四川大学学报(医学版)最新文献

Objective: To investigate the characteristics of the pathogens isolated from the specimens of tumor patients and detection rates of multidrug-resistant bacteria in a hospital in the past five years, so as to provide references for infection prevention and control.

Methods: The results of pathogenic culture and in vitro susceptibility of the strains isolated from the specimens collected between January 2019 and December 2023 from tumor patients were retrospectively collected, and the trends of the data were analyzed and summarized.

Results: A total of 16393 strains were isolated from 80386 specimens, producing a detection rate of 20.4%. After excluding the duplicate strains isolated from the same patients, Escherichia coli (14.5%), Klebsiella pneumoniae (13.2%), Staphylococcus aureus (9.4%), Acinetobacter baumannii complex (9.3%), and Pseudomonas aeruginosa (7.7%) predominated the 7951 (81.1%) bacterial strains. Among the 1857 (18.9%) fungal strains, Candida albicans (56.5%), Candida tropicalis (9.0%), and Candida parapsilosis (8.0%) were the most common ones. The specimen sources differed among the prevalent species, and the species distribution varied among specimens from different types of tumors (P<0.05). The detection rates of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae were 2.5% (29/1152) and 12.3% (129/1050), respectively. The detection rate of methicillin-resistant Staphylococcus aureus was 22.0% (165/749), maintaining an upward trend in the last four years (P<0.01). The detection rates of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa were 40.3% (298/739) and 8.8% (54/612), respectively.

Conclusion: Gram-negative bacteria were the prevalent pathogens of tumor patients. The detection rate of multidrug-resistant bacteria was relatively high, and the detection rate of methicillin-resistant Staphylococcus aureus showed an upward trend.

The rapid development of digital intelligence technologies is providing a powerful boost to the high-quality development of the healthcare system. Considering the current state of our healthcare services and guided by General Secretary Xi Jinping's insights on new quality productive forces and the directives from Third Plenary Session of Communist Party of China's 20th Central Committee, the high-quality development of the healthcare service system should focus on digital intelligence technologies such as cloud computing, big data, privacy computing, blockchain, Internet of Things (IoT), mobile computing, and AI. The key measures should include the optimization of production factors, services, and governance. Emphasis should be placed on enhancing the efficient and intensive development of the development model, ensuring the high-quality and continuous integration of the supply model, and transitioning to scientific and modern management methods. Herein, we analyzed the "factor optimization-service optimization-governance optimization" development mechanism driven by digital intelligence and proposed corresponding implementation pathways, intending to provide references for establishing a high-quality and efficient healthcare service system with Chinese characteristics.

Objective: Radioactive intestinal injury is a common complication during radiotherapy of tumors. The aim of this study is to observe the effect of ionizing radiation on short-term changes in intestinal bile acids and to investigate the radioprotective effect of bile acids on intestinal cells.

Methods: A rat model of small intestinal injury was constructed by exposing the abdomen of the rats to daily irradiation at 2 Gy for 4 d in succession. The bile acids were quantified using metabolomics analysis. IEC-6 cells, a small intestinal epithelial cell line, were divided into a dimethyl sulfoxide (DMSO) control group receiving DMSO and 0 Gy irradiation, a glycoursodeoxycholic acid (GUDCA) experimental group receiving GUDCA and 0 Gy irradiation, a DMSO irradiation group receiving DMSO and 10 Gy irradiation, and a GUDCA irradiation group receiving GUDCA and 10 Gy irradiation. Cell viability and cytotoxicity was assessed by CCK-8 assay test. The apoptosis rate of cells was determined by flow cytometry. The colony formation rate and the radiosensitivity of the cells were determined by colony formation assay on solid media. The expression levels of proteins associated with cell death were determined using Western blot.

Results: After exposure to irradiation, the small intestine tissues of the rats showed typical radioactive intestinal injury. In addition, various bile acids showed fluctuation before and after irradiation. Among the bile acids, GUDCA increased significantly at 3 d after irradiation, but returned to the pre-irradiation level at 7 d after irradiation. Compared with the control group, after GUDCA treatment at 20 μmol/L for 24 h, the cell viability rate after irradiation was significantly higher than that of the DMSO group (P<0.05); the expression levels of the proteins, including PARP, caspase-3, RIP, and GSDMD, were significantly lower than those in the control group (P<0.05). After GUDCA treatment at 20 μmol/L for 24 h and 48 h, the cell apoptosis rate of the cells after irradiation was lower than that of the DMSO group (P<0.05). Compared with the DMSO control group, the colony formation ability of the GUDCA experimental group was stronger than that of the DMSO group after irradiation at 0, 2, 4, and 6 Gy (P<0.05). D₀, or the mean lethal dose, of the GUDCA group was 6.374, while that of the DMSO group was 4.572. Compared with the DMSO control group, the D₀ value of the GUDCA treatment group increased, and the sensitization enhancement ratio (SER) was 0.717.

Conclusion: After exposing the abdomen of rats to irradiation, the intestinal bile acid metabolism of the rats will change significantly, and GUDCA can produce radioprotective effects on intestinal cells to a certain extent.

Objective: To explore the difference in myopia control efficacy between spectacle lenses with highly aspherical lenslets (HAL) combined with 0.01% atropine eye drops and spectacle lenses with HAL alone or single vision spectacle lenses (SVL) in children and adolescents.

Methods: A retrospective cohort study was conducted with a total of 105 myopic children aged 6-15 years. According to the specific myopia correction and control methods of each subject, they were evenly divided into the HAL+0.01% atropine (HAL+AT) group, the HAL group, and the SVL group, with 35 subjects in each group. Relevant data, such as cycloplegic refraction and axial length (AL) at baseline and 12 months after wearing spectacles, were retrieved. One-way analysis of variance, or the Kruskal-Wallis test, was used to analyze the changes in AL and spherical equivalent refraction (SER) after wearing spectacles for 12 months in comparison to those at baseline in the three groups.

Results: There was no statistically significant difference in the baseline parameters and duration of wearing spectacles among the three groups (P>0.05). After wearing spectacles for 12 months, the changes in SER were －0.13 (－0.25, 0.00) D, －0.25 (－0.63, －0.25) D, and －0.63 (－1.00, －0.25) D in the HAL+AT group, HAL group, and SVL group, respectively; AL elongation in the three groups was (0.09±0.11) mm, (0.19±0.16) mm, and (0.34±0.16) mm, respectively. The HAL+AT group exhibited slower SER changes (P _{HAL+AT vs. HAL}=0.001, P _{HAL+AT vs. SVL}=0.002) and AL elongation (P _{HAL+AT vs. HAL}=0.009, P _{HAL+AT vs. SVL}=0.001) than those of the HAL and the SVL groups. Compared with those of the SVL group, myopia progression was reduced by 79.4% and AL elongation was slowed down by 73.5% in the HAL+AT group, while in the HAL group, myopia progression and AL elongation were reduced by 60.3% and 44.1%, respectively. According to stratified analysis based on age and myopia progression rate, among younger children aged 6 to 8 years and older children aged 9 to 15 years, the HAL+AT group had a significantly lower proportion of subjects experiencing fast AL elongation (AL>0.36 mm/year) and a significantly higher proportion of subjects experiencing slow AL elongation (AL≤0.18 mm/year) compared to the SVL group (P<0.017).

Conclusion: The combination intervention of spectacle lenses with HAL and 0.01% atropine eye drops is effective in controlling myopia progression in children and adolescents, with better myopia control effect achieved using this combination intervention in myopic children of all ages.

Objective: To explore the potential role and mechanism of compound tetramethylpyrazine in gastric cancer therapy by using network pharmacology analysis combined with gene function annotation and clinical data analysis.

Methods: SwissTargetPrediction database was used to screen the potential drug action sites of compound tetramethylpyrazine, and the OMIM and Genecard databases were used in combination to obtain gastric cancer-related targets. Intersection analysis was performed to identify potential therapeutic targets. Subsequently, the method of ClusterProfiler was used to perform functional annotation of the downstream targets of intersection. In addition, The Cancer Genome Atlas (TCGA) database was used to obtain the original data of gastric cancer patients, and the immune infiltration analysis, miRNA analysis, transcriptional regulation analysis of key genes, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), nomogram model construction, and genome-wide association studies (GWAS) were performed.

Results: Through network pharmacological screening, we found 14 potential therapeutic targets through which tetramethylpyrazine acted on gastric cancer. Functional annotation showed that these targets were mainly involved in the pathways for hormone metabolism, drug metabolism, and signal transduction. Based on log rank test, the expression of the key genes, ELANE and MPO, showed significant difference in the comparison of gastric cancer survival curves (P<0.05), and were closely associated with immune cell infiltration. In addition, GSEA and GSVA results suggested that ELANE and MPO might influence the development of gastric cancer through multiple signaling pathways.

Conclusion: In this study, by using multiple analysis methods in an integrated way, we found that ligustrazine may have therapeutic effects on gastric cancer by regulating the potential targets of ELANE and MPO, as well as the relevant signaling pathways.

Objective: To investigate the effect and potential mechanisms of α-cyperone (CYP) on Crohn's disease (CD) -like colitis induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) in mice.

Methods: The mice were randomly and evenly divided into wild type (WT), TNBS, CYP and 5-aminosalicylic acid (5-ASA) groups, with 10 mice in each group. The symptoms of enteritis, the function and structure of the intestinal barrier, and the expression levels of inflammatory factors, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and gamma-interferon (IFN-γ), in the colon were assessed. The lipopolysaccharide (LPS)-induced inflammation model of Caco2 cells was constructed and the cells were divided into Control, LPS and LPS+CYP groups. The expression levels of tight junction protein and inflammatory factors in each group were assessed. Gene Ontology (GO) functional enrichment analysis was conducted to predict the possible pathways of action and potential molecular mechanisms of CYP, and to verify them in vivo and in vitro.

Results: In the in vivo study, compared with those of the TNBS group, the body mass and colon length of mice in the CYP group and the 5-ASA group were significantly increased, while the disease activity scores and histological inflammation scores were significantly decreased (P<0.05). The level of lucifcein-glucan isothiocyanate and the bacterial translocation rate (in the liver, the spleen, and mesenteric lymph nodes) were significantly decreased, while the transepithelial electric resistance (TEER) value and the expression levels of zonula occluden protein-1 (ZO-1), and claudin-1 were significantly increased (P<0.05). The expression of inflammatory factors was significantly decreased (P<0.05). In the in vitro study, compared with those of the LPS group, the TEER value and the expression of ZO-1 and claudin-1 in the Caco2 cells in the LPS+CYP group were significantly increased (P<0.05). The expression of inflammatory factors was significantly decreased (P<0.05). Enrichment analysis showed that CYP was correlated with inflammatory response (P<0.001). Western blot results showed that CYP could significantly reduce the expression of key proteins in toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway in vivo and in vitro (P<0.05).

Conclusion: CYP may protect the intestinal barrier by antagonizing the inflammatory response of the intestinal mucosa through regulating the expression of the TLR4/NF-κB signaling pathway, thereby alleviating TNBS-induced CD-like colitis in mice.

Objective: To examine the relationship between the expressions of mismatch repair proteins, MutS homolog 2 (MSH2) and MutS homolog 6 (MSH6), and villin and the pathological features in patients with colon cancer.

Methods: A total of 310 cases of colon cancer patients who were treated at our hospital between January 2017 and September 2021 were selected. The diagnosis of colon cancer of all patients was verified by pathological evaluation. Immunohistochemistry was used to determine the protein expressions of MSH2, MSH6, and villin. The correlation between the expressions of MSH2, MSH6, and villin and the clinicopathological parameters in patients with colon cancer was analyzed accordingly. Multivariate logistic regression was used to analyze the correlation between the expressions of MSH2, MSH6, and villin and the clinicopathological parameters of colon cancer. Kaplan-Meier survival curve was used to compare the 2-year survival rates of colon cancer patients with different expression levels of the proteins.

Results: Among the 310 patients with colon cancer, the negative expression rates of MSH2, MSH6, and villin proteins in cancer tissues were 8.71% (27/310), 9.35% (29/310), and 46.13% (143/310), respectively. The negative expression rates of the three proteins in tissues adjacent to cancer were 3.23% (10/310), 4.19% (13/310), and 9.68% (30/310), respectively. The negative expression rates of the three proteins in cancer tissues were all higher than those in adjacent tissues (P<0.05). Regression analysis showed that the expression of MSH2 and MSH6 in cancer tissues was correlated with the age, the location of tumor lesions, tumor differentiation degree, and lymph node metastasis in colon cancer patients (P<0.05). The expression of villin in the cancer tissue is correlated with the depth of tumor infiltration, lymph node metastasis, distant metastasis, and clinical staging status in colon cancer patients (P<0.05). The 2-year survival rates of patients with negative expressions of MSH2 and MSH6 were 51.85% and 44.83%, respectively, which were lower than those of patients with positive expression of MSH2 and MSH6 (79.51% and 80.43%, P<0.05). Thirteen patients (4.1%) had negative expression of MSH2, MSH6, and villin (referred to as "triple negative expressions") in the cancer tissues, and their 2-year survival rate was 30.77%, which was lower than that of colon cancer patients who did not meet the criteria for triple negative expressions (79.12% [235/297], P<0.05).

Conclusion: The expressions of MSH2, MSH6, and villin are closely correlated with the pathological features of colon cancer patients. Evaluating the expression of the three proteins may assist in the clinical diagnosis, treatment, and prognosis evaluation of colon cancer.

Objective: Small cell carcinoma of the bladder (SCCB) is a rare malignant tumor of the bladder. This study aims to explore its clinicopathological features and prognostic factors and to explore the role of perioperative treatment methods.

Methods: The clinical data of SCCB patients admitted to West China Hospital, Sichuan University over 8 years from January 2016 to January 2024 were collected. The clinicopathological features of SCCB were summarized. The survival outcomes and prognostic factors were analyzed. The effect of perioperative treatment on the improvement in prognosis was explored.

Results: A total of 31 confirmed cases of SCCB were enrolled. We observed a number of clinicopathologic features. All cases had advanced clinical staging, with the T staging status being above T2 in all cases, and distant metastasis was found in 23% of the newly diagnosed cases. A high proportion of the SCCB cases were combined with other histologic types, with 96% showing combination with urothelial carcinoma (UC). The SCCB patients had a poor prognosis, presenting a median survival of 12 months, 1-year overall survival (OS) of 57.9%, and 3-year OS of 27.6%. Patients with extensive-stage SCCB had a significantly worse prognosis than those with limited-stage SCCB did (median OS time of 17.0 months vs. 4.4 months, P<0.05). In limited-stage SCCB, the median OS of patients who underwent radical cystectomy (RC) was 19.9 months, while that of the patients who did not undergo RC was 15.2 months (P<0.05). The OS of patients who received perioperative therapy in combination with RC had longer OS than those who received only RC did (P<0.05). Among these, patients recevied neoadjuvant therapy (NAT) had a significantly longer OS than patients who didn't receive NAT (P<0.05). Subgroup analysis revealed that patients who were responsive to neoadjuvant therapy had longer disease-free survival and longer OS than those who were not responsive did (P<0.05). Lymph node metastasis was an independent factor of poor prognosis (hazard ratio [HR]=15.21, 95% confidence interval [CI]: 1.732-133.912, P=0.014). NAT prior to RS was an independent protective factor, significantly reducing the risk of death compared with RC alone (HR=0.03, 95% CI: 0.001-0.724, P=0.031).

Conclusion: RC is an effective treatment that prolongs the survival of patients with limited-stage SCCB. RS combined with NAT can further improve their survival.

Objective: To investigate the expression and clinical significance of circular RNA (circRNA) 051778 in lung adenocarcinoma-malignant pleural effusion (LA-MPE) and tuberculous pleural effusion (TPE).

Methods: This is a cross-sectional study. A total of 212 patients were recruited from the Jiangxi Chest Hospital between October 2018 and September 2019, and their pleural effusion samples and/or plasma samples were collected. The exosomal circRNA profile was sketched by circRNA microarray. Differentially expressed circRNAs (DECs) were verified by droplet digital PCR. In addition, a putative circRNA-miRNA-mRNA network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to predict the functions of the DECs. The diagnostic value of circRNA_051778 was evaluated by binary logistic regression and receiver operating characteristic curve.

Results: The expression level of circRNA_051778 in the LA-MPE samples was (3.92±0.48) copies/100 ng cDNA, while that in the TPE samples was (21.53±2.22) copies/100 ng cDNA. Compared to that in the TPE samples, circRNA_051778 was significantly downregulated in the LA-MPE samples (P<0.001). The potential targets of circRNA_051778 were enriched in positive regulation of GTPase activity, cytoplasm, protein binding, and cancer-related pathways. The area under the curve (AUC) for the combined assessment of circRNA_051778 with liquid-based thin-layer cytology (TCT), erythrocyte sedimentation rate (ESR), and tuberculosis antibody (TBA) was 0.98 (95% confidence interval: 0.97-1.00), with the sensitivity being 88.0% and the specificity being 100.0%.

Conclusion: Exosomal circRNA_051778 is downregulated in LA-MPE. According to the findings from the GO and KEGG analyses, exosomal circRNA_051778 may play a role in cancer development and has the potential to serve as a marker for differential diagnostic of LA-MPE and TPE when it is used in combination with TCT, ESR, and TBA.