Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by

Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT₇ receptor protein expression in the cells, indicating potential antidepressant activity.

Aim To investigate the effect of polyphyl-lin Ⅱ(PP Ⅱ)on autophagy of osteosarcoma(OS)cells and its related molecular mechanism.Methods U2OS and HOS cells were cultured in vitro and treated with different concentrations of PP Ⅱ(5,10,15,20 μmol·L-1)for 24 h.The changes of acid vesicles were detected by AO staining,the autophagosomes was ob-served by transmission electron microscopy,the ex-pressions of LC3B-Ⅱ/LC3B-Ⅰ,p62,caspase-3,cleaved caspase-3 were detected by Western blot,the intracellular reactive oxygen species(ROS)was detec-ted by DCFH-DA fluorescence probe,cell viability was detected by CCK-8,cell apoptosis rate was detected by Annexin V-FITC/PⅠ staining.Results PP Ⅱ signifi-cantly increased the number of acidic vesicles(P＜0.05,P＜0.01)and autophagosomes.PP Ⅱ signifi-cantly up-regulated the ratio of LC3B-Ⅱ/LC3B-Ⅰ,and down-regulated the expression level of p62 protein in a concentration-and time-dependent manner(P＜0.05,P＜0.01).PP Ⅱ significantly increased intra-cellular ROS levels(P＜0.01).Autophagy inhibitor 3-MA and CQ could reverse the regulation of cell via-bility,autophagy and apoptosis related proteins by PP Ⅱ in U2OS cells,endoplasmic reticulum stress inhibi-tor 4-PBA could also reverse the regulation of autoph-agy related proteins by PP Ⅱ in U2OS cells.Conclu-sion PP Ⅱ promotes OS cell autophagy by mediating ROS and endoplasmic reticulum stress.

Objective:To analyze the relationship between hypertension history and long-term coronary adverse prognosis in patients with acute coronary syndrome(ACS).Methods:The study was a retrospective,single-center,observational research.A total of 385 patients,who admitted in Department of Cardiology of First Affiliated Hos-pital of Xi'an Jiaotong University from January 2013 to February 2014,diagnosed as ACS and received coronary an-giography(CAG),were continuously collected.Ischemic events were defined as revascularization,in-stent throm-bosis,in-stent restenosis and active angina.Kaplan-Meier survival curve and Cox regression analysis were used to determine the relationship between hypertension history and long-term coronary adverse prognosis in ACS pa-tients.Results:The 385 patients were divided into hypertension history ≤1 year group(n=201)and hypertension history＞1 year group(n=184)according to the median of hypertension history.After follow-up of 2.6(2.3,2.8)years,39 cases(19.4％)and 46 cases(25.0％)suffered from ischemic events in hypertension history ≤1 year group and hypertension history＞1 year group respectively.Kaplan-Meier survival curve analysis revealed that the incidence rate of ischemic events in hypertension history＞1 year group was significantly higher than that of hyper-tension history ≤1 year group(x2=4.675,P=0.031).After adjusting possible confounding factors,multivariable Cox regression analysis indicated that hypertension history remained an independent risk factor of ischemic events in ACS patients(HR=1.033,95％CI 1.008-1.057,P=0.008).Conclusion:Hypertension history is an independent risk factor for long-term ischemic events in patients with acute coronary syndrome.And the risk of ischemic e-vents is significantly increasing with the longer hypertension history.

Coronary perforation is when a contrast agent or blood flows outside a blood vessel through a tear in a coronary artery.In this case,we reported a case of percutaneous coronary intervention for coronary calcified lesions,which led to iatrogenic coronary perforation and cardiac tamponade after the use of Shockwave balloon to treat intracoronary calcified nodules,and the management of PCI-related CAP was systematically reviewed through the literature.

Objective To investigate the value of optical coherence tomography(OCT)in predicting the risk of major adverse cardiovascular events(MACE)in patients of acute coronary syndrome(ACS).Methods Four hundred and forth-eight ACS patients admitted to the First Affiliated Hospital of Xinjiang Medical University who underwent percutaneous coronary intervention(PCI)and OCT from February 2015 to February 2022 were selected as the study subjects.We found 749 non-culprit coronary lesions.And follow up the patients,median follow-up was 5 years[interquartile interval(IQR):3-7 years].Kaplan-meier was used to estimate the cumulative incidence of MACE,multivariate Cox regression was used to analyze the risk of MACE with OCT parameters non-culprit coronary lesions,and receiver operating characteristic(ROC)curve was used to evaluate the predictive value of OCT parameters for MACE in non-culprit coronary lesions.Results A total of 749 non-culprit coronary lesions were detected,and 41 MACE cases were caused by non-culprit coronary lesions imaged by OCT.Compared with plaques without thin-cap fibroatheroma(TCFA)and minimal lumen area(MLA)＜3.5 mm2,the incidence of MACE was significantly associated with vulnerable plaques with TCFA and MLA＜3.5 mm2(33％vs.3％,HR 13.62,95％CI 6.71-27.65,P＜0.001).Multivariate Cox regression analysis showed that larger maximum lipid arc(HR 1.02,95％CI 1.01-1.03,P＜0.001),smaller maximum lipid cap thickness(HR 0.97,95％CI 0.96-0.99,P＜0.001)and MLA(HR 0.31,95％CI 0.18-0.55,P＜0.001)were independent risk factors for MACE.The area under ROC curve(AUC)of the thinnest fiber cap thickness for predicting MACE occurrence was 0.858(95％CI 0.802-0.913),and the optimal cutoff value was 66.5 μm.The AUC of maximum lipid arc for predicting MACE occurrence was 0.853(95％CI 0.786-0.920),and the optimal cut-off value was 180.35°.The AUC of MLA for predicting MACE was 0.821(95％CI 0.766-0.876),and the optimal cutoff was 3.575 mm2.Conclusions The non-culprit coronary lesions with TCFA and MLA＜3.5 mm2 were significantly associated with an increased risk of subsequent MACE development at the lesion level,and OCT imaging helps early identification of the risk of MACE development in non-culprit coronary lesions in patients of ACS.

Parabacteroides distasonis is a gram-negative bacterium initially isolated from a clinical specimen in the 1930s. The strain was re-classified to form the new genus Parabacteroides in 2006. P. distasonis can regulate intestinal barrier function and plays a key role in immune response and metabolic regulation of bodies. Traditional Chinese medicine(TCM) is closely related to the intestinal microbiota. Polysaccharides, saponins, and other ingredients of TCM can treat diseases by interacting with P. distasonis, but the specific mechanisms underlying these processes are still unclear, requiring further exploration. This study reviewed the roles and related mechanisms of P. distasonis in inflammatory-immune diseases, metabolic diseases, cardiovascular disease, neuropsychiatric diseases, cancer, and other diseases and summarized the relevant research results of TCM to prevent and treat diseases by regulating P. distasonis. This study provides a reference for subsequent exploration of P. distasonis and research on the interaction between TCM and intestinal microbiota.
Humans ; Gastrointestinal Microbiome/drug effects* ; Medicine, Chinese Traditional ; Animals ; Bacteroidetes ; Drugs, Chinese Herbal/pharmacology*

The neurovascular unit (NVU) is highly responsible for cerebral homeostasis and its dysfunction emerges as a critical contributor to Alzheimer's disease (AD) pathology. Hence, rescuing NVU dysfunction might be a viable approach to AD treatments. Here, we fabricated a self-regulated muti-functional nano-modulator (siR/PIO@RP) that can intelligently navigate to damaged blood-brain barrier and release therapeutical cargoes for synergetic AD therapy. The resulting siR/PIO@RP enables self-regulation of its distribution in accordance with the physio/pathological state (low/high RAGE expression) of the target site via a feedback loop. siR/PIO@RP is capable of performing intricate tasks and goes beyond the capabilities of single-target therapeutic agents utilized in AD therapy, such as reducing cerebral Aβ load, relieving neuroinflammation, and alleviating the dysfunction of NVU. Overall, the current study provides proof of concept that normalizing NVU holds promise as a means of alleviating AD symptoms.

Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/β-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knock-down.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/β-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alle-viated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*