Preoptimized phage cocktail for use in aerosols against nosocomial transmission of carbapenem-resistant Acinetobacter baumannii: A 3-year prospective intervention study.

Using bacteriophages (phages) as environmental sanitizers has been recognized as a potential alternative method to remove bacterial contamination in vitro; however, very few studies are available on the application of phages for infection control in hospitals. Here, we performed a 3-year prospective intervention study using aerosolized phage cocktails as biocontrol agents against carbapenem-resistant Acinetobacter baumannii (CRAB) infection in the hospital. When a CRAB-infected patient was identified in an intensive care unit (ICU), their surrounding environment was chosen for phage aerosol decontamination. Before decontamination, 501 clinical specimens from the patients were subjected to antibiotic resistance analysis and phage typing. The optimal phage cocktails were a combination of different phage families or were constructed by next-evolutionary phage typing with the highest score for the host lysis zone to prevent the development of environmental CRAB phage resistance. The phage infection percentage of the antibiotic-resistant A. baumannii strains was 97.1%, whereas the infection percentage in the antibiotic-susceptible strains was 79.3%. During the phage decontamination periods from 2017 to 2019, the percentage of carbapenem-resistant A. baumannii in test ICUs decreased significantly from 65.3% to 55%. The rate of new acquisitions of CRAB infection over the three years was 4.4 per 1000 patient-days, which was significantly lower than that in the control wards (8.9 per 1000 patient-days) where phage decontamination had never been performed. In conclusion, our results support the potential of phage cocktails to decrease CRAB infection rates, and the aerosol generation process may make this approach more comprehensive and time-saving.

Serum NLRP3 Inflammasome and BDNF: Potential Biomarkers Differentiating Reactive and Endogenous Depression.

Background: The highly heterogeneous pathogenesis of depression and limited response to current antidepressants call for more objective evidence for depression subtypes. Reactive and endogenous depression are two etiologically distinct subtypes associated with different treatment responses. This study aims to explore the potential biomarkers that differentiate reactive and endogenous depressions. Methods: The clinical manifestations and biological indicators of 64 unmedicated mild-to-moderate depression patients (32 reactive depression patients and 32 endogenous depression patients) and 21 healthy subjects were observed. The 24-item Hamilton rating scale for depression (HAMD-24) was used to evaluate the severity of depression. Serum levels of depression-related biological indicators were measured by using the enzyme-linked immunosorbent assay. Results: The NLRP3 level of reactive depression was significantly lower than those of endogenous depression and healthy controls. There was a significant negative correlation between the BDNF level and the HAMD-24 total scores for patients with reactive depression. Conclusion: Our findings suggested the serum NLRP3 and BDNF levels could be potential biomarkers for detecting and evaluating the severity of reactive depression.

A program to improve the quality of dental unit water in a medical center.

ABSTRACT: The water quality of dental unit waterlines (DUWLs) is associated with patient safety. No program for DUWL water quality improvement has been formulated since the time they were established 20 years ago. This study provides an improvement program for the quality of dental unit water. The improvement program was implemented step by step: discharge of DUWLs for 5 minutes in the morning before clinical service to flush out the water left in the pipeline overnight; weekly disinfection of the handpiece connector with 75% alcohol and replacement of the old connector when the water quality of the same dental chair unit (DCU) was continuously found to be unqualified; monthly disinfection of the water supply system and pipeline; and establishment of DCU maintenance work standards and staff education and training. From 2016 to 2018, the water quality of 18 DCUs was tested by microorganism culture. The colonies >200 colony forming unit were categorized as unqualified. This program was divided into a pre-test phase, Phase 1, a maintenance phase, and Phase 2. A Chi-square test was used to calculate the difference of unqualified water quality numbers between each phase of the improvement program. In the pre-test phase, the water quality rate (high quality number/high-quality number + low-quality number) was 58.3%. In Phase 1, the quality rate before and after the intervention was 64.8% (35/54) and 92.2% (83/90) (P < .001), respectively. After Phase 1, the quality rate reached 100%. However, the quality rate dropped to 75% during the maintenance phase. Then, we proceeded into Phase 2 of the improvement program by further monthly disinfection to DUWLs. In Phase 2, the quality rate was 62/73 (84.9%) and improved to 142/144 (98.6%) after the intervention (P < .001). The quality rate reached 100% once again and was maintained at 100% thereafter. In conclusion, the 4 steps of the improvement program improved the water quality of the DUWL, which is important for patient safety.

Antidepressant effect of electroacupuncture on modulating the expression of c-Fos/AP-1 through the JNK signaling pathway.

The effectiveness and safety of electroacupuncture (EA) for depression have been identified by abundant clinical trials and experimental findings. The c-Jun-NH(2)-terminal kinase (JNK) signaling pathway is considered to be involved in the antidepressant mechanism of EA. However, the antidepressant effect of EA via modulating the expression of c-Fos/activator protein-1 (AP-1) under the condition of JNK inhibition remains unexplored. In this study, we investigated the antidepressant effect and possible mechanism of EA in regulating the expression of c-Fos/AP-1 under the condition of JNK inhibition by SP600125 in rats exposed to chronic unpredictable mild stress (CUMS). The depression-like behaviors were evaluated by the body weight, sucrose preference test (SPT), and open field test (OFT). The expression levels of c-Jun in the hypothalamus, c-Fos in the pituitary gland, and c-Fos and AP-1 in the serum of CUMS induced rat model of depression were detected by ELISA. The results indicated that treatment with EA and fluoxetine can reverse the CUMS-induced depression-like behaviors in rats and can up-regulate the expression levels of c-Jun in the hypothalamus, c-Fos in the pituitary gland, and c-Fos and AP-1 in the serum. Of note, the data demonstrated that SP600125, the inhibitor of JNK signaling pathway, can exert synergistic effect with EA in regulating CUMS-induced abnormal activation of the JNK signaling pathway. The antidepressant effect of EA might be mediated by modulating the expression of c-Fos/AP-1.

[Progress of researches on acupuncture and moxibustion for treating post-traumatic stress disorder in the past five years].

Post-traumatic stress disorder (PTSD) is a kind of chronic mental disorder after severe traumatic events. In this paper, the author reviewed the development of clinical and mechanism research of acupuncture and moxibustion for treating PTSD in the past 5 years. Clinical studies have shown that acupuncture could alleviate the symptoms of PTSD, and is an effective therapy for PTSD. The underlying mechanisms may include regulating neural circuit, neurotransmitters and receptors expression, signal pathway, apoptosis, immune cytokines and endocannabinoid system, et al. It could provide scientific basis of acupuncture and moxibustion for treating PTSD, and provide references for further study.

Effects of moxibustion on symptoms of mild cognitive impairment: protocol of a systematic review and meta-analysis.

INTRODUCTION: Mild cognitive impairment (MCI) is considered the intermediate phase between normal age-related cognitive decline and dementia. Moxibustion has gained increased popularity for the management of MCI in China.This study aimed to evaluate the effects and safety of moxibustion on symptoms of MCI. METHODS AND ANALYSIS: Four English databases and six Chinese databases will be searched from their inception to October 2019: Embase, MEDLINE, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database, China National Knowledge Infrastructure, Chongqing VIP Chinese Science and Technology Periodical Database, Wanfang Database, SinoMed, China Doctoral Dissertations Full-text Database and the China Master's Theses Full-text Database. Only clinical randomised controlled trials and the first period in randomised cross-over trial related to moxibustion for MCI will be included. The primary outcomes include the improvement of cognitive function, as measured by validated assessment tools. The secondary outcomes include changes in the activity of daily living scale, effective rate and the incidences of adverse events. The selection of studies, data extraction and risk of bias assessment will be carried out by two independent reviewers. Review Manager V.5.3 software will be used for statistical analyses. Heterogeneity test, data synthesis and subgroup analysis will be performed if necessary. The risk of bias of included studies will be assessed by the Cochrane Handbook risk of bias tool. Evidence quality will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. ETHICS AND DISSEMINATION: Ethics approval is not required as no private information from individuals are collected. The results will be published in a peer-reviewed journal or disseminated in relevant conferences. TRIAL REGISTRATION NUMBER: CRD42018112657.

[Acupuncture improved depressive behavior by regulating expression of hippocampal apoptosis-related factors in psychological stress-induced depression rats].

OBJECTIVE: To investigate the effect of acupuncture on behavior changes and the expression of reactive oxygen species (ROS), cytochrome C, cysteine-containing aspartate-specific proteases-3 (caspase-3), apoptosis inducing factor (AIF) in the hippocampus of rats exposed to chronic restraint stress (CRS), so as to provide experimental evidence for the prevention and treatment of depression. METHODS: Thirty two male SD rats were equally randomized into control, model, acupuncture and medication (Fluoxetine) groups according to the random number table. The depression model was established by chronic psychological stress stimulation (fasting, water deprivation, chronic restraint combined with solitary raising for 28 days). Manual acupuncture stimulation (2 circles/s) was applied to "Baihui" (GV20), "Yintang" (GV29) and bilateral "Sanyinjiao" (SP6) for 2 min, followed by retaining the needles for 20 min. Rats in the medication group were treated by gavage of Fluoxetine (0.18 mg/mL, 1 mL/100 g body weight). The treatment was conducted once daily for 28 days. The depression-like behavior was evaluated by using open-field test, sucrose preference test, and body weight. The content of ROS of the right hippocampus tissue was detected by using dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay, and the expression levels of cytochrome C, caspase-3 and AIF proteins of hippocampus were determined by using Western blot. RESULTS: After 28 days' stress procedure, the depression rats in the model group showed a significant decrease in the numbers of crossing and rearing of open-field test, sucrose preference index and the body weight compared to the control group (P<0.01). The content of ROS and expression levels of cytochrome C, caspase-3 and AIF in the hippocampus of the model group were significantly increased relevant to the control group (all P<0.01). After the intervention and compared with the model group, the decreased levels of the numbers of crossing and rearing, body weight and sucrose preference index, and the up-regulated levels of content of ROS and expression of cytochrome C, caspase-3 and AIF proteins were all reversed in both acupuncture and medication groups (P<0.01，P<0.05), displaying an anti-depressant effect. The effect of acupuncture was significantly superior to that of medication in up-regulating the numbers of crossing and rearing (P<0.01, P<0.05), and in down-regulating the expression of caspase-3 (P<0.01). No significant differences were found between the medication and acupuncture groups in increasing the body weight and sucrose preference index, and in down-regulating the expression of cytochrome C and AIF proteins (P>0.05). CONCLUSION: Acupuncture intervention can significantly reduce ROS content and expression level of cytochrome C, caspase-3 and AIF proteins in the hippocampus possibly by inhibiting the chronic psychological stress-hippocampal oxidative stress-mitochondrial apoptotic pathway in psychological stress-induced depression rats, which may contribute to its effect in relieving depression.

[Effect of Acupuncture Intervention on Depression Behavior and Expression of ERK 1/2 and BDNF in Prefrontal Cortex in Chronic Unpredictable Mild Stress Induced Depression Rats].

OBJECTIVE: To investigate the effect of acupuncture intervention on the depression behavior and expression of extracellular signal-regulated protein kinases (ERK 1/2), p-ERK 1/2 and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex of chronic unpredictable mild stress (CUMS) induced depression rats, so as to explore its antidepressant mechanism. METHODS: Sixty-four male SD rats were randomly divided into control, model, acupuncture, Fluoxetine, model ＋ Dimethyl sulfoxide (DMSO), model ＋ PD 98059(an ERK pathway inhibitor), acupuncture ＋ PD 98059 and Fluoxetine ＋ PD 98059 groups (n＝8 rats in each). The CUMS depression model was established by using chronic mild and unpredictable stress methods for 21 days. Manual acupuncture stimulation was applied to "Baihui" (GV 20) and "Yintang" (GV 29) for 10 min before modeling, once daily for 21 days. Fluoxetine hydrochloride suspension (1.8 mg•kg－1•d－1) was given to rats of the Fluoxetine group and Fluo-xetine ＋ PD 98059 group by gavage 30 min before CUMS. PD 98059 (dissolved in DMSO, 10 µL) was administered to rats of model ＋ PD 98059 group, acupuncture ＋ PD 98059 and Fluoxetine ＋ PD 98059 group, and DMSO (10 µL) to rats of model ＋ DMSO group by intracerebroventricular injection 1 h before CUMS. Sucrose consumption test was carried out to evaluate the depressive behavior. Western blot was performed to detect the expression of ERK 1/2, p-ERK 1/2 and BDNF of prefrontal cortex. RESULTS: Compared with the control group, the sucrose consumption and the expression levels of p-ERK 1/2 and BDNF protein in the prefrontal cortex were significantly reduced in the model and model＋DMSO group (P<0. 01). After the intervention, modeling induced decrease of the sucrose consumption, and p-ERK 1/2 and BDNF expression was significantly up-regulated in both acupuncture and Fluoxetine groups (P<0.01, P<0.05), but not in the model＋PD 98059, Fluoxetine ＋PD 98059 and acupuncture＋PD 98059 groups (P>0.05). No significant differences were found among the model＋PD 98059, Fluoxetine ＋PD 98059 and acupuncture＋PD 98059 groups in the sucrose consumption, and ERK 1/2, p-ERK 1/2 and BDNF expression levels (P>0.05), and in the expression levels of ERK 1/2 protein among the 8 groups (P>0.05). CONCLUSION: Acupuncture intervention has an anti-depressive role in CUMS induced depression rats, which may be related to its effects in up-regulating the expression of p-ERK 1/2 and BDNF in the prefrontal cortex tissue.

[Effect of Acupuncture on Expression of Glial Fibrillary Acidic Protein in Hippocampus and Prefrontal Cortex and Serum Interleukin-10 in Chronic Restraint Stress Depression Rats].

OBJECTIVE: To observe the effect of acupuncture on the expression of glial fibrillary acidic protein (GFAP) in hippocampus and prefrontal cortex and the level of serum interleukin 10 (IL-10) in rats with depression, so as to explore its mechanism underlying improvement of depression. METHODS: Thirty-two male SD rats were randomly divided into four groups: control, model, acupuncture, and medication (Fluoxetine, Flu) (n=8 rats in each). The depression model was established by using chronic restraint stress (constraint, fasting, water deprivation, etc.) combined with solitary raising for 28 days. Acupuncture was applied to "Baihui" (GV 20) and "Yintang" (GV 29), and bilateral "Sanyinjiao" (SP 6) for 20 min, once daily for 28 days. Fluoxetine (1.8 mg/kg) was given to rats of the medication group by gavage once every day for 28 days. Sucrose consumption test and open field test (crossing and rearing locomotion) were carried out to evaluate the behavioral changes. Western blot was used to detect the expression of GFAP in the hippocampus and prefrontal cortex, and the content of serum IL-10 was detected by enzyme linked immunosorbent assay (ELISA). RESULTS: After modeling, the sucrose consumption, the crossing numbers and rearing times, hippocampal GFAP protein expression and serum IL-10 content were significantly decreased and prefrontal GFAP protein expression was up-regulated markedly in the model group relevant to the control group (P<0.01). After the treatment, the decreased levels of sucrose consumption and crossing numbers, hippocampal GFAP protein expression and serum IL-10 content and the increased prefrontal GFAP protein expression were considerably suppressed in both medication and acupuncture groups compared with the model group (P<0.05, P<0.01). No significant differences were found between the acupuncture and medication groups in increasing the rats' locomotion, sucrose consumption, hippocampal GFAP protein expression (P>0.05) and in down-regulating prefrontal GFAP protein expression (P>0.05 ) except up-regulation of IL-10 level. CONCLUSION: Acupuncture intervention plays a positive role in anti-depression in rats, which may be related to its effects in regulating the expression of GFAP in the hippocampal and prefrontal astrocytes, and in increasing the content of serum anti-inflammatory cytokine IL-10.

The Risk Factors, Costs, and Survival Analysis of Invasive VRE Infections at a Medical Center in Eastern Taiwan.

OBJECTIVE: To analyze 48 cases the risk factors of vancomycin-resistant Enterococcus (VRE) infections, the antibiotic costs after infection, and the survival conditions. DESIGN: 1:3 matched case-control study a medical center in the eastern Taiwan area. The case group, patients with VRE bacterial strains detected at the sterile sites, and the control group were randomly selected from invasive vancomycin-sensitive Enterococcus (VSE) infected patients at the nearest time point by taking the occurrence time of each VRE infection case as the reference time. Fisher exact tests were conducted in order to verify the existence of differences between the case and control groups; survival analysis was applied to explore the prognoses of the VRE infection cases. RESULTS: The mortality rate of the invasive VRE infection cases was 64.6%, which is obviously higher than that of the invasive VSE infection cases (39.4%); the fact of taking chemotherapy during a hospital stay as well as the use of third-generation cephalosporin, glycopeptides, and medicines of the metronidazole category before the infections, are the risk factors of future invasive VRE infections. Moreover, the antibiotic costs after the infections of invasive VRE infection cases are much higher than those of the VSE infection cases (the average daily cost is 3,433 new Taiwan dollars (NTD) vs. 1,742 NTD). CONCLUSIONS: The history of receiving chemotherapy, the use of third-generation cephalosporin, glycopeptides, and medicines of the metronidazole category before the infections are the risk factors of VRE infections. The antibiotic costs after the infections of invasive VRE infection cases are much higher than those of the VSE infection cases.

Use of a Sampling Area-Adjusted Adenosine Triphosphate Bioluminescence Assay Based on Digital Image Quantification to Assess the Cleanliness of Hospital Surfaces.

Contaminated surfaces play an important role in the transmission of pathogens. We sought to establish a criterion that could indicate "cleanliness" using a sampling area-adjusted adenosine triphosphate (ATP) assay. In the first phase of the study, target surfaces were selected for swab sampling before and after daily cleaning; then, an aerobic colony count (ACC) plate assay of bacteria and antibiotic-resistant bacteria was conducted. ATP swabs were also tested, and the ATP readings were reported as relative light units (RLUs). The results of the ACC and ATP assays were adjusted according to the sampling area. During the second phase of the study, a new cleaning process employing sodium dichloroisocyanurate (NaDCC) was implemented for comparison. Using the criterion of 2.5 colony-forming units (CFU)/cm², 45% of the sampled sites were successfully cleaned during phase one of the study. During phase two, the pass rates of the surface samples (64%) were significantly improved, except under stringent (5 RLU/cm²) and lax (500 RLU) ATP criteria. Using receiver-operating characteristic curve analysis, the best cut-off point for an area-adjusted ATP level was 7.34 RLU/cm², which corresponded to culture-assay levels of <2.5 CFU/cm². An area adjustment of the ATP assay improved the degree of correlation with the ACC-assay results from weak to moderate.

[Development of Researches on Mechanisms of Acupoint Combination for Some Disorders in Nerve-humoral-immunological Modulation].

Proper combination of acupoints is one of the core issues of acupuncturology, and is also one of the factors affecting clinical outcomes. In the present paper, the authors make a review on the development of researches on the underlying mechanisms of acupoint combination for some clinical disorders from nerve system, humoral factors and immunological regulation. The neural mechanism involves both the peripheral nervous system (mainly the segmental innervation) and central nervous system (spinal cord, brainstem, hypothalamus, cerebral cortex and cerebellum) , while the humoral factors chiefly contain neurotransmitters and hormones of the endocrine system. The immunological mechanisms involve immunocytes and cytokines. Generally speaking, following acupuncture stimulation of different combined-acupoints or acupoint groups, some synergistic effects may be produced. In fact, the relatively specific clinical effect may be easy to be obtained at the peripheral segmental innervations level.

Astragaloside IV controls collagen reduction in photoaging skin by improving transforming growth factor-ß/Smad signaling suppression and inhibiting matrix metalloproteinase-1.

Exposure to ultraviolet (UV) light reduces levels of type I collagen in the dermis and results in human skin damage and premature skin aging (photoaging). This leads to a wrinkled appearance through the inhibition of transforming growth factor­ß (TGF­ß)/Smad signaling. UV irradiation increases type I collagen degradation through upregulating matrix metalloproteinase (MMP) expression. Astragaloside IV (AST) is one of the major active components extracted from Astragalus membranaceus. However, its multiple anti­photoaging effects remain to be elucidated. In the present study, the effects of AST against collagen reduction in UV­induced skin aging in human skin fibroblasts were investigated. The expression of type I procollagen (COL1), MMP­1, TGF­ßRⅡ and Smad7 were determined using reverse transcription­polymerase chain reaction, western blotting and ELISA, respectively. UV irradiation inhibits type I collagen production by suppressing the TGF­ß/Smad signaling pathway and increasing COL1 degradation by inducing MMP­1 expression. Transforming growth factor­ß type II protein and COL1 mRNA decreased but MMP­1 and Smad7 levels increased in the photoaging model group, which was reversed by topical application of AST. AST prevents collagen reduction from UV irradiation in photoaging skin by improving TGF­ß/Smad signaling suppression and inhibiting MMP­1, thus AST may be a potential agent against skin photoaging.

Analysis and strategy report on overseas large-scale systematic evaluation on clinical effectiveness of acupuncture / 中国针灸

In recent years, studies of large-scale systematic evaluation on clinical effectiveness of acupuncture were carried out in overseas. The literatures were conducted in Cochrane Library and overseas journals about systematic review of clinical effectiveness of acupuncture. The Cochrane Library contained a series of systematic reviews for the treatment of 67 kinds of diseases by acupuncture in 2009. Preliminary evaluations of clinical effectiveness of acupuncture on 37 kinds of disease were conducted. The results indicated that acupuncture therapy was effective for 7 kinds of disease, such as idiopathic headache, neck disorders, glaucoma, rheumatoid arthritis, chemotherapy-induced nausea or vomiting, primary dysmenorrhoea with TENS and knee osteoarthritis with TENS. However, these studies still need improved research designs and sufficient research evidence. The results also indicated that acupuncture was indecisive for the other 30 kinds of disease because of insufficient evidence. Through analysis, results of most systematic reviews indicated that there were no significant difference between therapeutic effects of acupuncture treatment and pseudo-acupuncture treatment. Effect of acupuncture treatment was equivalent to therapeutic effect of placebo. The likely reasons may be that some important clinical factors are disregarded in these researches, such as selection of acupoints, treatment with syndrome differentiation, the angel and depth of needle insertion, the proper time for treatment and so on. Therefore, the large-scale systematic evaluation on clinical effectiveness of acupuncture was criticized by acupuncturists. Thus, the pressing problem is to establish a rational evaluation system of clinical acupuncture. The suggestions are strengthening the research on diagnosis and treatment standard, strengthening the quality control of clinical acupuncture and establishing sound acupuncture control group and placebo acupuncture group. The basic researches on the relationship between diseases and acupoints need to be strengthened in order to explore the mechanism of acupoints reaction on diseases.