Intraventricular colistin sulphate as a last resort therapy in a patient with multidrug-resistant Acinetobacter baumannii induced post-neurosurgical ventriculitis.

Limited therapeutic options exist for multidrug-resistant/extensively drug-resistant Acinetobacter baumannii (MDR/XDR-Ab) meningitis/ventriculitis. A combination of intravenous and intraventricular (IVT)/intrathecal (IT) polymyxins achieves good therapeutic outcomes for cases of healthcare-associated MDR/XDR-Ab meningitis/ventriculitis. Colistin is commercially available as colistin sulphate and its sulphomethylated derivative. However, the effect and safety of colistin sulphate in the treatment of MDR/XDR-Ab meningitis/ventriculitis has not been reported. We report on a 66-year-old male patient who developed post-neurosurgical ventriculitis caused by MDR-Ab. IVT concomitant intravenous colistin sulphate was used as a last-resort antimicrobial therapy, the patient's ventriculitis was dramatically improved, and the concentrations of CSF colistin were higher than the MIC breakpoint throughout the treatment. Meanwhile, no nephrotoxicity or neurotoxicity was observed during the treatment.

Chemical constituents from the stems of Acanthopanax senticosus with their cytotoxic activities.

A new coumestan named 7,5'-dihydroxy-4'-(3''-hydroxy-3''-methyl-trans-isobut-1''-enyl) coumestan (1), together with five known compounds (2-6), was isolated from the EtOAc-soluble extract of the stems of Acanthopanax senticosus. Their structures were elucidated based on extensive spectroscopic analyses. All the isolates were evaluated for in vitro cytotoxic activities against four human cancer cells including HepG2, A549, HeLa and MCF-7. Among them, the new compound 1 was found to exhibit significant cytotoxic activity on HeLa cells with IC50 value of 6.5 µM.

[Chromosome polymorphisms and their influence on semen quality and sperm DNA integrity in males undergoing IVF/ICSI].

OBJECTIVE: To investigate the incidence of chromosome polymorphisms and their influence on semen quality and sperm DNA integrity in male patients receiving in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). METHODS: We retrospectively analyzed the chromosomal karyotypes and the types and incidence rate of chromosome polymorphisms in 2 370 male patients undergoing IVF/ICSI between June 2016 and June 2018. We classified the patients into groups A (with variation in the secondary constriction region in the autosomal long arm), B (with variation in the short arm of the D/G group chromosomes), C (with interbrachial inversion of chromosome 9) and D (with Y chromosome polymorphisms), and compared the semen parameters and sperm DNA fragmentation indexes (DFI) between the patients with chromosome polymorphisms and those with normal chromosomes. RESULTS: Totally, 154 (6.50%) of the patients undergoing IVF/ICSI were found with chromosome polymorphisms, including 34 cases of secondary constriction variation in the long arm of the autosome (1.43% ï¼»34/2 370ï¼½, 22.08% ï¼»34/154ï¼½), 82 cases of short arm polymorphisms of the D/G group chromosomes (3.46% ï¼»82/2 370ï¼½, 53.25% ï¼»82/154ï¼½), 26 cases of interbrachial inversion of chromosome 9 (1.10% ï¼»26/2 370ï¼½, 16.88% ï¼»26/154ï¼½), 10 cases of Y chromosome polymorphisms (0.42% ï¼»10/2 370ï¼½, 6.50% ï¼»10/154ï¼½), and 2 cases of mixed chromosome polymorphisms (0.08% ï¼»2/2 370ï¼½, 1.42% ï¼»2/154ï¼½). The total sperm count was lower in group D than in the other polymorphism groups and the normal chromosome group, but with no statistically significant difference among the five groups (P > 0.05). The sperm progressive motility was also lower in group D than in the other five groups, with statistically significant difference from group B (27.5 ± 13.5 vs. 41.5 ± 21.1, P = 0.027), but not from the other groups (P > 0.05). No statistically significant difference was observed in the sperm DFI between the polymorphism groups and the normal chromosome group (P > 0.05), or among the polymorphism groups (P > 0.05). The proportion of normal semen was lower in group D than in the other four groups, but with no statistically significant difference among the five groups (P > 0.05). The incidence rate of asthenospermia was higher in group D than in the other four groups, but with no statistically significant difference among the five groups (P > 0.05), and so was that of oligoasthenospermia, with statistically significant difference from the normal chromosome group (30.0% vs 8.0%, P = 0.041), but not from the other polymorphism groups (P > 0.05). CONCLUSIONS: Short arm polymorphisms of the D/G group chromosomes are the most common type of chromosome polymorphisms in male patients undergoing IVF/ICSI. Polymorphisms of the Y chromosome have a negative effect on semen quality, while those of the other chromosomes do not significantly affect semen quality and sperm DNA integrity.

[Fire resistance of 15 main economic tree species in Liangshan Prefecture, Sichuan, China.] / 凉山州15ç§ä¸»è¦ç»æµŽæ ‘ç§çš„é˜²ç«æ€§èƒ½.

Liangshan Prefecture is one of the three major forest areas in Sichuan Province and one of the three major disaster areas of forest fire. We measured the physicochemical properties and combustion performances of different organs (leaves and branches) of 15 main economic tree species in Liangshan, and analyzed the bioecology characteristics, silviculture characteristics and value characteristics of different tree species. We investigated the fire resistance of different tree species to screen out fire-resistant species suitable for economic forest development in Liangshan Prefecture, and improve the biological fire prevention ability. The seven physicochemical properties and combustion performances indices of 15 tree species showed significant differences. Except for crude ash and lignin, the weights of moisture content, caloric value, ignition point, crude fat, and crude fibre of leaves were higher than those of branches. Crude fibre index of leaves (9.6%) and the crude ash index of branches (9.9%) were the highest weight indices of the two organs, respectively. Based on the fire resistance, we divided all the species into three classes, i.e., class Ⅰ (excellent fire-resistance trees) Juglans regia and Morus alba; class Ⅱ (better fire-resistant trees) Sapium sebiferum, Mangifera indica, Phyllanthus emblica, Eriobotrya japonica, Ligustrum lucidum, Castanea mollissima, and Punica granatum; class Ⅲ (poor fire-resistant trees) Pinus armandii, Illicium simonsii, Morella rubra, Sapindus mukorossi, Olea europaea and Camellia oleifera. J. regia and M. alba had fireproof solid performance and could be used as the preferred species for fireproof economic forest in Liangshan region. It was suggested that to use class Ⅰ to Ⅱ fire-resistant tree species built the main fireproof isolated forest belt, and pay attention to fire prevention after planting class Ⅲ tree species in a large area.

Oral Administration of Quercetin or Its Derivatives Inhibit Bone Loss in Animal Model of Osteoporosis.

Objectives. Quercetin (Q) and its derivatives are the major members of the naturally occurring flavonoid family, which possess beneficial effects on disease prevention including osteoporosis. The present study is aimed at further investigating the efficacy of the Q and its derivatives on bone pathology, bone-related parameters under imageology, bone maximum load, and serum bone metabolism indexes in animal model of osteoporosis. Potential mechanisms of Q and its derivatives in the treatment of osteoporosis as well as the existing problems regarding the modeling method and limitations of researches in this area were also summarized. Eight databases were searched from their inception dates to February 2020. Nineteen eligible studies containing 21 comparisons were identified ultimately. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately. The results displayed the number of criteria met varied from 3/10 to 7/10 with an average of 5.05. The present study provided the preliminary preclinical evidence that oral administration of Q or its derivatives was capable of improving bone pathology, bone-related parameters under imageology and bone maximum load, increasing serum osteocalcin, alkaline phosphatase, and estradiol, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P < 0.05). No statistical difference was seen in survival rate, index of liver, or kidney function (P > 0.05). Q and its derivatives partially reverse osteopenia probably via antioxidant, anti-inflammatory, promoting osteogenesis, inhibiting osteoclasts, and its estrogen-like effect. The findings reveal the possibility of developing Q or its derivatives as a drug or an ingredient in diet for clinical treatment of osteoporosis.

Protective effect and possible mechanisms of ligustrazine isolated from Ligusticum wallichii on nephropathy in rats with diabetes: A preclinical systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligusticum wallichii has been used to treat renal diseases for thousands of years in China. Ligustrazine (Lig) is the active ingredient of Ligusticum wallichii that possesses a variety of biological activities against kidney disease. AIM OF THE STUDY: The purpose of this review is to further evaluate whether the supplementation with Lig has an effect on improving renal pathology, renal function indexes and blood glucose levels in animal model of diabetic nephropathy (DN). Potential mechanisms of Lig for DN as well as the existing problems regarding the modeling method and limitations in this area of research were also summarized. MATERIALS AND METHODS: The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist was used to organize the search of eight databases from inception to June 2019. We used Cochrane Collaboration's 10-item checklist and Rev-Man 5.3 software to analyze the data as well as risk of bias. RESULTS: The study quality scores ranged from 2 to 6 points with an average of 4.471. Compared with the control group, Lig significantly improved pathological changes of kidney including glomeruli and tubules, and induced significant decreases in levels of blood urea nitrogen, serum creatinine, 24-h urinary albumin and HbA1c, as well as increasing creatinine clearance rates. In subgroup analysis, the groups of high-dose STZ (≥60 mg/kg) and longer period of Lig treatment (>8 w) showed better results than those of the control group. No difference was seen between the high (>150 mg/kg, QD) and low (≤150 mg/kg, QD) dose of Lig treatment groups. CONCLUSION: Lig exerts renoprotective functions in an animal model of DN mediated by antioxidant action, inhibition of apoptosis, anti-inflammatory action, reduction of renal fibrosis, reduction of the proliferation of mesangial cells, inhibition of endotheliosis, inhibition of atherosclerosis and promotion of renal autophagy. The positive conclusion should be treated cautiously because of various methodological flaws. Further studies are recommended according to ARRIVE guidelines. The method of modeling with high-dose STZ should be avoided and improved STZ modeling schemes are recommended. Considering the large dosage range of Lig used clinically and in animals, the future studies on the basis of animal renal histology are urgently needed to determine the optimal dosages to delay histological changes. Nevertheless, together, our findings suggest that Lig is a renoprotective candidate drug for treatment of DN.

A Preclinical Systematic Review of Curcumin for Protecting the Kidney with Ischemia Reperfusion Injury.

Renal ischemia-reperfusion injury (RIRI) refers to a phenomenon associated with dysfunction of the kidney and tissue damage. Unfortunately, no specific drugs have been found that effectively prevent and treat RIRI. Curcumin (Cur), a polyphenol extracted from turmeric, possesses a variety of biological activities involving antioxidation, inhibition of apoptosis, inhibition of inflammation, and reduction of lipid peroxidation. Eight frequently used databases were searched using prespecified search strategies. The CAMARADES 10-item quality checklist was used to evaluate the risk of bias of included studies, and the RevMan 5.3 software was used to analyze the data. The risk of bias score of included studies ranged from 3 to 6 with an average score of 5.22. Compared with the control group, Cur significantly alleviated renal pathology, reduced blood urea nitrogen and serum creatinine levels, and improved inflammatory indexes, oxidant, and apoptosis in RIRI animal models. Despite the heterogeneity of the response to Cur in terms of serum creatinine, BUN, TNF-alpha, and SOD, its effectiveness for improving the injury of RIRI was remarkable. In the mouse model subgroup of serum creatinine, the effect size of the method of unilateral renal artery ligation with contralateral nephrectomy and shorter ischemic time showed a greater effect than that of the control group. No difference was seen in the methods of model establishment, mode administration, or medication times. The preclinical systematic review provided preliminary evidence that Cur partially improved RIRI in animal models, probably via anti-inflammatory, antioxidant, antiapoptosis, and antifibrosis activities and via improving microperfusion. ARRIVE guidelines are recommended; blinding and sample size calculation should be focused on in future studies. These data suggest that Cur is a potential renoprotective candidate for further clinical trials of RIRI.

Protective Effect and Possible Mechanisms of Astragaloside IV in Animal Models of Diabetic Nephropathy: A Preclinical Systematic Review and Meta-Analysis.

Astragaloside IV (AS-IV) has a variety of biological activities and is widely used to treat kidney diseases. We conducted a systematic review of 24 animal studies including 424 animals to evaluate the efficacy of AS-IV for diabetic nephropathy (DN); all current possible mechanisms were summarized. A search strategy was applied to eight databases from inception to June 2020. The CAMARADES 10-item quality checklist and Rev-Man 5.3 software were used to analyze the risks of bias of each study and data regarding outcome measures, respectively. The mean study quality score was 5.4 points (range 3-8 points). Meta-analyses data and comparisons between groups showed that AS-IV significantly slowed the progression of pathological signs in the kidney including glomeruli and tubules, increasing creatinine clearance rate, decreasing blood urea nitrogen, serum creatinine, 24-h urinary neutrophil gelatinase-associated lipocalin and N-acetyl-ß-D-glucosaminidase, 24-h urinary albumin, 24-h urinary microalbumin and HbA1c. There were no significant differences between experimental and control groups with respect to mortality or levels of alanine aminotransferase and aspartate aminotransferase. In terms of the possible mechanisms of treatment of DN, AS-IV acts through antifibrotic, antioxidant, and antiapoptotic mechanisms, thereby alleviating endoplasmic reticulum stress, inhibiting mitochondrial fission, and increasing autophagic activity. Taken together, our findings suggest that AS-IV is a multifaceted renoprotective candidate drug for DN.

[Application of RIFLE criteria for acute renal failure in patients treated with continuous renal replacement therapy].

OBJECTIVE: To determine the optimal timing of treating acute renal failure (ARF) patients in intensive care unit (ICU) with RIFLE (risk of renal failure, injury to the kidney, failure of kidney function, loss of kidney function and end-stage renal failure) classification using continuous renal replacement therapy (CRRT). And to evaluate the association between mortality and RIFLE classification in the same patients. METHODS: Clinical data were collected from 103 ARF patients in ICU from 2000 to 2007. RESULTS: The 30-days hospital mortality rate was 45.6%. The 30 days' hospital mortality rates of RIFLE-R, RIFLE-I and RIFLE-F were 25.0%, 20.0% and 57.3% respectively. CONCLUSION: Survival rate of ARF patients can be manifestly elevated if CRRT is performed before RIFLE-F. The patients in RIFLE-F category have a significantly higher mortality than RIFLE-R and -I patients. The RIFLE criteria is fit for ARF classification system.

Traditional Chinese Medicine for Coronary Heart Disease: Clinical Evidence and Possible Mechanisms.

Coronary heart disease (CHD) remains a major cause of mortality with a huge economic burden on healthcare worldwide. Here, we conducted a systematic review to investigate the efficacy and safety of Chinese herbal medicine (CHM) for CHD based on high-quality randomized controlled trials (RCTs) and summarized its possible mechanisms according to animal-based researches. 27 eligible studies were identified in eight database searches from inception to June 2018. The methodological quality was assessed using seven-item checklist recommended by Cochrane Collaboration. All the data were analyzed using Rev-Man 5.3 software. As a result, the score of study quality ranged from 4 to 7 points. Meta-analyses showed CHM can significantly reduce the incidence of myocardial infarction and percutaneous coronary intervention, and cardiovascular mortality (P < 0.05), and increase systolic function of heart, the ST-segment depression, and clinical efficacy (P < 0.05). Adverse events were reported in 11 studies, and CHMs were well tolerated in patients with CHD. In addition, CHM exerted cardioprotection for CHD, possibly altering multiple signal pathways through anti-inflammatory, anti-oxidation, anti-apoptosis, improving the circulation, and regulating energy metabolism. In conclusion, the evidence available from present study revealed that CHMs are beneficial for CHD and are generally safe.

Fasudil, a Rho-Kinase Inhibitor, Exerts Cardioprotective Function in Animal Models of Myocardial Ischemia/Reperfusion Injury: A Meta-Analysis and Review of Preclinical Evidence and Possible Mechanisms.

Fasudil, a Rho-kinase inhibitor, has shown outstanding therapeutic effects against cerebral vasospasm after subarachnoid hemorrhage (SAH) in humans. Studies show various biological effects of fasudil in the cardiovascular system. We conducted a preclinical systematic review to determine the efficacy and possible mechanisms of fasudil on animal models of myocardial ischemia/reperfusion (I/R) injury. Nineteen studies involving 400 animals were identified after searching 8 databases for articles published till June 2018. The methodological quality was assessed by the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) 10-item checklist. The data were analyzed using Rev-Man 5.3 software, and the score of study quality ranged from 3 to 6 points. Compared to the control group, fasudil treated animals showed reduced myocardial infarct size (P < 0.05), lower levels of cardiac enzymes (P < 0.05) and cardiac troponin T (P < 0.05), improved systolic and diastolic functions (P < 0.05), and increased degree of decline in the ST-segment (P < 0.05). The possible mechanisms of fasudil action against myocardial I/R injury are improvement in coronary vasodilation, inhibition of apoptosis and oxidative stress, relieving inflammation, and reduction in endoplasmic reticulum stress and metabolism. In conclusion, fasudil exerts a cardio-protective function through multiple signaling pathways in animal models of myocardial I/R injury.

Borneol, a messenger agent, improves central nervous system drug delivery through enhancing blood-brain barrier permeability: a preclinical systematic review and meta-analysis.

To achieve sufficient blood-brain barrier (BBB), penetration is one of the biggest challenges in the development of diagnostic and therapeutic for central nervous system (CNS) disorders. Here, we conducted a systematic review and meta-analysis to assess the preclinical evidence and possible mechanisms of borneol for improving co-administration of CNS drug delivery in animal models. The electronic literature search was conducted in six databases. Fifty-eight studies with 63 comparisons involved 1137 animals were included. Among 47 studies reporting the assessments of CNS drug concentration, 45 studies showed the significant effects of borneol for improving CNS drug delivery (p<.05), whereas 2 studies showed no difference (p>.05). Nineteen comparisons showed borneol up-regulated BBB permeability (p<.05) using brain EB content (n = 8), Rh 123 content (n = 4), brain imaging agent content (n = 2), brain water content (n = 1) and observing ultrastructure of BBB (n = 4), whereas three studies showed no difference or unclear results. Seven studies reported the safety, in which one study showed borneol was reversible changes in the BBB penetration; six studies showed borneol did not increase co-administration of blood drugs concentration of peripheral tissues (p > .05). Effects of borneol are closely associated with inhibition of efflux protein function, releasement of tight junction protein, increasement of vasodilatory neurotransmitters, and inhibition of active transport by ion channels. In conclusion, borneol is a promising candidate for CNS drug delivery, mainly through mediating a multi-targeted BBB permeability.

A Preclinical Systematic Review and Meta-Analysis of Astragaloside IV for Myocardial Ischemia/Reperfusion Injury.

Astragaloside IV (AS-IV), the major pharmacological extract from Astragalus membranaceus Bunge, possesses a variety of biological activities in the cardiovascular systems. Here, we aimed to evaluate preclinical evidence and possible mechanism of AS-IV for animal models of myocardial ischemia/reperfusion (I/R) injury. Studies of AS-IV in animal models with myocardial I/R injury were identified from 6 databases from inception to May, 2018. The methodological quality was assessed by using CAMARADES 10-item checklist. All the data were analyzed using Rev-Man 5.3 software. As a result, 22 studies with 484 animals were identified. The quality score of studies ranged from 3 to 6 points. Meta-analyses showed AS-IV can significantly decrease the myocardial infarct size and left ventricular ejection fraction, and increase shortening fraction compared with control group (P < 0.01). Significant decreasing of cardiac enzymes and cardiac troponin and increasing of decline degree in ST-segment were reported in one study each (P < 0.05). Additionally, the possible mechanisms of AS-IV for myocardial I/R injury are promoting angiogenesis, improving the circulation, antioxidant, anti-inflammatory and anti-apoptosis. Thus, AS-IV is a potential cardioprotective candidate for further clinical trials of myocardial infarction.

Ligustrazine Exerts Cardioprotection in Animal Models of Myocardial Ischemia/Reperfusion Injury: Preclinical Evidence and Possible Mechanisms.

Ligustrazine (Lig) is one of the main effective components of Ligusticum Chuanxiong Hort, which possesses a variety of biological activities in the cardiovascular system. Here, we conducted a preclinical systematic review to investigate the efficacy of Lig for animal models of myocardial ischemia/reperfusion injury and its possible mechanisms. Twenty-five studies involving 556 animals were identified by searching 6 databases from inception to August 2017. The methodological quality was assessed by using Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) 10-item checklist. All the data were analyzed using Rev-Man 5.3 software. As a result, the score of study quality ranged from 2 to 6 points. Meta-analyses showed Lig can significantly decrease the myocardial infarct size, cardiac enzymes and troponin compared with control (P < 0.01). The possible mechanisms of Lig for myocardial infarction are antioxidant, anti-inflammatory, anti-apoptosis activities and improving coronary blood flow and myocardial metabolism. In conclusion, the findings indicated that Lig exerts cardio protection through multiple signaling pathways in myocardial ischemia/reperfusion injury.

Down-regulated miR-148b increases resistance to CHOP in diffuse large B-cell lymphoma cells by rescuing Ezrin.

BACKGROUND: Aberrant microRNA (miRNAs) have recently been proposed as important regulators in acquiring resistance to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to establish the role of miR-148b in the development of CHOP resistance in DLBCL. METHODS: The expression patterns of miR-148b, HDAC6, and Ezrin were detected in CHOP-resistant clinical specimens and a DLBCL cell line. miR-148b, HDAC6, and Ezrin in DLBCL cells were manipulated by cell transfection to explore the functional correlation between them. Cell viability was determined using a CCK-8 assay. RESULTS: We found that miR-148b levels were markedly reduced and that the protein expressions of HDAC6 and Ezrin were increased in DLBCL CHOP-resistant clinical specimens and the cell line CRL2631/CHOP. Indeed, HDAC6 decreased the acetylation of histones H3 and H4 in the miR-148b promoter to inhibit miR-148b expression in DLBCL. Moreover, down-regulated miR-148b encouraged CHOP resistance in CRL2631 cells and miR-148b sensitized CRL2631 cells. We further revealed that Ezrin was negatively regulated by miR-148b and that the knockdown of Ezrin significantly attenuated CHOP resistance in CRL2631 cells induced by miR-148b silencing. MiR-148b also sensitized CRL2631/CHOP cell xenografts to CHOP in mice. CONCLUSION: Our data indicated that the high level of HDAC6 inhibited miR-148b via maintaining the low acetylation of histones H3 and H4 in the miR-148b promoter, thus rescuing Ezrin expression and promoting CHOP resistance in DLBCL.

Effect of sperm DNA fragmentation on clinical outcomes for Chinese couples undergoing in vitro fertilization or intracytoplasmic sperm injection.

Objective To investigate the effect of sperm DNA fragmentation on the fertilization rate, embryo development and pregnancy outcome of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in a cohort of Chinese couples. Methods Infertile couples that had undergone assisted reproductive technology at our centre between January 2011 and December 2013 were included in this retrospective study. Fractions of prepared sperm samples were evaluated for sperm DNA fragmentation on the day of oocyte recovery. Results Of the 550 couples selected, 415 had undergone IVF and 135 ICSI. Sperm DNA fragmentation rate was significantly negatively correlated with the fertilization rate in the ICSI cycles but not the IVF cycles. No association was found between sperm DNA fragmentation and cleavage rate or good quality embryo formation rates in IVF or ICSI cycles. Receiver operating characteristic (ROC) curve analysis showed that the sperm DNA fragmentation rate was a statistically significant prognostic indicator of the clinical fertilization rate in ICSI cycles; a rate > 22.3% was associated with a lower fertilization rate following ICSI compared with a rate ≤ 22.3%. Conclusions High values of sperm DNA fragmentation were associated with a low fertilization rate following ICSI but were not associated with alterations in pregnancy or live birth rates in either ICSI or IVF in this cohort of Chinese couples.