Research progress for microRNA in the pathological mechanism of brain injury after stroke

Ischemic stroke is a leading cause of death and disability.Despite extensive research,treatment for ischemic stroke is limited to thrombolytic therapy and symptom management.Identifying and testing new therapeutic targets is therefore critical for future clinical-ly viable stroke therapies.Noncoding RNAs,especially microRNAs(miRNAs),are one of many classes of mole-cules that cause functional changes before,during,and af-ter ischemic stroke.Current research finds that expression levels of many miRNAs are altered in the blood and brain of rodents and humans after stroke.In addition,miRNA can be regulated by external factors to improve functional outcomes after ischemic stroke.In certain studies,induction of ischemic tolerance by preconditioning(PC)also altered the levels of many miRNAs.This review focuses on miRNAs that modulate stroke-related risk factors and pathologic mechanisms of post-stroke brain injury.

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China(RWE-PCSK study)

BACKGROUND The efficacy and safety of proprotein convertase subtilisin/kexin type 9(PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease(ASCVD).METHODS This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention(PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events(MACE) over six months were compared between two groups.A propensity score-matched(PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE.RESULTS In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol(LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81%(P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group(P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE(hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250).CONCLUSIONS In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

Application of a rapid exchange extension catheter technique in type

BACKGROUND In transradial intervention procedures,poor back-up support and noncoaxial alignment of the guide catheter(GC)may result in failure of the balloon or stent to reach the targeted lesion.Methods to provide extra back-up support using the original GC and wire can improve procedural success with reduced complications.A rapid exchange guide extension catheter provides convenient and efficient back-up support while preserving the initial GC and inserted wire.AIM To evaluate the efficacy and safety of rapid exchange extension catheter in the treatment of type B2/C nonocclusive coronary lesions via the radial access.METHODS A total of 135 patients with type B2/C nonocclusive lesions who were treated via the transradial approach were enrolled in the study.The clinical characteristics,indications for use of the rapid exchange extension catheter,and procedural details and results were reviewed and analyzed.All procedure-related complications and major adverse cardiovascular events were recorded during the in-hospital stay and follow-up period.RESULTS The most common indication for the use of a rapid exchange extension catheter was vascular tortuosity(37.8%),followed by heavy calcification(28.9%),long lesions(20.0%),proximal stent(6.7%),in-stent restenosis(5.2%),and coronary origin anomalies(1.5%).The following technologies failed in passing targeted lesions before delivering the rapid exchange catheter:Multiple predilatation technique(57%),buddy wire technique(33.4%),balloon anchoring technique (5.9%), and cutting balloon modification (3.7%). The mean depth of the extensioncatheter intubation was 20.56 ± 13.05 mm, and the mean rapid exchange catheterservice time was 18.9 ± 9.7 min. The mean length and diameter of stents were 33.5± 14.4 mm and 2.75 ± 0.45 mm, respectively. The total rate of technique success(balloon or stent successful crossing of the target lesion with this technique) was94.8%.CONCLUSIONThe rapid exchange extension catheter technique showed acceptable safety andefficacy in the transradial coronary interventions of type B2/C nonocclusivecoronary lesions. We recommend this technique to assist in complex lesionintervention via radial access.

Advances in the pathogenesis and treatment of cognitive dysfunction after radiation therapy

Radiation therapy is an important part of the comprehensive treatment of brain tumors and one of the most effective treatment methods.However,brain inju-ry is a serious complication.In regards to long-term brain injury caused by radiation therapy,cognitive dysfunction is the most common and serious.As the treatment of brain tumors improves,the survival time of patients with malig-nant brain tumors is significantly prolonged and the prob-ability of cognitive dysfunction after radiation therapy is increased.Eliminating the delayed side effects caused by radiation therapy will significantly improve the quality of life of patients with malignant brain tumor and reduce the social burden.Therefore,the study of the pathogene-sis and treatment of cognitive dysfunction after radiation therapy is of great significance.This review focuses on the pathogenesis and treatment of cognitive dysfunction after radiation therapy.

Effect of continuous nursing on rehabilitation of older patients with joint replacement after discharge

BACKGROUND Joint replacement is a common treatment for older patients with high incidences of hip joint diseases.However,postoperative recovery is slow and complications are common,which reduces surgical effectiveness.Therefore,patients require long-term,high-quality,and effective nursing interventions to promote rehabilitation.Continuity of care has been used successfully in other diseases;however,little research has been conducted on older patients who have undergone hip replacement.AIM To explore the clinical effect of continuous nursing on rehabilitation after discharge of older individuals who have undergone joint replacement.METHODS A retrospective analysis was performed on the clinical data of 113 elderly patients.Patients receiving routine nursing were included in the convention group(n=60),and those receiving continuous nursing,according to various methods,were included in the continuation group(n=53).Harris score,short form 36(SF-36)score,complication rate,and readmission rate were compared between the convention and continuation groups.RESULTS After discharge,Harris and SF-36 scores of the continuation group were higher than those of the convention group.The Harris and SF-36 scores of the two groups showed an increasing trend with time,and there was an interaction effect between group and time(Harris score:F_(intergroup effect)=376.500,F_(time effect)=20.090,Finteraction effect=4.824;SF-36 score:F_(intergroup effect)=236.200,Ftime effect=16.710,Finteraction effect=5.584;all P<0.05).Furthermore,the total complication and readmission rates in the continuation group were lower(P<0.05).CONCLUSION Continuous nursing could significantly improve hip function and quality of life in older patients after joint replacement and reduce the incidence of complications and readmission rates.

Neuroprotective effect of ischemic postconditioning on sciatic nerve transection

Ischemic preconditioning or postconditioning has been shown to have neuroprotective effect on cerebral ischemia, but it has not been studied in peripheral nerve injury. In this study, a rat model of sciatic nerve transection was established, and subjected to three cycles of ischemia for 10 minutes ＋ reperfusion for 10 minutes, once a day. After ischemic postconditioning, serum insulin-like growth factor 1 expression increased; sciatic nerve Schwann cell myelination increased; sensory function and motor function were restored. These findings indicate that ischemic postconditioning can effectively protect injured sciatic nerve. The protective effect is possibly associated with upregulation of insulin-like growth factor 1.

Correlation analysis of carotid intima media thickness and function in patients with H-type hypertension and acute cerebral infarction

Objective:To explore the correlation of carotid intima media thickness with function in patients with H-type hypertension and acute cerebral infarction.Methods:A total of 150 patients with acute cerebral infarction who were admitted in our hospital from June, 2016 to June, 2017 were included in the study and divided into H-type hypertension group (H-type hypertension merged with acute cerebral infarction, Hcy≥10 μmol/L), non-H-type hypertension group (non- H-type hypertension merged with acute cerebral infarction, Hcy≥10 μmol/L), and the control group (no hypertension but with acute cerebral infarction) according to Hcy level and whether being suffered from hypertension or not with 50 cases in each group. Moreover, 50 healthy individuals who came for physical examinations were served as the healthy group. The morning fasting peripheral venous blood was collected at physical examination time for patients in the healthy group and after admission for patients with acute cerebral infarction. Hcy, sICAM-1, MCP-1, and YKL-40 were detected. The color Doppler ultrasound diagnostic apparatus was used to detect IMT, distensibility, and stiffness. Results: Hcy, MCP-1, sICAM-1, and YKL-40 levels in H-type hypertension group, non-H-type hypertension group, and the control group were significantly higher than those in the healthy group. Hcy, MCP-1, sICAM-1, and YKL-40 levels in H-type hypertension group and non-H-type hypertension group were significantly higher than those in the control group. Hcy, MCP-1, sICAM-1, and YKL-40 levels in H-type hypertension group were significantly higher than those in non-H-type hypertension group. IMT and stiffness in H-type hypertension group, non-H-type hypertension group, and the control group were significantly greater than those in the healthy group, while distensibility was significantly less than that in the healthy group. IMT and stiffness in H-type hypertension group and non-H-type hypertension group were significantly greater than those in the control group, while distensibility was significantly less than that in the control group. IMT and stiffness in H-type hypertension group were significantly greater than those in non-H-type hypertension group, while distensibility was significantly less than that in non-H-type hypertension group.Conclusions: Hcy can directly affect carotid AS, increase carotid IMT, and promote the occurrence of hypertension merged with acute cerebral infarction;therefore, positive monitoring of serum Hcy level and IMT thickness in patients with hypertension and acute cerebral infarction and early intervention are of great significance in reducing the occurrence of carotid AS, delaying the progression of carotid AS, and preventing hypertension and acute cerebral infarction.

Long noncoding RNA protein-disulfide isomerase-associated 3 regulated high glucose-induced podocyte apoptosis in diabetic nephropathy through targeting miR-139-3p

BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy(DN).The regulatory relationship between long noncoding RNAs(lncRNAs)and podocyte apoptosis has recently become another research hot spot in the DN field.AIM To investigate whether lncRNA protein-disulfide isomerase-associated 3(Pdia3)could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism.METHODS Using normal glucose or high glucose(HG)-cultured podocytes,the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress(ERS)were explored.LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction.Relative cell viability was detected through the cell counting kit-8 colorimetric assay.The podocyte apoptosis rate in each group was measured through flow cytometry.The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay.Finally,western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p.RESULTS The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes.Next,lncRNA Pdia3 was involved in HG-induced podocyte apoptosis.Furthermore,the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p.LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes.CONCLUSION Taken together,this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p,which might provide a potential therapeutic target for DN.

A Retrospective Survival Analysis of Anatomic and Prognostic Stage Group Based on the American Joint Committee on Cancer 8th Edition Cancer Staging Manual in Luminal B Human Epidermal Growth Factor Receptor 2-negative Breast Cancer

Background： Current understanding of tumor biology suggests that breast cancer is a group of diseases with different intrinsic molecular subtypes. Anatomic staging system alone is insufficient to provide future outcome information. The American Joint Committee on Cancer （AJCC） expert panel updated the 8th edition of the staging manual with prognostic stage groups by incorporating biomarkers into the anatomic stage groups. In this study, we retrospectively analyzed the data from our center in China using the anatomic and prognostic staging system based on the AJCC 8th edition staging manual. Methods： We reviewed the data from January 2008 to December 2014 for cases with Luminal B Human Epidermal Growth Factor Receptor 2 （HER2）-negative breast cancer in our center. All cases were restaged using the AJCC 8th edition anatomic and prognostic staging system. The Kaplan-Meier method and log-rank test were used to compare the survival differences between different subgroups. SPSS software version 19.0 （IBM Corp., Armonk, NY, USA） was used for the statistical analyses. Results： This study consisted of 796 patients with Luminal B HER-negative breast cancer. The 5-year disease-free survival （DFS） of 769 Stage I-III patients was 89.7%, and the 5-year overall survival （OS） of all 796 patients was 91.7%. Both 5-year DFS and 5-year OS were significantly different in the different anatomic and prognostic stage groups, There were 372 cases （46.7%） assigned to a different group. The prognostic Stage II and III patients restaged from anatomic Stage III had significant differences in 5-year DFS （v2 = 11.319; P = 0.001） and 5-year OS （χ2 = 5.225, P = 0.022）. In addition, cases restaged as prognostic Stage I, II, or III from the anatomic Stage II group had statistically significant differences in 5-year DFS （χ2 = 6.510, P = 0.039） but no significant differences in 5-year OS （χ2 = 5.087, P = 0.079）. However, the restaged prognostic Stage I and II cases from anatomic Stage I had no statistically significant differences in either 5-year DFS （χ2 = 0.440, P = 0.507） or 5-year OS （χ2= 1.530, P = 0.216）. Conclusions： The prognostic staging system proposed in the AJCC 8th edition refines the anatomic stage group in Luminal B HER2-negative breast cancer and will lead to a more personalized approach to breast cancer treatment.

Canagliflozin Regulates Ferroptosis, Potentially via Activating AMPK/PGC-1α/Nrf2 Signaling in HFpEF Rats

Aims:Sodium-glucose cotransporter-2(SGLT2)inhibitors have been found to ameliorate major adverse cardiovascular events in patients with heart failure with preserved ejection fraction(HFpEF),but the exact mechanism is unknown.Ferroptosis is a form of programmed necrosis.Herein,we verified that canagliflozin(CANA)ameliorates heart function in HFpEF rats,partly by regulating ferroptosis,which may be activated by AMPK/PGC-1α/Nrf2 signaling.Methods:An HFpEF model was established and subjected to CANA treatment.Blood pressure was monitored,and echocardiography was performed at the 12th week.Pathological examination was performed,and expression of ferroptosis-associated proteins and AMPK/PGC-1α/Nrf2 signaling related proteins was detected.Results:CANA had an antihypertensive effect and increased E/A ratios in HFpEF rats.Myocardial pathology was ameliorated,on the basis of decreased cross-sectional area and intercellular fibrosis.Acyl-CoA synthetase longchain family member 4(ACSL4)expression increased,whereas ferritin heavy chain 1(FTH1)expression decreased in HFpEF rats,which showed iron overload.CANA reversed changes in ACSL4 and FTH1,and decreased iron accumulation,but did not alter glutathione peroxidase 4(GPX4)expression.The expression of AMPK/PGC-1α/Nrf2 signaling related proteins and heme oxygenase 1(HO-1)in the HFpEF group decreased but was reverted after CANA treatment.Conclusions:CANA regulates ferroptosis,potentially via activating AMPK/PGC-1α/Nrf2 signaling in HFpEF rats.

Influence of Tirofiban maintenance duration on patients with acute myocardial infarction treated by percutaneous coronary intervention

Objective: To evaluate the efficacy and short term prognosis of Tirofiban in different treatment duration in patients with acute ST segment elevation myocardial infarction (STEMI) and percutaneous coronary intervention (PCI) combined with intracoronary injection. Methods: A total of 125 patients with acute STEMI were enrolled in this study. They were randomly divided into two groups: control group (n ? 61) and Tirofiban group (n ? 64). The Tirofiban was used by intracoronary and intravenous administration in Tirofiban group which was randomly divided into three sub-groups according to the duration of Tirofiban by persistent intravenous injection for 12 hours, 24 hours or 36 hours. Thrombolysis in myocardial infarction flow and myocardial perfusion grades were recorded immediately after PCI. The adverse cardiac events and cardiac death within 180 days of PCI, and the adverse effects (hemorrhage and thrombocytopenia) were compared between the two groups and within Tirofiban sub-groups. Results: Grade 3 in myocardial perfusion was significantly better in Tirofiban group than control group (85.94% vs. 72.13%, P ? 0.03) after PCI. There was one cardiac death in control group in 180 days after PCI. The adverse cardiac event rates between two groups was significant difference (16 patients in control group and only 8 in Tirofiban group, P ? 0.047). There was no significant difference in incidence of hemorrhage complications and platelet counts between two groups. Nevertheless, hemorrhage complications in the 12-and 24-hour subgroups were less than 36-hour subgroup (P ? 0.01). Conclusions: Intravenous Tirofiban treatment reduced the adverse cardiac events and improved short term prognosis without increasing the adverse reactions of the drugs in patients undergoing PCI. The less rate of hemorrhage complication can be achieved in short-duration of Tirofiban by intravenous injection after PCI. Copyright ? 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Fine Particulate Matter-Induced Exacerbation of Allergic Asthma via Activation of T-cell Immunoglobulin and Mucin Domain 1

Background： Fine particulate matter （PM2.5） exacerbates airway inflammation and hyperreactivity in patients with asthma, but the mechanism remains unclear. The aim of this study was to observe the effects of prolonged exposure to high concentrations of PM2.5 on the pathology and airway hyperresponsiveness （AHR） of BALB/c mice undergoing sensitization and challenge with ovalbumin （OVA） and to observe the effects of apoptosis and T-cell immunoglobulin and mucin domain 1 （TIM-1） in this process. Methods： Forty female BALB/c mice were divided into four groups： control group, OVA group, OVA/PM group, and PM group （n - 10 in each group）. Mice in the control group were exposed to filtered clean air. Mice in the OVA group were sensitized and challenged with OVA. Mice in the OVA/PM group were sensitized and challenged as in the OVA group and then exposed to PM2.5 for 4 h per day and 5 days per week for a total of 8 weeks using a nose-only ＂PM2.5 online enrichment system＂ in The Second Hospital of Hebei Medical University. Mice in the PM group were exposed to the PM2.5 online enrichment system only. AHR was detected. Bronchoalveolar lavage fluid （BALF） was collected for cell classification. The levels of interleukin-4 （IL-4）, IL-5, and IL-33 in BALF were measured using enzyme-linked immunosorbent assay. Changes in histological structures were examined by light microscopy, and changes in ultramicrostructures were detected by electron microscopy. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） assay in the lung tissues. Western blotting and immunohistochemistry were utilized to analyze the expression of Bcl-2, Bax, and TIM-1 in the lungs. Results： The results showed that AHR in the OVA/PM group was significantly more severe than that in the OVA and PM groups （P 〈 0.05）. AHR in the PM group was also considerably more severe than that in the control group （P 〈 0.05）. The BALF of OVA/PM group （28.00± 6.08 vs. 12.33 ±4.51, t = 4.631, P = 0.002） and PM group （29.00 ± 3.00 vs. 12.33 ± 4.51, t = 4.927, P = 0.001） had more lymphocytes than the BALF of the control group. The number of neutrophils in the BALF of the OVA/PM group （6.67 ± 1.53 vs. 3.33 ± 1.53, t = 2.886, P = 0.020） and PM group （6.67 ± 1.53 vs. 3.33 ± 1.53, t = 2.886, P = 0.020） was much higher than those in the BALF of OVA group （P 〈 0.05）. TUNEL assays showed that the number of apoptotic cells in the OVA/PM group was significantly higher than that in the OVA group （Tunel immunohistochemical scores [IHS%], 1.20 ± 0.18 vs. 0.51 ± 0.03, t = 8.094, P 〈 0.001） and PM group （Tunel IHS%, 1.20 ± 0.18 vs. 0.51 ±0.09, t = 8.094, P〈 0.001）, and that the number of apoptotic cells in the PM group was significantly higher than that in the control group （Tunel IHS%, 0.51 ± 0.09 vs. 0.26 ± 0.03, t = 2.894, P = 0.020）. The concentrations of IL-4 （77.44 ± 11.19 vs. 48.02 ±10.02 pg/ml, t = 4.595, P= 0.002） and IL-5 （15.65 ± 1.19vs. 12.35±0.95pg/ml, t=3.806,P=0.005） and the Bax/Bcl-2 ratio （1.51 ± 0.18 vs. 0.48 ± 0.10, t = 9.654, P 〈 0.001） and TIM-1/β-actin ratio （0.78 ± 0.11 vs. 0.40 ±0.06, t = 6.818, P 〈 0.001） in the OVA/PM group were increased compared to those in the OVA group. The concentrations of IL-4 （77.44 ± 11.19 vs. 41.47 ± 3.40 pg/ml, t = 5.617, P= 0.001） and IL-5 （ 15.65±1. 19 vs. 10.99 ± 1.40 pg/ml, t = 5.374, P = 0.001 ） and the Bax/Bcl-2 ratio （1.51 ±0.18 vs. 0.97 ± 0.16, t = 5.000, P = 0.001） and TIM-1/β-actin ratio （0.78 ± 0.11 vs. 0.31 ± 0.06,t = 8.545, P 〈 0.001 ） in the OVA/PM group were increased compared to those in the PM group. The concentration oflL-4 （41.47 ±3.40 vs. 25.46 ± 2.98 pg/ml, t = 2.501, P = 0.037） and the Bax/Bcl-2 ratio （0.97 ± 0.16 vs. 0.18 ± 0.03, t = 7.439, P 〈 0.001） and TIM-1/β-actin ratio （0.31 ± 0.06 vs. 0.02 ± 0.01, t = 5.109, P = 0.001） in the PM group were also higher than those in the control group. Conclusions： Exacerbated AHR associated with allergic asthma caused by PMz5 is related to increased apoptosis and TIM-1 activation. These data might provide insights into therapeutic targets for the treatment of acute exacerbations of asthma induced by PM2.5.

Influence of Tuina plus oxiracetam on serum inflammatory factors and oxidative stress in mild vascular dementia patients

Objective To observe the clinical efficacy of Tuina(Chinese therapeutic massage)plus oxiracetam in treating mild vascular dementia(VD)and seek its underlying mechanism.Methods Ninety-six patients with mild VD were randomized into an observation group and a control group,with 47 cases in the observation group and 49 cases in the control group.The control group received oral oxiracetam capsules for treatment,and the observation group was given additional Tuina treatment.Before and after treatment,the mini-mental state examination(MMSE)was adopted to assess the patient’s cognitive function;the activities of daily living(ADL)scale was used to evaluate their ability to conduct daily activities;changes in the serum inflammatory factors and oxidative stress indicators were also detected.Results After treatment,the serum content of malondialdehyde(MDA)decreased in both groups(P<0.05)and was lower in the observation group than in the control group(P<0.05);the serum contents of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)increased in both groups(P<0.05)and were higher in the observation group than in the control group(P<0.05);the serum contents of interleukin(IL)-1,tumor necrosis factor(TNF)-α,IL-6,and IL-8 declined in both groups(P<0.05)and were lower in the observation group than in the control group(P<0.05).After the intervention,the levels of systolic velocity(Vs)and mean velocity(Vm)of the middle cerebral artery elevated,and the pulsatility index(PI)dropped in patients in the two groups,showing significant intra-group differences(P<0.05);the levels of Vs and Vm in the observation group were higher than those in the control group,and the PI was lower in the observation group than in the control group,showing significant between-group differences(P<0.05).The MMSE and ADL scores increased in both groups after the intervention(P<0.05)and were higher in the observation group than in the control group(P<0.05).Conclusion In the treatment of mild VD,Tuina plus oxiracetam can improve the cerebral blood supply,ADL,and cognitive function;the mechanism may be associated with the reduction of oxidative stress damages and inflammatory reactions.

Electroacupuncture stimulating Neixiyan(EX-LE5)and Dubi(ST35)alleviates osteoarthritis in rats induced by anterior cruciate ligament transaction via affecting DNA methylation regulated transcription of miR-146a and miR-140-5p

OBJECTIVE:To explore whether electroacupuncture(EA could alleviate osteoarthritis(OA)through affecting the DNA methylation regulated transcription of miR-146a and mi R-140-5p.METHODS:Sixty male eight-week-old Sprague-Dawley rats were divided into three groups:normal group(normal healthy rats;no treatment),model group(OA rats;no treatment)and EA group(OA rats treated with EA).Safranin O staining and modified Mankin’s score were performed to evaluate the histopathological alterations and degeneration of cartilage 8 weeks after 8 consecutive weeks of treatment.Quantitative real time polymerase chain reaction(qR T-PCR)assay was employed to evaluate the expression of miR-146a in the cartilage tissue and miR-140-5p in the synovium tissue,respectively.The bisulfite sequencing analysis and quantitative methylation specific PCR(qMSP)were used to analyze the status of methylation in the regulatory regions of miR-146a and miR-140-5p.Chromatin immunoprecipitation(ChIP)assay were performed to assess the binding of nuclear factor-kappa B(NF-κB)and signal transducer and activator of transcription 3(SMAD-3)in the regulatory regions of miR-146a and miR-140-5p.Western blot analysis was performed to detect the expressions of DNA Methyltransferase 1(DMNT1),DNA Methyltransferase 3A(DMNT3A),and DNA Methyltransferase 3A(DMNT3b),NF-κB,SMAD3 levels.RESULTS:Our results showed that EA treatment significantly upregulated miR-146a and miR-140-5p expressions.qMSP analysis showed that EA significantly decreased methylation levels of miR-140-5p regulated region and miR-146a promoter in OA cartilage and synovium.Bisulfite DNA sequencing(BDS)and ChI P analysis showed that EA significantly increased binding affinity of SMAD3 and NF-kB on the hypermethylated miR-140 regulatory region and miR-146a promoter,respectively.Western Blot analysis demonstrated that EA also significantly decreased expressions of methylation related proteins-DMNT1,DMNT3a,and DMNT3b as well as NF-κB and SMAD3.CONCLUSIONS:Electroacupuncture stimulating Neixiyan(EX-LE5)and Dubi(ST35)may alleviate OA via affecting the DNA methylation regulated transcription of miR-146a and miR-140-5p.

振腹对幼龄厌食模型大鼠外周血中胃肠激素及胃肠动力的影响

目的:观察振腹对厌食症模型大鼠的治疗作用及对其外周血中八肽胆囊收缩素(CCK-8)和胃动素(MTL)含量的影响。方法:按照随机数字表法将40只幼龄大鼠进行分组,分为正常组10只和造模组30只。正常组给予普通饲料喂食。造模组采用病因模拟法构建厌食症模型,造模3周后将其随机分为药物组、振腹组和模型组,每组10只。药物组按0.72 g/(kg·bw)剂量给予健胃消食片灌胃(将0.72 g药物用纯水配制成10 mL药液);正常组和模型组每天上午灌服等体积纯水1次;振腹组予以振腹治疗,每日1次,共治疗21次。检测各组大鼠体质量、摄食量、外周血CCK-8、MTL、胃泌素(GAS)及神经降压素(NT)的含量和小肠推进率。结果:与模型组相比,振腹组与药物组的体质量和摄食量、血清MTL及GAS含量和小肠推进率明显提高,血浆CCK-8、NT含量及胃残留率降低,差异具有统计学意义(P<0.05);但振腹组与药物组比较无统计学差异(P>0.05)。结论:振腹可增加厌食症模型大鼠的进食量和体质量,减少胃内容物的残留,提高小肠推进率,对厌食症具有较好的治疗作用。其作用机理可能与抑制血浆CCK-8和NT分泌,促进血清MTL和GAS释放有关。

Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients:An Open-Label,Multicenter,and Randomized Controlled Trial

Objective: To investigate whether Naoxueshu Oral Liquid(NXS) could promote hematoma absorption in post-craniotomy hematoma(PCH) patients. Methods: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18–80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS(10 m L thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage(ICH). Results: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients(60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set(FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median(Q1, Q3): 85%(71%, 97%) vs. 76%(53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set(P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH(all P<0.05). Conclusions: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics.