ObjectiveTo investigate the effect of quercetin on acute gouty arthritis （GA） in rats by inhibiting the reactive oxygen species （ROS）/NOD-like receptor protein 3 （NLRP3）/interleukin-1β （IL-1β） signaling pathway. MethodsSixty SPF-grade male SD rats were randomized into normal， model， colchicine （0.3 mg·kg^-1）， and low-， medium-， and high-dose （25， 50， 100 mg·kg^-1， respectively） quercetin groups （n=10）. The rats in the dosing groups were administrated with the corresponding drugs （10 mL·kg^-1） by gavage once a day for one week. An equal volume of normal saline was given by gavage to rats in normal and model groups. One hour after drug administration on day 5， an acute GA model was established in other groups except the control group via intra-articular injection of monosodium urate （MSU） suspension into the right posterior ankle joint cavity. The joint swelling and gait were scored at the time points of 6， 12， 24， 48 h after modeling. Histopathological alterations in the ankle joint tissue from each group were assessed by hematoxylin-eosin （HE） staining. Malondialdehyde （MDA）， xanthine oxidase （XOD）， and total superoxide dismutase （T-SOD） assay kits were used to assess the levels of MDA， XOD， and T-SOD in the serum. The levels of tumor interleukin-6 （IL-6）， necrosis factor-α （TNF-α）， and IL-1β in the rat serum， as well as ROS in the ankle joint tissue， were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was performed to determine the protein levels of NLRP3， thioredoxin-interacting protein （TXNIP）， apoptosis-associated speck-like protein containing a CARD domain （ASC）， precursor cysteinyl aspartate-specific proteinase-1 （pro-Caspase-1）， cleaved Caspase-1 （Caspase-1 p20）， and IL-1β in the ankle joint tissue. Real-time PCR was employed to assess the mRNA levels of TXNIP， NLRP3， ASC， IL-1β， and TNF-α in the ankle joint tissue. ResultsCompared with the normal group， the model group exhibited decreased spontaneous activity， mental fatigue， increased ankle joint swelling and gait scores （P<0.01）， aggravated synovial tissue edema and inflammatory cell infiltration （P<0.01）， elevated levels of XOD， MDA， TNF-α， IL-1β， and IL-6 in the serum and ROS in the joint tissue （P<0.01）， a declined level of T-SOD （P<0.01）， up-regulated protein levels of NLRP3， TXNIP， ASC， pro-Caspase-1， Caspase-1 p20， and IL-1β in the ankle joint tissue （P<0.01）， and up-regulated mRNA levels of NLRP3， TXNIP， ASC， IL-1β， and TNF-α in the ankle joint tissue （P<0.01）. Compared with the model group， the medium- and high-dose quercetin groups showed improved general conditions， decreased gait scores （P<0.05， P<0.01）， reduced joint swelling （P<0.01）， alleviated synovial tissue edema and inflammatory cell infiltration （P<0.05， P<0.01）， lowered levels of XOD， MDA， TNF-α， IL-1β， and IL-6 in the serum and ROS in the joint tissue （P<0.01）， increased levels of T-SOD （P<0.01）， down-regulated protein levels of TXNIP， NLRP3， ASC， pro-Caspase-1， Caspase-1 p20， and IL-1β in the ankle joint tissue （P<0.05， P<0.01）， and down-regulated mRNA levels of TXNIP， NLRP3， ASC， IL-1β， and TNF-α in the ankle joint tissue （P<0.01）. Low-dose quercetin also ameliorated some of the above parameters （P<0.05， P<0.01）. ConclusionQuercetin exerts anti-GA effects by blocking the ROS/NLRP3/IL-1β signaling pathway， downregulating NLRP3 inflammasome activation， and inhibiting the production of pro-inflammatory cytokines including TNF-α， IL-1β， and IL-6.

ObjectiveTo establish a risk recognition model for coronary artery stenosis by using a machine learning method and to identify the key causative factors. MethodsPatients aged ≥18 years，diagnosed with coronary heart disease through coronary angiography from January 2013 to May 2020 in two prominent hospitals in Shanxi Province， were continuously enrolled. Logistic regression，back propagation neural network （BPNN）， and random forest（RF）algorithms were used to construct models for detecting the causative factors of coronary artery stenosis. Sensitivity （TPR）， specificity （TNR）， accuracy （ACC）， positive predictive value （PV+）， negative predictive value （PV-）， area under subject operating characteristic curve （AUC）， and calibration curve were used to compare the discrimination and calibration performance of the models. The best model was then employed to predict the main risk variables associated with coronary stenosis. ResultsThe RF model exhibited superior comprehensive performance compared to logistic regression and BPNN models. The TPR values for logistic regression，BPNN，and RF models were 75.76%， 74.30%， and 93.70%， while ACC values were 74.05%， 72.30%， and 79.49%， respectively. The AUC values were：logistic regression 0.739 9； BPNN 0.723 1； RF 0.752 2. Manifestations such as chest pains，abnormal ST segments on ECG，ventricular premature beats with hypertension， atrial fibrillation， regional wall motion abnormalities（RWMA） by color echocardiography， aortic regurgitation（AR）， pulmonary insufficiency （PI）， family history of cardiovascular diseases，and body mass index（BMI）were identified as top ten important variables affecting coronary stenosis according to the RF model. ConclusionsRandom forest model shows the best comprehensive performance in identification and accurate assessment of coronary artery stenosis. The prediction of risk factors affecting coronary artery stenosis can provide a scientific basis for clinical intervention and help to formulate further diagnosis and treatment strategies so as to delay the disease progression.

OBJECTIVE To evaluate the efficacy and safety of high-dose ilaprazole combined with amoxicillin for newly diagnosed elderly patients with Helicobacter pylori （Hp） infection， and analyze independent risk factors for failure of Hp infection eradication treatment. METHODS Totally 200 cases of newly diagnosed elderly patients with Hp infection in Xinxiang Central Hospital from August 1， 2021 to December 1， 2024 were selected and randomly divided into control group and study group， with 100 cases in each group. The control group was treated with classic quadruple therapy regimen （Amoxicillin capsules+ Clarithromycin tablets+Bismuth potassium citrate tablets+Ilaprazole enteric-coated tablets）. The study group was treated with high- dose Ilaprazole enteric-coated tablets+Amoxicillin capsules. All patients were administered medication for 2 weeks. Hp eradication rates in the two groups were compared using intention-to-treat （ITT） and per-protocol （PP） analyses. The incidence of adverse reactions in both groups was also recorded. The multiple-factor Logistic regression analysis was used to identify independent risk factors for failure of Hp infection eradication treatment. RESULTS In ITT and PP analyses， there was no significant difference of Hp eradication rates between the two groups （P＞0.05）. There was no significant difference in incidence of mild to moderate adverse reactions between the two groups （P＞0.05）. BMI ≤18.5 kg/m2， BMI ＞23.9 kg/m2， rural residence， concomitant diabetes and concomitant heart disease were identified as independent risk factors influencing the failure of Hp infection eradication treatment （P＜0.05）. CONCLUSIONS The efficacy and safety of high-dose ilaprazole combined with amoxicillin are comparable to classic quadruple therapy regimen in treating newly diagnosed elderly patients with Hp infection. Independent risk factors influencing the failure of Hp infection eradication treatment include BMI ≤18.5 kg/m2， BMI ＞23.9 kg/m2， rural residence， concomitant diabetes and concomitant heart disease.

BACKGROUND: Previous studies have demonstrated that short-term exposure to ambient particulate matter elevates the risk of ischemic stroke in major urban areas of various countries. However, there is a notable gap in research focusing on remote areas inhabited by ethnic minorities and the cumulative effects of air pollutants. Our study conducted in the area aims to explore the potential association between ischemic stroke and air pollutants and contribute to improving health outcomes among the community. METHODS: This retrospective observational study was conducted at the Xing'an League People's Hospital in Inner Mongolia. The medical records of 4,288 patients admitted for IS between November 1, 2019, and October 31, 2020, were reviewed. Data on demographics (age and sex), air pollutants (PM₁₀, PM_2.5, NO₂, NO, CO, and O₃), and meteorological factors (daily average temperature, daily average wind speed, and daily average atmosphere pressure) were collected and analyzed. The statistical analysis included descriptive statistics, Poisson distribution analysis to evaluate the adverse effects of atmospheric pollutants on daily hospitalizations, and subgroup analysis to determine whether gender and age could modify the impact on hospitalizations. RESULTS: A substantial correlation was revealed in single-day lags model. The peak delayed effects of PM₁₀, PM_2.5, SO₂, and NO₂ were observed at lag8 (PM₁₀ (OR = 1.016, 95%CI 1.002, 1.030), PM_2.5 (OR = 1.027, 95%CI 1.007, 1.048), SO₂ (OR = 1.153, 95%CI 1.040, 279) and NO₂ (OR = 1.054, 95%CI 1.005, 1.105)) while males exhibited a consistent trend from lag0 to lag8 (PM₁₀ (OR = 1.035, 95%CI 1.018, 1.053), PM_2.5 (OR = 1.056, 95%CI 1.030, 1.082), SO₂ (OR = 1.220, 95%CI 1.072, 1.389), NO₂ (OR = 1.126, 95%CI 1.061, 1.120), CO (OR = 10.059, 95%CI 1.697, 59.638) and O₃ (OR = 0.972, 95%CI 0.946, 0.999)). When gender and age were considered, a positive impact was also observed after three days cumulative effect in males. CONCLUSIONS There is a significant cumulative effect of exposure to air pollution on IS hospital admissions, especially the males and patients under the age of 65. Our results also suggested that a notable association between CO and NO₂ in two-pollutant models.
Humans ; Male ; Female ; Air Pollution/analysis* ; China/epidemiology* ; Retrospective Studies ; Middle Aged ; Air Pollutants/analysis* ; Aged ; Particulate Matter/analysis* ; Hospitalization/statistics & numerical data* ; Adult ; Ischemic Stroke/chemically induced* ; Environmental Exposure/adverse effects* ; Aged, 80 and over

Peptide-based drugs possess several advantages, including high specificity, low immunogenicity, minimal accumulation, and fewer drug-drug interactions, making them a novel and efficient therapeutic class for various diseases. In recent years, peptide-based drugs have shown great potential and broad application prospects in the treatment of oral infectious diseases, tissue injury and repair, tumors, and complex oral mucosal disorders, acting either through direct mechanisms or indirect modulation. Oral administration remains the preferred route due to its non-invasive, painless nature and ease of management; however, gastrointestinal pH can inactivate or even degrade peptide drugs. In the treatment of oral diseases, local administration is commonly employed, avoiding gastrointestinal degradation and first-pass metabolism. Nevertheless, limitations in current theoretical research and the high cost of peptide synthesis hinder their clinical application. Future efforts should focus on advancing related studies to promote the practical application of peptide-based drugs in the field of oral medicine.
Humans ; Peptides/administration & dosage* ; Mouth Diseases/drug therapy* ; Administration, Oral

Colorectal inflammatory cancer transformation poses a major risk to patients with colitis. Patients with chronic intestinal inflammation have an approximately 2-3 folds increased risk of developing colorectal cancer (CRC). Unfortunately, there is currently no effective intervention available. Huangqin decoction (HQD), a well-known traditional Chinese medicine (TCM) formula, is frequently clinically prescribed for treating patients with colitis, and its active ingredients have effective antitumour efficacy. Nonetheless, the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear. A strategy integrating metagenomic, lipidomic, and messenger RNA (mRNA) sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome, metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation. Our study revealed that HQD suppressed colorectal inflammatory cancer transformation, which was associated with enhanced intestinal barrier function, decreased the inflammatory response, and regulation of the gut microbiome. Notably, cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis. Moreover, gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism, especially the remodeling of arachidonic acid metabolism, which was associated with the amelioration of pathological transformation. Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase (ALOX12) were affected by HQD treatment, and no obvious protective effect of HQD was observed in Alox 12 ^-/- mice, which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation. In summary, multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.

Human keratinocyte growth factor-1 (hKGF-1), a member of the fibroblast growth factor (FGF) family, plays crucial roles in organ development, cell proliferation, wound healing, and tissue repair, representing one of the most effective and specific growth factors for skin repair. However, obtaining recombinant hKGF-1 remains challenging due to its universally low expression efficiency in vitro. This study employs the Bombyx mori baculovirus expression system to establish a technological platform that utilizes the economically important insect Bombyx mori as a bioreactor for high-efficiency and low-cost expression and production of recombinant human keratinocyte growth factor 1 (hKGF-1) protein, ultimately achieving high-level expression of hKGF-1 in Bombyx mori ovary cell line (BmN). In this study, we optimized the hKGF-1 sequence based on the codon preference of baculovirus. By fusing hKGF-1 with polyhedrin (highly expressed in this system) and adding extra promoters and enhancers, we significantly improved the expreesion level of hKGF-1 in Bombyx mori cells. The results demonstrated that the aforementioned strategies significantly enhanced the expression level of hKGF-1 in Bombyx mori cells. SDS-PAGE and Western blotting results revealed that the highest hKGF-1 expression (accounting for 8.7% of total cellular protein) was achieved when the Polh promoter was combined in tandem with the P6.9 promoter and hKGF-1 was fused with a 15-residue polyhedrin fragment for co-expression. The optimal harvest time was determined to be 120 h post transfection. This study achieved the efficient expression of hKGF-1 in Bombyx mori cells, establishing an ideal technological platform for the industrial utilization of recombinant hKGF-1. The developed methodology not only provides valuable technical references for the production of other growth factors and complex proteins, but also demonstrates significant implications for employing silkworms as bioreactors for recombinant human protein expression.
Bombyx/metabolism* ; Animals ; Baculoviridae/metabolism* ; Humans ; Fibroblast Growth Factor 7/biosynthesis* ; Recombinant Proteins/genetics* ; Cell Line ; Genetic Vectors/genetics*

Objective To investigate the effect of Yantiao Fang on apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis by regulating the Rho/ROCK signaling pathway.Methods Seventy BALB/c mice were randomly divided into normal,sham,and model groups.Except for normal and sham groups,mice were subjected to cecal ligation and perforation to establish a mouse model of acute gastrointestinal injury caused by sepsis.The mouse models were randomly divided into model,Low,Medium,and High dose of Yantiao Fang,and ROCK inhibitor groups.Histopathological changes of the ileum were observed by HE staining.Serum levels of IL-1β,IL-6,TNF-α,and IL-10 were measured by ELISA.PCNA and Ki-67 expression was detected by immunohistochemistry.Cleaved caspase3 and Bax expression was detected by Western blot.ROCK and MLC mRNA expression in the ileum was measured by RT-qPCR.Results Compared with normal and sham groups,Chiu's pathological score,proinflammatory factor(IL-1β,IL-6,and TNF-α)levels,cleaved caspase3 and Bax protein expression,and ROCK and MLC mRNA levels were increased in the model group(P＜0.05).Moreover,anti-inflammatory mediator IL-10 and expression of PCNA and Ki-67 in the ileum were decreased in the model group(P＜0.05).Compared with the model group,histopathological changes of the ileum in all Yantiao Fang groups were improved by various degrees with the increase in dose.Chiu's pathological score,IL-1β,IL-6,and TNF-α serum levels,cleaved caspase3 and Bax protein expression,and ROCK and MLC mRNA levels were decreased in Yantian Fang groups(P＜0.05).The IL-10 level and expression of PCNA and Ki-67 in the ileum were increased in Yantian Fang groups(P＜0.05).Conclusions Yantiao Fang may inhibit apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury due to sepsis by regulating the Rho/ROCK signaling pathway,thereby alleviating intestinal tissue inflammation and ultimately preventing intestinal mucosal tissue injury.

Objective:To investigate the risk factors and their warning effectiveness for meniscus tear secondary to delayed anterior cruciate ligament (ACL) reconstruction.Methods:A retrospective cohort study was conducted to analyze the clinical data of 114 patients (114 knees) with ACL injury, who were admitted to Affiliated Hospital of Nanjing University of Chinese Medicine from December 2018 to December 2023, including 78 males and 36 females, aged 11-50 years [29(21, 35)years]. The patients were divided into tear group ( n=46) and non-tear group ( n=68) according to whether combined with meniscus tear or not during the surgery. Gender, age, duration of disease, smoking history, Body Mass Index (BMI), cause of injury, mechanism of injury, side of the injury, Beighton score, difference of KT-2000 examination, Tegner activity scale of the knee joint, anterior tibial translation sign, medial posterior tibial slope angle, lateral posterior tibial slope angle, and pivot shift grading of the patients in the two groups were recorded. Correlations between the above-mentioned indicators and occurrence of meniscus tear secondary to delayed ACL reconstruction were assessed. In the meantime, the independent risk factors were determined by univariate and multivariate binary logistic regression analysis. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to evaluate the warning effectiveness of each risk factor for meniscal tear secondary to delayed ACL reconstruction. Results:Univariate analysis showed correlation of duration of disease, BMI, Tegner activity scale of the knee joint, medial posterior tibial slope angle, lateral posterior tibial slope angle and high-grade pivot shift with occurrence of meniscus tear secondary to delayed ACL reconstruction ( P<0.01). The results of multivariate binary logistic regression analysis showed that the duration of disease ≥14.5 weeks ( OR=1.20, 95% CI 1.05, 1.38, P<0.01), BMI≥26.9 kg/m 2 ( OR=1.36, 95% CI 1.03, 1.81, P<0.05), Tegner activity scale of the knee joint ≥4 points ( OR=2.29, 95% CI 1.18, 4.46, P<0.05), medial posterior tibial slope angle ≥11.2° ( OR=2.27, 95% CI 1.06, 4.89, P<0.05) and high-grade pivot shift ( OR=0.03, 95% CI 0.01, 0.03, P<0.05) were significantly correlated with occurrence of meniscus tear secondary to delayed ACL reconstruction. Results of ROC curve analysis showed that the medial posterior tibial slope angle (AUC=0.86, 95% CI 0.80, 0.93) and duration of disease (AUC=0.85, 95% CI 0.77, 0.92) had good warning value, BMI (AUC=0.78, 95% CI 0.69, 0.87) and Tegner activity scale of the knee joint (AUC=0.73, 95% CI 0.64, 0.83) had ordinary warning value, and the warning value of high-grade pivot shift (AUC=0.60, 95% CI 0.49, 0.71) was the lowest. The combination of the risk factors revealed superior warning effectiveness for meniscus tear second to delayed ACL reconstruction (AUC=0.97, 95% CI 0.96, 1.00). Conclusions:The duration of disease ≥14.5 weeks, BMI ≥26.9 kg/m 2, Tegner score ≥4 points, medial posterior tibial slope angle ≥11.2°and high-grade pivot shift are independent risk factors for meniscus tear secondary to delayed ACL reconstruction. The medial posterior tibial slope angle and duration of disease have good warning value, BMI and Tegner scores have ordinary warning value and high-grade pivot shift has the lowest warning value. The combination of the above risk factors has better warning effectiveness for meniscus tear secondary to delayed ACL reconstruction.

Objective To explore the mechanism of Suofeng Yuchuan Formula on inhibiting airway remodeling in asthma by regulating epithelial-mesenchymal transformation(EMT).Methods Sixty rats were randomly divided into normal control group,model control group,Dexamethasone group,high-,medium-and low-dose groups of Soufeng Yuchuan Formula,with 10 rats in each group.In addition to the normal control group,the other groups were injected and inhaled with ovalbumin(OVA)to replicate the asthma rat model.The rats in each group were killed after 21 days of administration of the corresponding drug.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of lung tissue.The ultrastructure of epithelial cells in rat lung was observed by transmission electron microscope.The contents of transforming growth factor β1(TGF-β1)and interleukin-17(IL-17)in serum were detected by enzyme-linked immunosorbent assay(ELISA).Real-time fluorescence quantitative polymerase chain reaction(RT-PCR)was used to detect mRNA expressions of TGF-β1,α-smooth muscle actin(α-SMA),E-cadherin and N-cadherin in lung homogenate.Protein expression levels of TGF-β1,α-SMA,E-cadherin and N-cadherin in lung tissue were detected by Western Blot.Results Compared with the normal control group,the serum contents of TGF-β1 and IL-17 in the model control group were significantly increased(P＜0.01).The mRNA and protein expressions of TGF-β1,α-SMA and N-cadherin in lung tissues were significantly up-regulated(P＜0.01),while the mRNA and protein expressions of E-cadherin were significantly down-regulated(P＜0.01).HE staining showed thickening of airway wall and alveolar wall,and a large number of inflammatory cells infiltrated in the visual field,and the inflammation score was significantly increased(P＜0.01).Transmission electron microscopy showed that the epithelial cells of lung tissue had severe edema.Local dissolution and thinning of intracellular matrix,and obvious swelling of organelles were observed.Compared with model control group,the contents of TGF-β1 and IL-17 in serum of dexamethasone group and all doses of Soufeng Yuchuan Formula groups were significantly decreased(P＜0.05,P＜0.01).The mRNA and protein expressions of TGF-β1,α-SMA and N-cadherin were significantly down-regulated(P＜0.05,P＜0.01),while the mRNA and protein expressions of E-cadherin were significantly up-regulated(P＜0.05,P＜0.01).The inflammatory cell infiltration of lung tissue and thickening of bronchial wall and alveolar wall were found to be reduced.The inflammation score of dexamethasone group and high-dose group of Suofeng Yuchuan Formula was reduced(P＜0.05).Ultrastructure showed that the degree of edema of epithelial cells was significantly reduced,the cell membrane was intact,the intracellular matrix was uniform,and most of the organelles were slightly swollen.Conclusion Soufeng Yuchuan Formula can reduce the level of TGF-β1,thereby improve EMT in lung tissue,and achieve the purpose of preventing and treating airway remodeling in asthma.