Background and Aims:Portal hypertensive colopathy(PHC)is a common complication of portal hypertension in patients with liver cirrhosis.It may lead to gastrointestinal bleeding,yet its underlying pathogenesis remains unclear,and systematic research in China is limited.This study aimed to analyze the colonoscopic features in cirrhotic patients and to explore their associations with relevant clinical factors.Methods:A retrospective analysis was conducted on 99 cirrhotic patients who underwent colonoscopy at Xingtai People's Hospital between July 2020 and December 2024.Colonoscopy,gastroscopy,and clinical data were reviewed.Differences between patients with PHC and those without were compared in terms of sex,Child-Pugh classification,platelet count,presence of ascites,and hepatic encephalopathy.Multivariate logistic regression was used to identify independent risk factors for PHC.Additionally,colorectal lesion detection rates were compared with those of a contemporaneous cohort of 444 participants undergoing national colorectal cancer(CRC)screening at the same center.Results:Among the 105 patients with cirrhosis,the detection rates of PHC,adenomatous polyps,and CRC were 32.32%,28.28%,and 3.03%,respectively,while only 37.37%had no abnormal findings.No serious colonoscopy-related complications were observed.The proportion of males in the PHC group was significantly higher than in the non-PHC group(78.13%vs.50.75%,P=0.009).The PHC group also showed significantly higher rates of Child-Pugh class B/C,and lower platelet count(all P<0.05).There was no statistically significant difference in the incidence of ascites and hepatic encephalopathy between the two groups(P>0.05).Multivariate analysis identified that male gender(OR=3.307,95%CI=1.219-8.971)and Child-Pugh class B/C(OR=2.867,95%CI=1.046-7.861)were independent risk factors for PHC.Compared to the CRC screening cohort,cirrhotic patients had a similar adenoma detection rate(28.28%vs.25.00%,P=0.499),and a slightly higher colorectal cancer detection rate that did not reach statistical significance(3.03%vs.0.68%,P=0.135).Conclusion:Colonoscopy revealed a high rate of abnormalities in cirrhotic patients,with PHC and adenomatous polyps being the most common findings.Routine colonoscopy is recommended for cirrhotic patients without contraindications,especially males,and patients with Child-Pugh class B/C,to facilitate early detection of PHC and precancerous lesions,thereby reducing the risk of lower gastrointestinal bleeding and missed diagnoses of malignancy.

Objective To investigate the effect of osthole(Ost)on neuroinflammation in IS rats by regulating the HMGB1-RAGE signaling pathway.Methods After rat IS model was established with middle cerebral artery occlusion by intraluminal suture,40 model rats were grouped into model group,low-and high-dose Ost(Ost-L and Ost-H)groups,and Ost-H+recombinant rHMGB1(Ost-H+rHMGB1)group,with 10 rats in each groups.Another 10 rats served as sham operation group.Zea-Longa scoring was used to evaluate the neurological function.Serum nerve growth factor(NGF)and LDH levels,and hippocampal TNF-α,IL-10,and IL-1β contents were detected by ELISA.Triphenyltetrazolium chloride staining,Nissl staining,and TUNEL staining were applied respectively to observe the volume of cerebral infarction,hippocampal morphology,and apoptosis in hippocampal tissue cells.The activity of superoxide dismutase(SOD)in the hip-pocampus was detected by hydroxylamine assay,and that of catalases(CAT)was by ammonium molybdate.The content of malonic dialdehyde(MDA)was determined by thiobarbituric acid method.Western blotting was used to measure the protein expression of cleaved Caspase-3,HMGB1,RAGE,NF-κB,and p-NF-κB in brain tissue.Results The model group showed obvious damage in the hippocampal tissues,higher neurological function score,increased stroke volume percentage,serum LDH level and hippocampal TNF-α and IL-1βlevels,elevated neuronal apoptot-ic rate and MDA content,and up-regulation of cleaved Caspase-3,HMGB1,RAGE,and p-NF-κB/NF-κB proteins,while decreased serum NGF level,hippocampal IL-10 content and SOD and CAT activities when compared with the sham group(P＜0.05).Low-and high-dose Ost treatment re-sulted in obviously declined damage in the hippocampal tissue,decreased neurological function score,lower stroke volume percentage,reduced serum LDH level and hippocampal tissue TNF-αand IL-1β contents,lower neuronal apoptotic rate and MDA content,and down-regulated cleaved Caspase-3,HMGB1,RAGE,and p-NF-κB/NF-κB protein,while raised serum NGF level,hipp-ocampal IL-10 content and SOD and CAT activities when compared with the model group(265.84±34.76 pg/ml and 394.52±41.68 pg/ml vs 187.56±23.54 pg/ml,P＜0.05;41.84±5.67 pg/ml and 68.57±8.39 pg/ml vs 16.73±3.52 pg/ml,P＜0.05;87.49±12.53 U/mg and 109.86±14.67 U/mg vs 52.73±8.46 U/mg,P＜0.05;45.38±5.72 U/mg and 67.43±8.91 U/mg vs 21.54±3.47 U/mg,P＜0.05).rHMGB1 could alleviate the improvement effect of Ost on nerve damage in IS rats.Conclusion Ost can attenuate neuroinflammation,oxidative stress,and neuronal apoptosis in IS rats,which may be through its inhibiting the HMGB1-RAGE signaling pathway.

Aim To explore the mechanism of action of Guizhi Jia Gegen decoction(GGD)in treating pneu-monia-enteritis induced by H1N1 influenza virus infec-tion in a mouse model,using network pharmacology and molecular docking techniques,followed by in vivo verification.Methods A pneumonia-enteritis mouse model was established,and the intervention effects of GGD on the model mice were evaluated using indica-tors such as body weight,rectal temperature,lung in-dex,colon length,H1N1 M gene expression,relative mRNA expression levels of inflammatory cytokines,and pathological sections of the lung and intestine.The targets of the blood-absorbed components of GGD were identified using the Swiss Target Prediction platform,and the disease targets were retrieved from the Gene-Cards platform.The intersecting targets were analyzed through PPI network analysis using the STRING data-base to identify core targets.GO analysis and KEGG pathway enrichment analysis were performed using the Metascape database.RT-qPCR was employed to vali-date the core targets and pathways.Molecular docking was conducted using AutoDock Tools software to verify the interactions between blood-absorbed components and key targets.Results GGD demonstrated signifi-cant therapeutic effects on the pneumonia-enteritis mouse model.The results of network pharmacology in-dicated that the therapeutic effects of GGD were strong-ly associated with targets such as TNF,ALB,PTGS2,MMP9,EGFR,ESR1,SRC,HSP90AA1,PPARG and MMP2.RT-qPCR results indicated that GGD could intervene in pneumonia-enteritis by regulating the targets TNF,ALB,EGFR and the related targets of the NF-κB pathway.Molecular docking results re-vealed that blood-absorbed components such as puerar-in and liquiritin could stably bind to TNF,ALB and EGFR.Conclusion Components such as puerarin and liquiritin in GGD may exert therapeutic effects on pneumonia-enteritis induced by H1N1 influenza virus infection by acting on targets such as TNF,ALB and EGFR.

In order to establish a simple,sensitive and specific diagnostic method for the simultane-ous detection of Mycoplasma hyorhinis(Mhr)and Mycoplasma hyopneumoniae(Mhp)in swine,specific primers and probes were designed using the Mhr p37 and Mhp p36 gene sequences as the target genes,and the dual LFD-RPA rapid test was established by screening the primers and probes,optimizing primer ratios and evaluating its effectiveness through the sensitivity,reproduc-ibility and clinical sample testing.The sensitivity,specificity,reproducibility and clinical samples were evaluated.The results showed that the established dual LFD-RPA assay could complete the amplification in 15 min at 39 ℃,and its optimal primer ratio was 1.6∶0.8,and the lowest detection limits were up to 3.63 and 3.60 copies/μL,respectively;the reproducibility was stable;and there was no cross-reactivity with Pasteurella multocida,Bordetella bronchiseptica,Haemophilus pa-rasuis,Actinobacillus pleuropneumoniae,Escherichia coli.The test successfully established a dual LFD-RPA assay,which can detect Mhr and Mhp simultaneously,and is simple,sensitive and spe-cific without relying on specialized equipment,and is suitable for carrying out on-site rapid diagno-sis of Mhr and Mhp.

Objective To investigate the role of Toll-like receptor 4(TLR4)in the regulation of homocys-teine(Hcy)-induced ferroptosis in macrophages.Methods Mouse macrophage cells RAW264.7 were cultured and divided into control group,Hcy intervention group(Hcy group),and Hcy plus ferroptosis inhibitor group(Hcy+Fer-1 group).After transfection with interference fragments,macrophages were treated with Hcy,and then divided into control group,Hcy intervention group(Hcy group),TLR4 interference negative control plus Hcy intervention group(si-NC+Hcy group),and TLR4 interference plus Hcy intervention group(si-TLR4+Hcy group).Macrophages were transfected with overexpression lentivirus and treated with Hcy,then were divided into control group,Hcy intervention group(Hcy group),a TLR4 overexpression negative control plus Hcy intervention group(OE-NC+Hcy group),and a TLR4 overexpression plus Hcy intervention group(OE-TLR4+Hcy group).After 48 hours of intervention,real-time fluorescent quantitative PCR and western blot were used to detect the expression levels of TLR4 in macrophages treated with Hcy;western blot was used to detect the expression levels of ferroptosis-related proteins ACSL4,GPX4,and FTH1 in macrophages,and ferrous ion assay kit to detect the concentration of Fe2+in macrophages;reactive oxygen species(ROS)assay kit and laser confocal microscopy were used to detect the content of intracellular reactive oxygen species.Results Compared with those in the control group,the expression level of the pro-ferroptosis protein ACSL4 was increased in the Hcy group(P<0.05),while the expression levels of anti-ferroptosis proteins GPX4 and FTH1 were decreased(P<0.05);the concentration of Fe2+was increased(P<0.05),and the content of ROS was increased.Meanwhile,the protein and mRNA expres-sion levels of TLR4 were both increased in the Hcy group(P<0.05).After macrophages were transfected with TLR4 interference fragments,compared with those in the si-NC+Hcy group,the expression levels of GPX4 and FTH1 were increased(P<0.05);the expression level of ACSL4 was decreased(P<0.05);the concentration of Fe2+was decreased(P<0.05),and the content of ROS was reduced in the si-TLR4+Hcy group.After macro-phages were transfected with TLR4 overexpression lentivirus,compared with those in the OE-NC+Hcy group,the expression levels of GPX4 and FTH1 were decreased(P<0.05),and the expression level of ACSL4 was increased(P<0.05)in the OE-TLR4+Hcy group.Conclusion Hcy induces the occurrence of ferroptosis in macrophages,and Toll-like receptor 4 has a positive feedback regulatory effect on ferroptosis in macrophages.

In order to establish a simple,sensitive and specific diagnostic method for the simultane-ous detection of Mycoplasma hyorhinis(Mhr)and Mycoplasma hyopneumoniae(Mhp)in swine,specific primers and probes were designed using the Mhr p37 and Mhp p36 gene sequences as the target genes,and the dual LFD-RPA rapid test was established by screening the primers and probes,optimizing primer ratios and evaluating its effectiveness through the sensitivity,reproduc-ibility and clinical sample testing.The sensitivity,specificity,reproducibility and clinical samples were evaluated.The results showed that the established dual LFD-RPA assay could complete the amplification in 15 min at 39 ℃,and its optimal primer ratio was 1.6∶0.8,and the lowest detection limits were up to 3.63 and 3.60 copies/μL,respectively;the reproducibility was stable;and there was no cross-reactivity with Pasteurella multocida,Bordetella bronchiseptica,Haemophilus pa-rasuis,Actinobacillus pleuropneumoniae,Escherichia coli.The test successfully established a dual LFD-RPA assay,which can detect Mhr and Mhp simultaneously,and is simple,sensitive and spe-cific without relying on specialized equipment,and is suitable for carrying out on-site rapid diagno-sis of Mhr and Mhp.

Background and Aims:Portal hypertensive colopathy(PHC)is a common complication of portal hypertension in patients with liver cirrhosis.It may lead to gastrointestinal bleeding,yet its underlying pathogenesis remains unclear,and systematic research in China is limited.This study aimed to analyze the colonoscopic features in cirrhotic patients and to explore their associations with relevant clinical factors.Methods:A retrospective analysis was conducted on 99 cirrhotic patients who underwent colonoscopy at Xingtai People's Hospital between July 2020 and December 2024.Colonoscopy,gastroscopy,and clinical data were reviewed.Differences between patients with PHC and those without were compared in terms of sex,Child-Pugh classification,platelet count,presence of ascites,and hepatic encephalopathy.Multivariate logistic regression was used to identify independent risk factors for PHC.Additionally,colorectal lesion detection rates were compared with those of a contemporaneous cohort of 444 participants undergoing national colorectal cancer(CRC)screening at the same center.Results:Among the 105 patients with cirrhosis,the detection rates of PHC,adenomatous polyps,and CRC were 32.32%,28.28%,and 3.03%,respectively,while only 37.37%had no abnormal findings.No serious colonoscopy-related complications were observed.The proportion of males in the PHC group was significantly higher than in the non-PHC group(78.13%vs.50.75%,P=0.009).The PHC group also showed significantly higher rates of Child-Pugh class B/C,and lower platelet count(all P<0.05).There was no statistically significant difference in the incidence of ascites and hepatic encephalopathy between the two groups(P>0.05).Multivariate analysis identified that male gender(OR=3.307,95%CI=1.219-8.971)and Child-Pugh class B/C(OR=2.867,95%CI=1.046-7.861)were independent risk factors for PHC.Compared to the CRC screening cohort,cirrhotic patients had a similar adenoma detection rate(28.28%vs.25.00%,P=0.499),and a slightly higher colorectal cancer detection rate that did not reach statistical significance(3.03%vs.0.68%,P=0.135).Conclusion:Colonoscopy revealed a high rate of abnormalities in cirrhotic patients,with PHC and adenomatous polyps being the most common findings.Routine colonoscopy is recommended for cirrhotic patients without contraindications,especially males,and patients with Child-Pugh class B/C,to facilitate early detection of PHC and precancerous lesions,thereby reducing the risk of lower gastrointestinal bleeding and missed diagnoses of malignancy.

Objective To compare the effects of different doses of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet in the treatment of cough variant asthma(CVA)and the improvement of airway function and inflammatory factors.Methods Elderly patients with cough variant asthma were randomly divided into group A and group B.Both groups of patients received budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet.Group A was given budesonide and formoterol fumarate powder for inhalation(Ⅱ),2 inhalation per time,twice a day;Group B was given budesonide and formoterol fumarate powder for inhalation,4 inhalation per time,twice a day;budesonide fumatrol inhalation powder mist for continuous treatment for 6 months,and montelukast sodium tablet 10 mg once a day for at least 3 months.The nighttime cough scores of the two groups were compared before treatment and after treatment.The percentage of forced expiratory volume in one second(FEV1)in the predicted value,the maximum mid expiratory flow(MMEF),the fractional exhaled nitric oxide(FeNO),interleukin-5(IL-5)and eosinophils were compared between the two groups.The incidence of adverse drug reactions and the recurrence rate within 1 year were compared between the two groups.Results A total of 45 cases were enrolled in both the group A and the group B.At 9 months after treatment,the nocturnal cough scores of the group A and the group B were(0.93±0.42)and(0.65±0.29)points,respectively;the percentage of FEV1 in the predicted value were(97.75±9.67)％and(100.93±11.06)％,respectively;the MMEF values were(2.81±1.04)and(3.08±1.09)L·s-1,respectively;the FeNO values were(18.94±9.75)and(15.94±7.96)ppb,respectively;the IL-5 levels were(10.88±7.06)and(8.11±5.56)pg·mL-1,respectively.The above indicators in group B showed statistically significant differences compared to group A(all P＜0.05).The total incidence of adverse drug reactions in group A and group B were 8.89％(5 cases/45 cases)and 13.33％(6 cases/45 cases),respectively.The recurrence rates was 15.56％(7 cases/45 cases)and 13.33％(6 cases/45 cases),respectively.There was no statistically significant difference in the above indicators between group B and group A(all P＞0.05).Conclusion For elderly patients with CVA,higher dose of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet can better improve cough symptoms,reduce the level of airway hyperresponsiveness and inflammatory factors,reduce the recurrence rate,and the patients are well tolerated.

Objective:To investigate the immuno-inflammatory regulatory effects of the Qing Gan San Jie Xiao Ying Formula(QGSJXYF)on Hashimoto's thyroiditis(HT)by modulating thyroid cell-derived exosomes to provide experi-mental evidence for its immunomodulatory mechanisms.Methods:Nthy-ori-3-1 thyroid cells were treated with QGSJXYF-medicated serum,with untreated cells serving as controls.Exosomes from both groups were extracted and analyzed using nanoparticle tracking analysis(NTA),transmission electron microscopy(TEM),and Western blot to assess concentration,size distribution,morphology,and the expression of characteristic exosomal markers.An inflammatory model of human T lymphocytes(H9)was established and co-incubated with normal exosomes(EXO-C group)or QGSJXYF-treated exosomes(EXO-T group).The levels of inflammatory cytokines in H9 cells were measured using Western blot(WB)and ELISA.Results:Exosome characterization showed that the particle concentration of Nthy-ori-3-1 cell-derived exosomes in both the control and QGSJXYF groups ranged from 1×109 to 1×1011/mL,with particle diameters between 80～300 nm.The exosomes exhibited a typical spherical or cup-shaped morphology with positive expression of TSG101,CD63,and HSP70.Compared with the inflammation model group and the EXO-C group,the EXO-T group significantly reduced the intracellular expression of IL-17A protein in H9 cells(P<0.05)and suppressed IL-17 and IL-6 levels in the cell supernatant(P<0.01).Conclusion:QGSJXYF may exert its anti-inflammatory and thyroid-protective effects by modulating the functional state of thyroid cell-derived exosomes,regulating the inflamma-tory microenvironment,and inhibiting the expression of inflammatory cytokines associated with Hashimoto's thyroiditis.

GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.