down RPS9 reduced overall protein synthesis. RPL4 interacted with TTC22 protein to enhance the binding of WTAP mRNA to RPL4, which was associated with immune diseases. The nucleoprotein OGFOD1 catalyzed the hydroxylation of RPS23 and participated in the inflammatory process. The chromosome conformation confirmed the single nucleotide polymorphism function of IL23R genomic locus in AS disease. Conclusion:Ribosomal protein may be an important target for exploring the mechanism of AS inflammation.

Objective To investigate the involvement of phosphofurin acidic cluster sorting protein-2(PACS-2)in mitochondrial function and apoptosis in N2a/APP695swe cells and further explore the role and significance of PACS-2 in the development of Alzheimer's disease(AD).Methods The CCK8 method was used to analyze the cell survival rate of N2a/APP695swe cells treated with different concentrations of tetrahydroxy stilbene glycoside(TSG)for 48h and to select the appropriate concentration of TSG for subsequent experiments.N2a/WT cells and N2a/APP695swe cells were routinely cultured in vitro,and the experimental cells were divided into 3 groups:blank control group(WT group):N2a/WT cells;model group(APP group):N2a/APP695swe cells;treatment group(TSG group):N2a/APP695swe cells with appropriate concentrations of TSG intervention.TUNEL method to observe apoptosis by fluorescence microscopy;JC-1 method for flow detection of cellular mitochondrial membrane potential;WB to detect protein expression of PACS-2;RT-qPCR to detect PACS-2 mRNA expression.Results CCK8 method was used to analyze the cell survival rate of different concentrations of TSG acting on cells after 48h:the protective effect of 100 μmol/L TSG was the most significant and the difference was statistically significant(P<0.01).The TUNEL method of fluorescence microscopy observed the apoptosis:compared with the WT group,the apoptosis rate of APP group was increased,compared with the APP group,the apoptosis rate of TSG group was decreased,and the differences were statistically significant(P<0.05).The JC-1 method was used to detect the mitochondrial membrane potential of cells:compared with the WT group,the membrane potential of APP group was decreased,compared with the APP group,the membrane potential of TSG group was increased,and the differences were statistically significant(P<0.05);Western blot(WB)detection of PACS-2 protein expression:compared with the WT group,PACS-2 expression was significantly higher in the APP group,and compared with the APP group,PACS-2 expression was significantly lower in the TSG group,with statistically significant differences(P<0.05);The RT-qPCR detected the mRNA expression of PACS-2:the expression of PACS-2 was elevated in the APP group compared with the WT group and decreased in the TSG group compared with the APP group,with statistically significant differences(P<0.05).Conclusion PACS-2 has an important role in the development of AD,and its upregulation may promote the development of AD.The cerebroprotective drug TSG may exert cytoprotective effects by downregulating PACS-2 to inhibit apoptosis and improve mitochondrial function in AD model cells.

Objective:To investigate the Correlation between ADC combined with serum C-reactive protein (CRP) and delayed encephalopathy after carbon monoxide poisoning (DEACMP), It provides scientific basis for early prediction of DEACMP.Methods:According to the design principle of case-control study, the data of acute carbon monoxide poisoning (ACOP) patients admitted to Shandong Provincial Hospital from December 2017 to December 2021 were retrospectively selected. Among them, patients with DEACMP were selected as the case group, without DEACMP were used as the control group. Univariate and multivariate analyses were performed on the two groups. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of ADC combined with CRP as a combined predictor for disease.Results:A total of 89 patients with ACOP were included, including 33 patients with DEACMP and 56 patients without DEACMP. There were no significant differences in gender, age, smoking, drinking, and underlying diseases (hypertension, coronary heart disease) between groups ( P>0.05). Logistic regression analysis showed that white blood cell count (WBC) ( OR=1.64, 95% CI: 1.19-2.26, P=0.003), CRP ( OR=1.22, 95% CI: 1.03-1.45, P=0.019) and ADC value of central semiovale white matter ( OR=0.99, 95% CI: 0.98-1.00, P=0.010) were associated with DEACMP in patients with ACOP. The ROC curve results showed that the area under the ROC of ADC combined with CRP in the center of semiovale was 0.765 (95% CI: 0.656-0.845), the specificity was 87.9%, the sensitivity was 23.2%, and the cut-off value was 3.5°. Conclusions:WBC, CRP and ADC value of central semiovale are independent factors for DEACMP. ADC value of central semiovale combined with CRP has more clinical value in the early diagnosis of DEACMP. For ACOP patients with DEACMP triggering factors, the diagnosis and treatment awareness of early screening of brain magnetic resonance imaging should be strengthened to avoid DEACMP.

The performance appraisal of tertiary public hospitals is key to their high-quality development. Since 2019, Children′s Hospital of Zhejiang University School of Medicine has taken the following measures to leverage performance appraisal. Namely promoting medical technology innovation to enhance the diagnosis and treatment capabilities of difficult and critical diseases; Reasonably setting a target system, improving the performance appraisal mechanism of the hospital; Improving operational efficiency, enhancing the sense of gain by children patients; Building a high-quality talent pool, promoting sustainable development, and effectively promoting high-quality development of hospitals. These measures can provide reference for promoting the high-quality development of hospitals.

Objectives:To investigate the relationship between visceral adipose index and glomerular filtration rate in patients with type 2 diabetes mellitus.Methods:A total of 1 036 patients with type 2 diabetes mellitus who received treatment in The Second Affiliated Hospital of Xi'an Jiaotong University from May 2017 to May 2018 were included in this study. The visceral adipose index was detected using a bioresistance assay. These patients were divided into four groups using the quartile method: Visceral adipose index < 8.10 (q1 group, n = 246), 9.60 > visceral adipose index ≥ 8.10 (q2 group, n = 64), 11.10 > visceral adipose index ≥ 9.60 (q3 group, n = 423), visceral adipose index ≥ 11.10 (q4 group, n = 233). One-way analysis of variance was performed to compare the differences among groups. Partial correlation and multiple regression were used to analyze the correlation between body mass index, waist circumference, waist-to-height ratio, waist-to-hip ratio, body fat content, visceral adipose index, and urinary microalbumin and glomerular filtration rate. Results:With the increase in the visceral adipose index, the glomerular filtration rate gradually decreased. The glomerular filtration rate in the q1, q2, q3, q4 groups was (112.19 ± 31.74) mL·min -1·1.73 m -2, (106.14 ± 28.26) mL·min -1·1.73 m -2, (104.73 ± 23.63) mL·min -1·1.73 m -2, (103.40 ± 27.51) mL·min -1·1.73 m -2, respectively. In the female group, with the increase in visceral adipose index, the glomerular filtration rate decreased gradually. After controlling for age, sex, diabetes, and hypertension, the visceral adipose index was significantly correlated with the glomerular filtration rate ( r = -0.10, P < 0.001). Multiple regression analysis showed that visceral adipose index and waist-to-height ratio were closely related to glomerular filtration rate ( F = 6.00, P < 0.001). Conclusion:With the increase of visceral adipose index, body mass index, waist circumference, waist-to-height ratio, waist-to-hip ratio, body fat content, and urinary microalbumin increased gradually. When the visceral adipose index is greater than 9.60, the glomerular filtration rate is significantly decreased. Therefore, it is suggested to adopt various methods to evaluate obesity in clinical work, and visceral fat index should be paid more attention, especially when the visceral fat index is greater than 9.60.