Second-Order Nonlinear-Optical-Active Selenide Borate YSeBO2: Featuring a [YSeBO2]n Planar Belt.

Chalcogenide borates were very rarely investigated in the past. As the second selenide borate, YSeBO2 obtained by a high-temperature solid-state reaction crystallizes in the noncentrosymmetric orthorhombic space group Cmc21 with a novel structure type. Its structure consists of two basic building units, [BO3]3- planar triangles and [YO3Se4]11- pentagonal bipyramids, and features the [YSeBO2]n planar belt. Second-harmonic-generation measurement shows its phase-matchable activity. YSeBO2 has an optical energy gap of 3.45 eV. Density functional theory calculation is also performed, addressing the electronic structure and nonlinear-optical property.

Quercetin protects against intestinal barrier disruption and inflammation in acute necrotizing pancreatitis through TLR4/MyD88/p38 MAPK and ERS inhibition.

OBJECTIVE: To investigate the effects of quercetin on intestinal barrier disruption and inflammation in acute necrotizing pancreatitis (ANP) in rats, and its possible mechanism. METHODS: ANP was established by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, and quercetin (50 mg/kg × 3) was administered by intraperitoneal injection prior to and after ANP induction. Pancreatitis was assessed by pancreatic histopathology, plasma amylase, pancreatic myeloperoxidase (MPO) activity, IL-1ß, TNFα and IL-6 levels. Injury of the distal ileum was assessed by histological evaluation. The ultrastructural changes of ileal epithelial cells were examined by transmission electron microscope (TEM). Intestinal barrier function was estimated by plasma diamine oxidase (DAO), d-lactate, endotoxin; and intestinal tight junction proteins including zonula occludens-1 (ZO-1), claudin 1, occludin; and bacterial translocation. Intestinal inflammation was determined by IL-1ß, TNFα and IL-17 A expression. TLR4, MyD88, pp38 MAPK, and endoplasmic reticulum stress (ERS)-related molecules (Bip, p-IRE1α, sXBP1, p-eIF2α, ATF6) were measured by immunohistochemistry and WB. RESULTS: Quercetin intervention attenuated pancreatic and ileal pathological damages in ANP (P < 0.05), ameliorated intestinal barrier disruption and inflammation (P < 0.05). Meantime, QE significantly suppressed intestinal TLR4/MyD88/p38 MAPK pathway and ERS activation. CONCLUSIONS: Quercetin plays a protective role against intestinal barrier disruption and inflammation in ANP, probably partly by inhibiting TLR4/MyD88/p38 MAPK and ERS activation.

Association Between Body Weight Change Before and After Delivery and Development of Nonmetabolic Syndrome: A Prospective Study.

The aim of the work was to investigate the association between body weight change before and after delivery and development of nonmetabolic syndrome in Chinese females aged ≥40 years. We selected 789 participants without metabolic syndrome randomly from a baseline survey performed in Luzhou, China in 2011. We took the group with decreasing or no increasing body mass index difference during a pregnancy as "R-Body Mass Index 1" (n=286) and divided the group with increasing body mass index difference during a pregnancy into "R-Body Mass Index 2" (n=254) and "R-Body Mass Index 3" (n=249) based upon P50. All study participants were followed up every year, and a questionnaire, physical examination, and biochemical detection were administered after 3 years. Of 789 participants, 82 nonmetabolic syndrome women developed metabolic syndrome during 3-year follow-up. The morbidity of metabolic syndrome in the R-BMI1, R-BMI2, and R-BMI3 groups was 5.2%, 11.8%, and 14.9%, respectively. Compared to the R-BMI1 group, the relative risk for R-BMI2 was 1.92 (95% confidence interval: 1.03-3.58, p=0.040) and for R-BMI3 was 2.20 (95% confidence interval: 1.20-4.03, p=0.011). After adjusting for age, BMI, WHR, baseline blood glucose, HbA1c, TG, HDL-C, SBP, DBP, age of menarche and menopause, and delivery times, the relative risks were similar to the unadjusted relative risks. In conclusion, body weight change after delivery was associated with metabolic syndrome: the higher the weight gain, the higher the risk of metabolic syndrome.

Association between serum gamma-glutamyl transferase and serum uric acid levels in Chinese females: A cross-sectional study.

OBJECTIVE: To investigate the association between serum gamma-glutamyl transferase (GGT) levels and serum uric acid levels in middle-aged and elderly Chinese females. METHODS: A cross-sectional population survey was performed in Luzhou, China (2014). Questionnaires, physical examinations and biochemical tests were conducted. Finally, we included 2486 females who were > 40 years old as participants. Multiple linear regression analysis was used to estimate the association of serum acid levels and other variables. Serum GGT levels were divided into four groups using the 25th, 50th and 75th percentiles as cut-off points. Finally, binary logistic regression analysis was used to investigate the association of different serum GGT quartiles with the risk of hyperuricemia. RESULTS: The prevalence of hyperuricemia was 25.1% in the studied population and gradually increased across the serum GGT quartiles (P < 0.05). Binary logistic regression analysis showed that compared with subjects in the lowest quartile of serum GGT levels, the adjusted odds ratio (ORs) for uric acid in the highest quartile was 2.34 (95% confidence interval (CI), 1.68-3.28, P < 0.001),after corrections for TG, TC, HDL-C, LDL-C, creatinine (CR), GGT, AST, ALT, fasting plasma glucose (FPG), postprandial 2-h plasma glucose, hemoglobin A1c(HbA1c), age, BMI, SBP, DBP, waist-to-hip ratio and neck circumference (NC). CONCLUSIONS: The serum GGT level is associated with hyperuricemia in middle-aged and elderly Chinese females.

Acupuncture, an effective treatment for post-stroke neurologic dysfunction.

Stroke episodes represent a significant subset of cerebrovascular diseases globally, often resulting in diverse neurological impairments such as hemiparesis, spasticity, dysphagia, sensory dysfunction, cognitive impairment, depression, aphasia, and other sequelae. These dysfunctions markedly diminish patients' quality of life and impose substantial burdens on their families and society. Consequently, the restoration of neurological function post-stroke remains a primary objective of clinical treatment. Acupuncture, a traditional Chinese medicine technique, is endorsed by the World Health Organization (WHO) for stroke treatment due to its distinct advantages in managing cerebrovascular diseases, including ischemic stroke. Numerous clinical studies have substantiated the efficacy of acupuncture in ameliorating neurological dysfunctions following stroke. This review systematically examines the improvements in post-stroke neurological dysfunction attributable to acupuncture treatment and elucidates potential mechanisms of action proposed in recent years. Additionally, this article aims to present novel therapeutic concepts and strategies for the clinical management of post-stroke neurological dysfunction.

[Study on the distribution of Chinese medical constitutions of hypertension complicated diabetes patients].

OBJECTIVE: To investigate the distribution features of Chinese medical constitutions in hypertension complicated diabetes patients. METHODS: Recruited were 251 primary hypertension inpatients at the Department of Neurology and the Department of Cardiology, Mindong Hospital of Ningde City from October 2010 to March 2011. They were assigned to two groups according to whether they were complicated with diabetes, i.e., the primary hypertension complicated diabetes (as the case group, 78 cases) and the primary hypertension without complicated diabetes (as the control group, 173 cases). The constitution types were investigated by questionnaire. The constitution type distribution was compared between the two groups. The data including gender, age, and the distribution of the constitution type were compared between the two groups. The levels of TG, TC, LDL-C, Hb, FPG, and ALB were detected on the 2nd day after admission. The levels of TG, TC, LDL-C, Hb, and ALB were compared be- tween the two groups in patients of yin deficiency constitution, phlegm dampness constitution, and qi deficiency constitution. RESULTS: There was no statistical difference in the hypertension grading, the disease course, and chronic disease complications between the two groups (P > 0.05). The main constitution types were yin deficiency (accounting for 26.0%), phlegm dampness (accounting for 19.1%), and qi deficiency (accounting for 19.1%) in the control group. The main constitution types were yin deficiency (accounting for 32.1%), phlegm dampness (accounting for 30.8%), and qi deficiency (accounting for 17.9%) in the case group. The ratio of phlegm dampness type in the case group was higher than that in the control group with statistical difference (P = 0.041). There was no statistical difference in the constitution distribution in the same gender between the two groups (P > 0.05). There was no statistical difference in the constitution distribution in those younger than 80 years between the two groups (P > 0.05). Compared with those older than 80 years in the control group, the ratio of phlegm dampness was higher, and the ratios of yang deficiency, yin deficiency, qi deficiency, and dampness heat were lower in the case group with statistical difference (P = 0.020). There was no statistical difference in the constitution distribution among different age stages in the case group (P > 0. 05). But there was statistical difference in the constitution distribution among different age stages in the control group (P < 0.05). The yin deficiency and qi deficiency constitutions were dominated in thinner patients of the control group, while yin deficiency constitution was dominated in thinner patients of the case group, showing no statistical difference between the two groups (P > 0.05). There was no statistical difference in the distribution of constitution type in overweight patients between the two groups (P = 0.458). Compared with those of gentle type constitution in the same group, the levels of TC and LDL-C increased in those of phlegm dampness constitution in the two groups (P < 0.05). The level of TC increased in those of qi deficiency constitution in the case group. The level of Hb decreased in those of qi deficiency constitution in the control group (P < 0.05). Compared with those of qi deficiency constitution in the same group, the levels of TC and Hb obviously increased in those of phlegm dampness constitution in the control group (P < 0.05). The level of ALB increased in those of yin deficiency constitution in the case group (P < 0. 05). Compared with the control group, the level of FPG of those of each constitution increased in the case group (P < 0.05) ,.and the level of TC increased in those of qi deficiency constitution (P = 0.007). CONCLUSIONS: The main constitution types of hypertension complicated diabetes patients were yin deficiency, phlegm dampness, and qi deficiency. The ratio of phlegm dampness was higher in hypertension complicated diabetes patients than hypertension without complicated diabetes patients. The levels of TC and LDL-C were higher in those of phlegm dampness constitution type. The level of TC was higher in hypertension complicated diabetes patients of qi deficiency constitution.

[Effect of electroacupuncture intervention on relieving pain and inflammation by suppressing TLR4/NF-κB signaling in rats with primary dysmenorrhea].

OBJECTIVE: To investigate the mechanism of electroacupuncture(EA) intervention in rats with primary dysmenorrhea(PDM) based on the Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB signaling pathway. METHODS: Forty female SD rats were randomly divided into blank control, model, EA and medication groups, with 10 rats in each group. PDM rat model was established by subcutaneous injection of estradiol benzoate combined with intraperitoneal injection of oxytocin. At the same time of model procedures, EA(50 Hz, dense wave) was applied to "Guanyuan" (CV4) and bilateral "Sanyinjiao" (SP6) of rats in the EA group, with needles retained for 20 min, for 10 consecutive days. Rats in the medication group received ibuprofen(125 mg/100 mL, 0.8 mL) by gavage for 10 consecutive days. At the 11th day, writhing behavior of rats was assessed. Uterine morphology was observed by eyes and uterine pathological changes were observed after HE staining. Content of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) in serum and uterine tissues was detected by ELISA; NF-κB p65 positive expression in nucleus was detected by immunofluorescence; protein expression levels of TLR4, NF-κB p65, p-NF-κB p65 and inflammatory factors interleukin (IL) -1ß and IL-18 were detected by Western blot. RESULTS: After modeling, uterus tissues were congested and edematous, with necrosis of luminal epithelium, severe edema and extensive shedding of endometrium, nuclear pyknosis, fragmentation and disappearance, neutrophils infiltration, and slight expansion of glandular cavity, which was milder in the EA and the medication groups. Compared with the blank control group, writhing times, scores and incubation period, HE pathological scores, PGF2α contents in serum and uterine tissues, ratio of NF-κB p65 positive expression in nucleus, TLR4, NF-κB p65, p-NF-κB p65, IL-1ß and IL-18 protein expression levels in uterine tissues of rats in the model group were all significantly increased(P<0.01), while PGE2 contents in serum and uterine tissues were significantly decreased(P<0.01). Compared with the model group, writhing times and scores, HE pathological scores, PGF2α contents in serum and uterine tissues, ratio of NF-κB p65 positive expression in nucleus, TLR4, NF-κB p65, p-NF-κB p65, IL-1ß and IL-18 protein expression levels in uterine tissues of rats in the EA and medication group were all significantly decreased(P<0.01), while writhing incubation period, PGE2 contents in serum and uterine tissues were significantly increased(P<0.05, P<0.01). CONCLUSION: EA intervention could relieve inflammatory response and pain in PDM rats, which may be related to its effect in reducing TLR4 expression, inhibiting NF-κB activation and down-regulating inflammatory factors levels of IL-1ß and IL-18.

[Effects of electroacupuncture on NLRP3 inflammasome and pyroptosis protein GSDMD in uterine tissue in rats with primary dysmenorrhea].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on NLRP3 inflammasome and its downstream protein gastermin D (GSDMD) in rats with primary dysmenorrhea (PDM), and to explore the potential mechanism of EA on the treatment of PDM. METHODS: Forty healthy female SD rats without pregnancy were randomly divided into a control group, a model group, an EA group and an ibuprofen group, 10 rats in each group. PDM model was prepared by injection of estradiol benzoate and oxytocin. Except the control group, the rats in each group were subcutaneously injected with estradiol benzoate for 10 days, and oxytocin was injected on the 11th day. The rats in the EA group were intervened with EA (dense wave, frequency of 50 Hz) at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) at the same time of modeling, once a day, 20 min each time, for 10 consecutive days. The rats in the ibuprofen group were treated with 0.8 mL of ibuprofen by gavage (concentration of ibuprofen solution was 1.25 mg/mL) for 10 consecutive days. After modeling, the writhing reaction was observed. After intervention, the HE staining method was used to observe the histological morphology of uterus and evaluate the pathological damage score of uterus; ELISA method was used to detect the serum levels of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α); Western blot method was used to detect the protein expression of NLRP3, apoptosis related spot like protein (ASC), caspase-1, GSDMD, GSDMD-N and inflammatory factors (interleukin [IL]-1ß, IL-18) in uterine tissue. RESULTS: In the model group, a large number of vacuolar degeneration and death of endometrial epithelial cells, spiral arterioles congestion in lamina propria and neutrophil infiltration were observed. In the EA group, there was a small amount of vacuolar degeneration and death of endometrial epithelial cells, a small amount of spiral arterioles congestion in the lamina propria, and a small amount of neutrophils infiltration. In the ibuprofen group, there was very small number of degeneration and death of endometrial epithelial cells, and no obvious arterial congestion was found in lamina propria, and neutrophil infiltration was occasionally seen. Compared with the control group, in the model group the number of writhing was increased (P<0.01), the writhing reaction score and serum level of PGF2α and PGF2α/PGE2 value were increased (P<0.01), the level of PGE2 was decreased (P<0.01). Compared with the model group, in the EA group and the ibuprofen group the number of writhing were decreased (P<0.05), the latency of writhing was prolonged (P<0.01), the writhing reaction scores and serum levels of PGF2α and PGF2α/PGE2 values were decreased (P<0.05, P<0.01), the levels of PGE2 were increased (P<0.01). Compared with the control group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1ß and IL-18 in the uterine tissues of rats was increased in the model group (P<0.01). Compared with the model group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1ß and IL-18 in the uterine tissues of rats was decreased in the EA group and the ibuprofen group (P<0.01, P<0.05). There was no significant difference between the EA group and the ibuprofen group in the above indexes (P>0.05). CONCLUSION: EA could alleviate pain and uterine tissue injury in rats with PDM. The mechanism may be related to the inhibition of the activation of NLRP3 inflammasome in rat uterine tissues, thereby inhibiting pyroptosis and its inflammatory factors release.

[Effects of electroacupuncture on N-methyl-D-aspartate receptor and mitogen activated protein kinase in spinal cord of rats with primary dysmenorrhea].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on the expression levels of N-methyl-D-aspartate receptor (NMDAR), extracellular signal-regulated kinase (ERK)1/2, p38 mitogen activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) in the spinal cord of rats with primary dysmenoramia (PDM), so as to explore the underlying mechanism of EA treating PDM. METHODS: Thirty female SD rats were randomly divided into normal group, model group and EA group, with 10 rats in each group. The PDM rat model was established by subcutaneous injection of estradiol benzoate and oxytocin into the thigh. At the same time of modeling, rats in the EA group were treated with EA (50 Hz) at "Sanyinjiao" (SP36) and "Guanyuan" (CV4) once daily, 20 min each time, for 10 consecutive days. The writhing times, writhing score and writhing latency were observed within 30 min after oxytocin injection. The uterine pathological morphology was observed by HE staining, and pathological score was calculated. Serum prostaglandin F2α (PGF2α) and prostaglandin E2 (PGE2) were determined by ELISA. The protein expression levels of NMDAR, ERK1/2, p38MAPK and JNK in spinal cord were detected by Western blot. RESULTS: Compared with the normal group, the writhing times and writhing score were significantly increased (P<0.05); the endometrial epithelial cells showed vacuolar degeneration, death and hyperemia, the uterine pathological score was increased (P<0.05); the content of serum PGF2α and the ratio of PGF2α/PGE2 were significantly increased (P<0.01), while the content of serum PGE2 was significantly decreased (P<0.01); the expression levels of NMDAR, ERK1/2, p38MAPK and JNK in spinal cord were significantly increased (P<0.05, P<0.01) in the model group. Compared with the model group, the writhing times and writhing score were significantly decreased (P<0.05), the writhing latency was prolonged (P<0.05); the endometrial epithelial cells still showed vacuolar degeneration, death and hyperemia, and the uterine pathological score was decreased (P<0.01); the content of serum PGF2α and the ratio of PGF2α/PGE2 were significantly decreased (P<0.01), while the content of serum PGE2 was significantly increased (P<0.01); the protein expression levels of ERK1/2 and JNK in spinal cord were significantly decreased (P<0.01) in the EA group. CONCLUSION: EA intervention at SP36 and GV4 has obvious analgesic effect on PDM rats, and its mechanisms may be related to reducing serum prostaglandin, alleviating uterine inflammation, and inhibiting the protein expressions of NMDAR, ERK1/2, p38 MAPK and JNK in spinal cord.

Mechanisms of acupuncture for primary dysmenorrhea based on PI3K/Akt/mTOR signaling pathway in rats. / 基于PI3K/Akt/mTORä¿¡å·é€šè·¯æŽ¢è®¨ç”µé’ˆæ²»ç–—åŽŸå‘æ€§ç—›ç»å¤§é¼ çš„æœºåˆ¶.

OBJECTIVES: To observe the effect of electroacupuncture(EA) on phosphatidylinositol-3-kinases(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway of uterus tissue in rats with primary dysmenorrhea(PDM), so as to investigate its mechanisms underlying improvement of PDM. METHODS: Thirty healthy non-pregnant female SD rats were randomly divided into blank, model and EA groups, with 10 rats in each group. The PDM model was established by subcutaneous injection of estradiol diphenhydrate combined with intraperitoneal injection of oxytocin. For rats of the EA group, EA(50 Hz, a tolerable current intensity) was applied to "Guanyuan"(CV4) and bilateral "Sanyinjiao"(SP6) for 20 min, once a day for 10 consecutive days. The number of writhing, wri-thing score, and writhing latency were observed. The uterine histopathological changes were observed by H.E. staining, and the ultrastructural changes of uterine tissue cells in each group were observed by transmission electron microscopy. The contents of prostaglandin E2(PGE2), prostaglandin F2α(PGF2α) and ratios of PGF2α/PGE2 in the serum and uterine tissue were detected by ELISA. The relative expression levels of PI3K, Akt and mTOR and their phosphorylation proteins in the uterine tissue were detected by Western blot and the ratios were calculated. RESULTS: Compared with the blank group, the number and score of writhing, latency of writhing, pathological injury score, contents of PGF2α and ratios of PGF2α/PGE2 in the serum and uterine tissue, and the levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in the uterine tissue were significantly increased in the model group(P<0.01, P<0.05), while contents of PGE2 in the serum and uterine tissue were reduced(P<0.05). In comparison with the model group, the number of writhing and writhing score, pathological injury score, contents of PGF2α and ratios of PGF2α/PGE2 in both the serum and uterine tissue, the levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR were obviously decreased(P<0.05, P<0.01), whereas the writhing latency was considerably prolonged in the EA group(P<0.01), with elevated contents of PGE2 in the serum and uterine tissue(P<0.05). H.E. staining showed slight dilation of uterine glandular cavity, and severe endometrial edema with extensive cell shedding and a large number of vacuole-like degeneration, apoptosis, pyknosis or fragmentation or disappearance of the nucleus, and neutrophil infiltration in the model group, which were relatively milder in the EA group. Ultrastructural results showed irregular fibroblasts of uterine tissue cells, obvious cytoplasmic edema, reduction in cytoplasmic electron density, seriously irregular nuclei, severe edema of mitochondria with dissolved matrix, fracture and disappearance of mitochondrial crests and vacuolation, and moderate dilation of rough endoplasmic reticulum in the model group, which were milder in the EA group. CONCLUSIONS: EA can improve pain and uterine inflammatory response in PDM rats, which may be associated with its functions in reducing uterine PGF2α and down-regulating PI3K/Akt/mTOR signaling.

Intestinal TLR4 deletion exacerbates acute pancreatitis through gut microbiota dysbiosis and Paneth cells deficiency.

Toll-like receptor 4 (TLR4) has been identified as a potentially promising therapeutic target in acute pancreatitis (AP). However, the role of intestinal TLR4 in AP and AP-associated gut injury remains unclear. This study aimed to explore the relationship between intestinal TLR4 and gut microbiota during AP. A mouse AP model was establish by intraperitoneal injection of L-arginine. Pancreatic injury and intestinal barrier function were evaluated in wild-type and intestinal epithelial TLR4 knockout (TLR4ΔIEC) mice. Gut microbiota was analyzed by 16S rRNA sequencing. Quadruple antibiotics were applied to induce microbiota-depleted mice. Differentially expressed genes in gut were detected by RNA sequencing. L. reuteri treatment was carried out in vivo and vitro study. Compared with wild-type mice, AP and AP-associated gut injury were exacerbated in TLR4ΔIEC mice in a gut microbiota-dependent manner. The relative abundance of Lactobacillus and number of Paneth cells remarkably decreased in TLR4ΔIEC mice. The KEGG pathway analysis derived from RNA sequencing suggested that genes affected by intestinal TLR4 deletion were related to the activation of nod-like receptor pathway. Furthermore, L. reuteri treatment could significantly improve the pancreatic and intestinal injury in TLR4ΔIEC mice through promoting Paneth cells in a NOD2-dependent manner. Loss of intestinal epithelial TLR4 exacerbated pancreatic and intestinal damage during AP, which might be attributed to the gut microbiota dysbiosis especially the exhausted Lactobacillus. L. reuteri might maintain intestinal homeostasis and alleviate AP via Paneth cells modulation.Abbreviations: AP Acute pancreatitis, TLR4 Toll-like receptor 4, IL-1ß Interleukin-1ß, IL-6 Interleukin-6, TNF-α Tumor necrosis factor-α, SIRS Systematic inflammatory response syndrome, LPS Lipopolysaccharides, SPF Specific pathogen-free, ZO-1 Zonula occludens-1, CON Control, H&E Hematoxylin and eosin, FISH Fluorescence in situ hybridization, DAPI 4',6-diamidino-2-phenylindole, PCoA Principal co-ordinates analysis, SCFA Short chain fatty acid, LEfSe Linear discriminant analysis Effect Size, ANOVA Analysis of variance, F/B Firmicutes/Bacteroidetes, PCA Principal component analysis, NOD2 Nod-like receptor 2, ABX antibiotics, PCNA proliferating cell nuclear antigen.

Effect of Statin Therapy on Diabetes Retinopathy in People With Type 2 Diabetes Mellitus: A Meta-Analysis.

Objective: We tried to find the relationship between statin and diabetes retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: We searched the databases of PubMed, EMBASE, and the Cochrane Library for eligible studies reporting on the relationships between statin use and DR, from inception to September 25, 2020. The terms searched including Diabetes Mellitus, Type 2, Hydroxymethylglutaryl-CoA Reductase Inhibitors, and Diabetic Retinopathy. We expressed the results as the odds ratios (ORs) with 95% confidence intervals (CIs) which were calculated using a random-effects model. Results: A total of 6 eligible studies, including 43 826 patients, were included in the meta-analysis. The meta-analysis showed that statin was not associated with elevated risk of DR [OR = 0.96 (95% CI: 0.80-1.16), P = .68]. Similarly, no differences were found between statin and placebo in participants ≥500 [OR = 0.98 (95% CI: 0.80-1.21)] or participants <500 [OR = 0.90 (95% CI: 0.49-1.66)]. Further, we conducted a meta-analysis to study the effect of statin therapy on DR in people with type 2 diabetes according to age and found that statin use was associated with a decreased risk of DR in patients with type 2 diabetes 40 years of age or older [OR = 0.87 (95% CI: 0.82-0.92)]. Conclusion: Our meta-analysis revealed that statin was not associated with elevated risk of DR in patients with T2DM. Moreover, statin use was associated with a lower incidence of DR in patients with type 2 diabetes 40 years of age or older.

[Acupuncture at acupoints along the meridians for primary insomnia: a multi-center randomized controlled trial].

OBJECTIVE: To compare the clinical effect differences among different acupoint selection methods for primary insomnia. METHODS: A total of 333 patients with primary insomnia were recruited from 3 study centers and randomly divided into a group A (111 cases, 7 cases dropped off), a group B (111 cases, 5 cases dropped off) and a group C (111 cases, 2 cases dropped off). The patients in the group A were treated with acupuncture at Shenmen (HT 7) and Baihui (GV 20), the patients in the group B were treated with acupuncture at Sanyinjiao (SP 6) and Baihui (GV 20), and the patients in the group C were treated with acupuncture at non-acupoint and Baihui (GV 20). All the treatment was given once a day, 30 min each time; 5 treatments were taken as a course and 5 courses of treatment were given. The Pittsburgh sleep quality index (PSQI) and Athens insomnia scale (AIS) scores were evaluated before and after treatment as well as 4 weeks after treatment. The encephalofluctuograph technology (ET) was observed before and after treatment. RESULTS: Compared before treatment, the PSQI scores after treatment and at follow-up were significantly decreased in three groups (P<0.01), and the decrease in the group A and the group B was greater than that in the group C (P<0.01). Compared before treatment, the AIS scores after treatment and at follow-up was significantly decreased in three groups (P<0.01), and the decrease in the group A was greater than that in the group C (P<0.05). The interclass and between-groups ET before and after treatment had no significant difference (P>0.05). CONCLUSION: The acupuncture at acupoints along the meridians could improve the sleep quality in patients with primary insomnia, and the therapeutic effect of acupoint along the meridians is better than that of non-acupoint.

Identification and characterization of human ARIP2 and its relation to breast cancer.

Activin, a member of the TGF-beta superfamily, inhibits the proliferation of breast cancer cells. Activin interacts with its type I and type II receptors to induce phosphorylation of intracellular signaling molecules known as Smads. Previous studies showed that mouse ARIP2 can reduce activin signaling by interacting with activin type II receptors (ActRIIs); however, the activity of ARIP2 in breast cancer is still unclear. In this study, we used RT-PCR to obtain a human homologue of mouse ARIP2, human activin receptor-interacting protein 2 (hARIP2). Like murine ARIP2, hARIP2 has a PDZ domain in its NH2-terminal region and can interact specifically with ActRIIs. Overexpression of hARIP2 reduced activin-induced transcriptional activity and enhanced cell proliferation and colony formation in human breast adenocarcinoma MCF-7 cells and MDA-MB-231 cells. However, down-regulation of hARIP2 expression by RNAi enhanced activin-induced transcriptional activity and reduced cell proliferation and colony formation. Immunohistochemistry revealed that hARIP2 was expressed more frequently and much more intensely in malignant breast tissues such as simple carcinoma, invasive ductal carcinoma and mucinous adenocarcinoma than in benign hyperplasia or fibroadenoma cases. These results suggest that hARIP2 is a putative growth-promoting factor involved in breast tumorigenesis and tumor development.

[Effects of large tumor suppressor homolog 2 gene overexpression on the proliferation and apoptosis of oral squamous cell carcinoma].

OBJECTIVE: To investigate the effect of large tumor suppressor homolog 2 (LATS2) gene overexpression on the proliferation and apoptosis of oral squamous cell carcinoma (OSCC). METHODS: Lentivirous particles were transferred into SCC-25 cell to upregulate LATS2 gene expression. Cell proliferation was detected by CCK-8 assay. Apoptosis was detected through flow cytometry. The expression changes of Bax, Bcl-2, and LATS2 were analyzed by Western blot. RESULTS: Gene transfection increased LATS2 expression. Compared with the control group and pEGFP-control group, SCC-25 cell proliferation in the pGFP-LATS2 group was inhibited, whereas the apoptosis ratio increased (P<0.05). Bcl-2 expression decreased, and Bax expression increased. CONCLUSIONS: Overexpression of LATS2 could inhibit SCC-25 cell proliferation and induce apoptosis.

[Manual Acupuncture Stimulation of Paired Acupoints Can Relieve Sleep Disorder Possibly by Upregulating Pineal Melatonin Protein and Its Receptor mRNA Levels in the Suprachiasmatic Nucleus in Insomnia Rats].

OBJECTIVE: To observe the effect of manual acupuncture stimulation of paired "Baihui" (GV 20)+ "Shenmen" (HT 7), GV 20+ "Sanyinjiao" (SP 6), and GV 20+ non-acupoint on expression of melatonine (MT) and suprachiasmatic melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) mRNAs in insomnia rats, so as to explore their action difference and the underlying mechanism in improving insomnia. METHODS: Male SD rats were randomly divided into normal control (n=12), mo-del (n=8), GV 20+HT 7(n=12), GV 20+SP 6(n=11), and GV 20+ non-acupoint (n=10) groups. The insomnia model was established by intraperitoneal injection of Para-chlorophenylalanine suspension (50 mg/mL, 50 mg/100 g), once daily for 2 days. The abovementioned acupoints GV 20, bilateral HT 7, SP 6 and non-acupoints (the midpoint between the elbow-tip and armpit on the medial side of the upper-arm) were punctured with filiform needles and manipulated by rotating the needle for about 1 min which was repeated once again every 10 min during 30 minutes' needle-retaining. The treatment was conducted once daily for 7 days. The expression levels of MT immunoactivity in the conarium tissue, and MT1 and MT2 mRNAs of the suprachiasmatic nucleus (SCN) region were detected using immunohistochemistry and fluorescence quantitative real time-PCR, respectively. RESULTS: After modeling, the expression levels of pineal MT (an increase of gray value means a decrease of immunoactivity), SCN MT1 and MT2 mRNAs were notably down-regulated in the model group relevant to the normal control group (P<0.05, P<0.01). Following the treatment, the down-regulated expression levels of MT protein, and MT1 and MT2 mRNAs were obviously reversed in the GV 20 + HT 7, GV 20 + SP 6 groups relevant to the model group (P<0.05, P<0.01). The therapeutic effect of GV 20+ HT 7 was superior to that of GV 20+ non-acupoint in up-regulating the expression of MT1 mRNA (P<0.01), and markedly superior to that of GV 20+ SP 6 and GV 20+ non-acupoint in increasing the sleep duration and in up-regulating the expression of MT2 mRNA (P<0.01). No significant differences were found among the 3 treatment groups in up-regulating the expression of MT (P>0.05). CONCLUSION: Manual acupuncture stimulation of GV 20+ HT 7 and GV 20+ SP 6 can improve the sleep disorder in insomnia rats, which may be related to its effects in increasing the levels of pineal MT protein, and MT1 and MT2 mRNAs in hypothalamic SCN.

[Effect of Different Stimulating Strength of Electroacupuncture on Gastrointestinal Motility and RhoA/ROCK Signaling in Gastric Antral Smooth Muscle in Diabetic Gastroparesis Rats].

OBJECTIVE: To observe the effect of different strength of electroacupuncture (EA) stimulation on gastrointestinal motility and Ras homolog gene family member (RhoA)/Rho associated coiled-coil forming protein kinase (ROCK) signaling in diabetic gastroparesis (DGP) rats, so as to reveal the underlying mechanisms of EA for improving DGP. METHODS: Sixty SD rats were randomly and equally divided into blank control, DGP model, weak EA, medium EA, and strong EA groups (n＝12 rats in each). The DGP model was established by intraperitoneal injection of streptozotocin (STZ, 55 mmol/kg, 2%) and high-sugar and high-fat fodder feeding for 8 weeks. EA (0.12, 0.24, 0.36 mA, 20 Hz/100 Hz) was applied to "Zusanli" (ST 36), "Sanyinjiao" (SP 6) and "Liangmen" (ST 21) for 20 min, once daily for 15 successive days. Blood glucose levels were measured weekly with blood glucose meter and blood glucose test paper. Fecal phenol red excretion method was used to display gastric emptying and small intestinal propulsion function. The expression of RhoA protein in the gastric antral smooth muscle tissue was detected by immunohistochemistry and Western blot (WB), separately, and that of ROCK, myosin phosphatase target subunit 1 (MYPT 1) and phosphorylated (p)-MYPT 1 proteins in gastric antrum detected by WB. RESULTS: Compared with the blank control group, the gastric emptying rate and small intestine propulsion rate of the model group were significantly decreased (P<0.05), and the blood glucose level was remarkably increased (P<0.05). Moreover, the expression levels of RhoA, ROCK, MYPT 1 and p-MYPT 1 proteins in the gastric antrum were significantly down-regulated relevant to the control group (P<0.05). After administration of EA, the decreased gastric emptying rate and intestinal propulsion rate, and the down-regulated expression of RhoA, ROCK, MYPT 1 and p-MYPT 1 proteins were significantly increased in the strong, medium and weak EA stimulation groups (P<0.05). Comparison among the 3 EA groups showed that the strong stimulation was significantly superior to weak stimulation in up-regulating the expression of RhoA, ROCK, MYPT 1 and p-MYPT 1 proteins, and obviously superior to the medium stimulation in up-regulating RhoA and MYPT 1 protein levels (P<0.05), while the medium stimulation was significantly stronger than the weak stimulation in up-regulating the expression of ROCK, MYPT 1 and p-MYPT 1 proteins (P<0.05). There were no significant differences among the 3 EA groups in up-regulating the gastric emptying rate and small intestinal propulsion rate, and between the strong stimulation and medium stimulation in the expression levels of ROCK and p-MYPT 1 proteins (P>0.05). CONCLUSION: Electroacupuncture stimulation of ST 36-SP 6-ST 21 at 0.12, 0.24 and 0.36 mA can promote the gastrointestinal motility in DGP rats, which may be associated with its effects in enhancing RhoA/ROCK signaling in the gastric antral smooth muscle at different degrees.

[Effects of Herbal-cake-separated Moxibustion on Blood Lipid Protein Levels and Expression of Toll-like Receptor and Nuclear Factor Genes in Atherosclerotic Plaques in Hyperglycemia Rabbits].

OBJECTIVE: To observe the effect of herbal cake-separated moxibustion on blood lipid-apoprotein levels and the expression of Toll-like receptor 2 (TLR 2), TLR 4 and nuclear factor kappa B(NF-κB) mRNAs in atherosclerotic (AS) vulnerable plaques of hyperglycemia rabbits, so as to explore its mechanism underlying improvement of atherosclerosis. METHODS: Sixty New Zealand rabbits were randomly divided into 5 groups: control, model, direct moxibustion, herbal-cake-separated moxibustion and medication groups(n＝12 rabbits in each group). The AS vulnerable plaque model was established by high-fat forage feeding plus balloon-induced abdominal aorta injury and gene transfection of Ad 5-p 53 recombinant vector. Direct moxibustion or herbal-cake-separated moxibustion was applied to "Juque" (CV 14) and bilateral "Tianshu" (ST 25), "Fenglong" (ST 40), or bilateral "Xinshu" (BL 15), "Pishu" (BL 20) and "Ganshu" (BL 18) for 15－20 min every time. The medication group was treated by feeding Atorvastatin. All the treatments were conducted once daily for 8 weeks. Plasma total cholesterol(TC) and triglyceri-de(TG) contents were detected by enzyme method, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) contents detected by colorimetric determination, and plasma apolipoprotein A(Apo-A) and apolipoprotein B(Apo-B) levels determined by electrophoretic method. The pathological changes of vulnerable plaque and the aortic intima and media thickness were observed under light microscope after H．E. staining. The expression levels of TLR 2, TLR 4 and NF-κB mRNAs in AS plaques were determined by quantitative real-time PCR. RESULTS: After modeling, the levels of plasma TC, TG, LDL and Apo-B in the model group were remarkably increased (P<0.01), and Apo-A and HDL/LDL were significantly decreased in comparison with the control group (P<0.01). Additionally, the aortic intima and media thickness and the expression levels of TLR 2, TLR 4 and NF-κB mRNAs in AS plaques were significantly increased (P<0.01). After the treatment, the elevated levels of plasma TC, TG, LDL and Apo-B, the aortic intima thickness and media thickness, and the expression levels of TLR 2, TLR 4 and NF-κB mRNAs in the 3 treatment groups were significantly down-regulated in comparison with the model group (P<0.05, P<0.01), while the decreased levels of Apo-A and HDL/LDL were considerably increased (P<0.01). Comparison among the 3 treatment groups showed that the therapeutic effects of the herbal-cake-separated moxibustion and medication were significantly superior to those of the direct moxibustion in down-regulating the levels of TC, TG, LDL, Apo-B, TLR 2 mRNA, TLR 4 mRNA and NF-κB mRNA, and reducing the thickness of the aortic intima and media, as well as in up-regulating the levels of Apo-A and HDL/LDL (P<0.05, P<0.01). No significant differences were found between the herbal-cake-separated moxibustion and medication groups in the above-mentioned indexes (P>0.05). CONCLUSION: Herbal-cake-separated moxibustion has a positive role in stabilizing AS vulnerable plaque in hyperglycemia rabbits, which may be associated with its effects in regulating blood lipid-apolipoprotein levels and inhibiting the expression of TLR 2, TLR 4 and NF-κB mRNAs in vulnerable plaques.

[Effect of Point-moxibustion and Electroacupuncture on the Expression of Endothelial Nitric Oxide Synthase mRNA and Angiotensin 2 mRNA in Gastric Antrum in Diabetic Gastroparesis Rats].

OBJECTIVE: To observe the effect of point-moxibustion and electroacupuncture(EA) on gastrointestinal motility, and expression of endothelial nitric oxide synthase(eNOS) mRNA and angiotensin 2(AT Ⅱ) mRNA in gastric antrum in diabetic gastroparesis(DGP) rats, so as to reveal the different effect between point-moxibustion and EA, and explore the mechanism underlying improvement of DGP. METHODS: Forty SD rats were randomly divided into normal, model, point-moxibustion and EA groups, 10 rats in each group. The DGP model was established by intraperitoneal injection of streptozotocin (STZ, 2%, 55 mmol/kg) and fed with high-sugar and high-fat fodder. "Zusanli" (ST 36), "Sanyinjiao" (SP 6) and "Liangmen" (ST 21) were chosen to be stimulated with moxibustion at 0, 10 and 20 min in the point-moxibustion group or with EA for 20 min in the EA group. The treatment was conducted once daily for 15 days. After treatment, blood glucose, gastric emptying rate and small intestinal propulsive rate were measured. The plasma endothelin 1(ET-1) content was detected by ELISA. The mRNA expression of eNOS and AT Ⅱ in gastric antrum were detected by Real-time PCR. RESULTS: Compared with the normal group, the blood glucose in the model group was significantly higher (P<0.01). Compared with the model group, the blood glucose decreased significantly in the point-moxibustion group and EA group (P<0.05). In comparison with the normal group, gastric emptying rate and small intestinal propulsive rate were decreased, the content of plasma ET-1 was increased, the expression of eNOS mRNA in gastric antrum was significantly reduced and the expression of ATⅡ mRNA was significantly increased in the model group(P<0.01). In comparison with the model group, gastric emptying rate and small intestinal propulsive rate were increased, the content of plasma ET-1 was decreased, the expression of eNOS mRNA in gastric antrum was higher and the expression of AT Ⅱ mRNA was significantly lower in both point-moxibustion group and EA group (P<0.05), and there were no significant differences between the two treatment groups in above mentioned indexes (P>0.05). CONCLUSIONS: Both point-moxibustion and EA can effectively promote gastrointestinal motility in DGP rats and improve the symptoms of delayed gastric emptying. The two therapies are effective, and their mechanism may be related to the increase of eNOS mRNA expression and the decrease of AT Ⅱ mRNA expression in gastric antrum.

[Effects of Electroacupuncture on Ultrastructure of Interstitial Cells of Cajal and Stem Cell Factor-kit Signal Pathway of Gastric Antrum in Diabetic Gastroparesis Rats].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on gastrointestinal motility and the ultrastructure of interstitial cells of Cajal (ICC) and the expressions of c-kit receptor protein and stem cell factor (SCF) mRNA in diabetic gastroparesis (DGP) rats, so as to explore its mechanism. METHODS: Fifty SD rats were randomly divided into normal, model, acupoint, non-acupoint and metoclopramide groups (n＝10 rats/group). DGP model was established by intraperitoneal injection of streptozotocin (STZ, 2%), and raised with high-sugar high-fat diet irregularly. EA (sparse-dense, 10 Hz/50 Hz, 2 mA, 20 min) was applied at "Zusanli" (ST 36), "Liangmen" (ST 21) and "Sanyinjiao" (SP 6), and the corresponding non-acupoints of the 3 acupoints, daily for 15 days. The rats in metoclopramide group received intragastric administration of metoclopramide (1.7%, 1 mL/100 g) for 15 days, once a day. Blood sugar was determined with One Touch blood glucose test paper. The gastric emptying rate (GER) and the intestinal propulsion rate (IPR) were measured by intragastric phenol red. The ultrastructure of ICC was detected by transmission electron microscopy. The expression levels of c-kit receptor protein and SCF mRNA of gastric antrum were examined respectively by Western blot and RT-PCR. RESULTS: Compared with the normal group, the blood glucose significantly increased in the model group (P<0.01), while the GER, IRP and the expression level of SCF mRNA in the gastric antrum significantly decreased (P<0.01), and the ultrastructure of ICC appeared apoptosis-like changes. The blood glucose of the EA group was obviously decreased compared with that of the model group (P<0.05); the GER and IRP significantly increased(P<0.05, P<0.01); the expression level of SCF mRNA increased (P<0.01), the number of ICC increased and its ultrastructure was repaired. There was some relief on ICC ultrastructure in the acupoint group compared with that in the non-acupoint group; and SCF mRNA increased (P<0.05). There was no significant difference on c-kit receptor expression among all the modeling groups (P＞0.05). CONCLUSIONS: EA at ST 36, etc. can regulate the blood glucose and improve gastrointestinal emptying in DGP rats. The mechanism may be related to up-regulating SCF mRNA, repairing ICC ultrastructure, restoring the pacing function, and improving gastrointestinal motility.