Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

Objective:To explore whether disrupted colonization of the gut microbiota in early life accelerates the development of obesity later in life through programming adipose thermogenesis.Methods:Neonatal mice were treated with a mixture of antibiotics (ABX), and 16S rRNA sequencing confirmed that ABX treatment disrupted the establishment of gut microbiota. The mice were monitored for changes in body weight and fat content at weaning, adulthood, and under a high-fat diet (HFD) to assess obesity phenotypes. Additionally, glucose tolerance and insulin tolerance tests were conducted, along with measurements of blood glucose and lipid levels, to evaluate changes in glucose and lipid metabolism. The expression of uncoupling protein 1 (UCP1) in adipose tissue was assessed through immunohistochemistry and Western blotting to evaluate alterations in adipocyte thermogenic capacity.Results:The analysis of 16S rRNA sequencing technology revealed that ABX treatment significantly reduced both α- and β-diversity of the gut microbiota. Compared to untreated mice, the microbial composition in ABX treated mice showed significant differences, with a notable reduction in the abundance of beneficial bacteria, including Lachnospiraceae_NK4A136_group and Akkermansia muciniphila ( A. muciniphia). Subsequent monitoring indicated that ABX treatment did not affect body weight or fat content during the lactation period. However, a significant decrease in surface temperature was observed in the ABX group, specifically in the interscapular region. Immunohistochemistry and Western blot of UCP1 demonstrated impaired thermogenic capacity in adipose tissue. Interestingly, the impaired thermogenesis persisted in adult mice, leading to a decreased cold tolerance, although no changes of metabolic dysfunction, including body weight, body fat percentage, serum insulin and triglyceride levels, glucose tolerance, and insulin sensitivity. Upon switching to HFD, ABX-exposed mice exhibited significant increases in body weight, fat mass, and serum glucose, indicating a greater susceptibility to obesity. Further thermographic analysis and UCP1 detection suggested that this susceptibility to obesity was also linked to impaired thermogenic capacity in adipose tissue. Conclusion:Early-life gut microbiota is a critical determinant of long-term adipose thermogenesis. Disruption of the microbiota enhances the effect of diet-induced obesity.

This paper aims to explore the main points of diagnosis， treatment and misdiagnosis of conversion disorder characterized by paroxysmal abdominal pain. The general hospitals had a high misdiagnose rate and no effective symptomatic treatment for conversion disorder patients with physical discomfort as main symptoms， which leading to heavy physical and mental burden of patients and waste of medical resources， so this paper retrospectively analyzed the etiology， diagnostic process， treatment and therapeutic effect of a case of conversion disorder with paroxysmal abdominal pain as the main symptom. Case analysis showed that the physical discomfort as chief complain of conversion disorder patients affected the rate of early correct diagnosis and treatment， so clinicians' ability of diagnosis and differential diagnosis of conversion disorder needs to be strengthened. At the same time， cognitive behavioral therapy （CBT） is effective in the clinical treatment and recurrence prevention of conversion disorder.

Objective To eva1uate the external quality assessment results of prenatal screening for maternal serum inhibin A in the second trimester in 2018 and to improve the accuracy of prenatal screening.Methods National Center for Clinical Laboratories provided three batches of quality control urine sample (Lot:201811-201813) to 94 prenatal screening laboratories nationwide in March 2018.Laboratories participated in the assessment voluntarily and reported the results,methods,equipment,reagents and other related information as required.Clinet EQA and Microsoft Excel 2010 were used for statistical analysis of the laboratory test results and for descriptive evaluation of the accuracy rate.Results A total of 55 laboratories submitted their testing results giving a return rate of 58.5％ (55/94),of which 52 (94.5％) were consistent with the expected results,while none of the results submitted by the other three laboratories was accurate.At the mean time,the bias of all three batches in each laboratory fell into the same side (two laboratories showed negative bias and one positive bias).Conclusions The results of the external quality assessment of prenatal screening for maternal serum inhibin A are generally satisfactory except for a few laboratories.It is necessary to incorporate prenatal screening for maternal serum inhibin A in the second trimester into the formal external quality assessment plan and regularly monitor the level of its detection quality.

Objective To investigate and analyze the source and upper and lower limits of the reference interval of children's complete blood count in 110 maternal and child health hospitals and chil-dren's hospitals nationwide. Methods Laboratories submitted the data of reference intervals via external quality assessment (EQA) software which was based on the web. To collect the results of reference intervals questionnaires on complete blood cell counting of children in laboratory departments of 110 maternal and child care service centers and children's hospitals in China in 2017. Questionnaires include information on the source of reference intervals for 18 items of complete blood count, whether to verify, upper and lower lim-its, grouping, methods used, instruments, reagents, and calibrators. Data was analyzed using Microsoft Excel 2007 and SPSS 22.0. The median, P25, P75were obtained, and rank sum test were used to determine wheth-er there were statistical differences between groups. Results The results of 110 laboratories were obtained after rejecting invalid data. The reference intervals were mainly derived from operating procedures and the laboratories themselves, of which 50.5％-53.6％ of the laboratories were validated. The white blood cell counting reference intervals gradually decreased from birth to adolescence, and the value was close to that of adults. The reference intervals of red blood cell counting and hemoglobin were close to that of adults except in the neonatal period. The value of the reference intervals of hematocrit slightly decreased with age. The dif-ference between RBC, Hgb, HCT in reference intervals between groups was statistically significant when grouped by gender(P<0.05). The reference intervals of white blood cell counting were less grouped by gender (5 laboratories), and the difference among groups was not statistically significant. There were no statistically significant differences in the reference intervals of elements between the two measurement systems that Sys-mex XN series and Sysmex XS-800i/XS-1000i/XS 500i/XS 900i series. Conclusions The establishment of reference intervals for children's complete blood cell counting was urgently needed. The reference inter-vals of the complete blood cell counting item had statistical significance in both age and gender. It was sug-gested that the industry standard of children's complete blood cell counting reference intervals should be es-tablished based on age and gender.

Objective To observe the clinical characteristics of ankylosing spondylitis (AS) patients with hyperuricemia (HUA), and to understand the correlation between AS and HUA, so as to improve the understanding of AS patients with HUA. Methods A retrospective analysis was carried out in patients with the diagnosis with AS from November 2012 to August 2016. Patients were divided into two groups based on complicated with and without HUA. The clinical manifestations, inflammatory indicators, imaging manifest-ations, treatment and outcomes of the two groups were statistically analyzed, and the follow-up results of some patients with HUA were analyzed. The chi-square test was used for the counting data. The measurement data in line with the normal distribution were tested by t test, and the measurement data in non-normal distribution were tested by Mann-Whitney U test. Results Three hundred and sixty-two patients with AS were collected, consisting of 288 males (79.6％) and 74 females (20.4％), aged from 14 to 72 years, a course of disease was 3 months to 40 years. There were 87 cases (24.0％) with hyperuricemia, 77 cases were male (88.5％, 21.3％of all AS patients), and 10 were female (11.5％, 2.8％ of all AS patients). Shorter morning stiffness time [(13 ±31) min and (22 ±48) min, Z=-2.231, P=0.026], lower IgM level [(1.4 ±1.3) g/L and (3.0 ±4.3) g/L, Z=-2.040, P=0.041], and lower erythrocyte sedimentation rate [(25±17) mm/1 h and (33±22) mm/1 h, t=-2.617, P=0.007] in the HUA group when compared with patients without HUA. The difference between the two groups was statistically significant. Four cases (4.6％) had gout arthritis in the group with HUA, all were male, blood uric acid level all>420 μmol/L. There were 7 cases (8.0％) of urolithiasis in the group with HUA, and 24 cases (8.7％) of urolithiasis in the group without HUA, but there was no statistically significant difference in the incidence of urolithiasis between the two groups. None developed hypertensive disease, heart disease, nephropathy, or diabetis. Conclusion The incidence of hyperuricemia is high in AS, and with lower disease activity, and fewer complications.

Objective: To evaluate the effectiveness and to explore the releated factors of antiretroviral therapy among HIV/AIDS patients in Liangshan Yi Autonomous Prefecture, Sichuan Province. Methods: The method of convenience sampling was adopted in July 2017 to select the research objects who were accepted antiretroviral therapy (ART) over 6 months, older than 18 years and had HIV viral load in 2016, totally 400 cases. A retrospective study was used to collect the data, including social demography, medicine use, information of medical service acquisition, their own behaviors and cognition. 395 questionnaires were effectively recovered. χ² test and logistic regression were performed to examine relationships between factors and effects. Results: All of the 395 respondents were Yi-nationality. The average age of all cases was (39.23±7.52) years old and 223 were male (56.5%). Among 395 cases patients who were detect Viral load in 2016, 221 cases were under the number of 400 copies, thze effective rate of ART was 55.9%. Multivariate analysis showed that HIV/AIDS patients who missed the medication during the antiviral therapy had poor antiviral effects. Compared to those who adhered to medication, the treatment-ineffective OR (95%CI) of the patients missing the medication during the therapy was 7.06 (3.67-13.58); Compared to those who had adverse reactions that affect the therapy, the treatment-ineffective OR (95%CI) of the patients with mild adverse reactions that did not affect the therapy was 0.45 (0.23-0.87); Compared to the patients who used drugs during the treatment, the treatment-ineffective OR (95%CI) value of the antiretroviral therapy effect of non-drug users was 0.39 (0.16-0.91);Compared to the patients who have a correct cognition that insisting on taking medicine correctly can extend their life expectancy as a common person, the treatment-ineffective OR (95%CI) values for those who hold the view that could be prolonged by 10-20 years and not/unknown were 4.18 (1.59-10.99) and 6.64 (2.67-16.53). Conclusion The HIV/AIDS patients who receive ART were less effective in Liangshan, Prefecture. Missings drugs is one of the main influencing factors for the ineffective treatment.

Objective To stuy the clinical value of combined DWI and PWI in diagnosis of cerebral infarction (CI) at different stages.Methods One hundred and sixty-eight elderly CI patients were divided into hyperacute phase group (n =32),acute phase group (n =64),subacute phase group (n=45) and chronic phase group (n=27).Their DWI and PWI parameters and abnormal brain regions were compared.Results The ADC on DWI for injured lateral brain tissue was significantly lower than that on DWI for unjured lateral brain tissue in hyperacute phase group and acute phase group (0.39±0.08 vs 0.83±0.03;0.32±0.07 vs 0.91±0.05,P＜0.01).However,the ADC on DWI for the injured lateral brain tissue was significantly higher than that on DWI for the uninjured lateral brain tissue in subacute phase group and chronic phase group (1.54±0.34 vs 0.85±0.07,2.01±1.29 vs 0.90±0.05,P＜0.01).The PWI showed that the CBV was smaller and the CBF was slower while the MTT and TTP were longer in CI patients at different stages.DWI＜PWI,DWI＞PWI,and DWI=PWI in abnormal signal region were more frequently detected in hyperacute phase,acute phase subacute phase and chronic phase respectively.Conclusion PWI can show ischemic penumbra while DWI can highlight infarct foci in CI patients.Combined PWI and DWI can display the CBF in CI patients at different stages,and can thus provide reference for the clinical treatment of CI.

Objective To explore the mechanisms of synergic action of commonly-used herb pair of Radix Sophorae Flavescentis (Kushen, KS) and Fructus Cnidii (Shechuangzi, SCZ) for the treatment of pruritus. Methods We predicted and analyzed the potential targets of KS and SCZ based on network pharmacology method, and then established Chinese herbs-compound skeletons-targets networks to reveal anti-pruritus targets, predicting targets, and the interaction of KS and SCZ, as well as the components of the herb pair. The RAW264.7 inflammatory cell model was established to observe the synergistic anti-inflammatory activity of KS and SCZ. Results KS and SCZ had possible synergic action on the pruritus-related targets such as histamine receptors, cannabinoid receptors and proteinase-activated receptor 2. Additionally, KS and SCZ probably had synergic regulation of inflammation-related pathway (Toll -like receptor signaling pathway , chemokine signaling and Fc epsilon RI signaling pathway) and nerve-related pathway(neurotrophin signaling pathway) during the treatment of pruritus. Flavones from KS and coumarin of SCZ had various synergistic anti-inflammatory activities(P<0.05), indicating that they played an important role in inhibiting pruritus induced by inflammation. Conclusion The method may reveal the molecular mechanism of KS and SCZ in inhibiting pruritus, which is important for the modernization of Chinese medicine and new drug development.