Objective To investigate the mechanism by which Senegenin(SEN)alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)pathway.Methods BV2 mouse microglia cells were randomly divided into control group,model group,SEN group and MCC950 group.Cells in control group were not treated,and cells in model group were added with 1 μg/ml lipopolysaccharide(LPS);Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN,and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours.CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells.Griess method was used to determine the release amount of nitric oxide(NO)in the supernatant.Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3,lymphocyte apoptosis-associated spect-like protein containing a CARD(ASC),caspase-1,interleukin(IL)-1β and IL-18 mRNA.Immunofluorescence staining was used to detect the expression levels of ASC,IL-1β,Nrf2 and heme oxygenase-1(HO-1).Western blotting was used to detect the expression levels of NLRP3,caspase-1,ASC,IL-1β,IL-18,Nrf2,HO-1,nuclear factor kappa B(NF-κB)and inducible nitric oxide synthase(iNOS).Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2～20 μmol/L SEN compared with control group(P>0.05).Compared with control group,the viability of BV2 cells in model group decreased significantly(P<0.05).Compared with model group,the viability of BV2 cells in 4 μmol/L SEN group was significantly restored(P<0.05).Compared with control group,the results of Griess method showed that the release amount of NO in cells of model group increased significantly(P<0.05);the results of real-time PCR showed that the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA in cells of model group increased significantly(P<0.05);the results of Western blotting showed that the protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 proteins in cells of model group increased significantly(P<0.05),and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased,and the expression levels of Nrf2 and HO-1 decreased,with statistically significant differences(P<0.05).Compared with model group,the release amount of NO in cells of SEN group and MCC950 group decreased,and the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA and proteins decreased,with statistically significant differences(P<0.05);in the SEN group,the expression levels of iNOS and NF-κB decreased,and immunofluorescence staining showed that Nrf2 was translocated into the nucleus,and the expression levels of Nrf2 and HO-1 proteins increased significantly,with statistically significant differences(P<0.05).Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome,with an effect comparable to that of the inflammasome inhibitor MCC950.The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.

OBJECTIVES: To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress. METHODS: Twenty male SD rats were randomized equally into control group and heat stress group. After exposure to 32 ℃ for 2 weeks in the latter group, the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry. In the cell experiments, cultured rat thoracic aortic endothelial cells (RTAECs) were incubated at 40 ℃ for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA (si-Bmal1) or a negative sequence. In both rat thoracic aorta and RTAECs, the expressions of Bmal1, the cell cycle proteins CDK1, CDK4, CDK6, and cyclin B1, and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting. TUNEL staining was used to detect cell apoptosis in rat thoracic aorta, and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry. RESULTS: Compared with the control rats, the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1, cyclin B1 and CDK1 in the thoracic aorta (P<0.05). In cultured RTAECs, heat stress caused significant increase of Bmal1, cyclin B1 and CDK1 protein expression levels, which were obviously lowered in cells with prior si-Bmal1 transfection. Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2. CONCLUSIONS Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells, which can be partly alleviated by suppressing Bmal1 expression.
Animals ; ARNTL Transcription Factors/genetics* ; Male ; Aorta, Thoracic/metabolism* ; Rats ; Rats, Sprague-Dawley ; Endothelial Cells/metabolism* ; Apoptosis ; Cells, Cultured ; Heat-Shock Response ; Cyclin B1/metabolism* ; CDC2 Protein Kinase/metabolism* ; Cyclins/metabolism* ; RNA, Small Interfering ; bcl-2-Associated X Protein/metabolism*

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Integrative Medicine ; Drugs, Chinese Herbal/therapeutic use* ; Practice Guidelines as Topic

Objective To explore the effects of oleanolic acid on NF-κB/caspase-9 signaling pathway in kidneys of rat with diabetic nephropathy.Methods The diabetic nephropathy model rats were established,and the model rats were randomly divided intooleanolic acid low,medium and high dose groups,metformin group,and model group,with another 12 healthy SD rats as control group.The levels of blood glucose were measured at weeks 1,2 and 3 post-drug administration,and blood lipid and 24h urine urinary microalbumin(UMA)were measured after entire drug administration.Furthermore,we also detected the renal histopathology of rats,apoptosis of renal tubular,glomerular cells,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and protein expression of NF-κB/caspase-9 signaling pathway.Results Compared with the control group,the model group demonstrated higher levels of blood glucose at weeks 1,2 and 3,blood lipid,UMA,TNF-α and IL-6,higher proportion of apoptotic renal tubular and glomerular,and higher expressions of caspase-9 protein and p-NF-κB p65/NF-κB p65(P＜0.05).Compared with the model group,the pathological damage of renal tissue in the metformin group and oleanolic acid low,middle and high dose groups were alleviated,the levels of blood glucose at weeks 1,2 and 3,blood lipid,UMA,TNF-α and IL-6,the proportion of apoptotic renal tubular and glomerular,and the expressions of caspase-9 proteins and p-NF-κB p65/NF-κB p65 were decreased,and these indexes in oleanolic acid groups showed a dose-dependent manner(P＜0.05).Conclusion Oleanolic acid can improve the metabolism of glucose and lipid,reduce the pathological damage of renal tissue,inhibit the apoptosis of renal tubular and glomerular,and inhibit the NF-κB/caspase-9 pathway in diabetic nephropathy rats.

Objective To explore the effects of oleanolic acid on NF-κB/caspase-9 signaling pathway in kidneys of rat with diabetic nephropathy.Methods The diabetic nephropathy model rats were established,and the model rats were randomly divided intooleanolic acid low,medium and high dose groups,metformin group,and model group,with another 12 healthy SD rats as control group.The levels of blood glucose were measured at weeks 1,2 and 3 post-drug administration,and blood lipid and 24h urine urinary microalbumin(UMA)were measured after entire drug administration.Furthermore,we also detected the renal histopathology of rats,apoptosis of renal tubular,glomerular cells,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and protein expression of NF-κB/caspase-9 signaling pathway.Results Compared with the control group,the model group demonstrated higher levels of blood glucose at weeks 1,2 and 3,blood lipid,UMA,TNF-α and IL-6,higher proportion of apoptotic renal tubular and glomerular,and higher expressions of caspase-9 protein and p-NF-κB p65/NF-κB p65(P＜0.05).Compared with the model group,the pathological damage of renal tissue in the metformin group and oleanolic acid low,middle and high dose groups were alleviated,the levels of blood glucose at weeks 1,2 and 3,blood lipid,UMA,TNF-α and IL-6,the proportion of apoptotic renal tubular and glomerular,and the expressions of caspase-9 proteins and p-NF-κB p65/NF-κB p65 were decreased,and these indexes in oleanolic acid groups showed a dose-dependent manner(P＜0.05).Conclusion Oleanolic acid can improve the metabolism of glucose and lipid,reduce the pathological damage of renal tissue,inhibit the apoptosis of renal tubular and glomerular,and inhibit the NF-κB/caspase-9 pathway in diabetic nephropathy rats.

The fluid status and rate of blood flow through the arteriovenous fistula (AVF) are two important factors affecting hemodynamic in hemodialysis patients; however, their effects on pulmonary hypertension have rarely been studied. Hence, we aimed to evaluate the effects of these factors in hemodialysis patients with pulmonary hypertension. Methods: This single-center cross-sectional survey included 219 maintenance hemodialysis patients (139 [63.5%] male). The prevalence of pulmonary hypertension was 13.6% (30 of 219). Pulmonary artery pressure was measured by echocardiography, fluid status was measured objectively using bioimpedance spectroscopy, and blood flow rate in the AVF (Qa) was determined using Doppler ultrasound. Results: The overall mean overhydration before hemodialysis was 1.5 L (range, 0.6–2.8 L). The mean overhydration in patients with and without pulmonary hypertension was 3.6 L (range, 2.3–4.6 L) and 1.4 L (range, 0.6–2.4 L), respectively (p < 0.001). The overall mean Qa was 780 mL/min (range, 570–1,015.5 mL/min). The mean Qa of patients with and without pulmonary hypertension was 672 mL/min (range, 505.7–982.2 mL/min) and 790 mL/min (range, 591–1,026 mL/min), respectively (p = 0.27). Overhydration (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.08–1.97; p = 0.01), N-terminal prohormone of brain natriuretic peptide (NT-proBNP; OR, 1.36; 95% CI, 1.09–1.71; p = 0.007), and left atrial diameter (OR, 1.14; 95% CI, 1.01–1.28; p = 0.03) were risk factors. Conclusion: Pulmonary hypertension is strongly associated with overhydration, NT-proBNP, and left atrial diameter in hemodialysis patients

Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

BACKGROUND:High tibial osteotomy results in massive blood loss during the perioperative period.Tranexamic acid can effectively reduce perioperative blood loss.However,the method of tranexamic acid application has not been unified. OBJECTIVE:To investigate the effect and safety of different methods of tranexamic acid on perioperative blood loss in the high tibial osteotomy. METHODS:A total of 160 patients who underwent primary unilateral high tibial osteotomy in the Binzhou Medical University Hospital from January 2019 to December 2021,including 69 males and 91 females,were randomly divided into four groups(n=40 per group).Among them,40 patients were given an intravenous infusion of saline containing 2 g tranexamic acid 10 minutes before tourniquet release(venous group);40 patients were given an intravenous infusion of 1 g tranexamic acid and 1 g tranexamic acid was injected through a drainage tube after the closure of the incision(combined group);40 patients were given 2 g tranexamic acid infusion into drainage tube after the closure of the incision(perfusion group);an additional 40 patients were given an intravenous infusion of the same amount of normal saline(blank group).The general information was compared among the four groups of patients.The hemoglobin,hematocrit,intraoperative blood loss,drainage volume,blood transfusion rate,incision complication,and the incidence of deep vein thrombosis were recorded on days 1,3 and 5 after operation in the four groups.The total blood loss and hidden blood loss were calculated. RESULTS AND CONCLUSION:(1)There was no statistically significant difference in general information among the four groups.(2)No significant difference was found in intraoperative blood loss among the four groups.(3)The maximum decreased values of hemoglobin and hematocrit on days 1,3 and 5 after operation,drainage volume,total blood loss and hidden blood loss were all ranked as the combined group

Objective To establish a simultaneous detection approach for 34 emerging contaminants(ECs)in tap water by liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Human health risk assessment was performed according to the detection results from 43 tap water samples.Methods Tap water samples were concentrated and extracted by solid phase extraction,and then blown to near dry by nitrogen at 40℃.The sample extracts were dissolved in methanol-water solution(95:5,VN)to 0.5 mL for analyzing.Agilent Jet Stream Electrospray Ionization(AJS ESI)and the multiple reaction monitoring(MRM)mode were performed for MS to acquire the data of 34 ECs.A database including precursor ion,product ion and retention times was established accordingly.Results The average linear correlation coefficients(r)of 34 kinds of ECs was 0.995 9.The limits of detection were 0.01～0.60 ng/L and the recoveries were between 60.7％and 119.8％.The intra-group precisions were between 0.05％～9.89％and the intra-day precisions were between 0.20％～14.40％for the spiked samples.The method was applied to analyze 43 tap water samples and a total of 15 ECs were detected.According to the results,the detection rate of caffeine was the highest(84％),and the concentration range was ND～74.42 ng/L.Among all the ECs detected,1,2,3-benzotriazole had the highest concentration(ND～361.15 ng/L),where detection rate was 44％.Humans may be exposed to these ECs by drinking the tap water.The human health risk assessments of 12 kinds of ECs were carried out,however,the estimated risk was negligible(risk quotient＜0.01).Conclusion The method is simple,highly sensitive and selective,and could meet the detection needs of ECs at trace level in tap water.There was no human health risk posed for ECs identified in 43 tap water samples analyzed by this method.

A triplex RT-qPCR assay with human genes as internal references was established for detection of the Dengue and Zika viruses(DENV and ZIKV,respectively).The conserved regions of the four serotypes of DENV,along with the NS1 gene of ZIKV and the human β-actin gene,which is stably ex-pressed in various human tissues,were targeted by three sets of specific primers and probes.Standard plasmids for four se-rotypes of DENV,ZIKV,and β-actin were constructed as pos-itive controls.Optimal reaction conditions were determined through an L9(34)orthogonal experiment.The specificity,sensitivity,and coverage of the assay were verified and evalua-ted clinically,and the consistency was evaluated against a com-mercial kit for detection of DENV.The triplex RT-qPCR assay established exhibited no non-specific cross reactions with 12 similar arboviruses.The detection sensitivity for DENV and ZIKV were 2.99 and 2.18 copies/μL,respectively,and the intra-group and inter-group repeatability coefficients of variation were within 1.5％.As compared to the commercial kit,the proposed assay obtained positive results for 13 epidemic strains of DENV.Bland-Altman consistency analysis confirmed that the consistency of the detection results of clinical positive samples between the commercial kit and the proposed assay was 92.59％.The highly specific and sensitive triplex RT-qPCR assay with internal references is an effective tool for early and rapid differential identification of DENV and ZIKV.