[Effect of Zhenwu Decoction on electrical remodeling of cardiomyocytes in heart failure via I_(to)/Kv channels].

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.

Elimination of hepatitis C in a hospital characterized by infectious diseases.

Background: The World Health Organization has proposed to eliminate hepatitis C by 2030, yet there is still a large gap to the goal. Screening for hepatitis C is cost-effective and efficient in medical institutions. The aim of this study was to identify the key populations for HCV antibody screening in hospital characterized by infectious diseases, and provide estimates of the proportion of HCV-infected persons in the Beijing Ditan hospital completing each step along a proposed HCV treatment cascade. Methods: A total of 105,112 patients who underwent HCV antibody testing in Beijing Ditan hospital between 2017 and 2020 were included in this study. HCV antibody and HCV RNA positivity rate were calculated and compared by chi-square test. Results: The positivity rate of HCV antibody was 6.78%. The HCV antibody positivity rate and the proportion of positive patients showed an upward trend along with age in the five groups between 10-59 years. In the contrary, a decreasing trend was observed in the three groups above 60 years. Patients with positive HCV antibody were mainly from the Liver Disease Center (36.53%), the Department of Integrative Medicine (16.10%), the Department of Infectious Diseases (15.93%) and the Department of Obstetrics and Gynecology (9.44%). Among HCV antibody positive patients, 6,129 (85.95%) underwent further HCV RNA testing, of whom 2097 were HCV RNA positive, the positivity rate was 34.21%. Of the patients who were HCV RNA positive, 64.33% did not continue with HCV RNA testing. The cure rate for HCV antibody positive patients was 64.98%. Besides, there was a significant positive correlation between HCV RNA positivity rate and HCV antibody level (r = 0.992, P < 0.001). The detection rate of HCV antibody among inpatients showed an upward trend (Z = 5.567, P < 0.001), while the positivity rate showed a downward trend (Z = 2.2926, P = 0.0219). Conclusions: We found that even in hospitals characterized by infectious diseases, a large proportion of patients did not complete each step along a proposed HCV treatment cascade. Besides, we identified key populations for HCV antibody screening, namely: (1) patients over 40 years of age, especially those aged 50-59 years; (2) the Department of Infectious Diseases and the Department of Obstetrics and Gynecology patients. In addition, HCV RNA testing was highly recommended for patients with HCV antibody levels above 8 S/CO.

Efficacy and safety of sinomenine for diabetic kidney diseases: A meta-analysis.

BACKGROUND: In traditional Chinese medicine, Sinomenii Caulis contains Sinomenine (SIN), one of the major active ingredients. According to some studies, SIN can reduce proteinuria and provides clinical effectiveness rates in diabetic kidney disease (DKD) patients, however, the evidence is not strong and mechanisms of action are unclear. The efficacy and safety of SIN in treating DKD were evaluated by meta-analysis, and the potential mechanism of SIN therapy for DKD was initially explored by network pharmacology. METHODS: PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP, and SinoMed databases were comprehensively searched until March 28, 2022. Randomized controlled trials on DKD treated with SIN were selected. The main results were clinical effective rate and the secondary results were the decrease in 24-hour urine total protein (24-hour UTP), serum creatinine, adverse reactions, etc. Drug combinations and disease stages were analyzed in subgroups. Sensitivity analysis was performed for 24-hour UTP. The potential target genes and pathways of SIN in treating DKD were studied using protein-protein interactions, gene ontology, and the Kyoto Genome Encyclopedia and Genomes enrichment analysis. RESULTS: The meta-analysis included 7 randomized controlled trials. SIN treatment had a higher clinical effectiveness rate than conventional treatment (relative risk = 1.53, 95% confidence interval [1.30; 1.80], Z = 5.14, P < .0001); the decrease in 24-hour UTP, treatment group was higher than control group (standardized mean difference = -1.12, 95% confidence interval [-1.71; -0.52], Z = -3.69, P = .0002); In the experimental group, adverse reactions were more common than in the control group. SIN mainly affected 5 target genes, NFκB-1, TNF, interleukin 6, interleukin 1ß and signal transducer and activator of transcription 3, and IL-17, AGE-RAGE signaling pathways, lipids, and atherosclerosis were all controlled to achieve therapeutic effects. CONCLUSION: SIN is an effective and safe drug for treating DKD, enhancing clinical efficacy, and reducing proteinuria. The main potential mechanism is anti-inflammatory.

Non-clinical safety evaluation of salvianolic acid A: acute, 4-week intravenous toxicities and genotoxicity evaluations.

BACKGROUND: Toxicological problem associated with herbal medicine is a significant public health problem. Hence, it is necessary to elaborate on the safety of herbal medicine. Salvianolic acid A (SAA) is a major active compound isolated from Danshen, a popular herbal drug and medicinal food plant in China. The aim of the present study was to explore the toxicological profile of SAA. METHODS: The acute toxicity studies were performed in mice and Beagle dogs with single administration with SAA. A 4-week subchronic toxicity was test in dogs. SAA was intravenously administered at doses of 20, 80 and 300 mg/kg. Clinical observation, laboratory testing and necropsy and histopathological examination were performed. The genotoxic potential of SAA was evaluated by 2 types of genotoxicity tests: a reverse mutation test in bacteria and bone marrow micronucleus test in mice. RESULTS: In acute toxicities, the LD50 of SAA is 1161.2 mg/kg in mice. The minimum lethal dose (MLD) and maximal non-lethal dose (MNLD) of SAA were 682 mg/kg and 455 mg/kg in dogs, respectively. The approximate lethal dose range was 455-682 mg/kg. In the study of 4-week repeated-dose toxicity in dogs, focal necrosis in liver and renal tubular epithelial cell, the decrease in relative thymus weight, as well as abnormal changes in biochemical parameters, were observed in SAA 80 or 300 mg/kg group. The no observed adverse effect level (NOAEL) of SAA was 20 mg/kg. Thymus, liver and kidneys were the toxic targets. These toxic effects were transient and reversible. These results indicated that it should note examination of liver and kidney function during the administration of SAA in clinic. Furthermore, SAA had no mutagenic effect at any tested doses. CONCLUSION: These results provide new toxicological information of SAA for its clinical application and functional food consumption.

The potential mechanism of Astragali Radix in the treatment of children with nephrotic syndrome.

BACKGROUND: The molecular mechanism of Astragali Radix in the treatment of children with nephrotic syndrome (NS) is unclear. This study aimed to use network pharmacology to explore this potential mechanism. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to identify the main active ingredients of Astragali Radix. The PharmMapper, Online Mendelian Inheritance in Man (OMIM), and GeneCards databases were then used to identify the active ingredients of Astragali Radix. The String database and Cytoscape software were used to construct the protein-protein network. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using DAVID Database. RESULTS: In the TCMSP Database, a total of 20 chemical constituents of Astragali Radix were screened. After removing the duplicates and false positive genes, 394 targets of these active ingredients were obtained from PharmMapper. By comparing the NS-related genes in the GeneCards and OMIM Databases, a total of 39 potential NS-related targets were ultimately identified. The protein-protein-interaction network included 39 nodes and 366 edges. The top 5 proteins were albumin (ALB), serine/threonine kinase (AKT1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), and matrix metallopeptidase 9 (MMP9). The GO analysis showed that the target genes were mainly involved in biological processes (e.g., signal transduction, the positive regulation of cell proliferation, and the positive regulation of migration). The cellular components included a plasma membrane, extracellular exosome, and extracellular space. The molecular functions included protein binding, zinc-ion binding, protein tyrosine kinase activity, and enzyme binding. The KEGG analysis showed that the treatment of NS by Astragali Radix mainly involved pathways in cancer, proteoglycans in cancer, the phosphatidylinositol 3-kinase and protein kinase B (PI3K-Akt) signaling pathway, the rennin-angiotensin-system (Ras) signaling pathways, and Forkhead box protein O1 (FoxO) signaling pathways. CONCLUSIONS: In the present study, the network pharmacology method was used to explore the potential targets and pathways of Astragali Radix in the treatment of NS. We also provided future research directions for the treatment of NS with a complex pathogenesis.

Application Value of Rehabilitation Nursing in Patients with Stroke Based on the Theory of Interactive Standard: A Randomized Controlled Study.

OBJECTIVE: To explore the application value of rehabilitation nursing based on the theory of interactive standards in stroke patients. METHODS: A total of 120 stroke patients who were treated in our hospital from December 2018 to September 2020 were selected as the research objects, and the patients were divided into a control group (60 cases) and an observation group (60 cases) according to the random number table method. The control group used routine nursing care, and the observation group used interactive rehabilitation care based on the control group. The Barthel Index, National Institute of Health Stroke Scale (NIHSS) score, Specific Quality Of Life Scale (SS-QOL) score, rehabilitation standard rate, nursing satisfaction, improvement time of limb function, and compliance with rehabilitation exercise were compared between the two groups of patients. RESULTS: After intervention, the Barthel Index of the two groups increased, and the Barthel Index of the observation group was comparatively higher (P < 0.05); the NIHSS scores of the two groups of patients reduced, and the NIHSS scores of the observation group were significantly lower than those of the control group (P < 0.05); the SS-QOL scores of the two groups of patients improved, and the increase in SS-QOL scores in the observation group was found to be significantly higher than those in the control group (P < 0.05); the compliance rate was found to be in favor of the observation group (83.33 (50/60) vs 63.33 (38/60)) (χ 2 = 6.136, P˂0.05); the total satisfaction of nursing care of patients in the observation group was superior to the control group (96.67% vs 78.33%) (χ 2 = 9.219, P˂0.05); the limb function improvement time of the observation group was significantly shorter (P < 0.05); the observation group had significantly higher rehabilitation exercise compliance scores (P < 0.05). CONCLUSION: The rehabilitation nursing based on the interactive standard theory can promote the stroke patients to complete the rehabilitation goals, improve the neurological and limb functions, and enhance the patients' daily living ability, quality of life, and nursing satisfaction, which is worthy of clinical promotion and application.

Chemotherapy based on "Domino-effect" combined with immunotherapy amplifying the efficacy of an anti-metastatic treatment.

In tumor immunotherapy, Treg cells are immunosuppressive cells. In general, the main strategy of chemo immune-therapy for Treg cells is to eliminate them using chemotherapy drugs combined with immune checkpoint inhibitors. However, the dead Treg cells still exert immunosuppressive effects via the nucleoside adenosine pathway. To improve immunosuppression, we designed a nanosystem to deliver synthetic chemotherapeutics and immune activators. The homemade curcumin analog (CA) was encapsulated by α-lactalbumin (α-LA), and the Treg cell specific antibody (mAb), as a therapeutic agent, was linked to the drug-loaded protein via matrix metalloproteinase-responded peptide (P). After the cleavage peptide responded to matrix metalloproteinase (MMP-2), the CA@α-LA-P-mAb nanoparticles were separated into CA@α-LA and antibody, which can specifically enter cancer cells and Treg cells via membrane fusion and Nrp-1 receptors, respectively. Finally, we found that CA can not only lead to cell death by the chondriosome apoptosis approach but also reduce the production of Treg cells by inhibiting the expression of foxp3 (a key transcription factor of Treg cells). In addition, specific antibodies can improve the immunosuppression of existing Treg cells. The combined effect of CA and antibodies amplifies the role of chemotherapy in metastatic breast cancer.

[Effect of wrist-ankle acupuncture on the expression of glutamate and NMDA receptor of the spinal dorsal horn in rats with neuropathic pain].

OBJECTIVE: To observe the effect of wrist-ankle acupuncture (WA) stimulation at "R4"- "R5" - "R6" on the expression of glutamate (Glu) and phosphorylated protein NMDAR1(p-NMDAR1) of the spinal dorsal horn in spared nerve injury (SNI) rats, so as to explore its mechanism underlying improvement of SNI. METHODS: A total of 36 SD rats were randomly divi-ded into sham operation, model and WA groups, with 12 rats in each group. The SNI procedure comprised an axotomy and ligation of the tibial and common peroneal nerves leaving the sural nerve intact. Rats of the WA group were treated by acupuncture at "R4"-"R5"-"R6" points from the 5th day to the 14th day after modeling. The mechanical pain thresholds were measured before and 5, 10 and 14 d after SNI, respectively. The cold allodynia was dectected by Acetone solution dropped onto the lateral plantar surface of the paw. Glu content and p-NMDAR1 expression of spinal dorsal horn were detected by 1H-MRS, ELISA and immunohistochemistry Methods. RESULTS: Compared with the sham operation group, the mechanical pain threshold of the model group was significantly decreased (P<0.01), the duration of cold stimulation foot contraction was increased (P<0.01), and the Glu content and p-NMDAR1 expression in the spinal dorsal horn were significantly increased (P<0.05, P<0.01). After WA intervention, the mechanical pain threshold was significantly increased (P<0.01), the duration of cold stimulation was significantly shortened (P<0.01), and Glu content and p-NMDAR1 protein expression of spinal dorsal horn were decreased significantly (P<0.05, P<0.01) in the WA group compared with the model group. CONCLUSION: WA can reduce pain sensitivity in rats with neuropathic pain, possibly by inhibiting the expression of Glu and p-NMDAR1 in the spinal dorsal horn.

[Soil ecological effect of attapulgite and its application prospect in ecological planting of Chinese materia medica].

The long-term and extensive use of chemical fertilizers and pesticides in the cultivation of Chinese materia medica has resulted in serious soil ecological and environmental problems such as secondary salinization, soil consolidation, soil acidification, continuous cropping obstacles, micro-ecological imbalance, and serious soil pests and diseases in the production areas of Chinese materia medica. Therefore, promoting the ecological planting of Chinese materia medica is the only way for the production of Chinese materia medica. Attapulgite(ATP) is a kind of water-rich magnesium-rich aluminosilicate clay mineral with layered and chain structure. It has abundant reserves in China, possesses nano-material properties, strong adsorption and ion exchange properties, and has huge high value utilization space. ATP and its functional products have the potential of water and fertilizer conservation, regulating soil structure and micro-ecology, and are widely used in ecological planting of Chinese materia medica. This paper reviews the resource distribution, structural characteristics, the research and application progress in soil ecological effects of ATP, and prospects the application prospects of it in the ecological planting of Chinese materia medica.

Comparative proteomics reveals protective effect of resveratrol on a high-fat diet-induced damage to mice testis.

In recent years, resveratrol has been shown to protect against metabolic damage, including obesity-associated subfertility/infertility. In the present study, proteomic alterations in testicular tissues were investigated by tandem mass tag (TMT) in mice fed with a high-fat diet (HFD) without or with resveratrol supplementation (HFD+RSV). Serum testosterone levels, spermatozoa parameters and testicular histological morphology were assessed. Resveratrol treatment was shown to significantly reduce serum cholesterol, prevent the HFD-induced reductions in serum testosterone and spermatozoa parameters, and decrease the ultrastructural degeneration of testicular tissues. The comparative proteomics analysis revealed 58 differentially expressed proteins between the HFD and control groups and 38 differentially expressed proteins between the HFD and HFD+RSV groups. Gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the most highly enriched differential proteins were correlated to spermatozoa function and cholesterol metabolism. The real-time RT-PCR and western blotting results confirmed the differential expression of the corresponding proteins related to spermatozoa function that were identified by proteomics. The present study provides new insight into the mechanisms of the beneficial effects of resveratrol, and may present it as a potential therapeutic strategy for obesity-associated male subfertility/infertility.Abbreviations:TMT: Tandem mass tag; HFD: High-fat diet; RSV: Resveratrol; GO: Gene ontology; Protein-proteinKEGG: Kyoto Encyclopedia of Genes and Genomes; RT-PCR: Reverse transcription-polymerase chain reaction; SDS-PAGE: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis; PVDF: Polyvinylidene fluoride; ECL: Enhanced chemiluminescence; RIPA: Radio-immunoprecipitation assay; CTRL: Control; PPI: interaction; RIA: Radioimmunoassay; T: Testosterone; TG: Triglycerides; TC: Total cholesterol; LDL-c: Low-density lipoprotein cholesterol; HDL-c: High-density lipoprotein cholesterol; Crisp1: Cysteine-rich secretory protein 1; SIRT1: Sirtuin 1; GPx5: Glutathione peroxidase 5; Svs4: Seminal vesicle secretory protein 4; Tssk3: Testis-specific serine kinase 3; Pate4: Prostate and testis expressed 4; Sva: Seminal vesicle antigen; Lcn5: Lipocalin 5; Spinkl: Serine protease inhibitor, Kazal type-like.

Soil ecological effect of attapulgite and its application prospect in ecological planting of Chinese materia medica / 中国中药杂志

The long-term and extensive use of chemical fertilizers and pesticides in the cultivation of Chinese materia medica has resulted in serious soil ecological and environmental problems such as secondary salinization, soil consolidation, soil acidification, continuous cropping obstacles, micro-ecological imbalance, and serious soil pests and diseases in the production areas of Chinese materia medica. Therefore, promoting the ecological planting of Chinese materia medica is the only way for the production of Chinese materia medica. Attapulgite(ATP) is a kind of water-rich magnesium-rich aluminosilicate clay mineral with layered and chain structure. It has abundant reserves in China, possesses nano-material properties, strong adsorption and ion exchange properties, and has huge high value utilization space. ATP and its functional products have the potential of water and fertilizer conservation, regulating soil structure and micro-ecology, and are widely used in ecological planting of Chinese materia medica. This paper reviews the resource distribution, structural characteristics, the research and application progress in soil ecological effects of ATP, and prospects the application prospects of it in the ecological planting of Chinese materia medica.

Association Between Serum Cotinine Level and Serological Markers of Epstein-Barr Virus in Healthy Subjects in South China Where Nasopharyngeal Carcinoma Is Endemic.

Introduction: Self-reported smoking has been associated with higher seropositivity for the IgA response to Epstein-Barr virus (EBV) viral capsid antigen (VCA-IgA) and transcription activator protein (Zta) in healthy men in southern China where nasopharyngeal carcinoma (NPC) is endemic. Results on the association of biochemically verified smoking status with EBV reactivation are scarce. We aimed to investigate the relations of serum cotinine level with serological markers of EBV in healthy women, in addition to men. Methods: We collected information on demographic, lifestyle, environmental factors, and EBV serological markers in a cross-sectional study on 2,275 healthy subjects who were recruited from physical examination centers in Guangdong Province, China. In the present analysis, 901 subjects' serum cotinine levels have been measured by enzyme-linked immunosorbent assay (ELISA). Odds ratios (seropositivity of four EBV serological markers vs. seronegativity) for categorical serum cotinine levels were calculated by unconditional logistic regression with a group-specific confidence interval (CI). Results: In women, compared with lower serum cotinine level (0-0.71 ng/ml), higher cotinine level (>0.71-1.20 ng/ml; >1.20-228.40 ng/ml) was associated but non-significantly with higher seropositivity for EBV VCA-IgA (age- and education-adjusted OR = 1.18, 95% CIs = 0.84-1.64, 1.06, 0.75-1.50). These associations remained but still non-significant after adjusting for 5-year age group, education, family history of cancer, consumption of tea, Chinese herbal tea, salted fish at childhood, and exposure to occupational dust, chemical, fume, and radiation (multivariable adjusted OR = 1.21, 95% CIs = 0.85-1.71, 1.09, 0.76-1.55). In men, compared with lower serum cotinine level (0-2.15 ng/ml), higher cotinine level (>2.15-103.6 ng/ml; >103.6-419.4 ng/ml) was significantly associated with higher seropositivity for EBV VCA-IgA and Zta-IgA (age- and education-adjusted OR = 2.16, 95% CIs = 1.37-3.41, 1.79, 1.11-2.90; 1.98, 1.17-3.34, 1.95, 1.14-3.34). The association remained significant after adjusting for potential confounders for Zta-IgA (OR = 2.32, 95% CI = 1.37-3.93 for >2.15-103.6, and 2.50, 1.43-4.38 for >103.6-419.4 ng/ml), but not for VCA-IgA (2.06, 1.29-3.27, and 1.61, 0.96-2.71). Conclusions: Higher serum cotinine level is associated with higher seropositivity for EBV serological markers in healthy men in southern China. Such positive association was also observed in women but became non-significant. If confirmed to be causal, this finding has important implications for tobacco control and prevention of EBV-related disease, particularly for NPC.

Associations between environmental factors and serological Epstein-Barr virus antibodies in patients with nasopharyngeal carcinoma in South China.

Epstein-Barr virus (EBV) reactivation, reflected by aberrantly increased levels of various serological antibodies, has been suggested to be an early indicator of nasopharyngeal carcinoma (NPC) onset and progression. We have previously suggested that certain lifestyle and dietary factors were associated with elevated serological levels of the antibody against various EBV antigens namely VCA, Zta, EBNA1, and oral EBV DNA loads among healthy population. It remains unclear whether these potential environmental factors would also influence EBV serological antibodies in NPC patients. We conducted an epidemiological study to evaluate the associations between such environmental factors and EBV antibody levels among 1701 NPC patients in South China. Pretreatment serums were collected and examined for VCA-IgA and EA-IgA by immunoenzymatic assays and antienzyme rate (AER) of EBV DNase-specific neutralizing antibody. We found that consumption of Canton-style herbal tea was significantly correlated with increased serological antibody levels of VCA-IgA and EA-IgA, with adjusted ORs of 1.35 (95% CI: 1.03-1.76) and 1.32 (95% CI: 1.01-1.73), respectively, in the weekly intake frequency stratum, while not related to AER of EBV DNase-specific neutralizing antibody. Smoking was found to be not only an apparent risk factor for higher antibody levels of AER in stage III-IV patients (OR = 1.60, 95% CI: 1.11-2.30), but also associated closely with NPC stage at diagnosis (OR = 2.17, 95% CI: 1.47-3.22), with dose-response effects. In conclusion, we found consumption of Canton-style herbal tea and cigarette smoking were in positive associations with elevated EBV antibodies in NPC patients, which may be of public health significance for the primary prevention of EBV-associated diseases especially NPC.

Activities of Biapenem against Mycobacterium tuberculosis in Macrophages and Mice.

OBJECTIVE: To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis. METHODS: Biapenem/clavulanate (BP/CL) was evaluated for in vitro activity against Mycobacterium tuberculosis (Mtb) multidrug-resistant (MDR) isolates, extensively drug-resistant (XDR) isolates, and the H37RV strain. BP/CL activity against the H37Rv strain was assessed in liquid cultures, in macrophages, and in mice.. RESULTS: BP/CL exhibited activity against MDR and XDR Mtb isolates in liquid cultures. BP/CL treatment significantly reduced the number of colony forming units (CFU) of Mtb within macrophages compared with control untreated infected macrophages. Notably, BP/CL synergized in pairwise combinations with protionamide, aminosalicylate, and capreomycin to achieve a fractional inhibitory concentration for each pairing of 0.375 in vitro. In a mouse tuberculosis infection model, the efficacy of a cocktail of levofloxacin + pyrazinamide + protionamide + aminosalicylate against Mtb increased when the cocktail was combined with BP/CL, achieving efficacy similar to that of the positive control treatment (isoniazid + rifampin + pyrazinamide) after 2 months of treatment. CONCLUSION: BP/CL may provide a new option to clinically treat MDR tuberculosis.

Melatonin appears to protect against steroidogenic collapse in both mice fed with high-fat diet and H2 O2 -treated TM3 cells.

High-fat diets (HFDs) are detrimental to steroidogenesis and male fertility. This study aimed to investigate the protective effects of melatonin (MT) treatment on testicular dysfunction in mice fed with HFD. C57BL/6J male mice were randomly divided into three groups: CTRL, HFD and HFD + MT. MT treatment mitigated the increase in body weight and adipose tissue in HFD-fed mice. Serum levels of sex hormones were improved upon MT supplementation, and the expression of the testosterone synthesis proteins, StAR and P450scc was rescued as well. MT treatment significantly up-regulated the expression of SIRT1, SOD2, and GPx4 and down-regulated the expression of GRP78 and CHOP, indicating an attenuation of oxidative stress (OS) and endoplasmic reticulum (ER) stress. In TM3 cells, MT treatment protected against H2 O2 -induced steroidogenic collapse by improving mitochondrial function and attenuating OS and ER stress. These results indicate that MT treatment can improve steroidogenesis in mice fed with HFD and may have therapeutic value in the treatment of obesity-associated hypogonadism.

A randomized controlled trial on the blood pressure-lowering effect of amlodipine and nifedipine-GITS in sustained hypertension.

In a multicenter, randomized trial, we investigated whether the long half-time dihydropyridine calcium channel blocker amlodipine was more efficacious than the gastrointestinal therapeutic system (GITS) formulation of nifedipine in lowering ambulatory blood pressure (BP) in sustained hypertension (clinic systolic/diastolic BP 140-179/90-109 mm Hg and 24-hour systolic/diastolic BP ≥ 130/80 mm Hg). Eligible patients were randomly assigned to amlodipine 5-10 mg/day or nifedipine-GITS 30-60 mg/day. Ambulatory BP monitoring was performed for 24 hours at baseline and 4-week treatment and for 48 hours at 8-week treatment with a dose of medication missed on the second day. After 8-week treatment, BP was similarly reduced in the amlodipine (n = 257) and nifedipine-GITS groups (n = 248) for both clinic and ambulatory (24-hour systolic/diastolic BP 10.3/6.5 vs 10.9/6.3 mm Hg, P ≥ 0.24) measurements. However, after missing a dose of medication, ambulatory BP reductions were greater in the amlodipine than nifedipine-GITS group, with a significant (P ≤ 0.04) between-group difference in 24-hour (-1.2 mm Hg) and daytime diastolic BP (-1.5 mm Hg). In conclusion, amlodipine and nifedipine-GITS were efficacious in reducing 24-hour BP. When a dose of medication was missed, amlodipine became more efficacious than nifedipine-GITS.

Novel partners with colistin to increase its in vivo therapeutic effectiveness and prevent the occurrence of colistin resistance in NDM- and MCR-co-producing Escherichia coli in a murine infection model.

Objectives: The emergence of NDM- and MCR-1-co-producing Escherichia coli has compromised the use of carbapenems and colistin, which are critically important in clinical therapy, and represents a severe threat to public health worldwide. Here, we demonstrate synergism of colistin combined with existing antibiotics as a potential strategy to overcome XDR E. coli co-harbouring NDM and MCR-1 genes. Methods: To comprehensively evaluate their combined activity, antibiotic combinations were tested against 34 different E. coli strains carrying both NDM and MCR-1 genes. Antibiotic resistance profiles and molecular characteristics were investigated by susceptibility testing, PCR, MLST, S1-PFGE and WGS. Antibiotic synergistic efficacy was evaluated through in vitro chequerboard experiments and dose-response assays. A mouse model was used to confirm active combination therapies. Additionally, combinations were tested for their ability to prevent high-level colistin-resistant mutants (HLCRMs). Results: Combinations of colistin with rifampicin, rifabutin and minocycline showed synergistic activity against 34 XDR NDM- and MCR-1-co-producing E. coli strains, restoring, in part, susceptibility to both colistin and the partnering antibiotics. The therapeutic effectiveness of colistin combined with rifampicin or minocycline was demonstrated in a mouse model. Furthermore, colistin plus rifampicin showed significant activity in preventing the occurrence of HLCRMs. Conclusions: The synergism of colistin in combinations with rifampicin, rifabutin or minocycline offers viable therapeutic alternatives against XDR NDM- and MCR-positive E. coli.

[Warming Needle Moxibustion Relieves Symptoms of Lumbar Disc Herniation Patients and Upregulates Plasma ß-endorphin].

OBJECTIVE: To analyze the effect of warming needle moxibustion of Jiaji (EX-B 2), Huantiao (GB 30), etc. on lumbago and other symptoms of lumbar disc herniation (LDH) patients and changes of plasma ß-endorphin (ß-EP) content. METHODS: A total of 60 LDH patients were equally randomized into warming needle moxibustion group and conventional acupuncture group. Patients of the conventional acupuncture group were treated by puncturing lumbar Jiaji (EX-B 2), Huantiao (GB 30), Weizhong (BL 40), and Yanglingquan (GB 34) with filiform acupuncture needles. Patients of the warming needle moxibustion group were treated by puncturing the same 4 acupoints, and with the acupuncture needle in lumbar EX-B 2 attached an ignited moxa-stick segment. The treatment in both groups lasted for 30 min every time, once every other day for 15 times, with 5 times being a therapeutic course and two days' rest between every two courses. The therapeutic effect was evaluated according to the "Criteria for Evaluating the Therapeutic Effect of Disorders of Traditional Chinese Medicine". The lumbago severity was assessed using visual analogue scale (VAS), and the lumbar functional activity assessed using modified Oswestry dysfunction (in objects-lifting, sitting, standing, walking, sleeping, pain, activity of daily living, social activity, outing, etc.) index (ODI). The plasma ß-EP content was assayed using ELISA. RESULTS: After the treatment, of the two 30 cases in the conventional acupuncture and warming needle moxibustion groups, 8 (26.67%) and 12 (40.00%) were under control, 8 (26.67%) and 10 (33.33%) had a marked improvement, 3 (10.00%) and 4 (13.33%) were effective, and 11 (36.66%) and 4 (13.33%) ineffective, with the effective rates being 63.34% and 86.66%, respectively. The effective rate of the warming needle moxibustion was significantly higher than that of the conventional acupuncture (P<0.05). The VAS scores and ODI values of the two groups were gradually decreased along with the prolongation of treatment, and significantly lower in the warming needle moxibustion group than in the acupuncture group at the 1st, 2nd and 3rd course of treatment (P<0.01). The levels of plasma ß-EP were gradually increased in the two groups at the 1st, 2nd and 3rd course of treatment, and were obviously higher in the warming needle moxibustion group than in the conventional acupuncture group at each of the 3 courses (P<0.01). No obvious adverse reactions were observed in the two groups. CONCLUSION: Warming needle moxibustion has a better therapeutic effect in relieving lumbago and lumbar dysfunction, and can up-regulate blood ß-EP level.

[Current Researches and Ideas Regarding Correlation Between Meridians and Viscera].

The correlation between meridians and viscera is the key content of the meridian theory in acupuncture medicine. This paper introduces the close relationship between the meridians running on the body surface and viscera from ancient lite-rature, modern experimental studies (such as acupoint sensitization, neuro-endocrine-immune networks, etc.), and clinical application in the treatment of various conditions with acupuncture, moxibustion, Guasha (scraping) therapies, etc. We also presented some related research ideas (i.e., taking the clinical treatment as the forerunner, paying more attention to multi-disciplinary integration, combining clinical and basic research together, doing research from tridimensional point of review, and making full use of advanced technology, etc.) in order to provide a possibly favorable help for researchers to further reveal the scientific mechanisms underlying correlation between the meridian and viscera in the future.