BACKGROUND:Lijin manipulation can promote skeletal muscle repair and treat skeletal muscle injury.However,the formation of fibrosis and scar tissue hyperplasia are closely related to the quality of skeletal muscle repair.To study the regulatory effect of Lijin manipulation on the formation of fibrosis and scar tissue hyperplasia is helpful to explain the related mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury. OBJECTIVE:To explore the mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury in rabbits,thereby providing a scientific basis for clinical treatment. METHODS:Forty-five healthy adult Japanese large-ear white rabbits were randomly divided into blank group,model group and Lijin group,with 15 rats in each group.Gastrocnemius strike modeling was performed in both model group and Lijin group.The Lijin group began to intervene with tendon manipulation on the 3rd day after modeling,once a day,and 15 minutes at a time.Five animals in each group were killed on the 7th,14th and 21st days after modeling.The morphology and inflammatory cell count of gastrocnemius were observed by hematoxylin-eosin staining,the collagen fiber amount was observed by Masson staining,the expression of interleukin-6 and interleukin-10 in gastrocnemius was detected by ELISA.The protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin,alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen were detected by western blot and RT-PCR,respectively,and the expression of type Ⅰ collagen protein was detected by immunohistochemistry. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and Masson staining showed that compared with the model group,inflammatory cell infiltration and collagen fiber content decreased in the Lijin group(P<0.01),and the muscle fibers gradually healed.ELISA results showed that compared with the model group,the expression of interleukin-6 in the Lijin group continued to decrease(P<0.05),and the expression of interleukin-10 increased on the 7th day after modeling(P<0.05)and then showed a decreasing trend(P<0.05).Western blot and RT-PCR results showed that compared with the model group,the protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin in the Lijin group were significantly increased on the 14th day after modeling(P<0.05),but decreased on the 21st day(P<0.05);the protein and mRNA expressions of alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen in the Lijin group were significantly decreased compared with those in the model group(P<0.05).Immunohistochemical results showed that the expression of type Ⅰ collagen in the Lijin group was significantly lower than that in the model group(P<0.05).To conclude,Lijin manipulation could improve the repair quality of skeletal muscle injury by inhibiting inflammation,promoting the proliferation and differentiation of muscle satellite cells,and reducing fibrosis.

[Objective]To explore the effects of electricity on sperm quality,sex hormone levels,and related proteins in TGF-β 1/smads signaling in testicular tissue.[Methods]Forty male SD rats were randomly divided into blank group,model group,electroacupuncture group,and positive drug group.Adenine gavage method was used to establish the model,in the electroacupuncture group,rats received electroacupuncture treatment at the acupoints Zhongji,Guanyuan,Zusanli,and Sanyinjiao once daily for 30 minutes;in the positive drug group,rats were administered L-carnitine oral solution via gavage at a dosage of 10 mL/kg,both intervention groups underwent continuous treatment for 28 days.After treatment,the changes of sperm number,sperm motility rate,follicle-stimulating hormone(FSH),luteizing hormone(LH)and serum sex hormone testosterone(T)were detected by HE staining,and the expression of TGF-β-1/smads signaling pathway in testicular tissue was examined by Western Blot.[Results]Compared to the blank group,the model group showed a significant decrease in sperm count and sperm motility rate(P<0.05),both the electroacupuncture group and the positive drug group exhibited significant increases compared to the model group(P<0.05).Compared to the blank group,the model group had a significant decrease in serum testosterone(T)levels(P<0.05),and significant increases in serum FSH and LH levels(P<0.05);in comparison to the model group,the electroacupuncture group and the positive drug group showed significant increases in serum T levels(P<0.05),and significant decreases in serum FSH and LH levels(P<0.05).The HE staining results showed typical pathological features of AR in the testicular tissue of model group rats,with varying degrees of improvement observed in electroacupuncture and positive drug group rats.Western Blot analysis revealed that in the model group,the protein levels of TGF-β,p-smad2,and p-smad3 in the TGF-β1/smads pathway in testicular tissue were significantly increased(P<0.05);in comparison to the model group,the electroacupuncture group and the positive drug group showed significant decreases in the protein levels of TGF-β,p-smad2,and p-smad3(P<0.05).[Conclusion]Acupuncture can improve the sperm number and sperm motility rate,regulate sex hormone level and improve the spermatogenic environment,and affect the spermatogenesis process via TGF-β 1/smads signaling pathway.

OBJECTIVE To investigate the protective effect of interleukin-35(IL-35)mRNA-lipid nanoparticles(LNP)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice.METHODS Fifity-six mice were randomly divided into 7 groups with 8 mice in each,including the normal control group,IL-35 mRNA-LNP(250 μg·kg-1)group,LPS group,LPS+IL-35 mRNA-LNP(50,125 and 250 μg·kg-1)group and LPS+Dexamethasone(DXM)group.Except for the normal control group and IL-35 mRNA-LNP(250 μg·kg-1)group and ALI model was established by tracheal infusion of LPS in each of the other groups.IL-35 mRNA-LNP(250 μg·kg-1)group and LPS+IL-35 mRNA-LNP(50,125 and 250 μg·kg-1)group were injected with a corresponding dose of LNP encapsulated mRNA complex via the tail vein while the LPS+DXM group was injected with DXM via the tail vein.Lung coefficient and the wet to dry weight ratio(W/D)of lung tissue were recorded.The mRNA levels of inflammatory cytokines tumor necrosis factor-α(TNF-α),Interleukin-6(IL-6)and IL-1βof lung homogenates were detected by real-time fluorescence quantitative PCR(RT-qPCR).LDH activity of lung homogenates and the protein levels of IL-35,TNF-α,IL-6 and IL-1β in lung homogenate were detected by corresponding kits.Hematoxylin-eosin(HE)staining was used to observe and analyze the pathological injury to lung tissue.The expres-sion of Lymphocyte antigen 6G(Ly6G)was detected by Immunofluorescence to reflect the infiltration of neutrophils.RESULTS Compared with the normal control group,LPS group and LPS+DXM group,IL-35 protein expression levels in lung homogenates of the other groups were more significant(P<0.01).Compared with the normal control group,lung coefficient,W/D ratio of lung tissue,LDH activity,mRNA levels and the protein levels of TNF-α,IL-6 and IL-1β in lung homogenates were significantly increased in the LPS group(P<0.01),accompanied by alveolar hemorrhage,alveolar wall thickening and neutro-phils infiltration.After IL-35 mRNA-LNP administration,lung coefficient,W/D ratio of lung tissue,LDH activity,mRNA levels and the protein levels of TNF-α,IL-6 and IL-1β in lung homogenates were signifi-cantly decreased(P<0.01),and alveolar hemorrhage,alveolar wall thickening and neutrophil infiltration were obviously improved.CONCLUSION IL-35 mRNA-LNP can express IL-35 protein in lung tissue of mice,and effectively improve LPS-induced ALI in mice by inhibiting the expression of proinflammatory factors.

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Objective:To assess the efficacy and safety of cinepazide maleate injection in the treatment of patients with acute ischemic stroke.Methods:A multicenter, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial, led by Peking Union Medical College Hospital, was conducted in 65 Hospitals in China. The efficacy of cinepazide maleate injection in patients with acute anterior circulation cerebral infarction with onset time of ≤48 hours, 7≤National Institute of Health stroke scale (NIHSS) score ≤25 was assessed from August 2016 to February 2019, using the proportion of modified Rankin scale (mRS) score≤1 and Barthel index (BI) score≤95 on day 14 as efficacy endpoint. The patients were divided into treatment group who were treated with cinepazide maleate injection and control group who were treated with placebo.Results:A total 937 patients were involved in the final efficacy analysis (466 in treatment group and 471 in control group). The proportion of subjects with mRS score≤1 on day 14 after treatment were higher in the treatment group than that in the control group (102/466(21.89%) vs76/471(16.14%)). Logistic regression analysis showed that patients treated with cinepazide maleate were significantly more likely to have a favorable outcome (mRS score≤1) than patients treated with placebo on day 14 ( OR=0.677, 95% CI 0.484-0.948 , P=0.023), and patients treated with cinepazide maleate were more likely to reach independence in activities of daily living (Barthel Index ≥95) than those treated with placebo on day 14 (125/466(26.82%) vs 91/471(19.32%); OR=0.632, 95% CI0.459-0.869, P=0.005). The rate of adverse events was similar between the treatment and control groups. Conclusion:The 14-day treatment with cinepazide maleate injection could reduce the degree of disability whereas did not increase the risk of adverse events.

Objective: To evaluate the effect of irisin preconditioning on global cerebral ischemia-reperfusion (I/R) injury in rats. Methods: Thirty-six healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 3 groups (n=12 each) using a random number table method: sham operation group (group S), global cerebral I/R group (group I/R) and irisin preconditioning group (group I). Global cerebral I/R was induced by occlusion of bilateral common carotid arteries combined with hypotension (MAP maintained at 35-45 mmHg) in anesthetized rats.At 30 min before ischemia, irisin 10 μg/kg (diluted to 10 μg/ml in normal saline) was intravenously injected in group I, and the equal volume of normal saline was intravenously injected in S and I/R groups.Morris water maze test was performed at day 3 of reperfusion to assess the cognitive function.Rats were sacrificed after the end of morris water maze test, and brains were removed for determination of histopathologic changes in hippocampal CA1 region (using HE staining), neuronal apoptosis in hippocampal CA1 region (Tunel staining), glial fibrillary acidic protein (GFAP) expression (by Western blot), myeloperoxidase (MPO) activity in the hippocampal tissues (by colorimetric assay), and contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in hippocampal tissues (by enzyme-linked immunosorbent assay). The cell necrosis rate and apoptotic rate were calculated. Results: Compared with group S, the escape latency was significantly prolonged on 1-5 days in group I/R and on 1-3 days in group I, the time of staying at 1st quadrant was significantly shortened, the cell necrosis rate and apoptotic rate were increased, the expression of GFAP was up-regulated, and the activity of MPO and contents of TNF-α and IL-1β were increased in I/R and I groups (P<0.05 or 0.01). Compared with group I/R, the escape latency was significantly shortened on 1-5 days, the time of staying at 1st quadrant was prolonged, the cell necrosis rate and apoptotic rate were decreased, the expression of GFAP was down-regulated, and the MPO activity and contents of TNF-α and IL-1β were decreased in group I (P<0.05 or 0.01). Conclusion Irisin preconditioning can reduce the global cerebral I/R injury in rats, and the mechanism may be related to inhibiting activation of astrocytes in hippocampus and reducing inflammatory responses.

In recent years, acupuncture has been used widely as an adjuvant treatment for the in vitro fertilization (IVF). " " published in on May 15, 2018, the research findings do not support the use of acupuncture to improve the rate of live births among the women undergoing IVF. In order to avoid the misunderstanding of the scholars at home and abroad for the clinical effects of acupuncture on IVF assistance, the authors put forward the doubts after the analysis from the following 3 aspects, including the acupuncture scheme, outcomes and result explanation. Additionally, the thinking and suggestions are proposed for the future development of the clinical trials of acupuncture IVF assistance in terms of selecting the proper participants, being abided by the standards of the evidence-based medicine, designing multi-acupuncture schemes and setting up the rational control, as well as conducting the overall analysis of the trial data.
Acupuncture ; American Medical Association ; Embryo Transfer ; Female ; Fertilization in Vitro ; Humans ; Live Birth ; Pregnancy ; Pregnancy Rate ; United States

OBJECTIVETo investigate the effect and safety of acupuncture with regulating menstruation to promote pregnancy for diminished ovarian reverse (DOR).

METHODSAccording to prospective case series, 46 patients were observed and finally 40 cases were included. The acupoints were ① Baihui (GV 20), Shenting (GV 24), Guanyuan (CV 4) and bilateral Benshen (GB 13), Huangshu (KI 16), Dahe (KI 12), Luanchao (Extra), Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3), Taichong (LR 3) and ② bilateral Shenshu (BL 23) and Ciliao (BL 32). The points in the two groups were used alternately. Acupuncture was given for 3 courses, 12 times as a course and 3 times a week. Before and after treatment, and 3 months after treatment, follicle-stimulating hormone (FSH), follicle-stimulating hormone/luteinizing hormone (FSH/LH), estradiol (E), antral follicle count (AFC) and TCM symptom score were observed. The safety was evaluated.

RESULTSCompared with before treatment, the levels of FSH, FSH/LH decreased, and the levels of Eand AFC increased after treatment and at follow-up (all<0.05). And the TCM symptom scores were significantly lower than those before treatment (both<0.05). The rate of pregnancy after treatment was 15% (6/40). There was no infection and organ injury.

CONCLUSIONAcupuncture with regulating menstruation to promote pregnancy can safely improve the ovarian reserve of patients with DOR.

Objective To systematically assess the efficacy and safety of acupuncture in treating type 2 diabetes.Methods Related literature was retrieved with a computer. After the data were sifted out from the literature according to the established criteria, they were collected and crossly checked by two researchers independently. The data were input to RevMan5.2 for statistical analysis. Results A total of ten studies were included with a total of 743 patients. The results of Meta analysis showed 1) Post-treatment total efficacy rate was higher in the acupuncture or combined acupuncture and medicine group than in the control group [OR=3.60, 95%CI (2.11,6.13)] and there was a statistically significant difference (Z=4.71,P<0.00001); 2) Post-treatment range of decrease in fasting blood glucose (FBG) was significantly higher in the experiment group than in the control group [WMD=-1.20,95%CI (-1.38,-1.02)] and there was a statistically significant difference (Z=12.88,P<0.00001); 3) Post-treatment range of decrease in 2-h postprandial blood glucose (2hPBG) was significantly higher in the experiment group than in the control group [WMD=-1.27, 95%CI (-1.47,-1.06)] and there was a statistically significant difference (Z=12.02,P<0.00001).Conclusion Clinically acupuncture or combined acupuncture and medicine is more effective than Chinese herbal medicine or Western medication alone in treating T2DM and has no toxic and side effects.