Melatonin promotes sleep by activating the BK channel in C. elegans.

Melatonin (Mel) promotes sleep through G protein-coupled receptors. However, the downstream molecular target(s) is unknown. We identified the Caenorhabditis elegans BK channel SLO-1 as a molecular target of the Mel receptor PCDR-1-. Knockout of pcdr-1, slo-1, or homt-1 (a gene required for Mel synthesis) causes substantially increased neurotransmitter release and shortened sleep duration, and these effects are nonadditive in double knockouts. Exogenous Mel inhibits neurotransmitter release and promotes sleep in wild-type (WT) but not pcdr-1 and slo-1 mutants. In a heterologous expression system, Mel activates the human BK channel (hSlo1) in a membrane-delimited manner in the presence of the Mel receptor MT1 but not MT2 A peptide acting to release free Gßγ also activates hSlo1 in a MT1-dependent and membrane-delimited manner, whereas a Gßλ inhibitor abolishes the stimulating effect of Mel. Our results suggest that Mel promotes sleep by activating the BK channel through a specific Mel receptor and Gßλ.

[Ameliorative Effects of Cang-ai Volatile Oil on Left Ventricular Remodeling in Rats].

Objective: To evaluate with 7T cardiac magnetic resonance tissue tracking imaging (CMR-TT) the ameliorative effect of Cang-ai volatile oil (CAVO) on left ventricular remodeling (LVR) in rats induced by isoproterenol (ISO), and to make preliminary investigation into CAVO's effects on endothelial dysfunction in LVR. Methods: A total of 35 healthy male Sprague-Dawley (SD) rats were randomly assigned to two groups, the experimental group ( n=27) and the normal control group ( n=8). The rat model of LVR was established by subcutaneous injection of ISO solution at 10 mg·kg -1·d -1 at multiple sites for 10 consecutive days. After modeling was completed, the surviving rats ( n=24) in the experimental group were then randomly assigned to the blank experimental group, CAVO group, and Shexiang Baoxin pill (SXBXP) group ( n=8 in each group). Rats in each group were given via gavage the corresponding intervention medicine or an equivalent amount of normal saline solution for 28 consecutive days. At the end of modeling and intragastric intervention, 7T CMR cine sequence scanning was conducted to collect data. Then, post-processing software CVI42 was used to analyze the images and to compare and contrast the changes in the parameters of left ventricular cardiac function and myocardial strain in each group before and after the administration of the medication. The rats were sacrificed after MRI scanning, and their hearts were harvested for pathological examination. The levels of serum biochemical indicators were measured by enzyme-linked immunosorbent assay (ELISA). Results: CAVO significantly increased LV ejection fraction and overall myocardial strain parameters in LVR rats, while it decreased LV volume, mass, and serum levels of endothelial function indicators in LVR rats. In addition, pathological staining showed marked improvements in the hypertrophy, necrosis and interstitial fibrosis of cardiomyocytes. Conclusion: Through the regulation of myocardial vascular endothelial function, CAVO can significantly improve cardiac functions in LVR rats, delay the process of ventricular remodeling, and have a certain amount of protective effect on cardiac structure and function in rats.

Using 7.0 T cardiac magnetic resonance to investigate the effect of estradiol on biventricular structure and function of ovariectomized rats exposed to chronic hypobaric hypoxia at high altitude.

BACKGROUND: Despite that estradiol can reduce the risk of cardiovascular diseases in ovariectomized animals in the plains, its effect on animals at high altitude has seldom been reported. We hypothesize that estradiol can ameliorate cardiac damage to ovariectomized rats induced by chronic exposure to hypobaric hypoxia at high altitude. PURPOSE: This study was intended to investigate whether cardiovascular magnetic resonance (CMR) imaging could reveal cardioprotective effect of estradiol on ovariectomized rats under chronic exposure to hypobaric hypoxia at high altitude. METHODS: Thirty-two rats were randomized into the Control group (Plain), HH + Sham group (Hypobaric Hypoxia + Sham), HH + OVX group (Hypobaric Hypoxia + Bilateral Ovariectomy) and HH-OVX + E2 group (Hypobaric Hypoxia + Bilateral Ovariectomy + Estradiol, 50 µg/kg, 3 times a week, for 6 weeks) (n = 8 per group). Except the Control group (altitude: 500 m), rats in other groups were subcutaneously injected with 17ß -estradiol or vehicle and exposed to chronic hypobaric hypoxia in Qinghai-Tibet Plateau (altitude: 4250 m), China, for 6 weeks. Biventricular cardiac function and global strain of the rats were measured by CMR and analyzed using the cine tissue tracking techniques. Biochemical tests, histopathology and electronic microscopy were used to evaluate the protective effect of estradiol on the heart tissue of ovariectomized rats exposed to a high-altitude environment. RESULTS: The biventricular ejection fraction and global strains decreased in the HH + OVX group compared with that in the Control group (all p < 0.05). All the aforementioned changes in the HH + OVX group ameliorated in the HH-OVX + E2 group (all p < 0.05). Estradiol also alleviated the right ventricular dilatation and hypertrophy in the HH + OVX group (all p < 0.05). In addition, histological and biochemical analyses also supported these in vivo results. CONCLUSIONS: Estradiol ameliorated the biventricular structural and functional damage in ovariectomized rats exposed to chronic hypobaric hypoxia at high altitude.

TNFα Triggers an Augmented Inflammatory Response in Brain Neurons from Dahl Salt-Sensitive Rats Compared with Normal Sprague Dawley Rats.

Tumor Necrosis Factor (TNF)-α is a proinflammatory cytokine (PIC) and has been implicated in a variety of illness including cardiovascular disease. The current study investigated the inflammatory response trigged by TNFα in both cultured brain neurons and the hypothalamic paraventricular nucleus (PVN), a key cardiovascular relevant brain area, of the Sprague Dawley (SD) rats. Our results demonstrated that TNFα treatment induces a dose- and time-dependent increase in mRNA expression of PICs including Interleukin (IL)-1ß and Interleukin-6 (IL6); chemokines including C-C Motif Chemokine Ligand 5 (CCL5) and C-C Motif Chemokine Ligand 12 (CCL12), inducible nitric oxide synthase (iNOS), as well as transcription factor NF-kB in cultured brain neurons from neonatal SD rats. Consistent with this finding, immunostaining shows that TNFα treatment increases immunoreactivity of IL1ß, CCL5, iNOS and stimulates activation or expression of NF-kB, in both cultured brain neurons and the PVN of adult SD rats. We further compared mRNA expression of the aforementioned genes in basal level as well as in response to TNFα challenge between SD rats and Dahl Salt-sensitive (Dahl-S) rats, an animal model of salt-sensitive hypertension. Dahl-S brain neurons presented higher baseline levels as well as greater response to TNFα challenge in mRNA expression of CCL5, iNOS and IL1ß. Furthermore, central administration of TNFα caused significant higher response in CCL12 in the PVN of Dahl-S rats. The increased inflammatory response to TNFα in Dahl-S rats may be indicative of an underlying mechanism for enhanced pressor reactivity to salt intake in the Dahl-S rat model.

Efficacy and safety of integrated traditional Chinese and Western medicine against COVID-19: A systematic review and meta-analysis.

Although plenty of clinical trials have confirmed the efficacy and safety of integrated traditional Chinese and Western medicine (ITCWM) against COVID-19, the role of ITCWM remains controversial. So we conducted a systematic review and meta-analysis of published studies in eight major databases that report the outcomes of interest in COVID-19 patients receiving ITCWM. RevMan5.4 software was used for meta-analysis, while the quality of RCTs was assessed by the Cochrane risk of bias tool and the retrospective studies were assessed by Newcastle-Ottawa Scale. Eventually, a total of 53 studies with 5425 COVID-19 patients was identified. The meta-analysis results showed that ITCWM was significantly better than western medicine treatment (WMT) alone in the percentage of cases changing to severe/critical [RR = 0.40, 95%CI (0.33, 0.49), p < .00001, I2  = 10%], overall clinical effectiveness [RR = 1.26, 95% CI (1.18, 1.35), p < .00001, I2  = 50%], time to defervescencer [MD = -1.45, 95% CI (-1.82, -1.07), p < .00001, I2  = 83%], disappearing time of cough [MD = -2.11, 95% CI (-2.98, -1.25), p < .00001, I2  = 93%], time of RT-PCR negativity [MD = -3.35, 95% CI (-4.74, -1.95), p < .00001, I2  = 92%], length of hospital stay [MD = -4.05, 95% CI (-5.24, -2.85), p < .00001, I2  = 91%], improvement in CT scan [RR = 1.22, 95% CI (1.17, 1.28), p < .00001, I2  = 46%], TCM syndrome score [MD = -3.95, 95% CI (-5.07, -2.82), p < .00001, I2  = 92%], disappearance rate of fever [RR = 1.23, 95% CI (1.10, 1.38), p < .00001, I2  = 85%], disappearance rate of cough [RR = 1.43, 95% CI (1.25, 1.63), p < .00001, I2  = 60%], level of CRP [MD = -9.23, 95% CI (-10.94, -7.52), p < .00001, I2  = 97%], and WBC [MD = -9.23, 95% CI (-10.94, -7.52), p < .00001, I2  = 97%]. There is no significant difference between ITCWM and WMT in the adverse reaction rate [RR = 0.85, 95% CI(0.71, 1.03), p = .10, I2  = 25%]. Our results showed evidence of clinical efficacy and safety benefit in COVID-19 patients treated with ITCWM. In spite of some limitations, the rapidly developing global pandemic warrants further high-quality and multicenter clinical studies to confirm the contribution of ITCWM.

Effect of Chinese medicine for promoting blood circulation on microvascular angina: A systematic review and meta-analysis.

BACKGROUND: Blood-activating drugs (BADs) are widely used to treat microvascular angina in China. This study aims to summarize relevant evidence from randomized controlled trials (RCTs) to assess the efficacy and safety of BADs in the treatment of microvascular angina. METHODS: We searched for relevant studies before June 2019 from seven databases. Twenty-four studies were included of 1903 patients with microvascular angina. All studies compared the use of traditional Chinese medicine for activating blood circulation (BADs) and Western medicine (WM) with the use of Western medicine alone. RESULTS: In all, 15 trials reported a significant effect of BADs on improving clinical symptoms compared with the control treatment (P < .00001), and 8 trials reported significant effects of BADs on reducing the frequency of angina pectoris attacks compared with Western medicine treatment (P < .00001). The pooled results also demonstrated that BADs provided a significant benefit in reducing the dosage of nitroglycerin required (P = .02), the maximum range of ST-segment depression (P = .003) and the descending degree of the ST-T segment of ECG (P = .0002); prolonging the total time of treadmill exercise (P < .00001) and the time of ST-segment depression of 1 mm (P = .002); enhancing the total effective rate of Traditional Chinese Medicine (TCM) syndromes (P < .00001); improving endothelial function (P < .00001); and reducing the levels of high-sensitivity C-reactive protein (hs-CRP) (P < .00001). BAD treatment showed no statistically significant effect on the levels of TNF-a (P = .8) or IL-6 (P = .13). No severe adverse events were reported. CONCLUSION: This meta-analysis shows that BADs are effective for the treatment of microvascular angina. Although concerns regarding selective bias and low methodological quality were raised, our findings suggest that BADs are beneficial for patients with microvascular angina and should be given priority for future clinical studies.

A meta-analysis for Kuanxiong Aerosol on the treatment of angina pectoris.

BACKGROUND: Kuanxiong Aerosol (KA) has been used in patients with angina pectoris (AP) attacks for many years, this systematic review and meta-analysis aims to evaluate the clinical efficacy and safety of KA versus nitrates in the treatment of AP. METHODS: Seven databases (PubMed, EMBASE, CENTRAL, CNKI, VIP, CBM and Wanfang) were searched from inception to November 2019 to include randomized controlled trials (RCTs) that compare the efficacy and safety of KA with nitrates on the treatment of AP. And two reviewers independently assessed the risk of bias. RESULT: A total of 12 RCTs were eventually included, involving 2001 patients. Compared with the Nitrates group, the KA group showed great significant improvement on the 3-min [relative risk (RR) = 1.12, 95% confidence interval (CI) (1.03,1.23), P < .05;11 studies,1875 patients] and 5-min [RR = 1.05, 95%CI (1.01,1.08), P < 0.05; 11 studies,1875 patients] angina remission rates, the incidence of adverse reactions [RR = 0.42,95% CI (0.33,0.54), P < 0.00001; 8 studies, 1350 patients], endothelin(ET) [SMD = -0.40, 95%CI (-0.74,-0.07), P < 0.05; 2 studies, 143 patients] and c-reactive protein (CRP) [SMD = -0.58, 95%CI (-0.87,-0.30), P < 0.00001;2 studies, 200 patients],but no significant improvement on electrocardiogram efficacy [RR = 1.03, 95%CI (0.98,1.10), P = 0.26;11 studies, 1549 patients], nitric oxide (NO) [SMD = -0.08, 95%CI (-0.61,0.45), P = 0.76;2 studies, 143 patients]. CONCLUSION: The clinical use of KA is effective and safe on the treatment of AP, which appears to be better than nitrates in terms of efficiency, adverse reactions, endothelial function and inflammatory response. Nevertheless, due to some limitations in the sample size and quality of the included studies, more high-quality RCTs were still needed for further verification.

[Basic Research on Neuroprotective Effect of Volatile Oil of Cang Ai after Cerebral Ischemia-Reperfusion Injury Based on Diffusion Tensor Imaging].

OBJECTIVE: To study the neuroprotective effect of inhalation of volatile oil of Cang Ai (VOCA) on cerebral ischemia-reperfusion injury model by MRI diffusion tensor imaging. METHODS: Twenty-four healthy adult male SD rats were randomly divided into sham operation group, model (middle cerebral artery occlusion (MCAO) ) group and VOCA group. Evaluated the degree of neurological impairment of rats in each group immediately after successful establishment of model or 7 d later according to Zea Longa scoring. Coronal diffusion tensor imaging (DTI) scan was performed at 3 h, 3 d, and 7 d after the model successfully established by using 7.0 T magnetic resonance imaging. Measured the apparent diffusion coefficient (ADC) and anisotropy score (FA) of the DTI in the striatal region and the motion flat zone of the maximum infarct level and then calculate the relative apparent diffusion coefficient (rADC) and relative anisotropy score (rFA). TTC staining was used to evaluate the cerebral infarction volume of rats in each group at 7 d post model establishment, and the correlation analysis of rFA, rADC and neural score was performed. RESULTS: No neurological defect was detected in mice in the sham operation group. The MCAO group and the VOCA group showed neurological defect to different degrees. The neurological function score of the VOCA group was obviously lower than that of MCAO group at 7 th day (P<0.05). The DTI scan results showed that the rADC value of striatum of rats in VOCA group was higher than that in MCAO group at 3 h and 3 d after modeling (P<0.05), while there was no significant difference between the three groups at 7 th day. The rADC value of the motor cortex in the VOCA group was higher than that in the MCAO group at 3 h after modeling (P<0.01), and there was no significant difference at 3 rdday and 7 thday. The rFA value of striatum in VOCA group was higher than that in MCAO group at 3 rd day and 7 th day after modeling (P<0.05). There were no significant differences in rFA value between the MCAO and the VOCA group at three time points. TTC staining results showed that there was no infarcted area in the sham operation group, and the infarct volume in the VOCA group was smaller than that of the MCAO group (P<0.05). Correlation analysis showed that the striatum rFA value was highly correlated with neurological scores (r=－0.847, P<0.01). CONCLUSION: For the first time, we found that VOCA can effectively protect the neurological function of MCAO rats by reducing the toxic edema of cells in the ischemic area and accelerating the recovery of nerve fiber bundles after cerebral ischemia and reperfusion. rFA and rADC values can be used as effective indicators to evaluate the recovery of nerve function after cerebral ischemia and reperfusion.

HRPU-2, a Homolog of Mammalian hnRNP U, Regulates Synaptic Transmission by Controlling the Expression of SLO-2 Potassium Channel in Caenorhabditis elegans.

Slo2 channels are large-conductance potassium channels abundantly expressed in the nervous system. However, it is unclear how their expression level in neurons is regulated. Here we report that HRPU-2, an RNA-binding protein homologous to mammalian heterogeneous nuclear ribonucleoprotein U (hnRNP U), plays an important role in regulating the expression of SLO-2 (a homolog of mammalian Slo2) in Caenorhabditis elegans Loss-of-function (lf) mutants of hrpu-2 were isolated in a genetic screen for suppressors of a sluggish phenotype caused by a hyperactive SLO-2. In hrpu-2(lf) mutants, SLO-2-mediated delayed outward currents in neurons are greatly decreased, and neuromuscular synaptic transmission is enhanced. These mutant phenotypes can be rescued by expressing wild-type HRPU-2 in neurons. HRPU-2 binds to slo-2 mRNA, and hrpu-2(lf) mutants show decreased SLO-2 protein expression. In contrast, hrpu-2(lf) does not alter the expression of either the BK channel SLO-1 or the Shaker type potassium channel SHK-1. hrpu-2(lf) mutants are indistinguishable from wild type in gross motor neuron morphology and locomotion behavior. Together, these observations suggest that HRPU-2 plays important roles in SLO-2 function by regulating SLO-2 protein expression, and that SLO-2 is likely among a restricted set of proteins regulated by HRPU-2. Mutations of human Slo2 channel and hnRNP U are strongly linked to epileptic disorders and intellectual disability. The findings of this study suggest a potential link between these two molecules in human patients.SIGNIFICANCE STATEMENT Heterogeneous nuclear ribonucleoprotein U (hnRNP U) belongs to a family of RNA-binding proteins that play important roles in controlling gene expression. Recent studies have established a strong link between mutations of hnRNP U and human epilepsies and intellectual disability. However, it is unclear how mutations of hnRNP U may cause such disorders. This study shows that mutations of HRPU-2, a worm homolog of mammalian hnRNP U, result in dysfunction of a Slo2 potassium channel, which is critical to neuronal function. Because mutations of Slo2 channels are also strongly associated with epileptic encephalopathies and intellectual disability in humans, the findings of this study point to a potential mechanism underlying neurological disorders caused by hnRNP U mutations.

Efficacy and safety of oral Guanxinshutong capsules in patients with stable angina pectoris in China: a prospective, multicenter, double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: To assess the efficacy and safety of oral Guanxinshutong (GXST) capsules in Chinese patients with stable angina pectoris (SAP) in a prospective, multicenter, double-Blind, placebo-controlled, randomized clinical trial (clinicaltrials.gov Identifier: NCT02280850). METHODS: Eligible patients were randomized 1:1 to the GXST or placebo group. Current standard antianginal treatment except for nitrate drugs was continued in both groups, who received an additional 4-week treatment of GXST capsule or placebo. Primary endpoint was the change from baseline in angina attack frequency after the 4-week treatment. Secondary endpoints included the reduction of nitroglycerin dose, score of Seatntle Agina Questionnaire, exercise tolerance test defined as time to onset of chest pain and ST-segment depression at least 1 mm greater than the resting one. RESULTS: A total of 300 SAP patients from 12 centers in China were enrolled between January 2013 and October 2015, and they were randomly divided into the GXST group and the placebo group (150 patients in each group). Of whom, 287 patients completed the study (143 patients in the GXST group, 144 patients in the placebo group). The baseline characteristics of the two groups were comparable. After 4-week treatment with GXST capsules, the number of angina attacks and the consumption of short-acting nitrates were significantly reduced. In addition, the quality of life of patients were also substantially improved in the GXST group. No significant differences in the time of onset of angina and 1-mm ST segment depression were noted between the two groups. 7 patients (4.1%) in the GXST group and 3 patients (2.1%) in the placebo group reported at least one adverse event, respectively. CONCLUSIONS: GXST capsules are beneficial for the treatment of SAP patients.

α-Catulin CTN-1 is required for BK channel subcellular localization in C. elegans body-wall muscle cells.

The BK channel, a voltage- and Ca(2+)-gated large-conductance potassium channel with many important functions, is often localized at specific subcellular domains. Although proper subcellular localization is likely a prerequisite for the channel to perform its physiological functions, little is known about the molecular basis of localization. Here, we show that CTN-1, a homologue of mammalian α-catulin, is required for subcellular localization of SLO-1, the Caenorhabditis elegans BK channel α-subunit, in body-wall muscle cells. CTN-1 was identified in a genetic screen for mutants that suppressed a lethargic phenotype caused by expressing a gain-of-function (gf) isoform of SLO-1. In body-wall muscle cells, CTN-1 coclusters with SLO-1 at regions of dense bodies, which are Z-disk analogs of mammalian skeletal muscle. In ctn-1 loss-of-function (lf) mutants, SLO-1 was mislocalized in body-wall muscle but its transcription and protein level were unchanged. Targeted rescue of ctn-1(lf) in muscle was sufficient to reinstate the lethargic phenotype in slo-1(gf);ctn-1(lf). These results suggest that CTN-1 plays an important role in BK channel function by mediating channel subcellular localization.

Comprehensive effect of Naoxintong capsule combined with Western medicine on coronary heart disease after percutaneous coronary intervention: a meta-analysis.

Aims: To systematically evaluate the comprehensive effect of combining Naoxintong capsule (NXT) with Western medicine (WM) on coronary heart disease post-percutaneous coronary intervention (PCI). Methods: Randomized controlled trials (RCTs) of NXT for patients with CHD after PCI were systematically searched across multiple databases, including the Cochrane Library, PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database (VIP), and Wan Fang, from inception until 31 January 2023. Study selection, data extraction, and quality assessment were performed by two independent reviewers. The quality of the included studies was evaluated using version 2 of the Cochrane risk-of-bias tool (RoB 2), and data analysis was performed using R4.2.2. Results: Fifteen RCTs conducted between 2011 and 2022 and involving 1,551 patients were identified, with 774 and 777 patients in the experimental and control groups respectively. It was found that the NXT and WM combination was superior to the WM therapy alone in terms of the effective clinical rate (odds ratio [OR] = 4.69, 95% confidence interval [CI] = 2.13-10.30), effective rate in electrocardiogram (OR = 6.92, 95% CI = 3.44-13.92), effective rate in angina (OR = 5.90, 95% CI = 3.04-11.46), left ventricular ejection fraction (mean difference [MD] = 4.94, 95% CI = 2.89-6.99), brain natriuretic peptide (MD = -294.00, 95% CI = -584.60 to -3.39), creatine kinase-MB (MD = -7.82, 95% CI = -13.26 to -2.37), major adverse cardiovascular events (OR = 0.24, 95% CI = 0.14-0.43), maximum platelet aggregation rate (MD = -8.33, 95% CI = -11.64 to -5.01), and Chinese medicine evidence score (OR = 9.79, 95% CI = 3.57-26.85). However, there was no significant difference in cardiac troponin I level reduction (MD = -0.13, 95% CI = 0.35-0.09) or the occurrence of adverse medicine events (OR = 0.92, 95% CI = 0.41-2.05). Meta-regression and subgroup analyses indicated that NXT capsule dosage, treatment duration, and patient baseline characteristics contributed to the heterogeneity. Conclusion: A combination of NXT and WM can improve clinical outcomes in patients undergoing PCI. However, further studies are needed to confirm the reliability and safety of this combined treatment approach. Systematic Review Registration: PROSPERO, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=369174, Identifier CRD42022369174.

Cang-ai volatile oil alleviates nasal inflammation via Th1/Th2 cell imbalance regulation in a rat model of ovalbumin-induced allergic rhinitis.

We previously revealed that Cang-ai volatile oil (CAVO) regulates T-cell activity, enhancing the immune response in people with chronic respiratory diseases. However, the effects of CAVO on allergic rhinitis (AR) have not been investigated. Herein, we established an ovalbumin (OVA)-induced AR rat model to determine these effects. Sprague-Dawley (SD) rats were exposed to OVA for 3 weeks. CAVO or loratadine (positive control) was given orally once daily for 2 weeks to OVA-exposed rats. Behavior modeling nasal allergies was observed. Nasal mucosa, serum, and spleen samples of AR rats were analyzed. CAVO treatment significantly reduced the number of nose rubs and sneezes, and ameliorated several hallmarks of nasal mucosa tissue remodeling: inflammation, eosinophilic infiltration, goblet cell metaplasia, and mast cell hyperplasia. CAVO administration markedly upregulated expressions of interferon-γ, interleukin (IL)-2, and IL-12, and downregulated expressions of serum tumor necrosis factor-α, IL-4, IL-5, IL-6, IL-13, immunoglobulin-E, and histamine. CAVO therapy also increased production of IFN-γ and T-helper type 1 (Th1)-specific T-box transcription factor (T-bet) of the cluster of differentiation-4+ T-cells in splenic lymphocytes, and protein and mRNA expressions of T-bet in nasal mucosa. In contrast, levels of the Th2 cytokine IL-4 and Th2-specific transcription factor GATA binding protein-3 were suppressed by CAVO. These cumulative findings demonstrate that CAVO therapy can alleviate AR by regulating the balance between Th1 and Th2 cells.

Case report of scrub typhus complicated by hypokalemia and multiple organ dysfunction syndrome.

CONTEXT: Scrub typhus, caused by Orientia tsutsugamushi, has a wide range of clinical manifestations, including meningoencephalitis, acute renal failure, pneumonitis, myocarditis, and septic shock. However, there are no documented cases of scrub typhus with hypokalemia. In this report, we present a case of scrub typhus with hypokalemia and multiple organ failure syndrome, highlighting the importance of electrolyte imbalance in patients with scrub typhus. CASE REPORT: A 59-year-old woman presented to the emergency department with abdominal pain that had been present for 1 day. On admission, the physical examination and laboratory test results indicated that the patient had renal, liver, and circulatory failure, and hypokalemia. She developed meningitis and disseminated intravascular coagulation during hospitalization. She recovered with appropriate management, and was discharged on day 17. CONCLUSION: This report highlights the potential for atypical presentations of scrub typhus, including a previously undocumented association with hypokalemia. Although the contribution of hypokalemia to the patient's clinical course remains uncertain, this case underscores the importance of considering electrolyte imbalance in the management of patients with scrub typhus. Further research is warranted to better understand the relationship between scrub typhus and electrolyte imbalance.

Potential shared gene signatures and molecular mechanisms between atherosclerosis and depression: Evidence from transcriptome data.

BACKGROUND: Atherosclerosis and depression contribute to each other; however, mechanisms linking them at the genetic level remain unexplored. This study aimed to identify shared gene signatures and related pathways between these comorbidities. METHODS: Atherosclerosis-related datasets were downloaded from the Gene Expression Omnibus database. Differential and weighted gene co-expression network analyses were employed to identify atherosclerosis-related genes. Depression-related genes were downloaded from the DisGeNET database, and the overlaps between atherosclerosis-related genes and depression-related genes were characterized as crosstalk genes. The functional enrichment analysis and protein-protein interaction network were performed in these gene sets. Subsequently, the Boruta algorithm and Recursive Feature Elimination algorithm were performed to identify feature-selection genes. A support vector machine was constructed to measure the accuracy of calculations, and two external validation sets were included to verify the results. RESULTS: Based on two atherosclerosis-related datasets (GSE28829 and GSE43292), 165 genes were determined as atherosclerosis-related genes. Meanwhile, 1478 depression-related genes were obtained. After intersecting, 24 crosstalk genes were identified, and two pathways, "lipid and atherosclerosis" and "tryptophan metabolism," were revealed as mutual pathways according to the enrichment analysis results. Through the protein-protein interaction network, Molecular Complex Detection plugin, and cytoHubba plugin, PTPRC and MMP9 were identified as the hub gene. Moreover, SLC22A3, CASP1, AMPD3, and PIK3CG were recognized as feature-selection genes. Based on two external validation sets, CASP1 and MMP9 were finally determined as the critical crosstalk genes. CONCLUSIONS: "Lipid and atherosclerosis" and "tryptophan metabolism" were possibly the pathways of atherosclerosis secondary to depression and depression due to atherosclerosis, respectively. CASP1 and MMP9 were revealed as the most pivotal candidates linking atherosclerosis and depression by mediating these two pathways. Further experimentation is needed to confirm these conclusions.

Efficacy and safety of Lianhua Qingwen granule in the treatment of non-influenza viral pneumonia: a randomized, double-blind, placebo-controlled, multicenter clinical study.

Objective: To observe the effectiveness and safety of Lianhua Qingwen granule in the treatment of non-influenza viral pneumonia. Methods: This study was a multicenter, randomized, double-blind, placebo-controlled trial. Subjects who met the inclusion and exclusion criteria and were clinically diagnosed with viral pneumonia (negative for influenza virus) were randomly divided into the Lianhua Qingwen granule trial group and placebo control group. Patients in the trial group was given Lianhua Qingwen granule, 2 bags at a time, 3 times a day, and the controls were given placebo, with a treatment course of 7 days. Patients' clinical symptoms and signs, and treatment-associated adverse events were observed. Subjects should be included in the full analysis set (FAS) as long as they were all given the medication and had an effectiveness test performed after randomization. Subjects should be included in the Per Protocol Set (PPS),a subset of the total analysis set, which should contain those with strong compliance, no protocol violations, and complete baseline values for the primary indicators. Results: A total of 169 subjects were enrolled in 12 subcenters, including 151 (76 in the trial group and 75 in the control group) in the FAS and 140 (68 in the trial group and 72 in the control group) in the PPS. After 7 days of treatment, the clinical symptom relief rates were 82.98% (FAS) and 87.12% (PPS) in the trial group, and 75.11% (FAS) and 76.02% (PPS) in the control group, respectively. The clinical symptom relief rates in the trial group were significantly higher than those in the control group (p < 0.001). Significant improvements in single symptoms of cough and expectoration in the trial group were observed compared with the control group (p < 0.05). There were no statistical differences in fever, sputum color change, chest pain, muscle pain, dyspnea, chills, and thirst between the two groups (p > 0.05). Safety: There were no significant differences in body weight, vital signs, blood routine, urine routine, stool routine, and blood biochemical indicators (CK, AST, ALT, Cr, and Bun) between the two groups before and after treatment (p > 0.05). During treatment, there were no significant differences in the incidence of adverse events and serious adverse events between the two groups (p > 0.05). Conclusion: Lianhua Qingwen granules improved the clinical symptoms of patients with non-influenza virus pneumonia, especially ameliorating cough and expectoration. Lianhua Qingwen granules were associated with good safety.

Dystrobrevin controls neurotransmitter release and muscle Ca(2+) transients by localizing BK channels in Caenorhabditis elegans.

Dystrobrevin is a major component of a dystrophin-associated protein complex. It is widely expressed in mammalian tissues, including the nervous system, in which it is localized to the presynaptic nerve terminal with unknown function. In a genetic screen for suppressors of a lethargic phenotype caused by a gain-of-function isoform of SLO-1 in Caenorhabditis elegans, we isolated multiple loss-of-function (lf) mutants of the dystrobrevin gene dyb-1.dyb-1(lf) phenocopied slo-1(lf), causing increased neurotransmitter release at the neuromuscular junction, increased frequency of Ca(2+) transients in body-wall muscle, and abnormal locomotion behavior. Neuron- and muscle-specific rescue experiments suggest that DYB-1 is required for SLO-1 function in both neurons and muscle cells. DYB-1 colocalized with SLO-1 at presynaptic sites in neurons and dense body regions in muscle cells, and dyb-1(lf) caused SLO-1 mislocalization in both types of cells without altering SLO-1 protein level. The neuronal phenotypes of dyb-1(lf) were partially rescued by mouse α-dystrobrevin-1. These observations revealed novel functions of the BK channel in regulating muscle Ca(2+) transients and of dystrobrevin in controlling neurotransmitter release and muscle Ca(2+) transients by localizing the BK channel.