OBJECTIVE: To explore the peripheral neural mechanism underlying representation along the distribution of stomach meridian induced by intestinal inflammatory reaction using diarrhea predominant-irritable bowel syndrome (IBS-D) mice. METHODS: Among 62 healthy male C57BL/6 mice of clean grade, 12 mice were randomly selected and divided into a control group and a model group, 6 mice in each group, additionally, 12 mice were randomly selected and divided into a Tianshu group, a Liangqiu group and a Zusanli group, 4 mice in each group. In the model group, citrobacter was administered orally to establish IBS-D model. In the control group and the model group, the visceral pain threshold was observed using fecal colorectal distension (fCRD) induced electromyography of external oblique muscle, the positive cell number of neutrophil in the colonic muscularis was detected by myeloperoxidase (MPO) staining, the number, location and distribution rule of Evans blue (EB) extravasation points were observed by injection of EB staining solution into the tail vein. In the Tianshu group, the Liangqiu group and the Zusanli group, fluorescent dye Dil was injected at bilateral "Tianshu" (ST25), "Liangqiu" (ST34) and "Zusanli" (ST36) respectively, to observe the dye-positive cell number in different dorsal root ganglion (DRG) segments. In the control group and the model group, the activation of satellite glial cells (SGCs) in different DRG segments was observed by immunofluorescence. RESULTS: Compared with the control group, in the model group, the area under curve of electromyography of external oblique muscle was increased at fCRD of 25, 50 and 75 μL distilled water (P<0.001, P<0.01); the MPO-positive cell number of neutrophil in the colonic muscularis was increased (P<0.01). Few EB extravasation points could be found in the control group, while there were much more EB extravasation points observed in the model group, which was specially distribution in the area of stomach meridian, from "Huaroumen" (ST24) to "Zusanli" (ST36), as well as the surface area dominated by L₂-L₅ segment of the spinal cord. The Dil-positive cells were mainly exhibited in the DRG of T₁₁, L₅ and L₄ segments in the Tianshu group, the Liangqiu group and the Zusanli group, respectively. Compared with the control group, the ratio of glial fibrillary acidic protein (GFAP)/glutamine synthetase (GS) co-expression was increased in the DRG of T₁₁, L₄ and L₅ segments in the model group (P<0.05, P<0.01). CONCLUSION The activation of SGCs within DRG of T₁₁, L₄ and L₅ segments may relate closely to the occurrence of the representation along the stomach meridian distribution in IBS-D mice.
Animals ; Male ; Mice ; Irritable Bowel Syndrome/therapy* ; Mice, Inbred C57BL ; Meridians ; Stomach/physiopathology* ; Humans ; Acupuncture Points ; Disease Models, Animal

Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*

OBJECTIVE: By analyzing the differential miRNA in seminal plasma between individuals with normal and abnormal sperm DNA fragmentation index（DFI）, we aim to identify miRNA that may impact sperm DNA integrity and target genes, and attempt to analyze their potential mechanisms of action. METHODS: A total of 161 study subjects were collected and divided into normal control group, DFI-medium group and DFI-abnormal group based on the DFI detection values. Differential miRNA were identified through miRNA chip analysis. Through bioinformatics analysis and target gene prediction, miRNA related to DFI and specific target genes were identified. The relative expression levels of differential miRNA and target genes in each group were compared to explore the impact of their differential expression on DFI. RESULTS: Through miRNA chip analysis, a total of 11 differential miRNA were detected. Bioinformatics analysis suggested that miR-26a-5p may be associated with reduced sperm DNA integrity. And gene prediction indicated that PTEN was a specific target gene of miR-26a-5p. Compared to the normal control group, the relative expression levels of miR-26a-5p in both the DFI-medium group and the DFI-abnormal group showed a decrease, while the relative expression levels of PTEN showed an increase. The relative expression levels of miR-26a-5p in all groups were negatively correlated with DFI values, while the relative expression levels of PTEN showed a positive correlation with DFI values in the DFI-medium group and the DFI-abnormal group. The AUC of miR-26a-5p in the DFI-medium group was 0.740 (P<0.05), with a sensitivity of 73.6% and a specificity of 71.5%; the AUC of PTEN was 0.797 (P<0.05), with a sensitivity of 76.5% and a specificity of 78.4%. In the DFI-abnormal group, the AUC of miR-26a-5p was 0.848 (P<0.05), with a sensitivity of 81.3% and a specificity of 78.1%. While the AUC of PTEN was 0.763 (P<0.05), with a sensitivity of 77.2% and a specificity of 80.2%. CONCLUSION miR-26a-5p affects the integrity of sperm DNA by regulating the expression of PTEN negatively. The relative expression levels of seminal plasma miR-26a-5p and PTEN have good diagnostic value for sperm DNA integrity damage, which can help in the etiological diagnosis and prognosis analysis of abnormal DFI. This provides a diagnostic and treatment approach for the study and diagnosis of DFI abnormalities without clear etiology.
Male ; Humans ; MicroRNAs/genetics* ; PTEN Phosphohydrolase/genetics* ; Spermatozoa ; Semen/metabolism* ; DNA Fragmentation

Osteoarthritis (OA), the most prevalent joint disease of late life, is closely linked to cellular senescence. Previously, we found that the senescence of fibroblast-like synoviocytes (FLS) played an essential role in the degradation of cartilage. In this work, single-cell sequencing data further demonstrated that cartilage acidic protein 1 (CRTAC1) is a critical secreted factor of senescent FLS, which suppresses mitophagy and induces mitochondrial dysfunction by regulating SIRT3 expression. In vivo, deletion of SIRT3 in chondrocytes accelerated cartilage degradation and aggravated the progression of OA. Oppositely, intra-articular injection of adeno-associated virus expressing SIRT3 effectively alleviated OA progression in mice. Mechanistically, we demonstrated that elevated CRTAC1 could bind with NRF2 in chondrocytes, which subsequently suppresses the transcription of SIRT3 in vitro. In addition, SIRT3 reduction could promote the acetylation of FOXO3a and result in mitochondrial dysfunction, which finally contributes to the degradation of chondrocytes. To conclude, this work revealed the critical role and underlying mechanism of senescent FLSs-derived CRTAC1 in OA progression, which provided a potential strategy for the OA therapy.

A method for simultaneous determination of 21 kinds of Aconitum alkaloids(ATS)in biological specimens and infused liquor using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was developed.The biological samples were pretreated with methanol-acetonitrile(1∶2,V/V)for protein precipitation,while infused liquors were diluted 100-fold with acetonitrile,followed by centrifugation,and filtration by a 0.22-μm membrane.Chromatographic separation was carried out on an EC-C18 column using gradient elution with the mixture of 10 mmol/L ammonium acetate and 0.2%formic acid as mobile phase A and acetonitrile as mobile phase B.With this method,all the analytes were separated within 9.5 min.The samples were detected in positive ESI mode with dynamic multiple reaction monitoring(MRM)and quantified via external standard calibration.The results showed that the concentrations of the analytes in the range of 2-1000 ng/mL had excellent linearity(R2>0.9992)with the peak area.The developed method was successfully used for detection of 21 kinds of aconitum alkaloids,with limits of detection of 0.5-2 ng/mL,quantification limits of 2-6 ng/mL,intra/inter-day precision≤6.0%,spiked recoveries of 89.4%-100.9%,extraction recoveries of 74.2%-104.4%,and matrix effects ranging from-11.1%to 9.2%in blood/urine.The method was applied to detection of 12 samples from 4 fatal aconite poisoning cases,and all 21 kinds of ATS with total alkaloid concentrations of 0.04-4.18 μg/mL in blood and 154.96-422.83 μg/mL in medicinal liquors were detected.Tissue distribution revealed that the order of concentrations from highest to lowest is as follows:urine(157.22 μg/mL)>gastric contents(51.37 μg/mL)>kidney(21.6 μg/g)>whole blood(4.18 μg/mL)>liver(0.03 μg/g).This method showed many advantages such as simple pretreatment,low detection limits,accurate quantification,broad analyte coverage,and superior anti-interference capability in complex matrices,proving ideal for forensic and toxicological analysis of aconitum alkaloids.

Objective To explore the influencing factors of different types of small intestinal bacterial overgrowth(SIBO).Methods A total of 539 patients who were hospitalized in the Department of Gastroenterology,the Sixth Medical Center of PLA General Hospital from June 2021 to December 2021 and who underwent methane-hydrogen breath test were retrospectively selected.Based on breath test results,patients were divided into SIBO-negative group(n=300)and SIBO-positive group(n=239).The clinical data were compared between two groups.According to the specific values of breath test results,SIBO-positive patients were further divided into hydrogen-producing bacterial overgrowth(hydrogen-positive,n=103),intestinal methanogen overgrowth(methanogen-positive,n=80),and simultaneous methanogen and hydrogen-producing bacterial overgrowth(double positive,n=56)groups.Multivariate logistic regression analysis was employed to identify influencing factors of different SIBO types.Additionally,SIBO-positive patients were categorized by age into<45 years(n=23),45-60 years(n=82),60-75 years(n=124),and≥75 years(n=10)to compare SIBO positivity rates across age groups.Results The patients in SIBO-positive and double positive groups were older and had a lower body mass index(BMI)than those in SIBO-negative group,with statistically significant differences(P<0.05).Compared with the patients in SIBO-negative group,those in hydrogen-positive group showed a higher proportion of history of coronary heart disease,those in methanogen-positive group were older,and higher proportion of statin use,with statistically significant differences(P<0.05).Multivariate logistic regression analysis revealed that,among different SIBO types,a history of coronary heart disease served as an independent risk factor for hydrogen-producing bacterial overgrowth(OR=2.728,95%CI 1.271-5.857,P=0.010).For methanogen overgrowth,increasing age was identified as an independent risk factor(OR=1.040,95%CI 1.009-1.063,P=0.010),while the application of statin played the role of an independent protective factor(OR=0.420,95%CI 0.236-0.754,P=0.003).As for the simultaneous overgrowth of methane-producing and hydrogen-producing bacteria,increased BMI was found to be an independent protective factor(OR=0.870,95%CI 0.786-0.964,P=0.008).In SIBO-positive group,it was found that for patients aged<45 years,both the methane-positive rate and the double-positive rate were significantly lower than the hydrogen positivity rate(P<0.05).Moreover,among patients aged 45-60 years,the double-positive rate was significantly lower than the hydrogen positivity rate(P<0.01).When it comes to the hydrogen-positive rate,it was significantly lower for patients aged 45-60 and 60-75 years compared with that of patients aged<45 years(P<0.05).In contrast,the methane-positive rate and the double-positive rate were significantly higher for patients aged 45-60 and 60-75 years than those of patients aged<45 years(P<0.01).Conclusion A history of coronary heart disease and increasing age are independent risk factors for intestinal hydrogen-producing bacterial overgrowth and methanogen overgrowth,respectively.The application of statins and increased BMI are independent protective factors for intestinal methanogen simultaneous overgrowth of methanogen and hydrogen-producing bacteria,respectively.

Objective lo investigate the predictive value of serum growth differentiation factor 11(GDF-11)and calprotectin A4(S100A4)for contrast-induced nephropathy(CIN)after coronary angiography(CAG).Methods A total of 528 patients who underwent CAG in the First Affiliated Hospital of Xi'an Jiao-tong University from December 2020 to November 2023 were selected as the research objects.According to whether the patients had CIN,they were divided into non-nephropathy group(472 cases)and nephropathy group(56 cases).Enzyme-linked immunosorbent assay was used to detect serum levels of GDF-11 and S100A4.Multivariate Logistic regression analysis was used to explore the influencing factors of CIN after CAG.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum GDF-11 and S100A4 for CIN after CAG.Results The serum levels of GDF-11 and S100A4 in nephropathy group were higher than those in non-nephropathy group(P＜0.05).The contrast agent dose and postoperative ser-um creatinine level in the nephropathy group were higher than those in the non-nephropathy group(P＜0.05).Multivariate Logistic regression analysis showed that contrast agent dose ≥131.84 mL(OR=2.158,95％CI 1.284-3.627),postoperative serum creatinine ≥ 87.57 μmol/L(OR=2.445,95％CI 1.533-3.898),GDF-1 1 ≥4 50.84 ng/mL(OR=2.445,95％CI 1.533-3.898)were the influencing factors of CIN af-ter CAG(P＜0.05).The area under the curve(95％CI)of serum GDF-11 and S100A4 for predicting CIN af-ter CAG was 0.861(95％CI 0.810-0.912)and 0.798(95％CI 0.747-0.849),respectively.The optimal cut-off values were 450.84 ng/mL and 86.98 μg/mL,the specificity were 65.89％and 57.62％,and the sensi-tivity were 94.74％and 94.74％,respectively.The area under the curve of the combination of the two was 0.906(95％CI 0.856-0.957),the specificity was 87.09％,and the sensitivity was 84.26％.Conclusion The elevated levels of serum GDF-11 and S100A4 are closely related to the occurrence of CIN in patients after CAG surgery,which can be used as biological indicators to evaluate the occurrence of CIN in patients after CAG surgery,and the combined prediction efficiency of GDF-11 and S100A4 is higher.

Objective To investigate the prognosis of childhood T-lymphoblastic lymphoma(T-LBL)treated with acute lymphoblastic leukemia(ALL)regimen and related influencing factors.Methods A retrospective analysis was performed for the prognostic characteristics of 29 children with T-LBL who were treated with ALL regimen(ALL-2009 or CCCG-ALL-2015 regimen)from May 2010 to May 2022.Results The 29 children with T-LBL had a 5-year overall survival(OS)rate of 84％±7％and an event-free survival(EFS)rate of 81％±8％.The children with B systemic symptoms(unexplained fever＞38° C for more than 3 days;night sweats;weight loss＞10％within 6 months)at initial diagnosis had a lower 5-year EFS rate compared to the children without B symptoms(P＜0.05).The children with platelet count＞400x109/L and involvement of both mediastinum and lymph nodes at initial diagnosis had lower 5-year OS rates(P＜0.05).There were no significant differences in 5-year OS and EFS rates between the children treated with CCCG-ALL-2015 regimen and those treated with ALL-2009 regimen(P＞0.05).Compared with the ALL-2009 regimen,the CCCG-ALL-2015 regimen reduced the frequency of high-dose methotrexate chemotherapy and the incidence rate of severe infections(P＜0.05).Conclusions The ALL regimen is safe and effective in children with T-LBL.Children with B systemic symptoms,platelet count＞400x109/L,and involvement of both mediastinum and lymph nodes at initial diagnosis tend to have a poor prognosis.Reduction in the frequency of high-dose methotrexate chemotherapy can reduce the incidence rate of severe infections,but it does not affect prognosis.

ObjectiveTo explore the compliance related factors of repeated screening for colorectal cancer in Jiading District， and to provide a scientific basis for the prevention and control of colorectal cancer. MethodsBased on the natural population cohort in Jiading District， and the screening situation in 2017‒2019 and 2020‒2022， the study subjects were divided into the groups of never participating in screening and participating in screening. Subjects in the participating group were further divided into participating in one round of screening or having repeated screening. SPSS 21.0 software was used to analyze the demographic characteristics of each group. χ² test or Fisher precise probability test were used to conduct univariate analysis of the factors such as gender， age， education level， marital status， retirement status， and type of medical insurance. Factors with the significant difference （P<0.05） were selected for inclusion in multivariate analysis， and factors related to compliance with repeated screening were analyzed by multivariate logistic regression. ResultsA total of 8 179 subjects were included in the study， including 3 323 males （40.6%） and 4 856 females （59.4%）. The average age of the subjects was （61.26±6.06） years old. A total of2 652 （32.4%） had educated in primary school or below， 4 242 （51.9%） in secondary school， and 1 285 （15.7%） in higher secondary school. Mostly， 7 579 （92.7%） were married. Among the participants， 4 062 people had never participated in screening， 4 117 people had participated in screening， and 1 485 of them had repeated screening， with a repeated screening rate of 18.2%. Multivariate logistic regression analysis showed that women had better compliance with repeated screening than men （OR=1.31， 95%CI： 1.14‒1.50）. Compared with the population aged 50 to 54 years， the population aged 55‒59 years （OR=1.57， 95%CI： 1.19‒2.08）， 60-64 years （OR=2.77， 95%CI： 2.13‒3.61）， and 65-69 years （OR=3.31， 95%CI： 2.51‒4.36） had higher compliance with repeated screening. Compared with employees' medical insurance， residents' medical insurance group had worse compliance with repeated screening （OR=0.76， 95%CI： 0.66‒0.87）. People with a history of intestinal polyps were more likely to undergo repeat screening than those without （OR=2.07， 95%CI： 1.50‒2.87）. ConclusionCompliance with repeated screening for colorectal cancer still needs to be improved， and there are differences in compliance with repeated screening for different populations with different characteristics. Identifying groups that are unlikely to adhere to community-based colorectal cancer screening and taking targeted interventions can help improve the continued compliance of residents with colorectal cancer screening.