OBJECTIVE: To explore the clinical features of the sepsis in immunocompromised hosts and establish an early warning equation. METHODS: A retrospective study was conducted on sepsis patients admitted to the intensive care unit (ICU) of Binzhou Medical University Hospital from October 2011 to October 2022. General information, infection site, etiology results and drug susceptibility, clinical symptoms, inflammatory indicators, acute physiology and chronic health status evaluation II (APACHE II), sequential organ failure assessment (SOFA), incidence of immune paralysis, and outcome during hospitalization were collected. Based on whether they met the diagnostic criteria for immunocompromised hosts, patients were divided into immunocompromised group and immune normal group. The clinical information of the two groups were compared. Multivariate Logistic regression was used to analyze the risk factors of patients with immunocompromised sepsis and the regression equation model was initially established. Omnibus test and Hosmer-Lemeshow test were used to evaluate the model. RESULTS: A total of 169 patients with sepsis were included, including 61 in the immunocompromised group and 108 in the normal immune group. The top 3 infection sites in the immunocompromised group were bloodstream infection, pulmonary infection and abdominal infection. The top 3 infection sites in the normal immune group were pulmonary infection, bloodstream infection and abdominal infection. The infection rate of Gram-negative bacteria in the immunocompromised group was significantly lower than that in the normal group [49.2% (30/61) vs. 64.8% (70/108), P < 0.05]. The infection rate of Gram-positive bacteria [27.9% (17/61) vs. 13.9% (15/108)] and multidrug-resistant bacteria [54.1% (33/61) vs. 29.6% (32/108)] were significantly higher than those in normal immune group (both P < 0.05). In terms of clinical symptoms, the proportion of fever in the immunocompromised group was significantly lower than that in the immune normal group [49.2% (30/61) vs. 66.7% (72/108), P < 0.05]. Neutrophil count (NEU) and neutrophil percentage (NEU%) in the immunocompromised group were significantly lower than those in the normal immune group. Lymphocyte percentage (LYM%), neutrophil/lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), APACHE II score, combined shock rate, incidence of immune paralysis, and mortality during hospitalization in the immunocompromised group were significantly higher than those in the normal immune group. Logistic regression analysis showed that NLR, CRP and PCT were risk factors for patients with immunocompromised sepsis (all P < 0.05). The above indicators were used as covariables to construct a Logistic regression equation, that was, Logit (P) = 0.025X₁+0.010X₂+0.013X₃-2.945, where X₁, X₂ and X₃ represent NLR, CRP and PCT respectively. Omnibus test and Hosmer-Lemeshow test show that the model fits well and has certain early warning value. CONCLUSIONS Patients with immunocompromised sepsis have more intense inflammatory response, with Gram-negative bacteria being the predominant pathogen, and a higher incidence of Gram-positive bacterial infections and multi-drug resistant infections. The severity of the disease, in-hospital mortality, the incidence of shock and the incidence of immune paralysis after sepsis were significantly higher. NLR, CRP and PCT were independent risk factors for sepsis in immunocompromised hosts. The regression equation constructed based on this may have early warning significance for patients with immunocompromised sepsis.
Humans ; Sepsis/immunology* ; Immunocompromised Host ; Retrospective Studies ; Risk Factors ; Intensive Care Units ; Logistic Models ; Male ; APACHE ; Female ; Middle Aged ; Aged

OBJECTIVE: To identify and validate novel biomarkers for the early diagnosis of sepsis-associated acute kidney injury (SA-AKI) and precise continuous renal replacement therapy (CRRT) using proteomics. METHODS: A prospective multicenter cohort study was conducted. Patients with sepsis admitted to five hospitals in Taizhou City of Zhejiang Province from April 2019 to December 2021 were continuously enrolled, based on the occurrence of acute kidney injury (AKI). Sepsis patients were divided into SA-AKI group and non-SA-AKI group, and healthy individuals who underwent physical examinations during the same period were used as control (NC group). Peripheral blood samples from participants were collected for protein mass spectrometry analysis. Differentially expressed proteins were identified, and functional enrichment analysis was conducted on these proteins. The levels of target proteins were detected by enzyme linked immunosorbent assay (ELISA), and the predictive value of target protein for SA-AKI were evaluated by receiver operator characteristic curve (ROC curve). Additionally, sepsis patients and healthy individuals were selected from one hospital to externally verify the expression level of the target protein and its predictive value for SA-AKI, as well as the accuracy of CRRT treatment. RESULTS: A total of 37 patients with sepsis (including 19 with AKI and 18 without AKI) and 31 healthy individuals were enrolled for proteomic analysis. Seven proteins were identified with significantly differential expression between the SA-AKI group and non-SA-AKI group: namely cystatin C (CST3), β ₂-microglobulin (β ₂M), insulin-like growth factor-binding protein 4 (IGFBP4), complement factor I (CFI), complement factor D (CFD), CD59, and glycoprotein prostaglandin D2 synthase (PTGDS). Functional enrichment analysis revealed that these proteins were involved in immune response, complement activation, coagulation cascade, and neutrophil degranulation. ELISA results demonstrated specific expression of each target protein in the SA-AKI group. Additionally, 65 patients with sepsis (38 with AKI and 27 without AKI) and 20 healthy individuals were selected for external validation of the 7 target proteins. ELISA results showed that there were statistically significant differences in the expression levels of CST3, β ₂M, IGFBP4, CFD, and CD59 between the SA-AKI group and non-SA-AKI group. ROC curve analysis indicated that the area under the curve (AUC) values of CST3, β ₂M, IGFBP4, CFD, and CD59 for predicting SA-AKI were 0.788, 0.723, 0.723, 0.795, and 0.836, respectively, all exceeding 0.7. Further analysis of patients who underwent CRRT or not revealed that IGFBP4 had a good predictive value, with an AUC of 0.84. CONCLUSIONS Based on proteomic analysis, CST3, β ₂M, IGFBP4, CFD, and CD59 may serve as potential biomarkers for the diagnosis of SA-AKI, among which IGFBP4 might be a potential biomarker for predicting the need for CRRT in SA-AKI patients. However, further clinical validation is required.
Humans ; Sepsis/complications* ; Acute Kidney Injury/blood* ; Proteomics ; Prospective Studies ; Biomarkers/blood* ; Male ; Female ; beta 2-Microglobulin/blood* ; Middle Aged ; Cystatin C/blood* ; Aged

BACKGROUND:Acute exercise tends to cause skeletal muscle tissue damage and lipid metabolism disorders in vivo,but the mechanism by which acute exercise combined with electroacupuncture modulates metabolic and autophagic pathways in vivo is unclear. OBJECTIVE:To observe the changes in metabolic enzymes and autophagy levels in skeletal muscle of rats subjected to acute exercise by electroacupuncture at the acupoints of"Zusanli"and"Huantiao." METHODS:Fifty male Sprague-Dawley rats were randomly divided into three groups:quiet control group(n=10),model group(n=20),and reverse electroacupuncture group(n=20).The latter two groups were set up with two time points,i.e.immediate and 3 hours after exercise groups(n=10 per time point).The model group and the reverse electroacupuncture group underwent acute exercise training after adaptive treadmill training.The rats in the reverse electroacupuncture group underwent electroacupuncture treatment(parameters:electroacupuncture on both sides of the rats at the acupoints of"Zusanli"and"Huantiao,"continuous wave,frequency of 2 Hz,intensity of 2 mA,leaving the needle in the body for 30 minutes,once a day for 7 consecutive days)before treadmill training.Bilateral gastrocnemius muscle tissues were taken under anesthesia immediately after exercise and 3 hours after exercise,and hematoxylin-eosin staining was used to observe the histopathological changes of rat skeletal muscle.ELISA kit was used to detect the activities of hepatic lipase,fatty acid synthase,hormone-sensitive lipase,and carnitine palmitoyltransferase 1 in rat skeletal muscle tissues.Immunohistochemistry and western blot were used to detect the changes in the expression of autophagy genes. RESULTS AND CONCLUSION:After hematoxylin-eosin staining,the arrangement of gastrocnemius muscle fibers in the model group was disturbed,swollen and ruptured immediately after exercise and 3 hours after exercise.In the reverse electroacupuncture group,gastrocnemius muscle fibers were tightly arranged and the number of swollen and ruptured cells was greatly reduced immediately after exercise and 3 hours after exercise,and there was no significant difference when compared with the quiet control group.Compared with the quiet control group,the activities of hepatic lipase and fatty acid synthase were lower while the activities of lipoprotein lipase,hormone-sensitive lipase,and carnitine palmitoyltransferase 1 were higher in the model group and the reverse electroacupuncture group 3 hours after exercise(P＜0.05 or P＜0.01).Compared with the model group,the activities of lipoprotein lipase and carnitine palmitoyltransferase 1 were higher in the reverse electroacupuncture group immediately after exercise(P＜0.05),while the activity of lipoprotein lipase was higher and the activity of hormone-sensitive lipase was lower in the reverse electroacupuncture group 3 hours after exercise(P＜0.01).Immunohistochemical results showed that compared with the quiet control group,the expression of P62,autophagy-related gene 5 and autophagy-related gene 7 was higher in the model group immediately and 3 hours after exercise,as well as in the reverse electroacupuncture group immediately after exercise(P＜0.05 or P＜0.01);compared with the model group,the expression of P62 and autophagy-related gene 7 was lower in the reverse electroacupuncture group immediately and 3 hours after exercise(P＜0.05).Western blot results showed that the protein expression of P62 and autophagy-related gene 7 in the reverse electroacupuncture group was lower than that in the model group immediately after exercise(P＜0.05);the protein expression of Parkin in the model group was higher than that in the quiet control group immediately and 3 hours after exercise(P＜0.05);and the protein expression of Parkin in the reverse electroacupuncture group was lower than that in the model group immediately and 3 hours after exercise(P＜0.05).To conclude,acute exercise induces disorders,swelling and rupture of gastrocnemius muscle fibers in rats and electroacupuncture on both sides of the acupoints of"Zusanli"and"Huantiao"can improve the level of lipid metabolism and regulate autophagy cells in rat skeletal muscle,preventing the disorders of lipid metabolism and damage of gastrocnemius muscle tissues caused by acute exercise.The mechanism may be closely related to the regulation of autophagy-related factor P62,autophagy-related gene 5,autophagy-related gene 7,and Parkin protein expression to promote the occurrence of autophagy or regulate the autophagy pathway in rat skeletal muscle cells.

Objective:To explore the incidence of Crohn's disease-like pouch (CDP) after ileal pouch-anal anastomosis (IPAA) and analyze the clinical characteristics and risk factors in ulcerative colitis (UC) patients.Methods:A retrospective cohort study was conducted. One hundred and eighty-two UC patients undergoing IPAA at Jinling Hospital affiliated to Nanjing University from November 2003 to November 2024 were enrolled. Patients were categorized into CDP and non-CDP groups. Clinical features and prognosis were compared, and multivariate Cox regression was performed to identify risk factors for CDP.Results:A total of 182 UC patients were included, with a median follow-up time of 45.00 (30.00, 75.25) months. The patients were divided into two groups based on the diagnosis of CDP, with 23 patients (12.64%) in the CDP group and 159 patients (87.30%) in the non-CDP group. Compared to the non-CDP group, patients in the CDP group had a lower body mass index (BMI) ( Z=-2.87, P=0.004), and were more likely to develop early postoperative pouchitis (χ 2=4.50, P=0.034). The median time from ileostomy closure to the development of CDP was 12 .00 (6.00, 28.00) months. Cox regression analysis showed that a preoperative BMI<18.5 kg/m 2 ( HR=2.84, 95% CI: 1.24~6.49, P=0.013) and early postoperative pouchitis ( HR=3.11, 95% CI: 1.22~7.93, P=0.018) were associated with an increased risk of CDP. Conclusions:Preoperative low BMI and pouchitis occurring within 3 months postoperatively are significant risk factors for CDP. Close monitoring and early intervention are recommended for high-risk patients.

Objective To analyze the related factors of prognosis in patients with primary Sjogren’s syndrome (SS) complicated with renal damage, and to provide reference for clinical development of personalized prevention and treatment measures. Methods A total of 508 patients with primary SS complicated with renal damage in the First Affiliated Hospital of Xinjiang Medical University from February 2020 to February 2022 were enrolled as study subjects. According to the prognosis status within 3 years, the enrolled patients were divided into good prognosis group (n=426) and poor prognosis group (n=82). Univariate and logistic multivariate regression analyses were adopted to analyze the influencing factors of poor prognosis. Results There were significant differences in hypertension, anemia, renal interstitial chronicity grading, and levels of globulin (GLO), immunoglobulin G (IgG) and hemoglobin between the two groups (P<0.05). Logistic multivariate analysis showed that concurrent hypertension, anemia, increased grade of renal interstitial chronicity, and elevated GLO and IgG levels were risk factors of poor prognosis in patients with primary SS complicated with renal damage, while hemoglobin level was a protective factor (OR: 1.962, 95%CI: 1.056-3.645; OR: 2.467, 95%CI: 1.153-5.278; OR: 17.796, 95%CI: 5.157-61.419; OR: 3.655, 95%CI: 1.812-7.372; OR: 5.732, 95%CI: 2.632-12.480; OR: 0.325, 95%CI: 0.165-0.640, P<0.05). Conclusion Patients with primary SS complicated with renal damage have a higher risk of poor prognosis, which is affected by factors such as hypertension, anemia, and GLO, IgG and hemoglobin levels. Clinically, it is necessary to take active prevention and treatment measures to improve the prognosis of patients.

Objective To investigate the expression characteristics of granzyme B(GZMB)and C-X-C motif chemokine ligand 9(CXCL9)in gastric cancer(GC)tissues,explore their association with the tumor immune microenvironment(TME),and evaluate their clinical prognostic significance.Methods Bioinformatic analyses were conducted using public databases(TIMER,GEPIA,UALCAN)to validate the expression levels of GZMB and CXCL9 across various cancer types,with a focus on GC.Paired tumor and adjacent normal tissue samples were collected from 89 GC patients who underwent radical gastrectomy at Nanyang First People's Hospital between 2018 and 2019.The mRNA expression levels of GZMB and CXCL9 were measured using quantitative real-time PCR(qRT-PCR),and their associations with clinicopathological characteristics were statistically analyzed.Immune cell infiltration levels were estimated using the TIMER and GSCA databases.Diagnostic performance was evaluated through receiver operating characteristic(ROC)curve analysis,while survival outcomes were assessed using data from the Kaplan-Meier Plotter database and patient follow-up records.Results Both database analysis and qRT-PCR results demonstrated that GZMB and CXCL9 expression levels were significantly elevated in GC tissues compared to adjacent non-tumor tissues(P<0.05).Clinical correlation analysis revealed no significant associations between mRNA expression levels of GZMB and CXCL9 and clinicopathological parameters,including gender,age,pathological type,tumor differentiation,TNM stage,tumor size,or lymph node metastasis(P>0.05).Immune infiltration analysis indicated that both genes were significantly positively correlated with CD8+T cell and dendritic cell infiltration(P<0.05),while showing a negative correlation with B cell infiltration(P<0.05).ROC curve analysis showed that the combined detection of GZMB and CXCL9 yielded an AUC of 0.890(95%CI:0.843～0.936),which was higher than that of GZMB alone(AUC=0.832,95%CI:0.772～0.891)or CXCL9 alone(AUC=0.782,95%CI:0.715～0.850).Survival analysis further revealed that patients with high expression of GZMB and CXCL9 had significantly improved overall survival compared to those with low expression(P<0.05).Conclusion GZMB and CXCL9 are highly expressed in GC and are strongly associated with the infiltration of anti-tumor immune cells.These molecules represent promising diagnostic biomarkers for GC,and their elevated expression is correlated with a more favorable prognosis in patients.

Objective:To investigate the curative effect and mechanism of hyperbaric oxygen therapy on nonalcoholic fatty liver disease in mice.Methods:Twenty-one 8-week-old male C57BL/6J mice were divided into three groups: control group (normal diet), model group (high-fat and high-cholesterol diet), and hyperbaric oxygen group (high-fat and high-cholesterol diet + hyperbaric oxygen therapy), with seven mice in each group. The changes in body weight, serum liver enzymes, and blood lipids were compared after treatment between the three groups. Hematoxylin-eosin staining, Oil Red O staining, Sirius red staining, and F4/80 immunohistochemical staining were used to observe the pathological changes in liver tissues. RT-qPCR and Western blot methods were used to detect the expression levels of oxidative stress and inflammatory factors. One-way analysis of variance was used for comparison among the groups.Results:Mice in the hyperbaric oxygen group had significantly improved liver histopathology. The serological levels of alanine aminotransferase, aspartate aminotransferase, and cholesterol were (77.50±13.59) U/L, (156.06±23.68) U/L, and (4.80±0.53) mmol/L, which were significantly lower than those in the model group [(109.43±16.88) U/L, (216.62±18.79) U/L, and (5.86±0.53) mmol/L, P<0.05], and accompanied by lower levels of lipid deposition, macrophage infiltration, and fibrosis. In addition, compared with the model group, the expression of antioxidant stress protein nuclear transcription factor erythroid 2-related factor 2 [(0.30±0.06) and (2.16±1.21), P<0.05] and heme oxygenase-1 [(0.48±0.19) and (1.01±0.18), P<0.05] in liver tissue showed an upward trend following hyperbaric oxygen treatment, which was also validated at the transcriptional level ( P<0.05). Simultaneously, compared with the model group, the mRNA expressions of tumor necrosis factor-α [(2.60±0.71) and (0.66±0.15), P<0.05], interleukin-1β [(2.41±1.01) and (0.78±0.23), P<0.05], and interleukin-6 [(3.61±2.17) and (0.94±0.25), P<0.05] in the liver tissue of mice in the hyperbaric oxygen group were decreased. The tumor necrosis factor-α protein level [(7.50±4.73) and (1.05±0.58), P<0.05] and interleukin-1β [(1.65±0.35) and (1.02±0.02), P<0.05] was reduced following hyperbaric oxygen treatment compared with those in the model group. Conclusion:Hyperbaric oxygen therapy can slow down the progression of nonalcoholic fatty liver disease by regulating the levels of oxidative stress and inflammation in the mice.

Metabolic associated fatty liver disease(MAFLD)is a type of fatty liver disease associated with systemic metabolic disorders,and its prevalence has been increasing year by year,becoming a major challenge to global public health.The development of MAFLD is associated with various factors,including obesity,dyslipidemia,diabetes and other factors.Excessive body fat,particularly increased visceral adiposity,contributes to hepatic fat accumulation.Abnormal blood lipid levels can also disrupt liver fat metabolism.The risk of MAFLD in patients with diabetes is greatly increased due to insulin resistance and other problems.Dietary interventions are considered an effective strategy for the prevention and treatment of MAFLD.In recent years,several dietary patterns,such as low-carbohydrate diets,intermittent fasting,and the Mediterranean diet,have been applied in clinical practice.Their primary mechanisms include reducing oxidative stress,regulating gut microbiota,and inducing fat autophagy.However,the responses to different dietary patterns vary among individuals due to differences in genes,lifestyle,and disease severity.Therefore,systematically evaluating the effects and mechanisms of these dietary patterns in the prevention and treatment of MAFLD has significant clinical importance.This review compares the effects of different dietary patterns on improving liver function,hepatic fat content,blood glucose,and lipid levels,and analyzes their underlying mechanisms of intervention,to explore how to select personalized dietary strategies based on individual differences.It is intended to provide new insights for the precise prevention and treatment of MAFLD,thereby improving patients' outcomes and alleviating the burden on public health.

Objective To investigate the key targets and pathways of Juhongtai formula granules in improving acute lung injury(ALI).Methods Juhongtai formula granules and their drug-containing serum components were analyzed by UPLC-QTOF-MS/MS,and the active ingredients were screened based on the"Lipinski Rule of Five".The action targets of the above active ingredients were obtained through the TCMSP,Swiss Target Prediction and SuperPred databases,and the ALI-related targets were obtained from the GeneCards,OMIM,PharmGKB,CTD databases and GEO chip.The target protein-protein interaction network was constructed using the String database and Cytoscape to analyze the key targets.The DAVID database was used for GO functional annotation and KEGG pathway enrichment analysis,and the CB-dock2 platform was used for molecular docking verification.After one week of adaptive feeding,the experimental SD rats were randomly divided into the blank group,the model group,the positive control group,the negative control group and the Juhongtai formula granules group,with 6 rats in each group.The rat model of ALI was replicated by tracheal infusion of lipopolysaccharide.The pathological morphology of lung tissues in each group of rats was observed by HE staining,and the mRNA expressions of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1 β(IL-1β)and nitric oxide were detected by reverse transcription quantitative polymerase chain reaction(RT-qPCR).Results In total,44 components of the Juhongtai formula granules were identified,including 26 drug-containing serum components,and 21 key compounds were screened.A total of 22 intersection targets were obtained.The pathway enrichment results indicated the action of these targets on the advanced glycation end product receptor(AGE-RAGE)and TNF signaling pathways.The docking results showed that limonin,kaempferol and naringenin could be matched with prostaglandin peroxidase 2,nitric oxide synthase 2 and TNF.Animal experiments confirmed that the Juhongtai formula granules can alleviate inflammatory infiltration in lung tissue and reduce the expressions of TNF-α,IL6,IL-1β mRNA and nitric oxide.Conclusion Juhongtai formula granules can inhibit ALI-related inflammatory targets through the synergistic effects of multiple components such as limonin and kaempferol,regulate signaling pathways such as AGE-RAGE and TNF,reduce the production of inflammatory factors and nitric oxide,and improve ALI.