Staphylococcus aureus is a Gram-positive bacterium with strong pathogenicity. With the widespread use of antibiotics， its multi-drug resistance has gradually increased. Among them， methicillin-resistant S. aureus （MRSA） is one of the main pathogens of hospital and community infections. Antimicrobial peptides are short-chain peptides with good antibacterial effects and low drug resistance， which have been widely studied in recent years. This study summarizes the mechanism of action of antimicrobial peptides and related study on antimicrobial peptides against MRSA from different sources. It is found that the mechanisms of action of antimicrobial peptides include targeting bacterial cell membranes， bacterial cells， and bacterial cell walls， etc. Besides isolating antimicrobial peptides with anti-MRSA activity from animals， plants， and microorganisms， antimicrobial peptides can also be obtained through synthetic methods. Among them， GHa-derived peptides from animal sources， Ib-AMP4 from plant sources， Ph-SA from microbial sources， the synthetic peptide LLKLLLKLL-NH2， and so on， due to their effective antibacterial activity， rapid bactericidal speed， and low toxicity， are promising candidates for anti-MRSA drugs.

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

OBJECTIVES: To investigate the regulatory role of the NLRP3 signaling pathway in hepatocyte pyroptosis in nonalcoholic steatohepatitis (NASH) under hypoxia. METHODS: Twenty-four male C57BL/6 mice were randomized equally into hypoxic control (A), hypoxic NASH model (B), hypoxic NASH+NLRP3 inhibitor (C), and hypoxic NASH+caspase-1 inhibitor (D) groups. In groups B-D, the mice were fed a methionine choline-deficient (MCD) diet under hypoxic conditions (to simulate a 5000 m altitude) for 6 weeks; the mice in groups C and D received intraperitoneal injections of the respective inhibitors every other day. RESULTS: Compared with those in group A, the mice in group B showed significantly elevated serum levels of FBG, TC, TG, ALT and AST, increased liver lipid content, inflammatory cell infiltration and collagen fiber deposition, and enhanced hepatic expressions of NLRP3, caspase-1, IL-1β and GSDMD proteins, with obvious swelling, cristae breakage, vacuolization, and outer membrane disruption of the mitochondria, ribosome loss in the cytoplasm, destruction of the nuclear membrane, and pathological changes of the rough endoplasmic reticulum. Treatment with NLRP3 inhibitor and caspase-1 inhibitor both significantly lowered serum levels of TC, TG, ALT and AST (but without significantly affecting FBG) in the mouse models, and reduced liver lipid content, inflammatory cell infiltration, collagen deposition, and expression levels of NLRP3, caspase-1, GSDMD and IL-1β. The treatments also significantly improved pathological changes in the mitochondria, ribosomes and endoplasmic reticulum in liver tissues of the mice. CONCLUSIONS NLRP3 signaling pathway plays a key role in promoting hepatocyte pyroptosis in NASH mice under hypoxic condition, and inhibiting this pathway can effectively reduce liver inflammation, suggesting its potential as a therapeutic target for NASH treatment.
Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis ; Mice, Inbred C57BL ; Male ; Hepatocytes/pathology* ; Signal Transduction ; Mice ; Hypoxia/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.

Objective:To explore the predictive value of peripheral blood CD34-positive cell count for the stem cell mobilization effect of plerixafor in patients with multiple myeloma (MM).Methods:The clinical data of 12 MM patients who used plerixafor for stem cell mobilization in the First Affiliated Hospital of Guangxi Medical University from December 2019 to February 2021 were retrospectively analyzed. The changes of peripheral blood CD34-positive cell count and the collection status of stem cell in all patients before and after the mobilization of plerixafor were analyzed.Results:Twelve patients were included in this study. These patients were in international staging system (ISS) stage Ⅱ-Ⅲ, and the induction therapy was mainly VRD regimen. The CD34-positive cell count was increased after the use of plerixafor in all patients no matter which mobilization strategies were used before plerixafor. The CD34-positive cell count was 3.63/μl (0.72-13.53/μl) and 32.11/μl (8.52-53.68/μl) before and after the use of plerixafor, and the difference was statistically significant ( Z = -0.40, P<0.001); the median increasing time was 11.50 times (1.61-23.71 times). The mobilization failure occurred in 1 patient. The CD34-positive cell count in his blood was less than 1/μl before the use of plerixafor; though increased 11.83 times after the use of plerixafor, the CD34-positive cell count was still less than 10/μl. Pearson analysis showed that among the patients with CD34-positive cell count less than 4/μl before the use of plerixafor, there was a positive correlation in peripheral blood CD34-positive cell count before and after the use of plerixafor ( r = 0.80, P = 0.032). Conclusions:The peripheral blood CD34-positive cell count has a certain predictive value for the stem cell mobilization effect of plerixafor in MM patients.

Objective:To investigate the effectiveness of mindfulness training on the emotional regulation and resilience of college students.Methods:Eighty one college students were recruited and randomly divided into mindfulness training group and control group, of which 74 completed the study (36 in mindfulness training group and 38 in control group). Participants in mindfulness training group received an 8-week mindfulness training, while participants in control group received no intervention. Participants were assessed with the Five Facet Mindfulness Questionnaire (FFMQ, measuring mindfulness level), Profile of Mood State (POMS, measuring emotion) and the Resilience Scale for Chinese Adolescent(RSCA, measuring resilience) before and after intervention (4 and 8 weeks).Results:Before and after the intervention, the interaction effects of total score of five factors mindfulness, scores of observing, actaware, non-judging, total score of resilience, scores of goal planning, help-seeking and the fatigue score were significant(all P<0.05). There were significant differences in mindfulness level, mood state and resilience scores in mindfulness training group before and after intervention(all P<0.05). There were significant differences of scores of FFMQ , POMS and RSCA post-training compared with baseline( P<0.05). The total score of FFMQ was improved significantly after 4 weeks of intervention ((114.92±11.70) vs(110.36±11.24), P<0.05), while the scores of observing((26.19±5.21) vs(24.00±5.34)), describing((23.36±4.82) vs(21.19±4.76)), non-judging((23.75±4.20) vs(22.06±4.99)) and non-reacting((19.72±3.16) vs(18.58±3.61)) were improved significantly after 8 weeks of intervention. There were significant differences of the scores of fatigue, depression-dejection, panic, vigor-activity and total mood disturbance before and after the intervention in mindfulness training group (all P<0.05). The scores of fatigue((12.31±4.08) vs(13.39±5.12)), panic((12.08±3.57) vs(13.67±4.35)) and total mood disturbance((132.94±17.71) vs(145.75±22.68)) were reduced significantly after 8 weeks of intervention (all P<0.05), while the scores of vigor-activity were improved significantly after 8 weeks of intervention ((18.31±4.61) vs (15.39±4.99), P<0.01). The participants in mindfulness training group got significantly higher total score, scores of goal planning, help-seeking, and affect control of RSCA after intervention compared with baseline (all P<0.05). Conclusion:Mindfulness training can enhance the mindfulness level and resilience of college students, decrease negative affect such as fatigue, depression, panic, and increase positive affect such as activity.

Objective TostudythevalueofquantitativeparametersofDCE-MRIandthreedimensionalarterialspinlabeling(3D-ASL) inpreoperativegliomagrading.Methods 70patientsdiagnosedpathologicallywithinitialgliomawereassessedretrospectively,including 32caseswithlow-gradeglioma(LGG)and38caseswithhigh-gradeglioma(HGG).Allpatientsunderwentconventional,enhanced, DCEand3D-ASL MRIat3.0Tbeforesurgery.TheparametricvaluesofDCEsuchasvolumetransferconstant(Ktrans),extravascular extracellularspacevolumefraction(Ve),therateconstant(Kep),fractionalplasmavolume(Vp),cerebralbloodflow (CBF)andcerebral bloodvolume(CBV)wereobtainedbycorrespondingpost-processingsoftware.ThecerebralbloodflowofASL (ASL-CBF)wasalso obtained.Ttestoftwoindependentsampleswasusedtoanalyzewhetherthemaximumandaveragevaluesofeachparameterwere statisticallydifferentbetweenLGGand HGG.Thediagnosticaccuracyofdifferenttechniqueforgliomagradingwasdeterminedby ROCcurveanalysis.Results ThemaximumvaluesofDCE-Ktrans,Ve,rCBVandmaximumvalueofASL-rCBFwerestatisticallydifferent betweentheHGGandLGG (P＜0.05).AlltheparametricaveragevalueswerestatisticallydifferentbetweentheHGGandLGG (P＜0.05).ThemaximumandaveragevaluesofKtranshadarelativelyhighestdiagnosticefficiencyinallparameters,withtheAUCwere0.986 and0.971,theoptimumthresholdwere0.264and0.068,thesensitivitywere93.3%and94.1%,andthespecificitywere100%and 100%,respectively.ThemaximumvaluesofVe,rCBV,ASL-rCBFandtheaveragevaluesofallparametershadarelativelyhigher diagnosticefficiency.Conclusion ThemaximumvaluesofKtrans,VeandrCBFofDCE,themaximumvalueofASL-rCBFandtheaverage valueofeachparameterwereusefultodistinguishbetweenLGGand HGG.ThemaximumandaveragevaluesofKtransarethebest parametersforidentifyingHGGandLGG.

Objective: To evaluate the intervention effects of response to heatwave in communities of four cities, China. Methods: Baseline survey on heatwave and climate change related knowledge, attitude and practice (KAP) was conducted in the pilot communities in Harbin, Nanjing, Shenzhen and Chongqing, using face-to-face questionnaire interview in November, 2011 to November, 2013. Finally, 1 604 residents were interviewed. Intervention measures were implemented in summers of 2013 and 2014, including delivering early warning information of heatwave health risk and launching health education and promotion. The second survey was conducted in same communities using the same questionnaire and sampling method as baseline survey in November, 2014, and 1 640 residents were interviewed. The Chi-square test was used to compare the demographic characteristics and KAP of community residents between before and after intervention, and the factors that affected the intervention effect were selected by logistic multiple stepwise regression model. Results: The age of the residents interviewed before and after intervention was (46.4 ± 15.5) years and (45.0 ± 15.9) years, respectively. Overall, the residents' awareness rates of heatwave before and after intervention were 70.5% (1 131/1 604) and 82.9% (1 359/1 640) (χ²=69.40, P<0.001). The rate of residents who had wished to receive early warning information increased 6.3% (χ²=41.11, P<0.001), which reached 94.6% (1 551/1 604) after intervention from 88.3% (1 416/1 604) in baseline survey. Both heatwave health risk early warning and health education had big impacts to residents. There were 92.7% (1 105 residents) among the 1 192 residents who had received the early warning information arrange work and rest time according to the early warning information and 93.0% (1 231 residents) among the 1 323 residents who knew about health education activities being conducted in community thought that the community health education activities had made active role in protecting health from heatwaves. After a series of intervention, male had a effect on attitude about hot wave than female in Nanjing and Chongqing, OR (95%CI) were 1.48(1.02-2.16) and 1.45 (1.18-2.05) , respectively; compared with subjects below primary school education, people with college degree or above had higer KAP in all cities (ORs range from 1.18 to 2.05), P<0.05; regular physical exercise (ORs range from 1.39 to 2.70) also had profound impacts on KAP in all cities (P<0.05). Conclusion s Early warning and health education were effective measures to enhance residents' response capacity to climate change.

Objective To understand the associations between extremely low and high air temperature and the years of life lost (YLL) due to diabetes deaths in Chongqing and Harbin with different climatic characteristics in China.Methods A double threshold B-spline distributed lag non-linear model (DLNM) was used to investigate the lag and cumulative effects of extremely low and high air temperature on YLL due to diabetes for lag 0-30 days by using the urban meteorological and diabetes mortality data of Chongqing (2011-2013) and Harbin (2008-2010).The effects were expressed as relative risk (RR).Results In Chongqing,the cold effects on YLL due to diabetes were delayed by four days and lasted for three days (lag4-6) with the highest RR of 1.304 (95％ CI:1.033-1.647) at lag5.The hot effects were delayed by one day (lagl) with RR of 1.321 (95％ CI:1.061-1.646).In Harbin,the extreme cold effects on YLL were delayed by four days and lasted for seven days (lag4-10) with the highest RR of 1.309 (95％CI:1.088-1.575) at lag6.The hot effects were delayed by one day and lasted for four days (lagl-4) with the highest RR of 1.460 (95％ CI:1.114-1.915) at lag2.The unit risk for cold and hot effects was 43.7％ (P=0.005 5) and 18.0％ (P=0.000 2) in Chongqing and 15.0％ (P=0.000 8) and 29.5％(P=0.001 2) in Harbin,respectively.Conclusions Both extremely low air temperature and extremely high air temperature might increase the years of life lost due to diabetes in cities with different climate characteristics.Health education about diabetes prevention should provide information about the effects of extreme weather events.

OBJECTIVETo investigate the relationship between acute graft rejection early after renal transplantation and the variations of platelet parameters.

METHODSWe retrospectively analyzed the clinical data of 167 renal transplant recipients before and within 2 months after the surgery. Before and at 1-10 days, 15 days, 30 days, 45 days and 60 days after the transplantation, 5 platelet parameters, including platelet count (PLT), platelet hematocrit (PCT), mean platelet volume (MPV), platelet volume distribution width (PDW), and large platelet ratio (P-LCR), were detected in the 35 patients with acute graft rejection within two months (AR group) and in the other 132 recipients with good graft recovery (control group).

RESULTSThe AR group and control group showed no significant difference in PLT, PCT, MPV, or P-LCR before the surgery, but the PDW was significantly higher in the AR group (t=2.18, P=0.035). These parameters were similar within 5 postoperative days between the two groups (P>0.05), but in postoperative days 6-15, the AR group showed significantly increased MPV, PDW and P-LCR compared with the control group (P<0.05). In postoperative days 6-9, MPV, PDW and P-LCR became stable in AR group but tended to decrease in the control group, showing obviously different patterns of variation between the two groups (P<0.05).

CONCLUSIONSPreoperative PDW may have a positive correlation with acute graft rejection after renal transplantation. Monitoring the variations of MPV, PDW and P-LCR may help in the diagnosis of acute graft rejection early after renal transplantation.