Objective::This study aimed to elucidate the effect of the lipopolysaccharides/toll-like receptor 4 (LPS/TLR4) pathway on early atherosclerosis (AS) development and its associated changes in fecal metabolites, thereby providing an experimental foundation for strategies to prevent and treat early AS.Methods::Twelve Tibetan miniature pigs aged 4-5 months were divided into normal control (NC) group and AS group (6 pigs in each). The group assignment was primarily based on body weight; Secondary criteria, including glucose, lipid profiles, and inflammatory indices, were considered to ensure balanced baseline characteristics between the 2 groups (all P > 0.05). AS group received a high-fat diet for 16 weeks to establish an AS model, while the NC group received a normal diet. Subsequently, serum levels of lipids and various inflammation and oxidative stress markers were measured. Pathological changes in the aorta and colon tissue, LPS/TLR4 pathway-associated protein expressions in the aorta, as well as occludin and zonula occludens-1 in the colon were also assessed. Proton nuclear magnetic resonance spectra technology was employed for the metabolomic analysis of fecal extracts. Results::The lipid metabolism was disrupted in AS group, with significantly higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels ((12.24 ± 5.24) mmol/L vs. (1.86 ± 0.27) mmol/L, P = 0.004,6; (2.39 ± 0.50) mmol/L vs. (0.83 ± 0.07) mmol/L, P = 0.000,5; (6.94 ± 2.87) mmol/L vs. (0.77 ± 0.18) mmol/L, P = 0.003,3), as compared to that in NC group. Serum factors, including LPS, tumor necrosis factor-α, and malondialdehyde levels of AS group were significantly higher than that of NC group ((1,230.00 ± 192.70) EU/L vs. (695.70 ± 213.70) EU/L), P = 0.001,1; (424.20 ± 176.90) ng/L vs. (51.20 ± 26.61) ng/L, P = 0.023,5; (3.60 ± 0.77) nmol/mL vs. (2.62 ± 0.21) nmol/mL, P = 0.025,4). Pathological evaluations revealed prominent lipid deposition area in the aortic arch, thoracic aorta, and abdominal aorta of the AS group compared with that of the NC group (4.17% ± 2.30% vs. 0, P = 0.006,7; 6.23% ± 2.95% vs. 0, P = 0.003,6; 3.78% ± 2.18% vs. 0, P = 0.008,1). TLR4, nuclear factor kappa-B p65, and tumor necrosis factor-α expression in the aorta tissue of the AS group were upregulated, whereas occludin and zonula occludens-1 expression in colon tissues was downregulated. Additionally, metabolomics identified significant differences in 21 metabolites in the feces of the AS group compared to the NC group, with further analysis linking these differences to amino acid metabolism. Conclusions::The Tibetan miniature pig model of early AS induced by high-fat intake displayed pronounced chronic inflammation. Preliminary findings suggest that the underlying mechanisms may be associated with the LPS/TLR4 pathway and intestinal metabolic disorders.

Objective::This study aimed to elucidate the effect of the lipopolysaccharides/toll-like receptor 4 (LPS/TLR4) pathway on early atherosclerosis (AS) development and its associated changes in fecal metabolites, thereby providing an experimental foundation for strategies to prevent and treat early AS.Methods::Twelve Tibetan miniature pigs aged 4-5 months were divided into normal control (NC) group and AS group (6 pigs in each). The group assignment was primarily based on body weight; Secondary criteria, including glucose, lipid profiles, and inflammatory indices, were considered to ensure balanced baseline characteristics between the 2 groups (all P > 0.05). AS group received a high-fat diet for 16 weeks to establish an AS model, while the NC group received a normal diet. Subsequently, serum levels of lipids and various inflammation and oxidative stress markers were measured. Pathological changes in the aorta and colon tissue, LPS/TLR4 pathway-associated protein expressions in the aorta, as well as occludin and zonula occludens-1 in the colon were also assessed. Proton nuclear magnetic resonance spectra technology was employed for the metabolomic analysis of fecal extracts. Results::The lipid metabolism was disrupted in AS group, with significantly higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels ((12.24 ± 5.24) mmol/L vs. (1.86 ± 0.27) mmol/L, P = 0.004,6; (2.39 ± 0.50) mmol/L vs. (0.83 ± 0.07) mmol/L, P = 0.000,5; (6.94 ± 2.87) mmol/L vs. (0.77 ± 0.18) mmol/L, P = 0.003,3), as compared to that in NC group. Serum factors, including LPS, tumor necrosis factor-α, and malondialdehyde levels of AS group were significantly higher than that of NC group ((1,230.00 ± 192.70) EU/L vs. (695.70 ± 213.70) EU/L), P = 0.001,1; (424.20 ± 176.90) ng/L vs. (51.20 ± 26.61) ng/L, P = 0.023,5; (3.60 ± 0.77) nmol/mL vs. (2.62 ± 0.21) nmol/mL, P = 0.025,4). Pathological evaluations revealed prominent lipid deposition area in the aortic arch, thoracic aorta, and abdominal aorta of the AS group compared with that of the NC group (4.17% ± 2.30% vs. 0, P = 0.006,7; 6.23% ± 2.95% vs. 0, P = 0.003,6; 3.78% ± 2.18% vs. 0, P = 0.008,1). TLR4, nuclear factor kappa-B p65, and tumor necrosis factor-α expression in the aorta tissue of the AS group were upregulated, whereas occludin and zonula occludens-1 expression in colon tissues was downregulated. Additionally, metabolomics identified significant differences in 21 metabolites in the feces of the AS group compared to the NC group, with further analysis linking these differences to amino acid metabolism. Conclusions::The Tibetan miniature pig model of early AS induced by high-fat intake displayed pronounced chronic inflammation. Preliminary findings suggest that the underlying mechanisms may be associated with the LPS/TLR4 pathway and intestinal metabolic disorders.

Objective : To explore the feasibility of machine learning methods in the discrimination of tuberculosis patients. Methods : The data of 15 observation indicators of 860 patients were obtained from a tertiary hospital. Through in-depth mining and analysis of the data, support vector machine, random forest and neural network model methods were used to discriminate the diseases of patients. Results : The accuracies of the TB suspected patient discrimination models based on support vector machine, random forest and neural network were 90%, 91% and 88%, respectively. Conclusion All three machine learning methods can be used for discriminative analysis of suspected tuberculosis patients. In comparison, random forest performs better in discriminating patients with tuberculosis from those with pneumonia.

Objective: To investigate the characteristics of temporal and spatial distribution of tuberculosis epidemics in Shache County, Kashgar Region, Xinjiang. Methods: Information on the incidence of tuberculosis in Sacha County from 2019—2021 was collected and spatiotemporally analyzed by applying the circular distribution method, local spatial autocorrelation analysis, hot and cold spot analysis, directional distribution and spatial center of gravity methods. Results : The total number of tuberculosis cases in Shache County in 2019—2021 was 8 345, of which 52.03%were male and 47.97% were female, and the patients were predominantly 60-75 years old. The number of reported incidences of TB in Tagarqi Township, Shache Township, and Chajek Township ranked among the top three in the county. Spring and summer were the disease-prone seasons for TB, and mid-March to mid-July was the period of high disease incidence. Misha Township and Ishkuli Township are the “high and high” gathering areas, while the “low and low” gathering areas are mainly concentrated in Khoshrav Township and Karasu Township. The hotspots of TB incidence in Shache county were Tagarqi township, Misha township, and Ishkuli township. During the study period, the center of gravity of TB incidence in Shache county of Kashgar area gradually shifted from the southwest to the northeast. Conclusion In Shache county, there is a certain degree of aggregation of tuberculosis outbreaks, with more men than women reporting illnesses, a larger proportion of older people, and a strong seasonal incidence of the disease, with Mixia township and Ishikuli township being the key areas of incidence. Relevant departments should continue to strengthen the disease surveillance of key populations and regions during the high incidence of tuberculosis, and take appropriate intervention measures to reduce the risk of tuberculosis transmission.

Background:Ischemic colitis is a gastrointestinal emergency caused by intestinal wall ischemia,and in severe cases,it can even be life-threatening.Currently,there is a lack of reliable detection methods for ischemic colitis.Clinically,there is an urgent need for a specific detection method to improve the early diagnosis rate of ischemic colitis.Aims:To explore the values of serum vascular endothelial growth factor(VEGF)and plasma D-dimer levels for early diagnosis of ischemic colitis.Methods:A total of 40 patients with ischemic colitis admitted from June 2021 to June 2023 at the Affiliated Jinhua Hospital,Zhejiang University School of Medicine were served as the experimental group.Meanwhile,51 patients with acute enteritis were served as controls.The clinical manifestations,as well as the laboratory,radiological,and endoscopic results were compared between the two groups.A binary Logistic regression model was employed to analyze the risk factors for the onset of ischemic colitis.ROC curve was used to assess the diagnostic performance of serum VEGF and plasma D-dimer levels for the early diagnosis of ischemic colitis.Results:Compared with the control group,the proportion of patients with abdominal pain accompanied by hematochezia,and the serum VEGF and plasma D-dimer levels in the experimental group were significantly increased(all P<0.05).The results of binary Logistic regression model indicated that serum VEGF and plasma D-dimer levels were the risk factors for onset of ischemic colitis(all P<0.05).ROC curve analysis showed that the area under the curve(AUC)of serum VEGF and plasma D-dimer for diagnosing ischemic colitis were 0.93 and 0.88,respectively.The combination of these two indicators could further increase the diagnostic specificity and the AUC.Conclusions:Serum VEGF and plasma D-dimer levels can be served as early diagnostic markers for ischemic colitis.The combination of these two indicators can greatly improve the early diagnostic performance.

Uric acid (UA), the final product of human purine metabolism, can cause hyperuricemia (HUA) when excessively accumulated. HUA is closely linked to chronic kidney diseases (CKD) and is considered an independent risk factor. Hyperuricemic nephropathy, a form of CKD induced by HUA, has seen significant advances in understanding through research into the pathogenic roles of uric acid and the development of HUA animal models. Although progress has been made in understanding the pathophysiological mechanisms by which UA induces CKD, much remains to be learned about its pathological molecular mechanisms. New approaches in animal modeling or the selection of model animals may potentially lead to significant breakthroughs in research on hyperuricemia as well as related CKD. This paper reviews the research progress on the molecular mechanisms of hyperuricemic nephropathy, focusing on oxidative stress, inflammation, autophagy, fibrosis, and gut microbiota. Oxidative stress is induced by uric acid intracellularly through xanthine oxidase, NADPH oxidases, and mitochondria, leading to cellular damage. In terms of inflammation, uric acid crystals can activate the NLRP3 inflammasome, triggering an inflammatory cascade. The role of free uric acid as a pro-inflammatory agent, however, remains controversial. Depending on the study conducted, autophagy has been found to either alleviate or exacerbate inflammation induced by uric acid. Fibrosis, particularly through epithelial-mesenchymal transition (EMT), is a major mechanism by which uric acid causes glomerulosclerosis and tubulointerstitial fibrosis. Extensive research has explored various signaling pathways involved in uric acid-induced EMT. Beneficial gut microbiota protect the kidneys by synthesizing short-chain fatty acids, reducing urea’s enterohepatic circulation, and decreasing uric acid production. This paper aims to enhance understanding of the complex relationships between HUA and CKD, serving as a reference for further research and new drug development.

OBJECTIVE To investigate the effect of Guanxinning tablets(GXN) on early heart failure model rats, and to explore the protective mechanism of GXN on heart failure rats from the perspective of intestinal flora. METHODS Six rats who underwent sham operation were set as sham operation group. Took 80 SD rats to undergo aortic arch stenosis and established a heart failure rat model. The surviving rats were divided into 4 groups, namely the model control group, the positive control group(captopril tablets 12.5 mg·kg–1), high-dose and low-dose of GXN group(600, 1 200 mg·kg–1). The 4 groups were administered continuously for 8 weeks. Cardiac ultrasonography was performed every 4 week. Serum NT-proBNP, hs-CRP, IL-6, TNF-α, SOD and MDA levels were measured. The effects of GXN on the structure and function of intestinal flora were observed based on the high-throughput sequencing technology and bioinformatics analysis of 16S gut microbiome. RESULTS Compared to the model control group, after giving different doses of GXN, the survival rate of rats increased, and the thickness of the ventricular wall decreased to varying degrees. The weight of the heart and coefficient of the heart were all reduced. GXN could also reduce the level of inflammatory factors, inhibit the level increase of NT-proBNP in rats, and increase the activity of serum SOD. In addition, GXN intervention could significantly improve the intestinal flora diversity of rats with heart failure, the possible target genera of GXN were Akkermansia genera, Phascolarctobacterium genera and Oxalobacter genera. The effect of GXN on intestinal function in rats with heart failure might be concentrated in non-homologous end-joining, influenza A, carotenoid synthesis, indole alkaloids biosynthesis, betalain biosynthesis, renin-angiotensin system and other biological pathways. CONCLUSION The protective effect of GXN on early heart failure rats may be related to the regulation of intestinal flora pathway.

Objective To observe the effects of a 1 470 nm semiconductor laser on vaporization cutting,coagulation,and thermal injury of ex vivo animal tissues,aiming to explore the feasibility of its application in the treatment of benign prostatic hyperplasia.Methods The experimental group and control group were treated with HANS-D1 and ML-DD01FI 1 470 nm semiconductor laser therapy equipment,respectively.Fresh ex vivo pig bladder tissue was exposed to lasers with the optical fiber placed at distances of 0.5 cm and 1 cm from the tissue for 5 s.The effects of layers at powers of 60,90,120,150,and 160 W on tissue injury were observed.Ex vivo dog prostate and pig kidney tissues were used for vaporization ablation and cutting to observe the effects of lasers at the same power levels on tissue vaporization and cutting thermal injury.Additionally,in coagulation mode,the effects of 30,40,and 50 W semiconductor lasers on tissue coagulation were observed after irradiating ex vivo pig kidney tissue for 5,10,and 15 seconds.Results When the optical fiber was placed 1 cm away from the tissue,the 1 470 nm semiconductor lasers did not cause accidental damage to adjacent normal bladder tissue.However,at a distance of 0.5 cm,the 120 W,150 W,or 160 W lasers caused slight damage to the bladder tissue.In addition,with the increase in output power,the vaporization ablation efficiency of 60-160 W lasers on dog prostate tissue gradually increased,showing a good linear correlation between vaporization volume and total energy consumption(P＜0.001).Histopathological HE staining results indicated that the coagulation layer thickness in the experimental group was 292.20-309.98 μm,and the vaporization layer depth was 1.49-4.52 mm.In the control group,the coagulation layer thickness was 289.91-303.53 μm,and the vaporization layer depth was 1.88-4.43 mm.There was no significant difference between the two groups(P＞0.05).Moreover,when performing vaporization cutting on ex vivo pig kidney tissue with a cross-sectional area of 1 cm2,the efficiency of vaporization cutting by the 60-160 W 1 470 nm semiconductor lasers increased with the increase in output power(P＜0.05).The coagulated layer thickness in the experimental group was 496.04-514.47 μm,while that in the control group was 489.39-518.53 μm.Additionally,in coagulation mode,when ex vivo pig kidney tissue was irradiated for 5,10,and 15 s with 30,40,and 50 W semiconductor lasers,the coagulation diameter,groove depth,and coagulation efficiency gradually increased with the increase in laser output power(P＜0.05).The coagulation layer thickness in the experimental group and control group was 399.10-449.98 μm and 392.97-447.65 μm,respectively,and the vaporization layer depth was 3.05-7.09 mm and 2.70-7.14 mm,respectively.There was no significant difference between the two groups(P＞0.05).Conclusion The 1 470 nm semiconductor laser shows good vaporization ablation,cutting,and coagulation effect on ex vivo tissues,with a good linear correlation between the effect and the output energy.

Objective To observe the effects of different ligation sites and fasting method on a C57BL/6J mouse model of partial bile duct ligation(pBDL)-induced cholestasis,to establish a pBDL modeling method with a high modeling rate,typical symptoms,and good stability.Methods C57BL/6J mice were subjected to selective ligation of the left hepatic bile duct(L-pBDL)and left-to-median bile duct junction ligation(ML-pBDL)for modeling,and the effects of different pBDL ligation method on serum alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase(ALP),total bilirubin,total bile acid,and liver histopathology were observed.The effects of different fasting method on symptoms and liver injury in the ML-pBDL model were also observed after fasting for 12 and 16 h before surgery,and for 4 h after surgery.Results(1)The incidence of jaundice in the ML-pBDL group was 52.94%and the survival rate within 3 weeks after surgery was 64.71%,while the incidence of jaundice in the L-pBDL group was 11.76%and the survival rate within 3 weeks after surgery was 82.35%.Compared with those in the sham surgery group,serum liver function indicators were significantly increased in the L-pBDL and ML-pBDL groups(P＜0.01),and ALP activity was significantly higher in the ML-pBDL group than in the L-pBDL group(P＜0.05).Compared with mice in the L-pBDL group,mice in the ML-pBDL group had more severe liver fibrosis at 3 weeks post-surgery(P＜0.01).(2)In addition,the incidence of jaundice in the 16 h fasting group was 93.33%and the survival rate within 3 weeks after surgery was 73.77%,while the incidence of jaundice in the 12 h fasting group was 42.86%and the survival rate within 3 weeks after surgery was 71.42%.Compared with those in the normal group,ALP activity,alanine aminotransferase/aspartate aminotransferase ratio,total bile acid level,and proportion of collagen fiber area were all significantly increased in the 16 h and 12 h fasting groups(P＜0.05).Although the observed indicators were higher in the 16 h fasting group compared with those in the 12 h fasting group,the difference was not significant(P＞0.05).Mice in the 12 h and 16 h fasting groups both showed significant bile duct hyperplasia and liver fibrosis(P＜0.01),with more severe liver fibrosis in the 16 h fasting group(P＜0.01).Conclusions Both L-pBDL and ML-pBDL ligation method can be used to establish a mouse model of cholestasis;however,symptoms in the L-pBDL model only exhibit transient damage characteristics,while the liver lesions in the ML-pBDL model are typical and stable.Prolonging the preoperative fasting time can improve the modeling rate and stability of the ML-pBDL model and produce more-typical pathological symptoms.

Objective To investigate the mechanism of cartilage injury and inflammation in the WHBE rabbit KOA model and the effect of platelet-rich fibrin releasates(PRFr)treatment on the KOA process,we established a WHBE rabbit KOA model by excision of medial collateral and partial patellar ligaments and administered a PRFr solution.Methods Twenty-four WHBE rabbits were randomly divided into three groups:normal control(NC)group(n=6),model(KOA)group(n=12),and cure(PRFr)group(n=6).KOA and PRFr groups were injected with 0.5 mL saline and PRFr into both joint cavities on 7 and 14 postoperative days,respectively.At 4 and 8 weeks of modeling,the knee joint grade scoring,X-ray imaging,and gross scoring were performed.Serum levels of IL-1β,TNF-α,and MMP-13 were measured by ELISA.At 4 weeks,6 animals in the KOA group were euthanized,and at 8 weeks,the remaining animals in each group were euthanized.Pathological sections were prepared after decalcification,and then HE,toluidine blue,and safranin O-fast green staining and immunohistochemical analysis of TGF-β,BMP3,and NF-κB were conducted.Results The Lequesne MG behavioral score,Mankin's score,and Pelletier score of WHBE rabbits after the operation were significantly increased compared with the NC group(P＜0.01).Pathological observations revealed surface defects of the cartilage and partial loss of chondrocytes.These result indicated that the KOA model was established successfully.In KOA rabbits,knee joint swelling,joint pain stimulation,and movement limitation were obvious.X-rays showed a high-density soft tissue shadow,indicating more joint effusion and a rough articular surface in general.After PRFr treatment,the serum levels of proinflammatory factors IL-1β,TNF-α,and MMP-13 in KOA model rabbits were significantly reversed(P＜0.05,P＜0.01).Additionally,the cartilage surface became smooth,and most chondrocytes were neatly distributed.Expression levels of TGF-β,BMP3,and NF-κB induced by KOA were also significantly decreased(P＜0.01).Conclusions We successfully established a KOA model in WHBE rabbits,and PRFr improved the cartilage injury and inflammation of the WHBE rabbit KOA model through TGF-β/BMP and NF-κB pathways.