Effects of electroacupuncture on rats with cognitive impairment: An iTRAQ-based proteomics analysis.

OBJECTIVE: The study explores the effects of electroacupuncture (EA) at the governing vessel (GV) on proteomic changes in the hippocampus of rats with cognitive impairment. METHODS: Healthy male rats were randomly divided into 3 groups: sham, model and EA. Cognitive impairment was induced by left middle cerebral artery occlusion in the model and EA groups. Rats in the EA group were treated with EA at Shenting (GV24) and Baihui (GV20) for 7 d. Neurological deficit was scored using the Longa scale, the learning and memory ability was detected using the Morris water maze (MWM) test, and the proteomic profiling in the hippocampus was analyzed using protein-labeling technology based on the isobaric tag for relative and absolute quantitation (iTRAQ). The Western blot (WB) analysis was used to detect the proteins and validate the results of iTRAQ. RESULTS: Compared with the model group, the neurological deficit score was significantly reduced, and the escape latency in the MWM test was significantly shortened, while the number of platform crossings increased in the EA group. A total of 2872 proteins were identified by iTRAQ. Differentially expressed proteins (DEPs) were identified between different groups: 92 proteins were upregulated and 103 were downregulated in the model group compared with the sham group, while 142 proteins were upregulated and 126 were downregulated in the EA group compared with the model group. Most of the DEPs were involved in oxidative phosphorylation, glycolipid metabolism and synaptic transmission. Furthermore, we also verified 4 DEPs using WB technology. Although the WB results were not exactly the same as the iTRAQ results, the expression trends of the DEPs were consistent. The upregulation of heat-shock protein ß1 (Hspb1) was the highest in the EA group compared to the model group. CONCLUSION: EA can effect proteomic changes in the hippocampus of rats with cognitive impairment. Hspb1 may be involved in the molecular mechanism by which acupuncture improves cognitive impairment.

Comparison of Net Clinical Benefit Between Clopidogrel and Ticagrelor Following Percutaneous Coronary Intervention in Patients in China With Acute Coronary Syndrome.

INTRODUCTION: The objective of the present study was to evaluate the difference in net clinical benefit of clopidogrel plus aspirin compared with ticagrelor plus aspirin after 12 months in patients in mainland China with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with newer-generation drug-eluting stents (DESs). METHODS: In this multicenter, retrospective, real-world study, the data were sourced from three databases: BRIC-ACS(I) study, COSTIC study, and 301 Hospital PCI patient database from January 2014 to October 2017. The primary endpoint of the study was net adverse clinical and cerebral events (NACCE) comprised of all-cause death, non-fatal myocardial infarction (MI), non-fatal stroke or Bleeding Academic Research Consortium (BARC) type ≥ 2 (excluding BARC type = 4) bleeding, whereas the secondary end point was evaluation of major adverse cardiovascular events (MACE) and BARC type ≥ 2 bleeding events. RESULTS: A total of 7862 ACS patients were included in the final analysis, of whom propensity score matching (PSM) analysis yielded 2165 patients in each cohort. After PSM analysis, cumulative incidence of NACCE was significantly lower with clopidogrel and aspirin than with ticagrelor and aspirin [117 (5.4%) vs. 180 (8.3%), P < 0.001] at 12 months. Effect estimates showed reduced risk of NACCE occurrence in patients treated with clopidogrel and aspirin [adjusted hazard ratio (aHR): 0.61, 95% CI 0.48-0.77, P < 0.001]. Incidence of bleeding was significantly lower in the clopidogrel cohort than in the ticagrelor cohort (aHR: 0.48, 95% CI 0.35-0.66, P < 0.001). Clopidogrel and aspirin therapy was comparable to ticagrelor and aspirin in reducing the incidence of MACE after PSM analysis. CONCLUSION: In Chinese ACS patients who underwent PCI with second-generation DESs, outpatient use of clopidogrel dual antiplatelet therapy (DAPT) was associated with reduction in NACCE and bleeding.

Hyperuricemia prevalence and its association with metabolic disorders: a multicenter retrospective real-world study in China.

BACKGROUND: The prevalence of hyperuricemia (HUA) and gout continues to increase in China. Research suggests that HUA may be related to many diseases other than gout. However, further population research is required to investigate the association between HUA and metabolic syndromes. This study sought to investigate the prevalence of HUA in an average population in China, and the association between serum uric acid (UA) levels and related metabolic disorders. METHODS: This multicenter retrospective real-world study examined the hospital information system data of 4 tertiary hospitals in 3 provinces in China. The data of patients aged between 18 and 80 years, who had attended at least 1 medical appointment at which their UA level was recorded, were analyzed to evaluate associations between UA levels and metabolic disorders. RESULTS: Among the 374,506 enrolled subjects (49.7% male; mean age 51.5 years old), the overall prevalence of HUA and gout were 14.8% and 0.5%, respectively. The prevalence was higher among males than females (17.6% vs. 12.0%, 0.8% vs. 0.1%; both P<0.001). Groups exhibiting higher UA levels had increased adjusted odds ratios for dyslipidemia and chronic kidney disease (CKD) in both sexes. Changes in UA levels from the baseline were negatively correlated with changes in the estimated glomerular filtration rate and hemoglobin A1c among both sexes (all P<0.001), and were positively correlated with changes in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) (all P<0.05) among males, and changes in TC, TG, LDL-C and glucose (all P<0.001) among females. CONCLUSIONS: HUA is associated with dyslipidemia and CKD both cross-sectionally and longitudinally. Similar phenomena were observed in both sexes.

Wide Pulse Width Electroacupuncture Ameliorates Denervation-Induced Skeletal Muscle Atrophy in Rats via IGF-1/PI3K/Akt Pathway.

OBJECTIVE: To evaluate the effect of the pulse width of electroacupuncture (EA) in the treatment of denervation-induced skeletal muscle atrophy in rats and examine the role of insulin-like growth factor 1 (IGF-1)/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway during EA. METHODS: Sciatic nerve functional index (SFI), muscle wet weight and the cross-sectional area (CSA) of the gastrocnemius muscle were analyzed after treatment in model rats with EA of various pulse widths (0.5, 50, 100 and 200 ms). The apoptosis index (AI) and paired box (PAX)3 and PAX7 protein expression were also determined. Further, the mRNA and protein expressions of components of IGF-1/PI3K/Akt pathway and their downstream targets were determined, along with the inhibiting effect of the pathway with a PI3-specific inhibitor. RESULTS: EA with a pulse width of 200 ms was found to have the best effect with regard to increasing SFI, CSA and muscle weight, decreasing AI, and increasing the expression of PAX3 and PAX7. The IGF-1/PI3K/Akt pathway was found to be activated by denervation, although the downstream forkhead box O (FoxO) pathway was not suppressed by its activation. The PI3K/Akt pathway and its downstream molecule mammalian target of rapamycin (mTOR) were up-regulated further by EA to promote muscle protein synthesis. Meanwhile, the expressions of downstream FoxO and F-box protein 32 (ATROGIN-1) were down-regulated to reduce protein degradation. CONCLUSIONS: EA with 200-ms pulse width was found to have a more significant effect than 0.5-ms EA. The positive effects of EA disappeared after inhibition of the PI3K/Akt pathway.

The prescription patterns and safety profiles of oral non-steroidal anti-inflammatory drugs in China: an 8-year real-life analysis.

BACKGROUND: This study aimed to evaluate the prescription patterns and safety profiles of oral nonsteroidal anti-inflammatory drugs (NSAIDs) in three Chinese hospitals. METHODS: The study analyzed the data of 50,732 patients who were prescribed oral NSAIDs from July 1, 2012 to August 31, 2019. The characteristics of these patients, the prescription patterns of NSAIDs, and the drug-related safety profiles were evaluated. RESULTS: Oral NSAIDs were prescribed to patients of all ages. Of the patients, 81.88% were prescribed NSAIDs on only one occasion, and 91.64% were prescribed one type of NSAID only. The combination of different NSAIDs accounted for 2,360 person-times. Orthopedic departments most commonly used selective cyclo-oxygenase-2 (COX-2) inhibitors, while emergency departments most commonly used traditional NSAIDs. The incidences of gastrointestinal (GI) complications, cardiovascular (CV) events, and newonset hypertension were lower in patients treated with selective COX-2 inhibitors than those treated with traditional NSAIDs and NSAID combinations (P<0.05). In relation to selective COX-2 inhibitors, incidences of new-onset hypertension were lower in patients treated with imrecoxib than those treated with other types of selective COX-2 inhibitors (P=0.0102). CONCLUSIONS: In respect of the at-risk patients (i.e., those with related disease, such as GI complications, CV events or other risks), the patterns with which oral NSAIDs were prescribed was not standardized. In terms of adverse effects, selective COX-2 inhibitors represent a better choice than traditional NSAIDs and NSAID combinations.

[Effect of electroacupuncture on denervated skeletal muscle atrophy and expression of IGF-1/PI3K/AKT in rats].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on denervated skeletal muscle atrophy and expression of IGF-1/PI3K/AKT signaling pathway in rats, and to explore the possible mechanisms of it. METHODS: Thirty-six male SD rats were randomly divided into a control group, a model group and an EA group. Denervated muscle atrophy model was made by cutting off the left hindlimb sciatic nerve in the model group and the EA group. In the EA group, EA, dense-disperse wave, 2 Hz/33 Hz and 1.5-2 mA, was connected at "Zusanli" (ST 36) and "Shangjuxu" (ST 37). The treatment was given for 30 min every time, once a day and a total of 20 times were needed, there was 2 days interval every 5 times. The rats in the control group and model group were fixed in the same cage every day but not applied EA. Sciatic nerve function index (SFI) and ratio of muscle wet weight (RWW) were measured after treatment. HE staining was used to determine the ratio of cross-sectional area (RCA) and the ratio of fiber diameter (RFD). TUNEL and double immunofluorescence staining were used to evaluate the myocyte apoptosis, proliferation and differentiation. The mRNA expressions of IGF-1 and AKT were detected by real-time PCR. The total protein of AKT, p-AKT (Ser473) and p-AKT (Thr308) were detected by western blot. RESULTS: Compared with the control group, SFI, RWW, RCA and RFD of the model group were significantly decreased and apoptotic index of myocytes were significantly increased (all P<0.01). Compared with the model group, the above indexes of the EA group were improved (all P<0.05), and the expressions of PAX3 and PAX7 related to proliferation and differentiation of muscle satellite cells were significantly increased (both P<0.01), p-AKT (Ser473) protein level was increased (P<0.05). CONCLUSION: EA can improve the atrophy of denervated muscles, reduce myocyte apoptosis, and promote the proliferation and differentiation of muscle satellite cells. The mechanism may be related to the increase of p-AKT (Ser473) level and activation of AKT signaling pathway.

CTLA-4 CT60 (rs3087243) polymorphism and autoimmune thyroid diseases susceptibility: a comprehensive meta-analysis.

OBJECTIVE: To determine whether the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) CT60 polymorphism (rs3087243) confers susceptibility to autoimmune thyroid disease (AITDs). METHODS: A meta-analysis was performed using: (1) allelic contrast, (2) recessive model and (3) dominant model. Electronic search of PubMed, Medline and Chinese National Knowledge Infrastructure (CNKI) was conducted to select studies. RESULTS: Finally, a total of 20 separate studies were available for the current meta-analysis: Graves' disease (GD): 18 studies including 1 Iranian, 6 Caucasian and 11 Asian populations; Hashimoto's thyroiditis (HT): seven studies including one Iranian, three Caucasian and three Asian populations. A significant association was found between the CTLA-4 CT60 polymorphism (rs3087243) and GD, with regard to comparisons between allele and genotype frequencies (all p < 0.001). After stratification by ethnicity, significant relationships were consistently identified both in Caucasian and Asian populations. Furthermore, the association between this allelic variant and HT risk was also found in overall and Asian populations (OR: 1.26, 95% CI: 1.10-1.44; OR: 1.45, 95% CI: 1.19-1.76, respectively). CONCLUSION: Taken together, our study suggested that the CT60 polymorphism (rs3087243) in CTLA-4 gene might confer susceptibility to the AITDs (GD/HT).

Effect of acupuncture on rabbit bladder with urodynamic indexes.

OBJECTIVE: To study the effect of acupuncture on rabbit bladder with urodynamic indexes. METHODS: New Zealand male rabbits were divided into control group, model group, treatment group 1 treated by acupuncture at Shenshu (BL 23) and treatment group 2 treated by acupuncture at Zhongji (CV 3). The urine dynamic parameters through the urethral catheter were detected in each group in order: fluctuation of pressure at filling phase of urinary bladder and flow rate in urination phase, which were used as quantification indexes of urinary bladder function. The urinary bladder abnormal model was prepared by administration of cholinergic stimulant; Regulatory effects of acupuncture at Shenshu (BL 23) and Zhongji (CV 3) on the abnormal state of the urinary bladder were respectively observed. RESULTS: 1) In the filling phase of urinary bladder and in the urination phase, the intravesical pressure wave in infilling (IPWI) and intravesical discharge rate (IDR) could be respectively recorded. 2) IPWI and IDR could become abnormality by neostigmine methyl sulfate [stability type IPWI: the control group (n = 20, 80%) vs the model group (n = 15, 14.3%), P < 0.01; IDR and time regression equation: the control group (n = 20, y = 24.3 - 0.878x) vs the model group (n = 15, y = 40.0 - 5.15x), P < 0.01]. 3) Abnormal IPWI's could be normalized respectively by acupuncture at Shenshu (BL 23) and Zhongji (CV 3) [the stability type IPWI wave: the model group (n = 2, 14.3%) vs the treatment group 1 (n = 3, 30%), P > 0.05; the instability type IPWI wave: the model group (n = 13, 85.7%) in vs the treatment group 2 (n = 6, 60%), P > 0.05]; 4) Abnormal IDR also could be turned to normality by acupuncture at Shenshu (BL 23) and Zhongji (CV 3), respectively [IDR and the time regression equation: the model group (n = 15, y = 40.0 - 5.15x) vs the treatment group 1 (n = 10, y = 18.9 - 0.499x), P < 0.01; the model group (n = 15, y = 40.0 - 5.15x) vs the treatment group 2 (n = 10, y = 17.5 - 0.251x), P < 0.01]. CONCLUSION: 1) Urodynamic indexes can be used for study of mechanism of acupuncture effects; 2) The effect of acupuncture in the bladder filling phase is smaller than that in the urination phase; 3) Acupuncture has a very obvious effect on intravesical discharge rate.