Aim To study the mechanism of adipose mesenchymal stem cell exosomes(ASC-exo)inhibition of fluorescein isothiocyanate(FITC)-induced atopic dermatitis(AD).Methods The mouse age,extrac-tion method,and the concentration of a solution of typeⅠ collagen enzyme and other conditions were compared to study the effects on the morphology and quantity of adipose mesenchymal stem cells(ASCs)after extrac-ted.FITC-induced mouse model in vivo was estab-lished and different doses of ASC-exo were given to measure ear thickness,ear weight and ear scratching times of mice.HE staining was used to observe the pathological changes of ear tissue of mice.The non-toxicity of ASC-exo was detected.IgE,IL-5,IL-13 and other cytokines were detected by ELISA.The gene ex-pressions of TSLP,IL-33,occludin,Claudin-1(CLDN-1)and E-cadherin were detected by RT-qPCR.The protein expression was detected by immunohistochemis-try.Results An efficient method for extracting ASCs was established.Compared with the blank group,mice in the model group showed obvious AD symptoms.Compared with the model group,ASC-exo administra-tion group significantly reduced the number of ear scratches,epidermal thickening,inflammatory cell infil-tration and the secretion of Th2 cytokines IL-5 and IL-13.Meanwhile,ASC-exo administration group signifi-cantly increased the expression of structural proteins CLDN-1 and occludin in epithelial cells and decreased the expression of TSLP and IL-33.Conclusions ASC-exo can significantly improve Th2 skin inflamma-tion in AD mice,and its mechanism may be through in-creasing the expression of tight junction proteins and adhesion link protein in epithelial cells,repairing the skin barrier,and inhibiting the key promoters of allergy TSLP and IL-33.

Aim To study the mechanism of adipose mesenchymal stem cell exosomes(ASC-exo)inhibition of fluorescein isothiocyanate(FITC)-induced atopic dermatitis(AD).Methods The mouse age,extrac-tion method,and the concentration of a solution of typeⅠ collagen enzyme and other conditions were compared to study the effects on the morphology and quantity of adipose mesenchymal stem cells(ASCs)after extrac-ted.FITC-induced mouse model in vivo was estab-lished and different doses of ASC-exo were given to measure ear thickness,ear weight and ear scratching times of mice.HE staining was used to observe the pathological changes of ear tissue of mice.The non-toxicity of ASC-exo was detected.IgE,IL-5,IL-13 and other cytokines were detected by ELISA.The gene ex-pressions of TSLP,IL-33,occludin,Claudin-1(CLDN-1)and E-cadherin were detected by RT-qPCR.The protein expression was detected by immunohistochemis-try.Results An efficient method for extracting ASCs was established.Compared with the blank group,mice in the model group showed obvious AD symptoms.Compared with the model group,ASC-exo administra-tion group significantly reduced the number of ear scratches,epidermal thickening,inflammatory cell infil-tration and the secretion of Th2 cytokines IL-5 and IL-13.Meanwhile,ASC-exo administration group signifi-cantly increased the expression of structural proteins CLDN-1 and occludin in epithelial cells and decreased the expression of TSLP and IL-33.Conclusions ASC-exo can significantly improve Th2 skin inflamma-tion in AD mice,and its mechanism may be through in-creasing the expression of tight junction proteins and adhesion link protein in epithelial cells,repairing the skin barrier,and inhibiting the key promoters of allergy TSLP and IL-33.

Objective:To evaluate the effect of tumor volume on the radiation dose and efficacy of locally advanced cervical cancer patients undergoing radical radiotherapy and chemotherapy.Methods:Clinical data of 126 patients who were diagnosed with cervical cancer (stage ⅡB-ⅣA) and underwent radical concurrent chemoradiotherapy in Guangxi Medical University Cancer Hospital from November 2019 to November 2022 were retrospectively analyzed. The cut-off values of tumor volume before (pre-TV) and after (post-TV) external radiotherapy and tumor volume reduction rate (TVRR) were calculated by Jamovi software. The effects of pre-TV, post-TV and TVRR on short-term efficacy, progression-free survival (PFS), brachytherapy (BT) mode , high-risk clinical target volume (HR-CTV) and organs at risk (OAR) dose were investigated by univariate and multivariate analyses.Results:Pre-TV≥67.03 cm 3 and post-TV≥14.88 cm 3 were poor prognostic factors for 6-month PFS and objective response rate (ORR) (both P<0.05), and post-TV was an independent prognostic factor. In the TVRR≥73.0% and <73.0% groups, no statistical differences were observed in the 6-month PFS and ORR. In the pre-TV≥67.03 cm 3 group, the cases number of intracavitary brachytherapy (ICBT) and intracavitary / interstitial brachytherapy (IC/IS-BT) was 36 (50.0%), while in the pre-TV<67.03 cm 3 group, the cases number of ICBT and IC/IS-BT was 41 (76%) and 13 (24%), respectively ( P=0.003). In the post-TV≥14.88 cm3 group, the cases number of ICBT and IC/IS-BT was 28 (47%) and 32 (53%), while 49 (72%) and 17 (26%) in the post-TV<14.88 cm3 group, respectively ( P=0.002). The dose of HR-CTV D 90% in the TVRR≥73.0% group was significantly higher than that in the TVRR<73.0% group ( P=0.014), but there was no significant difference in the dose of bladder D 2 cm3, rectal D 2 cm3 and small intestine D 2 cm3 (all P>0.05). The dose of HR-CTV D 90% in the post-TV<14.88 cm 3 group was significantly higher than that in post-TV≥14.88 cm 3 group ( P<0.001), and the dose of bladder D 2 cm3 in the post-TV≥14.88 cm 3 group was higher than that in the post-TV<14.88 cm 3 group ( P<0.05). There was no significant difference in the dose of rectal D 2 cm3 and small intestinal D 2 cm3 between two groups (both P>0.05). The number of concurrent chemotherapy (≥4 times vs.<4 times) had no statistical difference for 6-month PFS and TVRR. Conclusions:Pre-TV and post-TV are the influencing factors of short-term efficacy and BT mode selection for locally advanced cervical cancer. Post-TV is an independent prognostic factor and also indirectly affects the dose of HR-CTV D 90% and bladder D 2 cm3 Increasing the number of concurrent chemotherapy (≥4 times) does not improve TVRR and short-term efficacy.

This study adopted the policy text analysis method,review the historical background of the enactment,aimed to comparatively analyze the international pharmaceutical trade policies of the BRICS countries.The main objectives of the BRICS countries'international pharmaceutical trade policies included ensuring stable and accessible drug supply,expanding exports of domestic products and creating a favorable political environment.For these purposes,Brazil,Russia,and South Africa all ensure drug supply through substantial imports.However,they have also taken measures such as compulsory patent licensing and promoting localization of production by foreign companies to reduce import dependence.India,on the other hand,protects its domestic industry by resisting drug imports to ensure drug supply while simultaneously promoting the export of pharmaceutical products.China continually optimizes approval and data monitoring procedures to align with international standards,creating a favorable trade environment and expanding exports.China should further refine its international pharmaceutical trade policies while ensuring the autonomy of domestic drug research and supply,fostering stronger collaboration within BRICS nations and promoting global access to public healthcare products.

OBJECTIVES: To study the association of ventricular septal defect (VSD) with rare variations in the promoter region of HAND2 gene, as well as related molecular mechanisms. METHODS: Blood samples were collected from 349 children with VSD and 345 healthy controls. The target fragments were amplified by polymerase chain reaction and sequenced to identify the rare variation sites in the promoter region of the HAND2 gene. Dual-luciferase reporter assay was used to perform a functional analysis of the variation sites. Electrophoretic mobility shift assay (EMSA) was used to investigate related molecular mechanisms. TRANSFAC and JASPAR databases were used to predict transcription factors. RESULTS: Sequencing revealed that three variation sites (g.173530852A>G, g.173531173A>G, and g.173531213C>G) were only observed in the promoter region of the HAND2 gene in 10 children with VSD, among whom 4 children had only one variation site. The dual-luciferase reporter assay revealed that g.173531213C>G reduced the transcriptional activity of the HAND2 gene promoter. EMSA and transcription factor prediction revealed that g.173531213C>G created a binding site for transcription factor. CONCLUSIONS The rare variation, g.173531213C>G, in the promoter region of the HAND2 gene participates in the development and progression of VSD possibly by affecting the binding of transcription factors.
Child ; Humans ; Base Sequence ; Heart Septal Defects, Ventricular/genetics* ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Transcription Factors/genetics*

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To investigate the diagnostic efficiency and incremental value of quantitative myocardial blood flow measurements by Cadmium-Zine-Telluride (CZT) single photon emission computed tomography (SPECT) dynamic myocardial perfusion imaging (MPI) in patients with coronary artery disease (CAD) compared with traditional semi-quantitative measurements by MPI. Methods: This is a retrospective, cross-sectional study. We retrospectively analyzed clinical data of patients with suspected or known CAD, who underwent the dynamic MPI quantitative blood flow measurement of CZT SPECT in TEDA International Cardiovascular Hospital from October 2018 to December 2020. Clinical data, semi-quantitative parameters (stress score (SS), rest score (RS) and different score (DS)) and myocardial quantitative blood flow parameters (rest myocardial blood flow (rMBF), stress myocardial blood flow (sMBF) and myocardial flow reserve (MFR)) were analyzed. According to the results of coronary angiography, patients were divided into the stenosis group and the control group with coronary artery stenosis ≥50% or ≥75% as the diagnosis criteria. The differences of quantitative and semi-quantitative parameters between the two groups were compared, and the diagnostic efficacy was compared by receiver operating characteristic(ROC) curve. Results: A total of 98 patients with a mean age of (62.1±8.7) years were included in the study, including 66 males (67%). At the patient level, with the positive standard of coronary artery stenosis≥50%, the left ventricle (LV) stress MBF (LV-sMBF) ((1.36±0.45) ml·min^-1·g^-1) and LV-MFR (1.45±0.43) of the stenosis group were lower than the LV-sMBF ((2.09±0.64) ml·min^-1·g^-1) and LV-MFR (2.17±0.54) of control group; summed SS and summed DS were higher than control group (all P<0.05). With the positive standard of coronary artery stenosis ≥75%, the LV-sMBF ((1.19±0.34) ml·min^-1·g^-1) and LV-MFR (1.34±0.35) of stenosis group were lower than the LV-sMBF ((1.94±0.63) ml·min^-1·g^-1) and MFR (2.00±0.58) of control group; all semi-quantitative parameters were higher than control group (all P<0.05). At the vascular level, with coronary artery stenosis ≥50% as the diagnosis criteria, the sMBF ((1.26±0.49) ml·min^-1·g^-1) and MFR (1.35±0.46) of stenosis group were lower than the sMBF ((1.95±0.70) ml·min^-1·g^-1) and MFR (2.05±0.65) of control group; SS and DS were higher than control group (all P<0.05). With coronary artery stenosis≥75% as the diagnosis criteria, the sMBF ((1.12±0.41) ml·min^-1·g^-1) and MFR (1.25±0.38) of stenosis group were lower than the sMBF ((1.84±0.70) ml·min^-1·g^-1) and MFR (1.93±0.66) of control group; all semi-quantitative parameters were higher than control group (all P<0.05). With coronary artery stenosis≥50% as the diagnosis criteria and CAG as the reference standard, the AUC and 95%CI of myocardial quantitative blood flow parameters indicated by ROC curve for diagnosis of CAD were 0.830 (0.783-0.877). The sensitivity (86.1% vs. 61.5%), specificity (82.6% vs. 73.8%), positive predictive value (77.8% vs. 62.5%), negative predictive value (89.3% vs. 73.0%) and accuracy (84.0% vs. 68.7%) were all higher than the semi-quantitative parameters (all P<0.05). With coronary artery stenosis≥75% as the diagnosis criteria, the AUC and 95%CI of myocardial quantitative blood flow parameters indicated by ROC curve for diagnosis of CAD were 0.832(0.785-0.879). The sensitivity (89.2% vs. 67.6%), negative predictive value (95.5% vs. 86.2%) and accuracy (80.6% vs. 68.0%) were all higher than semi-quantitative parameters (all P<0.05). Conclusion: Compared with traditional SPECT MPI derived semi-quantitative parameters, diagnostic efficacy for CAD is higher using CZT SPECT quantitative myocardial blood flow parameters, this strategy thus has additional diagnostic benefits and incremental value on the diagnosis of CAD.
Aged ; Constriction, Pathologic ; Coronary Angiography ; Coronary Artery Disease/diagnostic imaging* ; Coronary Stenosis/diagnostic imaging* ; Cross-Sectional Studies ; Humans ; Male ; Middle Aged ; Myocardial Perfusion Imaging/methods* ; Retrospective Studies ; Tomography, Emission-Computed, Single-Photon/methods*

Objective: To investigate the related factors of myocardial fibrosis in patients with hypertrophic cardiomyopathy. Methods: Patients with hypertrophic cardiomyopathy, hospitalized in the First People's Hospital of Yunnan Province from January 2016 to May 2020, were included in this cross-sectional study. Patients were divided into delayed enhancement positive group (fibrosis group) and non-delayed enhancement group (non-fibrosis group). According to the maximum left ventricular end diastolic wall thickness (LVMWT), patients in the fibrosis group was further divided into mild hypertrophy group, moderate hypertrophy group and severe hypertrophy group. The baseline clinical data of patients were collected by medical record management system. All enrolled patients underwent cardiac magnetic resonance imaging (CMR). The presence and location of myocardial fibrosis were identified by CMR gadolinium contrast delayed enhancement (LGE). The range of LGE (LGE%) was calculated by visual analysis. The levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) in peripheral blood were measured . Results: A total of 48 patients ( age (46.4±14.3) years, 42 (87.5%) males) were enrolled. There were 34 LGE positive cases (fibrosis group) and 14 LGE negative cases (non-fibrosis group). Compared with non-fibrosis group, patients in fibrosis group were younger (P=0.038) and prevalence of NYHA grade Ⅲ/Ⅳ was higher (P=0.00). Compared with non-fibrosis group, patients in fibrosis group had thicker LVMWT (P= 0.008), higher left ventricular mass index(LVMI) (P=0.001), higher left ventricular end diastolic volume (LVEDV) (P=0.043), lower left ventricular ejection fraction (LVEF) and cardiac index (CI) (all P <0.05). The levels of NT-proBNP and cTnI were significantly higher in fibrosis group than in non-fibrosis group (2 760.5 (1 503.4, 3 783.6) ng / L vs. 861.3 (552.2, 1 092.8) ng / L, P=0.002; 0.970 (0.448, 1.684)μg / L vs. 0.147 (0.033, 0.251)μg / L, P=0.041).In fibrosis group, there were 15 cases of mild hypertrophy (mild hypertrophy group), 10 cases of moderate hypertrophy (moderate hypertrophy group), and 9 cases of severe hypertrophy (severe hypertrophy group). The LGE% and NT-proBNP and cTnI increased in proportion with increasing myocardial hypertrophy (P<0.05). LGE% was negatively correlated with age (r=-0.618, P=0.011), and positively correlated with NT-proBNP and cTnI levels (r=0.271, P=0.010; r=0.111,P=0.013, respectively), and positively correlated with LVEDV, LVMWT and LVMI (r=0.438, P=0.09; r=0.735, P=0.001; r=0.532, P=0.034, respectively). Conclusions: In patients with hypertrophic cardiomyopathy, the extent of myocardial fibrosis increases with the increase of myocardial hypertrophy. Myocardial fibrosis is negatively correlated with age, and positively correlated with NT-proBNP and cTnI, as well as LVEDV, LVMWT and LVMI in this patient cohort.

Objective:From a new perspective，to explore therapeutic effect of Huidouba (HDB) on alleviating kidney oxidative damage in rats with diabetic nephropathy (DN) and provide a scientific basis for developing HDB as a potential Tibetan medicine for treatment of DN. Method:Rats were fed with high-fat diet (HFD) and injected with streptozocin (STZ, 65 mg·kg^-1) intraperitoneally to induce DN model, while rats in Blank group were injected with an equal volume of vehicle and fed with normal chow. The successfully modeling DN rats were randomly divided into three groups, 8 rats per group, DN model group (10 mL·kg^-1·d^-1), Metformin group (0.045 g·kg^-1·d^-1) and HDB group (0.18 g·kg^-1·d^-1). Monitor body weight (BW) and fasting blood glucose (FBG) weekly, and collect 24 hours urine before and after medication to examine microalbuminuria (mAlb). Calculate kidney index (KI) after sacrificing, analyze mAlb, serum creatinine (SCr) and blood urea nitrogen (BUN) with a fully automatic biochemical analyzer. Histopathology of kidney was observed by Masson staining. Lipid peroxidation malondialdehyde (MDA) assay kit was used to examine MDA content in kidney tissue. Nox4, as a subtype of triphosphopyridine nucleotide (NADPH) oxidase family was determined by Western blot and immunofluorescence assay of kidney tissue. Result:Compared with blank group, levels of FBG, 24 h mAlb, SCr, BUN and MDA in DN model group were increased (P<0.01), tissue damage was obvious and Nox4 expression in glumeruli was increased significantly (P<0.01). Compared with DN model group, levels of FBG, 24 h mAlb, SCr, BUN and MDA in drug administration groups were decreased (P<0.01), kidney injury was alleviated and Nox4 expression was down-regulated（P<0.01）. Conclusion:HDB as a Yiqiyangyin Tibetan medicine, could ease oxidative stress injury of kidney and reduce proteinuria in DN rats, thus prevent the development of DN. Its mechanism is closely related to down-regulating Nox4 expression of kidney tissue in DN rats.