Overcoming addition of phosphoethanolamine to lipid A mediated colistin resistance in Acinetobacter baumannii clinical isolates with colistin-sulbactam combination therapy.

Overcoming colistin-resistant Acinetobacter baumannii (CoR-AB) has become a major concern due to the lack of effective antibiotics. This study aimed to explore the prevalence of CoR-AB clinical isolates in Thailand, their mechanisms of resistance, and test the efficacy of colistin plus sulbactam against CoR-AB isolates. The colistin resistance rate among carbapenem-resistant A. baumannii was 15.14%. The mcr gene or its variants were not detected in CoR-AB isolates by PCR screening. The lipid A mass spectra of CoR-AB isolates showed the additional [M-H]- ion peak at m/z = 2034 that correlated to the phosphoethanolamine (pEtN) addition to lipid A (N = 27/30). The important amino acid substitutions were found at position S14P, A138T, A227V in PmrB that are associated with overexpression of the pEtN transferase (PmrC) and contributed the pEtN addition. The lipopolysacccharide production genes (lpxACD) were not related to lipid A mass spectra. A colistin plus sulbactam combination exhibited the synergy rate at 86.7% against CoR-AB isolates compare to sulbactam (85.89% resistance) or colistin (15.14% resistance) alone. The excellent synergistic activity of colistin plus sulbactam combination has the potential for the treatment of CoR-AB infections.

High prevalence of mgrB-mediated colistin resistance among carbapenem-resistant Klebsiella pneumoniae is associated with biofilm formation, and can be overcome by colistin-EDTA combination therapy.

The global prevalence of colistin-resistant Klebsiella pneumoniae (ColRkp) facilitated by chromosomal and plasmid-mediated Ara4N or PEtN-remodeled LPS alterations has steadily increased with increased colistin usage for treating carbapenem-resistant K. pneumoniae (CRkp). Our study demonstrated the rising trend of ColRkp showing extensively and pandrug-resistant characteristics among CRkp, with a prevalence of 28.5%, which was mediated by chromosomal mgrB, pmrB, or phoQ mutations (91.5%), and plasmid-mediated mcr-1.1, mcr-8.1, mcr-8.2 alone or in conjunction with R256G PmrB (8.5%). Several genetic alterations in mgrB (85.1%) with increased expressions of Ara4N-related phoPQ and pmrK were critical for establishing colistin resistance in our isolates. In this study, we discovered the significant associations between extensively drug-resistant bacteria (XDR) and pandrug-resistant bacteria (PDR) ColRkp in terms of moderate, weak or no biofilm-producing abilities, and altered expressions of virulence factors. These ColRkp would therefore be very challenging to treat, emphasizing for innovative therapy to combat these infections. Regardless of the underlying colistin-resistant mechanisms, colistin-EDTA combination therapy in this study produced potent synergistic effects in both in vitro and in vivo murine bacteremia, with no ColRkp regrowth and improved animal survival, implying the significance of colistin-EDTA combination therapy as systemic therapy for unlocking colistin resistance in ColRkp-associated bacteremia.

Novel colistin-EDTA combination for successful eradication of colistin-resistant Klebsiella pneumoniae catheter-related biofilm infections.

Development of an effective therapy to overcome colistin resistance in Klebsiella pneumoniae, a common pathogen causing catheter-related biofilm infections in vascular catheters, has become a serious therapeutic challenge that must be addressed urgently. Although colistin and EDTA have successful roles for eradicating biofilms, no in vitro and in vivo studies have investigated their efficacy in catheter-related biofilm infections of colistin-resistant K. pneumoniae. In this study, colistin resistance was significantly reversed in both planktonic and mature biofilms of colistin-resistant K. pneumoniae by a combination of colistin (0.25-1 µg/ml) with EDTA (12 mg/ml). This novel colistin-EDTA combination was also demonstrated to have potent efficacy in eradicating colistin-resistant K. pneumoniae catheter-related biofilm infections, and eliminating the risk of recurrence in vivo. Furthermore, this study revealed significant therapeutic efficacy of colistin-EDTA combination in reducing bacterial load in internal organs, lowering serum creatinine, and protecting treated mice from mortality. Altered in vivo expression of different virulence genes indicate bacterial adaptive responses to survive in hostile environments under different treatments. According to these data discovered in this study, a novel colistin-EDTA combination provides favorable efficacy and safety for successful eradication of colistin-resistant K. pneumonia catheter-related biofilm infections.

Kiwi Root Extract Inhibits the Development of Endometriosis in Mice by Downregulating Inflammatory Factors.

PURPOSE: To determine whether the kiwi root extract inhibits the development of endometriosis in mice by suppressing inflammatory factors. MATERIALS AND METHODS: The mouse model of endometriosis was induced by surgery after which the mice were continuously injected with the drug for 14 days. On the 14th day, the mice were sacrificed, and the peritoneal fluid was obtained for enzyme-linked immunosorbent assay. Endometrial ectopic tissue was weighed and analyzed by tissue immunochemistry, RT-PCR, western blotting, and gelatin zymography experiment. RESULTS: Kiwi root extract significantly reduced endometriotic lesion volume and downregulated the proinflammatory cytokines IL-6, IL-8, IL-1ß, and TNF-α, as well as the angiogenic factor VEGF-A. It also inhibited the mRNA and protein expression of COX-1 and COX-2, IL-6, TGF-ß1, EP2 receptor, and ER-ß in endometriotic lesions but did not affect the expression of MMP-9 and MMP-2. CONCLUSIONS: Kiwi root extract could significantly inhibit the growth of surgery-induced endometriosis in mice. Our results suggest that the kiwi root extract may inhibit the development and progression of ectopic endometrium through disruption of neovascularization and reducing inflammation, which may be beneficial in treating this common gynecological disease.

Modified Maimendong decoction in the treatment of patients with idiopathic pulmonary fibrosis: Study protocol for a randomized controlled trial.

INTRODUCTION: With dissatisfaction of western medicine, traditional Chinese medicine becomes alternative treatment for idiopathic pulmonary fibrosis patients. The common syndrome of idiopathic pulmonary fibrosis (IPF) is qi and yin deficiency syndrome. The prescription, Modified Maimendong Decoction (MMD), is usually used for IPF patients with qi and yin deficiency syndrome. However, there is no convinced evidence for the efficacy and safety of MMD to treat IPF. METHODS: A double-blind, placebo-controlled, randomized clinical trial was put forward by us. After a 1-day run-in period, 60 eligible patients will be included in the study. These subjects will be allocated to the experiment group or control group in a 1:1 ratio. Patients in the experiment group will take MMD plus Pirfenidone capsule. At the same time, patients in the control group will receive a matched placebo plus Pirfenidone capsule. All subjects will receive 24 weeks of treatment and follow-up period. The primary outcomes are the mean change from the baseline in forced vital capacity and times of acute exacerbations at week 4, 12, 24. Secondary outcomes are the mean change from baseline in the St. George's respiratory questionnaire total score, forced expiratory volume in 1 second percentage/forced vital capacity, diffusing capacity of Carbon monoxide, brain natriuretic peptide, and curative effect of traditional Chinese medicine syndrome at week 4, 12, and 24. Any side effects of the treatment will be recorded. DISCUSSION: The results of this trial will provide the evidence for the effect of MMD in patients with idiopathic pulmonary fibrosis.

Clinical study on acupuncture acupoints around the eyes in treating myopia in children and adolescents: A study protocol.

INTRODUCTION: Myopia is the most common cause of avoidable visual impairment worldwide, which causes huge economic burden and social burden. There are several ways to treat and reduce myopia, but all have drawbacks; this reality drives us to search for additional effective and low-risk interventions of treatment for myopia. Acupuncture is an ancient therapy with a history of thousands of years and is now widely used in the medical system. Some randomized controlled trials have reported that acupuncture, as an adjuvant therapy, can effectively improve the diopter and vision in the sense of myopic children. Deqi is a long-standing belief to ensure the efficacy of acupuncture in the treatment of myopia, but this belief has not been confirmed by sufficient evidence of randomized controlled trials. METHODS: This clinical study is a parallel-group, randomized controlled, and single blind study. Three hundred eligible adolescents will randomly be divided into acupuncture Deqi group, acupuncture without Deqi group, and waiting list group. All groups will be given frame glasses for corrective treatment; patients in the acupuncture Deqi group will be treated with acupuncture at acupoints around the eyes and flat puncture to Deqi, while acupuncture without Deqi group will not flat puncture to Deqi. The waiting list group will not receive acupuncture treatment. The primary outcome will be diopter measurement. Adverse events and safety indexes will be recorded throughout the study. DISCUSSION: Our study will compare acupuncture Deqi with acupuncture without Deqi, and place it in a control group for the treatment of myopia. The results of this trial are expected to provide solid evidence for the effectiveness and safety of acupuncture combined with Deqi in the treatment of myopia, and hope to provide a reference for clinical practice. The primary outcome will be diopter measurement of the patients before treatment. TRIAL REGISTRATION: ChiCTR2000037874, registered September 3, 2020.

A randomized controlled trial study protocol of modified Mahuang-Fuzi-Xixin decoction in the treatment of patients with mild bronchial asthma during acute exacerbation.

INTRODUCTION: These years, due to dissatisfaction with western medicine treatments, traditional Chinese medicine (TCM) becomes a main treatment for bronchial asthma patients. Lung and kidney yang deficiency syndrome is a common type of asthma and the Chinese herbal medicine formula modified Mahuang-Fuzi-Xixin (MFX) decoction is prescribed for mild bronchial asthma patients with acute exacerbation syndrome. However, there is not obvious evidence to support the efficacy and safety of modified MFX decoction the efficacy and safety to treat mild bronchial asthma and the mechanism of this disease is still unclear. METHODS: A double-blind, placebo-controlled, randomized clinical trial was proposed by us. After a 10-day run-in period, 180 eligible objects will be recruited in this study. These subjects will be allocated to the experimental group or control group in a 1:1 ratio. Patients in the experimental group will take modified MFX decoction. At the same time, patients in the control group will receive a matched placebo. The budesonide inhalation powder will be used as a western medicine treatment for both groups. All subjects will receive 14 days of treatment and another 6 months of follow-up. The primary outcome is the mean change in peak expiratory flow rate from the baseline to 14 days in this research. The secondary outcome includes forced expiratory volume in one second, asthma control test score, Asthma Quality of Life Questionnaire score, curative effect of TCM syndrome, and salbutamol dosage. This trial will also explore the association between the change of immunoglobulin E and modified MFX decoction treatment. Any side effects of the treatment will be recorded. DISCUSSION: The results of this trial will provide the evidence for the effect of modified MFX decoction in patients with mild bronchial asthma during acute exacerbation. It also will explore the mechanism of this formula in the treatment of bronchial asthma, which will provide another treatment option for patients with mild bronchial asthma.

Effect of Ganduqing on common cold: A protocol for systematic review and meta-analysis based on existing evidence.

BACKGROUND: The common cold is an infectious viral disease of the upper respiratory tract that has become the most frequent infectious disease in humans. Currently there is no cure for the common cold, and treatment typically focuses on alleviating symptoms. Although antiviral treatment is an important focus of current research, more than 200 viral strains have been associated with the common cold, making antiviral drug interventions difficult. Ganduqing is a Chinese medicinal preparation composed of Astragalus and Shegan. Several randomized controlled trials have been conducted to evaluate treatment of the common cold, but their effectiveness and safety have not been scientifically evaluated. In this study, we will systematically examine the efficacy and safety of Ganduqing in patients with common cold. METHODS: The following electronic databases will be systematically and comprehensively searched: Cochrane Library, EMBASE, PubMed, Science Network, China National Knowledge Infrastructure, China Biomedical Literature Database, Wanfang Database and Chinese Journal Database, for randomized controlled trials that used Ganduqing for treating the common cold through June 2020. The primary outcomes were signs and symptoms of the common cold, including cough, sore throat, fever, nasal congestion and runny nose. Secondary outcomes included changes in the percentage of neutrophils and lymphocytes, and recurrence. Study selection, data extraction and quality assessment will be independently conducted by 2 researchers. Meta-analyses incorporating data derived from the literature will conduct using Review Manager (RevMan) v.5.3 and Stata 14 software. The Grading of Recommendations, Assessment, Development and Evaluations framework will be used to assess the quality of evidence derived from the meta-analyses. RESULTS: This systematic review and meta-analysis aims to provide an evidence of Ganduqing for the common cold and will be disseminated through publications in peer-reviewed journals and/or presentations at scientific conferences. CONCLUSIONS: This systematic review will provide evidence for the efficacy and safety of Ganduqing in treating common colds. TRIAL REGISTRATION NUMBER: INPLASY202060073.

A randomized controlled clinical trial study protocol of Liuwei Dihuang pills in the adjuvant treatment of diabetic kidney disease.

INTRODUCTION: A large number of patients with diabetic kidney disease (DKD) approach traditional Chinese medicine (TCM) owing to discontent with standard treatments. Based on TCM theory and clinical experience, the syndrome of kidney yin deficiency is a common type of DKD. Liuwei Dihuang pills (LDPs) is a common prescription of a Chinese herbal formula for patients presenting this syndrome of DKD. However, well-established data supporting the efficacy and safety of LDP in DKD treatment are lacking. METHODS: We have designed a double-blind, placebo-controlled, randomized trial. After a 2-week run-in period, 124 eligible participants with DKD will be assigned to either the experimental or the control group in a 1:1 ratio. Patients in the experimental group will receive LDP, while patients in the control group will receive a matched placebo. As the basic treatment in the 2 groups, metformin hydrochloride sustained-release tablets, for blood glucose control, and irbesartan tablets, for blood pressure regulation, will be provided. All participants will undergo 4 weeks of treatment and 12 weeks of follow-up. The primary outcome is the change in 24 hours urinary protein levels, measured from the baseline to the end of the treatment phase (week 24). The secondary outcomes to be assessed include the change in serum creatinine and estimated glomerular filtration rate, urinary albumin excretion rate, improvement of TCM syndromes and symptoms, fasting blood glucose and postprandial 2-hour blood glucose, blood lipids (total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, from baseline to weeks 12 and 24. DISCUSSION: The results of this study will provide high-quality evidence of the effects of LDP in DKD treatment, which will provide an alternative treatment strategy in patients with DKD.

Metformin and acupuncture for polycystic ovary syndrome: A protocol for a systematic review and meta-analysis.

BACKGROUNDS: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women and can lead to serious social burdens associated with various reproductive and metabolic abnormalities. Studies have demonstrated that metformin can reduce liver glucose in PCOS, lower testosterone levels and increase peripheral insulin sensitivity. There has been also evidence suggesting acupuncture may influence ovulation (release of the egg) by affecting levels of various hormones. We will conduct a systematic review and meta-analysis is to compare the efficacy and safety of metformin with or without acupuncture in PCOS. METHODS AND ANALYSIS: We will search publications from Web of Science, PubMed, Science Direct, Wan Fang Data Knowledge Service Platform, Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP database), China National Knowledge Infrastructure (CNKI) and EMBASE, which should be published from inception to February 2020. Two researchers will independently perform the selection of the studies, data extraction, and synthesis. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias of the randomized controlled trials. Statistical analysis will be performed by using the Cochrane Review Manager (RevMan 5.3) software. The I test will be used to identify the extent of heterogeneity. We will use the Egger funnel chart to evaluate possible publication biases, in addition, when possible we will perform a subgroup/meta-regression analysis. The strength of the evidence will be assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS AND CONCLUSION: This study will systematically evaluate the efficacy and safety of Metformin combined with acupuncture in the treatment of PCOS, thus providing evidence to the clinical application of this combination therapy. The results will be published in a peer-reviewed journal.