Metabolomics identifies and validates serum androstenedione as novel biomarker for diagnosing primary angle closure glaucoma and predicting the visual field progression.

Background: Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. We aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG. Methods: Here, we used a five-phase (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui Central Hospital), cross-sectional, prospective cohort study designed to perform widely targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-nearest neighbor, and GaussianNaive Bayes [NB]) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots. Results: Studied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, AUCs=1.0 [95% CI, 1.00-1.00]; discovery set 2, AUCs = 0.85 [95% CI, 0.80-0.90]) and validation phases (internal validation, AUCs = 0.86 [95% CI, 0.81-0.91]; external validation, AUCs = 0.87 [95% CI, 0.80-0.95]). Androstenedione also exhibited a higher AUC (0.92-0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, p=0.038) and significantly (p=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio = 2.71 [95% CI: 1.199-6.104], p=0.017) were associated with faster visual field progression. Conclusions: Our study identifies serum androstenedione as a potential biomarker for diagnosing PACG and indicating visual field progression. Funding: This work was supported by Youth Medical Talents - Clinical Laboratory Practitioner Program (2022-65), the National Natural Science Foundation of China (82302582), Shanghai Municipal Health Commission Project (20224Y0317), and Higher Education Industry-Academic-Research Innovation Fund of China (2023JQ006).

Expression characteristics of the cyp19a1b aromatase gene and its response to 17ß-estradiol treatment in largemouth bass (Micropterus salmoides).

To investigate the regulatory role of the cyp19a1b aromatase gene in the sexual differentiation of largemouth bass (Micropterus salmoides, LMB), we obtained the full-length cDNA sequence of cyp19a1b using rapid amplification of cDNA ends technique. Tissue expression characteristics and feedback with 17-ß-estradiol (E2) were determined using quantitative real-time PCR (qRT-PCR), while gonad development was assessed through histological section observations. The cDNA sequence of LMB cyp19a1b was found to be1950 base pairs (bp) in length, including a 5' untranslated region of 145 bp, a 3' untranslated region of 278 bp, and an open reading frame encoding a protein consisting of 1527 bp that encoded 508 amino acids. The qRT-PCR results indicated that cyp19a1b abundantly expressed in the brain, followed by the gonads, and its expression in the ovaries was significantly higher than that observed in the testes (P < 0.05). After feeding fish with E2 for 30 days, the expression of cyp19a1b in the pseudo-female gonads (XY-F) was significantly higher than that in males (XY-M) (P < 0.05), whereas expression did not differ significantly between XX-F and XY-F fish (P > 0.05). Although the expression of cyp19a1b in XY-F and XX-F fish was not significantly different after 60 days (P>0.05), both exhibited significantly higher levels than that of XY-M fish (P<0.05). Histological sections analysis showed the presence of oogonia in both XY-F and XX-F fish at 30 days, while spermatogonia were observed in XY-M fish. At 60 days, primary oocytes were abundantly observed in both XY-F and XX-F fish, while a few spermatogonia were visible in XY-M fish. At 90 days, the histological sections' results showed that a large number of oocytes were visible in XY-F and XX-F fish. Additionally, the gonads of XY-M fish contained numerous spermatocytes. These results suggest that cyp19a1b plays a pivotal role in the development of ovaries and nervous system development in LMB.

Akkermansia muciniphila attenuated lipopolysaccharide-induced acute lung injury by modulating the gut microbiota and SCFAs in mice.

Gut microbiota are closely related to lipopolysaccharide (LPS)-induced acute lung injury (ALI). Akkermansia muciniphila (A. muciniphila) maintains the intestinal barrier function and regulates the balance of reduced glutathione/oxidized glutathione. However, it may be useful as a treatment strategy for LPS-induced lung injury. Our study aimed to explore whether A. muciniphila could improve lung injury by affecting the gut microbiota. The administration of A. muciniphila effectively attenuated lung injury tissue damage and significantly decreased the oxidative stress and inflammatory reaction induced by LPS, with lower levels of myeloperoxidase (MDA), enhanced superoxide dismutase (SOD) activity, decreased pro-inflammatory cytokine levels, and reduced macrophage and neutrophil infiltration. Moreover, A. muciniphila maintained the intestinal barrier function, reshaped the disordered microbial community, and promoted the secretion of short-chain fatty acids (SCFAs). A. muciniphila significantly downregulated the expression of TLR2, MyD88 and NF-kappa B (P < 0.05). Butyrate supplementation demonstrated a significant improvement in the inflammatory response (P < 0.05) and mitigation of histopathological damage in mice with ALI, thereby restoring the intestinal butyric acid concentration. In conclusion, our findings indicate that A. muciniphila inhibits the accumulation of inflammatory cytokines and attenuates the activation of the TLR2/Myd88/NF-κB pathway due to exerting anti-inflammatory effects through butyrate. This study provides an experimental foundation for the potential application of A. muciniphila and butyrate in the prevention and treatment of ALI.

Effects of pork fat and linseed oil as additives on gel quality of fish cake.

Pork fat (PF) is a necessary ingredient in making traditional fish cakes (TFCs), which contains saturated fatty acids with potential health concerns. While linseed oil (LO) containing α-linolenic acid is a potential nutrient-enhancing fat substitute. In this study, the effect of pork fat and linseed oil level on gel quality, sensory characteristics, microstructure, and protein conformation of TFCs were characterized. Results showed that the TFCs with 30% pork fat (wt/wt) had the highest gel strength. Additionally, sensory evaluation determined that TFCs with 30% pork fat scored the best by a sensory panel with high gel strength, water-holding capacity, and fresh and sweet taste. The gel strength, chewiness, and hardness of nutrient-enriched fish cakes with 20% linseed oil replaced for pork fat were higher than that only with pork fat (wt/wt) without changing in tenderness and elasticity. Visual results showed that the network was uniform at a moderate level of linseed oil addition (20% LO/PF replacement ratio). The results of this study provided technical guidelines for standardizing the TFC manufacture processes, and useful insight for the development of fish cakes with reduced animal fat content for additional health benefits for consumers.

Identification of a protective Bacteroides strain of alcoholic liver disease and its synergistic effect with pectin.

The depletion of Bacteroides in the gut is closely correlated with the progression of alcoholic liver disease (ALD). This study aimed to identify Bacteroides strains with protective effects against ALD and evaluate the synergistic effects of Bacteroides and pectin in this disease. Mice were fed Lieber-DeCarli alcohol diet to establish an experimental ALD model and pre-treated with 4 Bacteroides strains. The severity of the liver injury, hepatic steatosis, and inflammation was evaluated through histological and biochemical assays. We found that Bacteroides fragilis ATCC25285 had the best protective effects against ALD strains by alleviating both ethanol-induced liver injury and steatosis. B. fragilis ATCC25285 could counteract inflammatory reactions in ALD by producing short-chain fat acids (SCFAs) and enhancing the intestinal barrier. In the subsequent experiment, the synbiotic combination of B. fragilis ATCC25285 and pectin was evaluated and the underlying mechanisms were investigated by metabolomic and microbiome analyses. The combination elicited superior anti-ALD effects than the individual agents used alone. The synergistic effects of B. fragilis ATCC25285 and pectin were driven by modulating gut microbiota, improving tryptophan metabolism, and regulating intestinal immune function. Based on our findings, the combination of B. fragilis ATCC25285 and pectin can be considered a potential treatment for ALD. KEY POINTS: • B. fragilis ATCC25285 was identified as a protective Bacteroides strain against ALD. • The synbiotic combination of B. fragilis and pectin has better anti-ALD effects. • The synbiotic combination modulates gut microbiota and tryptophan metabolism.

Preparation, physicochemical characterization, and cytotoxicity of selenium nanoparticles stabilized by Oudemansiella raphanipies polysaccharide.

Selenium nanoparticles (SeNPs) have attracted substantial attention recently owing to their excellent bioavailability and low toxicity. In the present study, Oudemansiella raphanipies polysaccharide (ORPS)-decorated selenium nanoparticles (ORPS-SeNPs) were synthesized, and their physicochemical, storage stability, and antiproliferative activities were assessed by cell cytotoxicity and apoptosis experiments. The results revealed that orange-red, zero-valent, amorphous and spherical SeNPs with a mean diameter of approximately 60 nm were successfully prepared by using ORPS as a capping agent. Furthermore, the ORPS-SeNPs solution stored at 4 °C in the dark was stable for at least 90 days. Moreover, ORPS-SeNPs treatment inhibited the proliferation of four cancer cell lines in a dose-dependent manner, while no significant cytotoxicity towards human mesangial cell (HMC) cell lines was observed. Compared with their sensitivities to the other cancer cell lines (SGC-7901 and HT-29), the sensitivity of ORPS-SeNPs towards 786-O cells was higher, with an IC50 value of 18.88 ± 1.52 mg/L. Furthermore, the apoptotic pathway triggered by ORPS-SeNPs in 786-O cells was determined to be induced by reactive oxygen species (ROS) imbalance and mitochondria-mediated pathways and to eventually result in cellular oxidative stress damage. The results of this study suggest that ORPS-SeNPs can be developed as a potential treatment for cancer, especially human renal carcinoma.

The synergy of dietary supplements Lactobacillus salivarius LI01 and Bifidobacterium longum TC01 in alleviating liver failure in rats treated with D-galactosamine.

Lactobacillus salivarius (L. salivarius) has been widely used in dietary supplements and clinical treatments. Previous studies demonstrated the protective effect of L. salivarius LI01 on liver injury induced by D-galactosamine (D-GaIN) in rats. Accumulating evidence indicates that Lactobacillus and Bifidobacterium are highly coordinated; so in this study, we focus on the synergistic effect of L. salivarius LI01 and B. longum TC01 on the alleviation of liver injury caused by D-GaIN in rats and aim to find out the underlying interaction between the two strains. We observed reduced hepatic damage in the D-GaIN-treated rats with probiotic pre-administration, characterized by lower levels of AST and ALT (p < 0.05) and decreased HAI (Histological Activity Index) scores. Moreover, cotreatment with LI01 and TC01 more effectively decreases proinflammatory cytokines TNF-α, MCP-1 and M-CSF (p < 0.05) so as to inhibit systemic inflammation. Gut barrier dysfunction was ameliorated with compound probiotic pretreatment, as evidenced by the ultrastructure integrity, decreased histological score and elevated TJP-1 expression. What's more, supplementation with LI01 and TC01 markedly alleviates gut dysbiosis in the G-DaIN-treated rats, with enrichment of short chain fatty acid (SCFA) producers Faecalibaculum and Eubacterium_xylanophilum_group, a decreased Firmicutes/Bacteroidetes (F/B) ratio and depletion of proinflammatory microbes, such as Peptococcaeae and Ruminococcaceae_UCG-005. This study highlights the synergistic effect of dietary supplements LI01 and TC01 on the protection against liver failure, which is probably via altering gut microbiota.

Chemical profiling of Zilong Jin tablets using ultra high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry.

Zilongjin tablets as a traditional Chinese medicine are widely used for primary lung cancer patients with deficiency of "qi " and "blood " syndrome undergoing chemotherapy. It is a compound preparation that consists of eight herbs. To clarify the chemical profiling of Zilong Jin tablets rapidly, a feasible and accurate strategy was developed by the ultra high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry. According to the accurate mass and fragment ion information provided by high resolution mass spectrometry, the compounds were reasonably identified. In total, 74 compounds were characterized, including 20 flavonoids, 14 quinones, 15 organic acids, 6 phthalide compounds, and 19 other compounds. Among them, 34 major compounds were unambiguously confirmed by comparing with reference standards. This study could provide an important scientific basis for further research on quality control, pharmacokinetics and pharmacodynamics, and clinical application of Zilong Jin tablets.

Combination of an engineered Lactococcus lactis expressing CXCL12 with light-emitting diode yellow light as a treatment for scalded skin in mice.

Impaired wound closure is an increasingly crucial clinical challenge. Recently, wound healing has shifted towards innovative treatments that exploit nanotechnology, biomaterials, biologics and phototherapy. Here, we constructed an engineered MG1363-pMG36e-mCXCL12 strain with pMG36e plasmid encoding stromal cell-derived factor 1α (named CXCL12) and evaluated the synergistic effects of light-emitting diode (LED) yellow light and MG1363-pMG36e-mCXCL12 on scald wounds in mice. The results indicated that the combined treatment with LED yellow light with mCXCL12 delivering strain accelerated wound closure, tissue remodelling, re-epithelialization and hair follicle regeneration and inhibited over-inflammation oppositely in the central and surrounding wounds by macroscopic, histopathologic and immunohistochemistry parameters. Furthermore, combination therapy increased the epidermal growth factor and Ki67-positive cells and upregulated beta-catenin (ß-catenin), cellular-myelocytomatosis (c-Myc), wingless-type MMTV integration site family member 1 (Wnt1), Jagged 1, neurogenic locus notch homolog protein 1 (Notch 1) and hairy and enhancer of split 1 (Hes 1) protein levels of the Wnt and Notch signalling pathways. It also facilitated collagen fibrogenesis and deposition and improved the activities of hydroxyproline, superoxide dismutase and glutathione peroxidase in scalded granulation tissue, in addition to reducing the inflammatory factors interleukin 1 beta (IL-1ß) and tumour necrosis factor alpha (TNF-α). The combined treatment effectively reduced skin pathogens Ralstonia and Acinetobacter to further reduce the risk of infection. Overall, combination of LED yellow light and MG1363-pMG36e-mCXCL12 represents a potential strategy for the treatment of cutaneous wounds.

Efficacy and safety of Chinese herbal medicine Xiao Yao San in hypertension: A systematic review and meta-analysis.

BACKGROUND: Xiao Yao San (XYS) is thought to be beneficial for the treatment of hypertension in China. PURPOSE: A systematic review and meta-analysis was performed to evaluate the efficacy and safety of XYS in hypertension. STUDY DESIGN: A comprehensive literature search was conducted in 7 electronic databases for randomized controlled trials from their inception until January 7, 2019. METHODS: Methodological quality was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: A total of 17 trials including 1460 hypertensive patients met the selection criteria. Pooled analysis favored XYS plus antihypertensive drugs on blood pressure (BP), Hamilton anxiety scale, self-rating anxiety scale, self-rating depression scale, 9-item patient health questionnaire scale, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, homocysteine, and C-reactive protein. No significant difference between XYS plus antihypertensive drugs and antihypertensive drugs on major cardiovascular and cerebrovascular events was identified. XYS was well tolerated in the treatment of hypertension. CONCLUSION: XYS adjuvant to antihypertensive drugs maybe beneficial for hypertensive patients in lowering BP, improving depression, regulating blood lipids, and inhibiting inflammation. However, the efficacy and safety of XYS are still uncertain due to methodological shortcomings. More long-term, randomized, double-blinded clinical trials are needed in future studies.

Blood-Letting Therapy for Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the efficacy and safety of blood-letting therapy (BLT) in treatment of hypertension. METHODS: A comprehensive electronic and manual bibliographic searches were performed in Cochrane Central Register of Controlled Trials, Excerpt Medica Database (EMBASE), PubMed, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Chinese Biomedical Literature Database, and Wanfang Database to identify randomized controlled trials (RCTs) in which hypertensive patients were treated with BLT or BLT plus antihypertensive drugs (BPAD) against placebo, no treatment or antihypertensive drugs. The Cochrane Risk Assessment Tool was used to assess the methodological quality of trials. The Review Manager 5.3 software was used for meta-analysis. RESULTS: A total of 7 RCTs with 637 hypertensive patients from 1989 to 2017 were identified. Compared with antihypertensive drugs, blood pressure was significantly reduced by BLT (RR=1.21, 95% CI: 1.01 to 1.44, P=0.03; heterogeneity: P=0.06, I2=60%) and BPAD (RR=1.25, 95% CI, 1.02 to 1.53, P=0.03; heterogeneity: P= 0.01, I2=71%). Moreover, a significant improvement in Chinese medicine syndrome by BLT (RR=1.32; 95% CI: 1.14 to 1.53, P=0.0002; heterogeneity: P=0.53, I2=0%) and BPAD (RR=1.47; 95% CI: 1.06 to 2.04, P=0.02; heterogeneity: P=0.13, I2=56%) was identified. The reported adverse effects were well tolerated. CONCLUSION: Although some positive findings were identified, no definite conclusions regarding the efficacy and safety of BLT as complementary and alternative approach for treatment of hypertension could be drew due to the generally poor methodological design, significant heterogeneity, and insufficient clinical data. Further rigorously designed trials are warranted to confirm the results.

Retrospective study on recovery of 521 gastrointestinal tumor patients after laparoscopic surgery.

Influencing factors for recovery of patients with gastrointestinal tumor after laparoscopic surgery were explored to promote recovery of patients. Clinical data from 521 gastrointestinal tumor patients who underwent laparoscopic surgery in Dalian Central Hospital were collected. The recovery of gastrointestinal function was recorded, and the factors that affected the recovery of gastrointestinal function were analyzed. All data were processed using Statistical Product and Service Solutions (SPSS) 21.0 software. t-test and F-test were used for univariate analysis, and multivariate linear regression was adopted for multivariate analysis. Results of univariate analysis displayed that age, starting time of postoperative activity, peritoneal drainage tube indwelling time, blood potassium level, sleep disorder, fasting and fluid deprivation time, duration of the first postoperative defecation/exhaustion, abdominal distention and pain reaction and social support level had significant influences on recovery of patients after operation (P<0.05). Results of multivariate analysis indicated that peritoneal drainage tube indwelling time, blood potassium level, fasting and fluid deprivation time and starting time of postoperative activity were independent factors affecting the recovery of patients after operation (P<0.05). Some methods are conducive to the recovery of gastrointestinal function in patients with gastrointestinal tumor, including the removal of peritoneal drainage tube, timely potassium supplementation, and diet recovery after laparoscopic surgery as soon as possible.

Traditional Chinese medicine suppresses left ventricular hypertrophy by targeting extracellular signal-regulated kinases signaling pathway in spontaneously hypertensive rats.

Chinese herbal medicine Bu-Shen-Jiang-Ya decoction (BSJYD) is reported to be beneficial for hypertension. Over expression of extracellular signal regulated kinases (ERK) pathway plays an important role in left ventricular hypertrophy (LVH). This study aimed to observe effects of BSJYD on LVH in spontaneously hypertensive rats (SHRs) and explore its possible mechanism on regulation of ERK pathway. Sixty 12-week-old SHRs were randomly allocated into 5 groups: BSJYD high dose group, middle dose group, low dose group, captopril group, and control group. Besides, a control group of Wistar-Kyoto rats was established. All rats were treated for 8 weeks. Systolic blood pressure (SBP), heart rate (HR), pathology, and left ventricular mass index (LVMI) were measured. Western blotting and Real-time PCR were used to assess the expressions of BDNF, Ras, ERK1/2, and c-fox levels. SBP and HR were significantly decreased compared with the control group and LVMI was markedly improved by BSJYD treatment in a dose-dependent manner. BSJYD inhibited the expression of BDNF, Ras, ERK1/2, and c-fox mRNA in LVH. In conclusion, BSJYD suppressed hypertension-induced cardiac hypertrophy by inhibiting the expression of ERK pathway. These changes in gene expression may be a possible mechanism by which BSJYD provides myocardial protection from hypertension.

Microbiological Isolates and Antibiotic Susceptibilities: A 10-Year Review of Culture-Proven Endophthalmitis Cases.

PURPOSE: To review the microbiological spectrum and antibiotic sensitivities of the pathogens that cause culture-proven endophthalmitis and to understand the status and trends of antibiotic susceptibility at a public hospital over a 10-year period. METHODS: The data of 577 culture-proven endophthalmitis isolates collected between April 2004 and April 2014 were reviewed retrospectively. The antibiotic sensitivities were determined according to the criteria of the Clinical and Laboratory Standards Institute. The changes in antibiotic susceptibility over the 10 years were subjected to χ2 tests for trends. RESULTS: Among these isolates, 65% were gram-positive organisms (375), 16.6% were gram-negative organisms (96), and 18.4% were fungi (106). The predominant pathogens were Staphylococcal species (Staphylococcus epidermidis in 175, other coagulase-negative Staphylococci in 41, and Staphylococcus aureus in 54 cases), followed by Bacillus cereus isolates. The Aspergillus species was the most frequently isolated fungus, and Pseudomonas aeruginosa was the most frequently isolated gram-negative bacteria. The antibiotic susceptibilities of gram-positive bacteria were as follows: vancomycin, 97.6%; levofloxacin, 85.1%; gentamicin, 78.7%; rifampin, 77.2%; ofloxacin, 77.2%; chloramphenicol, 76.4%; and ciprofloxacin, 73.7%. The antibiotic susceptibilities of gram-negative isolates were as follows: ceftazidime, 50.5%; ciprofloxacin, 82.2%; amikacin, 81.3%; tobramycin, 80.2%; imipenem, 79.7%; and gentamicin, 78%. Over the 10-year study, there were significant changes in the antibiotic susceptibilities to the following five antibiotics: vancomycin, imipenem, penicillin G, amikacin, and trimethoprim-sulfamethoxazole (TMP-SMX). CONCLUSIONS: Vancomycin remains the most appropriate empirical antibiotic for gram-positive bacteria. The susceptibilities of the gram-negative organisms to ciprofloxacin and amikacin were greater than that to ceftazidime. Trends toward increases in the susceptibilities to the following five antibiotics were observed: vancomycin, imipenem, penicillin G, amikacin, and TMP-SMX.

The effects of red yeast rice dietary supplement on blood pressure, lipid profile, and C-reactive protein in hypertension: A systematic review.

Interest is increasing regarding the potential health effects of red yeast rice (RYR) consumption, which is described as a "natural statin" in China. This review aims to evaluate the efficacy of RYR on blood pressure (BP), lipid profile, and C-reactive protein (CRP) in treating hypertension. Seven electronic databases including the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP), the Chinese Biomedical Literature Database (CBM), and the Wanfang database were searched. To investigate the role of RYR for hypertension, randomized controlled trials for the use of RYR either as monotherapy or in combination with conventional medicine versus placebo, no intervention, or conventional medicine for hypertension were identified. A total of 21 trials containing 4558 patients were analyzed, the majority of which had low methodological quality. "RYR plus conventional therapy" exhibited significant lowering effects on serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and CRP but exhibited no significant effect on systolic BP, diastolic BP, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) compared with "placebo plus conventional therapy." "RYR plus conventional therapy" showed significant lowering effects on systolic BP, TC, LDL-C, and CRP but no effect on diastolic BP, TG, and HDL-C compared with "placebo plus conventional therapy." No significant difference in BP and lipid profile between "RYR plus conventional therapy" and "statins plus conventional therapy" was observed. "RYR plus statins" appeared to be more effective in lowering BP, TC, TG, and LDL-C but without a significant difference in HDL-C compared to statins. No serious adverse events were reported. The results of this meta-analysis suggested some supportive but limited evidence regarding RYR for hypertension. Further rigorously designed trials are warranted before RYR could be recommended to hypertensive patients.

Phosphorylation of CaMKII in the rat dorsal raphe nucleus plays an important role in sleep-wake regulation.

The Ca(2+) modulation in the dorsal raphe nucleus (DRN) plays an important role in sleep-wake regulation. Calmodulin-dependent kinase II (CaMKII) is an important signal-transducing molecule that is activated by Ca(2+) . This study investigated the effects of intracellular Ca(2+) /CaMKII signaling in the DRN on sleep-wake states in rats. Maximum and minimum CaMKII phosphorylation was detected at Zeitgeber time 21 (ZT 21; wakefulness state) and ZT 3 (sleep state), respectively, across the light-dark rhythm in the DRN in rats. Six-hour sleep deprivation significantly reduced CaMKII phosphorylation in the DRN. Microinjection of the CAMKII activation inhibitor KN-93 (5 or 10 nmol) into the DRN suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REM sleep (NREMS). Application of a high dose of KN-93 (10 nmol) increased slow-wave sleep (SWS) time, SWS bouts, the mean duration of SWS, the percentage of SWS relative to total sleep, and delta power density during NREMS. Microinjection of CaCl2 (50 nmol) in the DRN increased CaMKII phosphorylation and decreased NREMS, SWS, and REMS. KN-93 abolished the inhibitory effects of CaCl2 on NREMS, SWS, and REMS. These data indicate a novel wake-promoting and sleep-suppressing role for the Ca(2+) /CaMKII signaling pathway in DRN neurons. We propose that the intracellular Ca(2+) /CaMKII signaling in the dorsal raphe nucleus (DRN) plays wake-promoting and sleep-suppressing role in rats. Intra-DRN application of KN-93 (CaMKII activation inhibitor) suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REMS (NREMS). Intra-DRN application of CaCl2 attenuated REMS and NREMS. We think these findings should provide a novel cellular and molecular mechanism of sleep-wake regulation.

Meta-analysis of the effectiveness of traditional Chinese herbal formula Zhen Wu Decoction for the treatment of hypertension.

OBJECTIVES: Zhen Wu Decoction (ZWD), a famous classic herbal formula documented in traditional Chinese medicine (TCM), is widely available in China for treating hypertensive patients with kidney yang deficiency and fluid retention syndrome. This systematic review aims to evaluate the effectiveness and safety of ZWD for hypertension. METHODS: Cochrane Central Register of Controlled Trials, PubMed, Embase, the Chinese National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Chinese Biomedical Literature Database, and the Wanfang Database were searched from their inception to November 2014. Randomised controlled trials of ZWD used alone or in combination with antihypertensive drugs against placebo, no intervention or antihypertensive drugs in hypertensive patients were identified. Two assessors independently reviewed each trial. The Cochrane risk of bias assessment tool was used for quality assessment. RESULTS: Seven trials involving 472 hypertensive patients were identified. Compared with antihypertensive drugs, ZWD showed no significant effects in lowering blood pressure (BP) (n=177; risk ratio (RR) 1.06; 95% CI 0.87 to 1.28; p=0.58); however, ZWD plus antihypertensive drugs (ZPAD) significantly lowered systolic BP (n=80; weighted mean difference (WMD) -14.00 mm Hg, 95% CI -18.84 to -9.16 mm Hg; p<0.00001), diastolic BP (n=80; WMD -8.00 mm Hg, 95% CI -11.35 to -4.65 mm Hg; p<0.00001), and BP (n=215; RR 1.21, 95% CI 1.08 to 1.37; p=0.001). TCM symptoms and syndromes were significantly improved by either ZWD (n=177; RR 1.58, 95% CI 1.28 to 1.95; p<0.0001) or ZPAD (n=215; RR 1.30, 95% CI 1.14 to 1.49; p=0.0001). Adverse effects were not reported. CONCLUSIONS: This systematic review revealed no definite conclusion about the application of ZWD for hypertension due to the poor methodological quality, high risk of bias, and inadequate reporting on clinical data. More rigorously designed trials, especially addressing continuous BP and adverse effects, are warranted.

Efficacy and Safety of a Traditional Chinese Herbal Formula Xuefu Zhuyu Decoction for Hypertension: A Systematic Review and Meta-Analysis.

The cardioprotective role of xuefu zhuyu decoction (XZD), a well-known classical herbal formula, has been documented for hypertension treatment recently. This study aims to summarize the efficacy and safety of XZD in treating hypertension.Seven databases were searched to identify randomized controlled trials evaluating the efficacy of XZD in hypertensive patients. Fifteen studies involving 1364 hypertensive patients were included. All studies compared XZD and antihypertensive drugs with antihypertensive drugs used alone.In all, 15 studies reported significant effects of XZD for lowering blood pressure compared with the control group (P < 0.05), and 7 studies reported significant effects of XZD for improving symptoms compared with the control group (P < 0.00001). Meanwhile, studies reported XZD was more efficacious than antihypertensive drugs in improving total cholesterol, triglycerides, low-density lipoprotein cholesterol, homocysteine, hemorheology, carotid intima-media thickness, and left ventricular mass index (P < 0.05). No severe adverse event was reported.This meta-analysis provides evidence that XZD is beneficial for hypertension. Although concerns regarding selective bias and methodologic flaws were raised, our findings suggests XZD as a new candidate cardioprotective drug for hypertension, which should be given priority for future preclinical and clinical studies.

Glucocorticoid receptors in the locus coeruleus mediate sleep disorders caused by repeated corticosterone treatment.

Stress induced constant increase of cortisol level may lead to sleep disorder, but the mechanism remains unclear. Here we described a novel model to investigate stress mimicked sleep disorders induced by repetitive administration of corticosterone (CORT). After 7 days treatment of CORT, rats showed significant sleep disturbance, meanwhile, the glucocorticoid receptor (GR) level was notably lowered in locus coeruleus (LC). We further discovered the activation of noradrenergic neuron in LC, the suppression of GABAergic neuron in ventrolateral preoptic area (VLPO), the remarkable elevation of norepinephrine in LC, VLPO and hypothalamus, as well as increase of tyrosine hydroxylase in LC and decrease of glutamic acid decarboxylase in VLPO after CORT treatment. Microinjection of GR antagonist RU486 into LC reversed the CORT-induced sleep changes. These results suggest that GR in LC may play a key role in stress-related sleep disorders and support the hypothesis that repeated CORT treatment may decrease GR levels and induce the activation of noradrenergic neurons in LC, consequently inhibit GABAergic neurons in VLPO and result in sleep disorders. Our findings provide novel insights into the effect of stress-inducing agent CORT on sleep and GRs' role in sleep regulation.

Effect of Baduanjin exercise for hypertension: a systematic review and meta-analysis of randomized controlled trials.

This study aims to evaluate the efficacy of Baduanjin exercise for hypertension. Cochrane Library, PubMed, EMBASE, CNKI, VIP, CBM and Wanfang databases were searched. Eight randomized controlled trials (RCTs) were identified. Baduanjin significantly lowered systolic blood pressure (SBP) (WMD=-13.00 mmHg; 95% CI: -21.24 to -4.77; P=0.002), diastolic blood pressure (DBP) (WMD=-6.13 mmHg; 95% CI: -11.20 to -1.07; P=0.02), body mass index, blood glucose, triglyceride, and low-density lipoprotein-cholesterol, and improved high-density lipoprotein-cholesterol and quality of life compared to no intervention. No significant difference between Baduanjin and antihypertensive drugs on SBP (WMD=1.05 mmHg; 95% CI: -2.07 to 4.17; P=0.51) or DBP (WMD=1.90 mmHg; 95% CI: -1.22 to 5.02; P=0.23) was identified. Baduanjin plus antihypertensive drugs significantly reduced SBP (WMD=-7.49 mmHg; 95% CI: -11.39 to -3.59; P=0.0002), DBP (WMD=-3.55 mmHg; 95% CI: -5.25 to -1.85; P<0.0001), blood glucose, and total cholesterol compared to antihypertensive drugs. Baduanjin is an effective therapy for hypertension. However, further rigorously designed RCTs are still warranted.