ObjectiveTo investigate the mechanisms by which Renshentang treats atherosclerosis （AS） in mice， focusing on the regulation of endothelial inflammatory responses mediated by transient receptor potential vanilloid subtype 1 （TRPV1）. MethodsAn AS model was established in apolipoprotein E knockout （ApoE^-/-） mice fed a high-fat diet. The mice were randomly divided into a simvastatin group （0.02 g·kg^-1·d^-1） and low-， medium-， and high-dose Renshentang groups （1.77， 3.54， 7.08 g·kg^-1·d^-1）， with 12 mice in each group. ApoE^-/- mice were fed a high-fat diet and treated simultaneously. C57BL/6J mice fed a normal diet served as the normal group （n=9）. After continuous administration for 12 weeks， mice were anesthetized and the aortas were collected. Oil Red O staining was used to observe lipid plaque formation in the aorta. Hematoxylin-eosin （HE） staining was performed to examine pathological changes in the aortic root. Immunohistochemistry was used to analyze the levels of pro-inflammatory factors tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， as well as the expression of TRPV1， phosphorylated phosphoinositide 3-kinase （p-PI3K）， and phosphorylated protein kinase B （p-Akt） in the aortic root. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect endothelial nitric oxide synthase （eNOS） mRNA expression in the aorta， and Western blot was used to detect TRPV1 protein expression. ResultsCompared with the normal group， the model group showed a significant increase in aortic plaque formation （P<0.01） and significantly elevated levels of TNF-α and IL-1β in the aortic root （P<0.01）. The expression levels of TRPV1， p-PI3K， and p-Akt were decreased （P<0.05， P<0.01）， and eNOS mRNA expression was reduced （P<0.05， P<0.01）. Compared with the model group， all Renshentang groups significantly reduced aortic plaque formation （P<0.01）， significantly decreased TNF-α and IL-1β levels （P<0.01）， and markedly increased the expression levels of TRPV1， p-PI3K， p-Akt， and eNOS mRNA （P<0.05， P<0.01）. ConclusionRenshentang may inhibit endothelial inflammation and suppress the formation of AS by increasing TRPV1 protein expression and up-regulating the PI3K/Akt/eNOS signaling pathway， which may be one of the molecular mechanisms underlying its therapeutic effect against AS.

ObjectiveTo investigate the mechanism of Huangqi Gegentang （HGT） in the treatment of type 2 diabetes mellitus （T2DM） through the application of proteomic techniques. MethodsThe rat model of T2DM was established by streptozotocin combined with a high-fat， high-sugar diet. Thirty-two male SD rats were randomized into four groups： blank， model， HGT （8.10 g·kg^-1·d^-1）， and positive control （metformin hydrochloride， 76.5 mg·kg^-1·d^-1）. After 6 weeks of drug intervention， the fasting blood glucose level was measured， and an oral glucose tolerance test （OGTT） was performed. The area under the curve （AUC） was calculated. Enzyme-linked immunosorbent assay was performed to assess the level of glycated hemoglobin （GHbA1c） in the serum. The limulus amebocyte lysate assay was employed to measure the serum level of lipopolysaccharide （LPS）. Pathological changes in the colon were observed by hematoxylin-eosin staining. The mRNA levels of pro-inflammatory cytokines including tumor necrosis factor （TNF）-α， interleukin （IL）-6， and IL-1β in the colon tissue were quantified via Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Additionally， the protein and mRNA levels of zonula occludens-1 （ZO-1）， Occludin， and Claudin-1 in the colon tissue were assessed by Western blot and Real-time PCR， respectively. Label-free quantitative proteomics was employed to identify the differentially expressed proteins between the colon tissue samples from the blank， model， and HGT groups. Key proteins identified were subsequently validated by Western blot and Real-time PCR. Finally， bioinformatics analysis was conducted on the differentially expressed proteins. ResultsCompared with the blank group， the model group exhibited increased fasting blood glucose， AUC， and GHbA1c levels （P<0.01）， damaged colonic mucosal epithelial structure and inflammatory cell infiltration， up-regulated mRNA levels of TNF-α， IL-6， and IL-1β in the colon and an increase in serum LPS content （P<0.05， P<0.01）， and down-regulated protein and mRNA levels of ZO-1， Occludin， and Claudin-1 in the colon （P<0.01）. Compared with the model group， the HGT group showed reductions in fasting blood glucose， AUC， and GHbA1c （P<0.01）， alleviated damage to the colonic mucosal epithelium， down-regulated mRNA levels of TNF-α， IL-6， and IL-1β in the colon， a reduction in serum LPS content （P<0.05， P<0.01）， and up-regulated protein and mRNA levels of ZO-1， Occludin， and Claudin-1 in the colon （P<0.05， P<0.01）. Proteomics analysis identified 70 differentially expressed proteins that exhibited a downward trend in the model group relative to the blank group and an upward trend in the HGT group relative to the model group. These findings were corroborated by Western blot and Real-time PCR， which confirmed that the protein and mRNA levels of mucin 2 （Muc2） and transforming growth factor （TGF）-beta receptor 1 （Tgfbr1） in the colon tissue were consistent with the proteomic data. Bioinformatics analysis showed that these 70 differentially expressed proteins identified were significantly enriched in multiple signaling pathways， among which the TGF-β and advanced glycation endproduct （AGE）/receptor for advanced glycation endproduct （RAGE） signaling pathways were closely associated with damage to the intestinal mucosal barrier. This suggests that HGT may ameliorate intestinal mucosal barrier damage by regulating these pathways. ConclusionHGT potentially exerts anti-T2DM effects by influencing AGE/RAGE and TGF-β signaling pathways， thereby contributing to the restoration of the intestinal mucosal barrier.

ObjectiveTo explore the effects of Renshentang on atherosclerosis （AS） in mice based on the role of transient receptor potential vanilloid1 （TRPV1） in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group， and 60 ApoE^-/- mice were randomized into model， positive drug （simvastatin， 0.02 g·kg^-1·d^-1）， and low-， medium-， and high-dose （1.77， 3.54， 7.08 g·kg^-1·d^-1， respectively） Renshentang groups （n=12） according to body weight. The normal group was fed with a normal diet， and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h， the aorta was collected. Plaque conditions， pathological changes， levels of total cholesterol （TC）， triglcerides （TG）， low-density lipoprotein-cholesterol （LDL-C）， and high-density lipoprotein-cholesterol （HDL-C）， and the expression of TRPV1， liver X receptor （LXR）， inducible degrader of the low-density lipoprotein receptor （IDOL）， and low-density lipoprotein receptor （LDLR） in the aortic tissue were observed and detected by gross oil red O staining， HE staining， Western blot， immunohistochemistry， and real-time PCR. ResultsCompared with the normal group， the model group presented obvious plaque deposition in the aorta， raised levels of TC， TG， and LDL-C in the serum （P<0.01）， up-regulated expression level of LDLR in the aorta （P<0.01）， lowered level of HDL-C in the serum， and down-regulated expression levels of TRPV1， LXR， and IDOL in the aorta （P<0.05， P<0.01）. Compared with the model group， the positive drug and Renshentang at different doses alleviated AS， elevated the levels of HDL-C， TRPV1， LXR， and IDOL （P<0.05， P<0.01）， while lowering the levels of TC， TG， LDL-C， and LDLR （P<0.05， P<0.01）. ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition， lipid levels， and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.

ObjectiveTo explore the effects of Renshentang on atherosclerosis （AS） in mice based on the role of transient receptor potential vanilloid1 （TRPV1） in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group， and 60 ApoE^-/- mice were randomized into model， positive drug （simvastatin， 0.02 g·kg^-1·d^-1）， and low-， medium-， and high-dose （1.77， 3.54， 7.08 g·kg^-1·d^-1， respectively） Renshentang groups （n=12） according to body weight. The normal group was fed with a normal diet， and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h， the aorta was collected. Plaque conditions， pathological changes， levels of total cholesterol （TC）， triglcerides （TG）， low-density lipoprotein-cholesterol （LDL-C）， and high-density lipoprotein-cholesterol （HDL-C）， and the expression of TRPV1， liver X receptor （LXR）， inducible degrader of the low-density lipoprotein receptor （IDOL）， and low-density lipoprotein receptor （LDLR） in the aortic tissue were observed and detected by gross oil red O staining， HE staining， Western blot， immunohistochemistry， and real-time PCR. ResultsCompared with the normal group， the model group presented obvious plaque deposition in the aorta， raised levels of TC， TG， and LDL-C in the serum （P<0.01）， up-regulated expression level of LDLR in the aorta （P<0.01）， lowered level of HDL-C in the serum， and down-regulated expression levels of TRPV1， LXR， and IDOL in the aorta （P<0.05， P<0.01）. Compared with the model group， the positive drug and Renshentang at different doses alleviated AS， elevated the levels of HDL-C， TRPV1， LXR， and IDOL （P<0.05， P<0.01）， while lowering the levels of TC， TG， LDL-C， and LDLR （P<0.05， P<0.01）. ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition， lipid levels， and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.

Objective: To analyze the impact of maternal metal exposure during early pregnancy on the physical development of offspring at 1 and 3 years of age, so as to provide scientific evidence for reducing the adverse effects of heavy metals on their health. Methods: From 2024 to 2018, a total of 1 588 mother child pairs from the Jiangsu Birth Cohort (JBC) were included in this study. Multiple linear regression models, generalized estimating equations (GEE), and weighted quantile sum (WQS) regression models were used to assess the associations between 24 urinary metal mass concentrations (adjusted for specific gravity, SG) during early pregnancy and offspring growth outcomes, including length/height for age Z score(HAZ), weight for age Z score(WAZ), weight for length/height Z score(WHZ), and head circumference for age Z score(HCAZ) at 1 and 3 years of age. Results: After adjusting for confounders, GEE analysis revealed that each natural log unit increase in maternal urinary concentrations of vanadium, tin, cerium, lead, and uranium during early pregnancy was associated with an average reduction in HCAZ by 14.29%, 4.82%, 2.62 %, 5.04 %, and 8.33%, respectively, at 1 and 3 years of age (FDR- P <0.05). Multiple linear regression analysis revealed that increased urinary vanadium concentration was associated with reduced HAZ at 1 year of age, while increased urinary concentrations of vanadium, chromium, tin, antimony, and uranium were associated with reduced HCAZ at 1 year of age (FDR- P <0.05). In the WQS regression model, each unit increase in the WQS index was associated with a 22.64% reduction in HCAZ at 1 year of age, with tin (22.2%) contributing the highest weight, followed by uranium (16.2%), lead (11.5%), vanadium (10.0%), arsenic (6.5%), and chromium (5.0%). Conclusions Prenatal exposure to specific metals and their mixtures may significantly impact the physical development of offspring at 1 and 3 years of age, particularly head circumference. These findings highlight the need to enhance monitoring of maternal metal exposure during early pregnancy to reduce the potential health risks posed by environmental metal pollution to infants and young children.

OBJECTIVES: The diagnostic value of ultrasonographic quantitative indicators of umbilical cord coiling, such as the umbilical coiling index (UCI) and pitch value, in identifying hypercoiling and predicting adverse pregnancy outcomes remains controversial. This study aims to evaluate the predictive value of UCI, pitch value, and the cerebroplacental ratio in pregnancies complicated by umbilical cord hypercoiling. METHODS: Pregnant women with densely coiled umbilical cords identified by routine obstetric ultrasound at Changsha Maternal and Child Health Hospital between November 2022 and November 2024 were enrolled. Complete clinical data, including UCI, pitch value, and cerebroplacental ratio (CPR), were collected. Pregnancy outcome scores were calculated, and newborns were categorized into the normal outcome group (n=177) and adverse outcome group (n=85), with the latter further subdivided into mild (n=51), moderate (n=19), and severe (n=15) subgroups. Differences in baseline data, UCI, pitch value, and incidence of CRP<1 were compared between groups and among subgroups. Correlations between UCI, pitch value, and adverse pregnancy outcomes were analyzed. Receiver operating characteristic (ROC) curve were used to assess the predictive performance of UCI, pitch value, CPR<1, and their combinations. RESULTS: Compared with the normal outcome group, the adverse outcome group had higher age, parity, parity, incidence of CPR<1, and UCI, while gestational age at delivery and pitch values were lower (all P<0.05). The incidence of obesity, gestational diabetes mellitus, and hypertensive disorders of pregnancy did not differ significantly between the 2 groups (all P>0.05). The normal outcome group showed lower UCI and higher pitch values than all 3 adverse outcome subgroups (all P<0.05), while differences among the 3 adverse subgroups were not significant (all P>0.05). UCI was positively correlated with adverse pregnancy outcomes (r_s=0.350, P<0.05), whereas pitch value was negatively correlated (r_s=-0.286, P<0.05). ROC curve analysis showed that the area under the curve (AUC) values for predicting adverse outcomes were 0.837 for UCI, 0.886 for pitch value, and 0.610 for CPR<1, with sensitivities of 77.6%, 82.4%, and 27.1% and specificities of 78.5%, 83.6%, and 94.9%, respectively. The combined UCI+CPR<1 and pitch value+CPR<1 models yielded AUCs of 0.841 and 0.886, with sensitivities of 78.8% and 81.2% and specificities of 78.5% and 84.2%, respectively. No significant differences were found between the AUCs of UCI and pitch value (P>0.05), but both outperformed CPR<1 alone (both P<0.001). The combined models showed no significant improvement over UCI or pitch value alone (both P>0.05), though both were superior to CPR<1 alone (both P<0.001). CONCLUSIONS Most umbilical cord hypercoiling cases had favorable outcomes, with UCI, pitch value, CPR<1 and their combinations demonstrating significant predictive value for adverse pregnancy outcomes.
Humans ; Female ; Pregnancy ; Pregnancy Outcome ; Adult ; Ultrasonography, Prenatal/methods* ; Umbilical Cord/diagnostic imaging* ; Hemodynamics ; Predictive Value of Tests ; Infant, Newborn ; ROC Curve

Brucella are a group of small gram-negative bacteria that infect the human body through various transmission routes. They can travel with the blood to various organs and tissues throughout the body, causing bacteremia, toxemia, sepsis, and local infections. Brucellosis is relatively rare in developed countries and more common in developing countries. Although the typical symptoms of brucellosis are easy to identify, some manifestations are not well-known, such as eye involvement in brucellosis patients. Eye inflammation is usually a late manifestation, and Brucella can cause different symptoms in the eyes, leading to misdiagnosis or missed diagnosis. Therefore, it should be considered in differential diagnosis. To further enhance the understanding of eye involvement in patients with brucellosis among healthcare workers, this article provides a review of its pathogenesis, clinical manifestations, auxiliary examinations, diagnosis, and treatment characteristics.

Objective To investigate the clinical distribution,antimicrobial resistance,carbapenemase resistance genes,virulence genes,capsular serotypes and ST subtypes of carbapenem-resistant Klebsiella pneumoniae(CRKP)strains in intensive care unit of a tertiary hospital in Hunan Province for better management of CRKP infections.Methods CRKP strains were isolated from 8 intensive care units of the First People's Hospital of Chenzhou City from January 2020 to December 2021.The isolates were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and tested by VITEK Compact 2 for antimicrobial susceptibility.Carbapenemase phenotype was detected by modified carbapenem inactivation method(mCIM).The capsular serotypes were determined by wzi sequencing.Carbapenem resistance genes and virulence genes were identified by PCR and Sanger sequencing.The strains were also analyzed by multilocus sequence typing(MLST)in terms of ST subtypes.Results The 75 CRKP strains were mainly isolated from geriatric ICU(28.0％)and neurosurgery ICU(20.0％).Overall,6.7％(5/75)and 16.0％(12/75)of the CRKP strains were resistant to tigecycline and ceftazidime-avibactam,respectively.The CRKP strains(＞96.0％resistant)were highly resistant to carbapenems,cephalosporins,β-lactam/β-lactamase inhibitor combinations,and levofloxacin.PCR and sequencing analysis found blaKPC-2 gene in 61 strains(81.3％),blaNDM-1 gene in 11 strains(14.7％),blaNDM-5 gene in 1 strain(1.3％),and blaOXA-48 gene in 2 strains(2.7％).MLST revealed that ST11(54.7％,41/75),ST1883(13.3％,10/75),and ST307(6.7％,5/75)were the top three ST subtypes.All ST11 and ST1883 CRKP strains harbored blaKPC-2.KL64(38.7％,29/75)and KL47(25.3％,19/75)were the most prevalent capsular serotypes among the 75 CRKP strains.The most common virulence genes among these CRKP strains were rmpA2(48.0％,36/75),iroN(38.7％,23/75)and iucA(37.3％,15/75).Conclusions The CRKP strains isolated from the intensive care units were mainly ST11-KL64 and ST11-KL47 types.Most of the strains harbor blaKPC-2 and virulence gene,and associated with high level antimicrobial resistance.It is urgent to strengthen the monitoring of molecular epidemiological characteristics of CRKP in order to inform individualized and precision treatment of CRKP infections.

Objective:To explore the incidence of postoperative delirium (POD) in patients with Stanford Type A aortic dissection and analyze the influencing factors and predictive efficacy of these factors for POD.Methods:Totally 237 patients with Stanford Type A aortic dissection who were treated at Beijing Anzhen Hospital, Capital Medical University, from May 2020 to February 2021 were selected by convenience sampling. Data were collected using a general information questionnaire, the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), the Pittsburgh Sleep Quality Index (PSQI), the State-Trait Anxiety Inventory (STAI), and the Chinese version of the Critical Care Pain Observation Tool (CPOT). Logistic regression analysis was employed to identify factors influencing POD, and receiver operating characteristic (ROC) curves were used to evaluate the predictive value of each influencing factor and determine the optimal cutoff values.Results:A total of 237 questionnaires were distributed, with 232 valid questionnaires returned, yielding a recovery rate of 97.89% (232/237). Among the 232 patients, 37 developed delirium, resulting in an incidence rate of 15.95% (37/232). Logistic regression analysis revealed that carotid artery involvement, preoperative anxiety scores, postoperative pain scores, and length of ICU stay were influencing factors for POD in patients with Stanford Type A aortic dissection ( P<0.05). ROC curve analysis indicated that the area under the curve ( AUC) values for preoperative anxiety scores, postoperative pain scores, length of ICU stay, and carotid artery involvement in predicting POD were 0.924, 0.927, 0.954, and 0.718, respectively. Conclusions:The incidence of POD in patients with Stanford Type A aortic dissection is relatively high. Preoperative anxiety, postoperative pain, length of ICU stay, and carotid artery involvement are key factors influencing the occurrence of POD in these patients.

Objective To investigate the effect of Inonotus obliquus extract on Crohn's disease and its mechanism by proteomics technology.Methods Crohn's disease(CD)model was induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS).A total of 48 SD male rats were randomized into control,model,Inonotus obliquus low-dose(200 mg/kg),medium-dose(400 mg/kg),high-dose(800 mg/kg)groups,and positive control group(mesalazine,225 mg/kg).The disease activity index(DAI)score and the colonic mucosal injury index(CMDI)score were assessed after one week of drug intervention.HE staining was used to observe the histopathological changes in the colon,and ELISA was used to detect the levels of IL-1β,IL-6,and TNF-α in the serum.Proteins were extracted from the colonic tissues of the control group,model group,and Inonotus obliquus high-dose group,and bioinformatics analysis was performed for the proteins identified by quantitative proteomics.Finally,Western blot and RT-qPCR were employed to verify the key proteins.Results Compared with the model group,the DAI,CMDI and HE staining scores were significantly decreased in the medium and high dose groups(P＜0.05 or P＜0.01),as well as the levels of inflammatory factors IL-1β,IL-6 and TNF-αin serum(P＜0.05 or P＜0.01).Proteomic tests showed that there were 199 differentially expressed proteins(DEPs)between the Inonotus obliquus high-dose group and the model group,of which 63 DEPs were related to CD.Bioinformatics analysis showed that these 63 DEPs were mainly involved in NOD-like receptor signaling pathway,calcium signaling pathway,necroptosis,and other pathways.Consistent with proteomic result,expressions of Vdac1 and Trpv2 were confirmed by Western blot and RT-qPCR in colon tissue.Conclusions Inonotus obliquus extract may regulate NOD-like receptor signaling pathway,calcium signaling pathway,and necroptosis by interfering with the expression of Vdac1 and Trpv2,so as to achieve the effect of treating CD.