Effects of glutaraldehyde and povidone-iodine on apoptosis of grass carp liver and hepatocytes.

Since disinfectants are used all over the world to treat illnesses in people and other animals, they pose a major risk to human health. The comprehensive effects of disinfectant treatments on fish liver, especially the impacts on oxidative stress, toxicological effects, transcriptome profiles, and apoptosis, have not yet been fully analyzed. In the current investigation, healthy grass carp were exposed to 80 µg/L glutaraldehyde or 50 µg/L povidone-iodine for 30 days. First, the findings of enzyme activity tests demonstrated that the administration of glutaraldehyde could considerably increase oxidative stress by lowering T-SOD, CAT, and GPx and raising MDA. Furthermore, KEGG research revealed that exposure to glutaraldehyde and povidone-iodine stimulated the PPAR signal pathway. To further elucidate the transcriptome results, the relative expressions of related DEGs in the PPAR signal pathway were verified. Glutaraldehyde induced apoptosis in liver tissue of grass carp; however, it activated cytotoxicity and apoptosis in grass carp hepatocytes when exposed to glutaraldehyde or povidone-iodine. According to the current study, disinfectants can cause the impairment of the immune system, oxidative stress, and attenuation of the PPAR signal pathway in the liver of grass carp, making them detrimental as dietary supplements for grass carp, particularly in the aquaculture sector.

An End-Tidal Carbon Monoxide Nomogram for Term and Late-Preterm Chinese Newborns.

OBJECTIVE: To establish a reference nomogram for end-tidal CO corrected for ambient CO (ETCOc) levels in term and late-preterm Chinese newborns and then assess its efficacy to identify hemolytic hyperbilirubinemia. STUDY DESIGN: We conducted a prospective study by measuring concurrent ETCOc and total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) levels collected postnatally at 12, 24, 48, 72, 96, and 120 hours of age. ETCOc at the 25th, 50th, 75th, and 95th percentiles at each epoch were used to construct the reference nomogram. We then explored the ability of predischarge ETCOc and TSB/TcB metrics to predict the development of hyperbilirubinemia requiring phototherapy in early postnatal period and jaundice readmission in late postnatal period. RESULTS: Our nomogram, based on 990 measurements from 455 infants who were not nonhemolytic, displayed a steady line within 3 postnatal days, followed by a subsequent decline. From a cohort of infants with a serial ETCOc measurements (n = 130) and those readmitted (n = 21), we found that ETCOc and TSB/TcB ≥75th percentile can identify most hemolytic hyperbilirubinemia between 12 and 72 hours after birth with an area under the curve (AUC) of 0.741. An ETCOc ≥1.7 ppm alone between 96 and 120 hours after birth can identify most hemolytic hyperbilirubinemia with an AUC of 0.816. In addition, 90.5% of readmitted infants had an ETCOc ≥75th percentile. CONCLUSIONS: An ETCOc reference nomogram during the first 5 postnatal days in nonhemolytic term and late-preterm newborns can be used to identify hemolytic hyperbilirubinemia requiring phototherapy in the early postnatal period and readmission in the late postnatal period.

Bacteria-Mediated Tumor Therapy via Photothermally-Programmed Cytolysin A Expression.

By leveraging the ability of bacteria to express therapeutic protein cytolysin A (ClyA) through plasmid transformation, a thermally-activated biohybrid (TAB@Au) is constructed by biomineralizing gold nanoparticles (AuNPs) on the E. coli surface. Due to the feature of anaerobic bacteria homing to tumor microenvironments, the bacteria-based antitumor vehicles can be efficaciously accumulated at tumor sites. Under NIR laser irradiation, the biomineralized AuNPs harvest transdermal photons and convert them into local heat for photothermal therapy. After that, the produced heat elicits the expression of ClyA for killing tumor cells. In vitro and in vivo experiments verify the conception that the current therapeutic modality greatly inhibits the proliferation of tumor cells. In terms of the spatial specificity and non-invasiveness of NIR laser, the bacteria-based phototherapy represents an appealing way for tumor therapy.

Synergizing sunitinib and radiofrequency ablation to treat hepatocellular cancer by triggering the antitumor immune response.

BACKGROUND: Minimally invasive radiofrequency ablation (RFA) is used as a first-line treatment option for hepatocellular cancer (HCC) with the weaknesses of incomplete ablation, tumor recurrence, and inferior outcomes. To overcome this limitation, we proposed to develop sunitinib-RFA integrated therapy with a potential of activating anti-HCC immune response. METHODS: Using our unique murine model, we developed a novel RFA platform with a modified human cardiac RF generator. Therapeutic efficacy of sunitinib-RFA combined treatment in HCC was tested in this platform. Tumor progression was monitored by MRI; tumor necrosis and apoptosis were detected by H&E and terminal deoxynucleotidyl transferase dUTP nick end labeling; immune reaction was defined by flow cytometry; and signaling molecules were examined with real-time PCR (qPCR), western blot, and immunohistochemical staining. RESULTS: A significantly reduced tumor growth and extended lift span were observed in the mice receiving combined treatment with RFA and sunitinib. This combined treatment significantly increased the frequency of CD8+ T cell, memory CD8+ T cell, and dendritic cells (DCs); decreased the frequency of regulatory T cells; and activated tumor-specific antigen (TSA) immune response in tumor microenvironment. We found that RFA caused PD-1 upregulation in tumor-infiltrated T cells by boosting hepatocyte growth factor (HGF) expression, which was suppressed by sunitinib treatment. We have also demonstrated that sunitinib suppressed VEGF's effect in enhancing PD-L1 expression in DCs and attenuated heat-sink effect. The results indicate that RFA induced tumor destruction and release of in situ TSAs which can activate a tumoricidal immune response in sunitinib-treated mice, significantly improving anti-HCC therapeutic efficacy. CONCLUSIONS: Sunitinib enables RFA-released in situ TSA to ignite an effective anti-tumor immune response by suppressing HGF and VEGF signaling pathways. Sunitinib-RFA as a synergistic therapeutic approach significantly suppresses HCC growth.

Effect of community based practice of Baduanjin on self-efficacy of adults with cardiovascular diseases.

BACKGROUND: Low self-efficacy in chronic disease patients is one of the main disturbances which require physical and mental rehabilitation, calling for the development of a home accessible way to improve self-management. OBJECTIVES: The purpose of this study was to explore the effectiveness of a community based Baduanjin exercise on self-efficacy in adults with cardiovascular disease. DESIGN: A randomized controlled trial, longitudinal research design was employed. PARTICIPANTS: After screening by health documents in Community Health Service Station, a total of 134 patients with records of cardiovascular diseases were had been enrolled according to the following inclusion criteria: (1) Community dwelling adults in Xili Community; (2) Patients diagnosed with cardiovascular diseases by community doctors, or other clinicians in health records in the past 3 years (2013-2015); (3) independent walking. Participants were excluded if they: (1) had impaired mobility and limited extremities functionality; (2) had not been in stable health condition and could not adhere to the exercise regime; (3) had communication difficulties and limited ability to follow instructions. METHODS: Participants were randomly assigned to the Baduanjin group or the control group. Those in the Baduanjin group received 16 weeks of Baduanjin exercise training, while those in the control group kept the original exercise mode unchanged. The Self-Efficacy for Managing Chronic Disease 6-item Scale (SEMCD6) was administered to subjects before and after intervention. RESULTS: Demographic data showed that 65.12% of the enrolled 129 participants were aged 65 or older, 92.25% received less than 12 years of education, and 68.21% participants' monthly income was less than 1999 RMB. Before intervention, SEMCD6 scores of 86.36% participants in Baduanjin group were below 7 points, while 85.71% in control group; after 16 weeks of Baduanjin exercise, SEMCD6 scores lower than 7 points in Baduanjin group (21.21%) were significantly lower than that of the control group (84.13%). The increase of SEMCD6 scores in Baduanjin group was statistically significant in the confidence to keep the fatigue, to keep the physical discomfort or pain, to keep the emotional distress and do the different tasks and activities (P<0.01). CONCLUSIONS: Adults with cardiovascular diseases in community have lower level of education, most of whom have a low monthly income; thus, community dwelling cardiovascular disease patients are more suitable for an economic program to persist their long term management of the disease. Baduanjin is a traditional Chinese medicine regimen with less physical and cognitive demand; community based exercise of Baduanjin could help to increase self-efficacy in patients with cardiovascular diseases, thus better self-management of rehabilitation process.

High-level expression and characterization of solvent-tolerant lipase.

In this study, the coding sequence of the lipase from Proteus sp. SW1 was optimized via codon optimization and subjected to expression in Pichia pastoris GS115. The maximum enzyme yield was 387 mg/L in the supernatants of the shake-flask culture. The purified recombinant lipase exhibited a specific activity of 130 U/mg toward p-nitrophenyl Laurate. Its optimum pH and temperature were 8.0 and 40°C, respectively. It was highly stable and even activated in water-miscible solvents, showing over 102% residual activity after 24 h incubation in ethanol, acetone, isopropanol and acetonitrile. In addition, the enzyme showed promoted activity with the increasing concentrations of methanol/ethanol and exhibited the maximum activity at 80%. In a solvent-free system for biodiesel synthesis with a one-step addition of methanol, the recombinant lipase displayed a 87% conversion rate toward palm oil at the high water content of 80%. The highly improved expression level and activity of the recombinant lipase may contribute to enable its commercial-scale production, and the unique properties would make it a particularly promising biocatalyst for biodiesel production in the future.

High-level expression and characterization of the Bacillus subtilis subsp. subtilis str. BSP1 YwaD aminopeptidase in Pichia pastoris.

Aminopeptidases are widely used for creating protein hydrolysates and peptide sequencing. The ywaD gene from a new Bacillus isolate, named Bacillus subtilis subsp. subtilis str. BSP1, was cloned into the yeast expression vector pHBM905A and expressed and secreted by Pichia pastoris strain GS115. The deduced amino acid sequence of the aminopeptidase encoded by the ywaD gene shared up to 98% identity with aminopeptidases from B. subtilis strains 168 and zj016. The yield (3.81 g/l) and specific activity (788 U/mg) of recombinant YwaD in high-density fermentation were extremely high. And 829.83 mg of the purified enzyme (4089.72 U/mg) were harvested. YwaD was glycosylated, and its activity decreased after deglycosylation, which was similar to that of the aminopeptidase from B. subtilis strain zj016. YwaD was most active toward l-arginine-4-nitroanilide. Moreover, it exhibited high resistance to carbamide, which was not true for aminopeptidases from B. subtilis strains 168 and zj016, which could simplify the purification of YwaD. Moreover, the expression and parts of characterization of the aminopeptidase from B. subtilis strain 168 in Pichia pastoris were added as supplementary material. The sequence and other characteristics of YwaD were compared with those of aminopeptidases from B. subtilis strains 168 and zj016, and they will provide a solid foundation for further research on the influence of amino acid mutations on the function of aminopeptidases.

Huangqi Jianzhong Tang for Treatment of Chronic Gastritis: A Systematic Review of Randomized Clinical Trials.

To assess the clinical effects and safety of Huangqi Jianzhong Tang (HQJZ) for the treatment of chronic gastritis (CG), three English databases and four Chinese databases were searched through the inception to January 2015. In randomized controlled trials (RCTs) comparing HQJZ with placebo, no intervention and western medicine were included. A total of 9 RCTs involving 979 participants were identified. The methodological quality of the included trials was generally poor. Meta-analyses demonstrated that HQJZ plus conventional medicine was more effective in improving overall gastroscopy outcome than western medicine alone for treatment of chronic superficial gastritis with the pooling result of overall improvement [OR 3.78 (1.29,11.06), P = 0.02]. In addition, the combination of HQJZ with antibiotics has higher overall effect rate than antibiotics alone for the treatment of CG [OR 2.60 (1.49,4.54), P = 0.0007]. There were no serious adverse events reported in both the intervention and controlled groups. HQJZ has the potential of improvement of the patients' gastroscopy outcomes, Helicobacter pylori clearance rate, traditional Chinese Medicine syndromes, and overall effect rate alone or in combination use with conventional western medicine for chronic atrophic gastritis. However, due to poor methodological quality, the beneficial effect and safeties of HQJZ for CG could not be confirmed.

Traditional Chinese medicine for chronic fatigue syndrome: a systematic review of randomized clinical trials.

BACKGROUND: There is no curative treatment for chronic fatigue syndrome (CFS). Traditional Chinese medicine (TCM) is widely used in the treatment of CFS in China. OBJECTIVE: To evaluate the effectiveness and safety of TCM for CFS. METHODS: The protocol of this review is registered at PROSPERO. We searched six main databases for randomized clinical trials (RCTs) on TCM for CFS from their inception to September 2013. The Cochrane risk of bias tool was used to assess the methodological quality. We used RevMan 5.1 to synthesize the results. RESULTS: 23 RCTs involving 1776 participants were identified. The risk of bias of the included studies was high. The types of TCM interventions varied, including Chinese herbal medicine, acupuncture, qigong, moxibustion, and acupoint application. The results of meta-analyses and several individual studies showed that TCM alone or in combination with other interventions significantly alleviated fatigue symptoms as measured by Chalder's fatigue scale, fatigue severity scale, fatigue assessment instrument by Joseph E. Schwartz, Bell's fatigue scale, and guiding principle of clinical research on new drugs of TCM for fatigue symptom. There was no enough evidence that TCM could improve the quality of life for CFS patients. The included studies did not report serious adverse events. CONCLUSIONS: TCM appears to be effective to alleviate the fatigue symptom for people with CFS. However, due to the high risk of bias of the included studies, larger, well-designed studies are needed to confirm the potential benefit in the future.

[Expertise-based randomized controlled trials and its application in acupuncture clinical research].

Through introduction of the methodological mechanism and comparison with classic randomized controlled trial, the status and the applicability of the expertise-based randomized controlled trials in clinic are explored, and its characteristics in acupuncture clinical application are analyzed. It is held that expertise-based randomized controlled trial is more suitable for the acupuncture clinical research, especially for acupuncture practice which emphasizes manipulations and different schools.

[An investigation of the statistical power of the effect size in randomized controlled trials for the treatment of patients with type 2 diabetes mellitus using Chinese medicine].

OBJECTIVE: To investigate whether the power of the effect size was based on adequate sample size in randomized controlled trials (RCTs) for the treatment of patients with type 2 diabetes mellitus (T2DM) using Chinese medicine. METHODS: China Knowledge Resource Integrated Database (CNKI), VIP Database for Chinese Technical Periodicals (VIP), Chinese Biomedical Database (CBM), and Wangfang Data were systematically recruited using terms like "Xiaoke" or diabetes, Chinese herbal medicine, patent medicine, traditional Chinese medicine, randomized, controlled, blinded, and placebo-controlled. Limitation was set on the intervention course > or = 3 months in order to identify the information of outcome assessement and the sample size. Data collection forms were made according to the checking lists found in the CONSORT statement. Independent double data extractions were performed on all included trials. The statistical power of the effects size for each RCT study was assessed using sample size calculation equations. RESULTS: (1) A total of 207 RCTs were included, including 111 superiority trials and 96 non-inferiority trials. (2) Among the 111 superiority trials, fasting plasma glucose (FPG) and glycosylated hemoglobin HbA1c (HbA1c) outcome measure were reported in 9% and 12% of the RCTs respectively with the sample size > 150 in each trial. For the outcome of HbA1c, only 10% of the RCTs had more than 80% power. For FPG, 23% of the RCTs had more than 80% power. (3) In the 96 non-inferiority trials, the outcomes FPG and HbA1c were reported as 31% and 36% respectively. These RCTs had a samples size > 150. For HbA1c only 36% of the RCTs had more than 80% power. For FPG, only 27% of the studies had more than 80% power. CONCLUSIONS: The sample size for statistical analysis was distressingly low and most RCTs did not achieve 80% power. In order to obtain a sufficient statistic power, it is recommended that clinical trials should establish clear research objective and hypothesis first, and choose scientific and evidence-based study design and outcome measurements. At the same time, calculate required sample size to ensure a precise research conclusion.

[Systematic review on methodology of randomized controlled trials of post-marketing Chinese patent drugs for treatment of type 2 diabetes].

BACKGROUND: Randomized controlled trial (RCT) is considered as the gold standard for the efficacy assessment of medicines. With the increasing number of Chinese patent drugs for treatment of type 2 diabetes, the methodology of post-marketing RCTs evaluating the efficacy and specific effect has become more important. OBJECTIVE: To investigate post-marketing Chinese patent drugs for treatment of type 2 diabetes, as well as the methodological quality of post-marketing RCTs. SEARCH STRATEGY: Literature was searched from the books of Newly Compiled Traditional Chinese Patent Medicine and Chinese Pharmacopeia, the websites of the State Food and Drug Administration and the Ministry of Human Resources and Social Security of the People's Republic of China, China National Knowledge Infrastructure Database, Chongqing VIP Chinese Science and Technology Periodical Database, Chinese Biomedical Database (SinoMed) and Wanfang Data. The time period for searching ran from the commencement of each database to August 2011. INCLUSION CRITERIA: RCTs of post-marketing Chinese patent drugs for treatment of type 2 diabetes with intervention course no less than 3 months. DATA EXTRACTION AND ANALYSIS: Two authors independently evaluated the research quality of the RCTs by the checklist of risk bias assessment and the data collection forms based on the CONSORT Statement. Independent double data-extraction was performed. RESULTS: The authors identified a total of 149 Chinese patent drugs for treatment of type 2 diabetes. According to different indicative syndromes, the Chinese patent drugs can be divided into the following types, namely, yin deficiency and interior heat (n=48, 32%), dual deficiency of qi and yin (n=58, 39%) and dual deficiency of qi and yin combined with blood stasis (n=22, 15%). A total of 41 RCTs meeting the inclusion criteria were included. Neither multicenter RCTs nor endpoint outcome reports were found. Risk bias analysis showed that 81% of the included studies reported randomization for grouping without sequence generation, 98% of these studies did not report concealment of random numbers, 5% used placebo, 10% reported outcome attrition bias and no study employed the analysis of intention-to-treat and 98% reported the diagnostic criteria for type 2 diabetes. The participants mainly consisted of outpatients without complications (76%). The minimum and maximum sample size was 40 and 300 (106 ± 60), respectively. CONCLUSION: The inclusion and exclusion criteria and outcome measures did not match the purposes and contents of post-marketing research in the included studies. They also failed to reflect the basic principles of traditional Chinese medicine in the process of diagnosis and treatment. The demographic characteristics of the patients, the indications for medicine and the syndrome differentiation process were not reported sufficiently and transparently. In order to improve the post-marketing research and promote the rational use of Chinese patent drugs, it is recommended that phase IV clinical trials should establish clear research purpose as well as hypothesis first, and choose scientific and evidence-based study design and outcome measures. In addition, guidelines for implementation of post-marketing research should be developed.

Traditional Chinese medicine in cancer care: a review of case reports published in Chinese literature.

BACKGROUND: Traditional Chinese Medicine (TCM) is widely used for cancer treatment in China. Many support its use in treatment for cancer, yet scientific evidence for the effect of TCM needs to be established. MATERIAL AND METHODS: In this review case reports on cancer patients treated by TCM therapies are included. Search runs were conducted in 4 main Chinese databases till December 2009. RESULTS: A total of 716 reports involving 1,198 cancer patients were identified and summarized. Top 5 of the reported cancers treated with TCM were lung cancer (14.44%; 173 patients), leukemia (14.11%; 169 patients), stomach cancer (10.85%; 130 patients), liver cancer (10.18%; 122 patients) and esophageal cancer (7.35%; 88 patients). In the majority of cases (66.44%; 772) combined treatments of Chinese and conventional medicine were applied. The use of herbal medicine was highly prevalent (98.50%; 1,168 patients), and the typical administration was an individually tailored treatment according to the pattern differentiation of symptoms (74.21%; 889 patients); the use of acupuncture was relatively rare (1.8%; 22 patients). Symptom improvement was the most frequently reported outcome (84.72%; 1,015 patients). Only 15 studies (2.1%) were structurally reported. Detailed information on patients' demography, pathologically confirmed diagnosis and safety was given in 275 (22.95%), 692 (57.76%) and 10 (0.83%) reports, respectively. CONCLUSION: The amount of information from case reports of TCM therapies in cancer is rich and can be valuable for the preliminary evaluation of TCM and for the planning of further clinical trials in cancer treatment. However, the quality of the reports was generally poor and we recommend that case reports should be published in a structured manner.

Resveratrol improves left ventricular diastolic relaxation in type 2 diabetes by inhibiting oxidative/nitrative stress: in vivo demonstration with magnetic resonance imaging.

Resveratrol is a natural phytophenol that exhibits cardioprotective effects. This study was designed to elucidate the mechanisms by which resveratrol protects against diabetes-induced cardiac dysfunction. Normal control (m-Lepr(db)) mice and type 2 diabetic (Lepr(db)) mice were treated with resveratrol orally for 4 wk. In vivo MRI showed that resveratrol improved cardiac function by increasing the left ventricular diastolic peak filling rate in Lepr(db) mice. This protective role is partially explained by resveratrol's effects in improving nitric oxide (NO) production and inhibiting oxidative/nitrative stress in cardiac tissue. Resveratrol increased NO production by enhancing endothelial NO synthase (eNOS) expression and reduced O(2)(·-) production by inhibiting NAD(P)H oxidase activity and gp91(phox) mRNA and protein expression. The increased nitrotyrosine (N-Tyr) protein expression in Lepr(db) mice was prevented by the inducible NO synthase (iNOS) inhibitor 1400W. Resveratrol reduced both N-Tyr and iNOS expression in Lepr(db) mice. Furthermore, TNF-α mRNA and protein expression, as well as NF-κB activation, were reduced in resveratrol-treated Lepr(db) mice. Both Lepr(db) mice null for TNF-α (db(TNF-)/db(TNF-) mice) and Lepr(db) mice treated with the NF-κB inhibitor MG-132 showed decreased NAD(P)H oxidase activity and iNOS expression as well as elevated eNOS expression, whereas m-Lepr(db) mice treated with TNF-α showed the opposite effects. Thus, resveratrol protects against cardiac dysfunction by inhibiting oxidative/nitrative stress and improving NO availability. This improvement is due to the role of resveratrol in inhibiting TNF-α-induced NF-κB activation, therefore subsequently inhibiting the expression and activation of NAD(P)H oxidase and iNOS as well as increasing eNOS expression in type 2 diabetes.