Temporal association between antibiotic use and resistance in Gram-negative bacteria

Abstract The -lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p 0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.

Resumo Os medicamentos combinados de -lactâmicos / inibidores da lactamase (BLBLIs) são considerados uma alternativa eficaz aos carbapenêmicos. No entanto, existe uma preocupação crescente de que o aumento do uso de BLBLIs pode levar ao aumento da resistência. Este estudo determinou a associação temporal entre o consumo de BLBLI e a resistência antimicrobiana em bactérias gram-negativas. Neste estudo retrospectivo, os dados eletrônicos sobre as bactérias gram-negativas isoladas, incluindo A. baumannii, P. aeruginosa, E. coli e K. pneumoniae de pacientes internados e os resultados dos testes de suscetibilidade foram recuperados dos registros médicos do laboratório clínico. Uma regressão linear e análise de correlação cruzada foram realizadas nos dados adquiridos. Foram observadas tendências crescentes (p 0,05) no consumo de BIBLI e carbapenem com uma mediana de uso de 27,68 e 34,46 DDD/1000 PD por trimestre, respectivamente. Foi observada uma tendência de diminuição (p = 0,023) no consumo de fluoroquinolonas com uma mediana de uso de 29,13 DDD/1000 PD por trimestre. A taxa de resistência de K. pneumoniae foi sincronizada com os consumos de BIBLI e carbapenem com coeficiente de correlação de 0,893 (p = 0,012) e 0,951 (p = 0,016), respectivamente. A análise de correlação cruzada contra o consumo de BIBLI e K. pneumoniae resistente ao meropenem atingiu o pico no intervalo de 0 quarto (r = 951, p = 0,016). Houve uma tendência de aumento no consumo de BLBLI e carbapenêmicos. A tendência crescente nas taxas de resistência a piperacilina/tazobactam, em linha com o consumo crescente de BLBLI, sugere que BLBLI deve ser usado com cautela e não pode ser considerado diretamente como alternativa de longo prazo aos carbapenêmicos.

Temporal association between antibiotic use and resistance in Gram-negative bacteria / Associação temporal entre o uso de antibióticos e resistência em bactérias gram-negativas

Abstract The β-lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p<0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.

Resumo Os medicamentos combinados de β-lactâmicos / inibidores da lactamase (BLBLIs) são considerados uma alternativa eficaz aos carbapenêmicos. No entanto, existe uma preocupação crescente de que o aumento do uso de BLBLIs pode levar ao aumento da resistência. Este estudo determinou a associação temporal entre o consumo de BLBLI e a resistência antimicrobiana em bactérias gram-negativas. Neste estudo retrospectivo, os dados eletrônicos sobre as bactérias gram-negativas isoladas, incluindo A. baumannii, P. aeruginosa, E. coli e K. pneumoniae de pacientes internados e os resultados dos testes de suscetibilidade foram recuperados dos registros médicos do laboratório clínico. Uma regressão linear e análise de correlação cruzada foram realizadas nos dados adquiridos. Foram observadas tendências crescentes (p < 0,05) no consumo de BIBLI e carbapenem com uma mediana de uso de 27,68 e 34,46 DDD/1000 PD por trimestre, respectivamente. Foi observada uma tendência de diminuição (p = 0,023) no consumo de fluoroquinolonas com uma mediana de uso de 29,13 DDD/1000 PD por trimestre. A taxa de resistência de K. pneumoniae foi sincronizada com os consumos de BIBLI e carbapenem com coeficiente de correlação de 0,893 (p = 0,012) e 0,951 (p = 0,016), respectivamente. A análise de correlação cruzada contra o consumo de BIBLI e K. pneumoniae resistente ao meropenem atingiu o pico no intervalo de 0 quarto (r = 951, p = 0,016). Houve uma tendência de aumento no consumo de BLBLI e carbapenêmicos. A tendência crescente nas taxas de resistência a piperacilina/tazobactam, em linha com o consumo crescente de BLBLI, sugere que BLBLI deve ser usado com cautela e não pode ser considerado diretamente como alternativa de longo prazo aos carbapenêmicos.

The effect of androgen on wool follicles and keratin production in Hetian sheep / Efeito do androgênio na produção de folículos e queratina em ovinos Hetianos

Abstract To investigate the optimal androgen concentration for culturing Hetian sheep wool follicle and to detect effects of androgen concentration on wool follicle cell proliferation and apoptosis using immunofluorescence labeling and real-time quantitative fluorescence determinations of wool keratin-associated protein gene expression levels. Wool follicles were isolated by microdissection and wool follicles and skin pieces were cultured in various concentrations of dihydrotestosterone (DHT) in culture medium. Next, daily lengthwise growth measurements of wool follicles were obtained using a microscopic micrometer. Cultured Hetian wool follicles were stained using the SACPIC method to reveal wool follicle structure, while sheep skin slices were used to observe cell proliferation by immunostaining and cell apoptosis using the TUNEL method. At the molecular biological level, keratin-associated protein (Kap) gene expression was studied using wool follicles cultured for various numbers of days in vitro. Effects of androgen concentrations on Hetian wool follicle growth and development were experimentally studied. EdU proliferation assays revealed that androgen promoted cell proliferation within wool follicle dermal papillae. TUNEL apoptosis detection demonstrated that androgen treatment could delay cell apoptosis. Quantitative reverse transcription polymerase chain reaction (qPCR) results demonstrated that gene expression level patterns of Hetian mountain sheep super-high sulfur protein. Kap1.1, KIF1.2, Kap2.12 and Kap4.2 gene expression level of the mountainous experimental group was significantly higher than plains Hetian sheep. An androgen concentration of 100 nM can promote the growth of Hetian wool follicle cells in vitro, resulting in overexpression of some genes of the Kap family.

Resumo Investigar a concentração ideal de andrógenos em cultura de folículos pilosos de carneiro Hetiano e detectar os efeitos da concentração de andrógenos na proliferação e apoptose de células foliculares, por meio de imunofluorescência e de determinação quantitativa, em tempo real, da fluorescência dos níveis de expressão gênica de proteína associada à queratina. Folículos pilosos foram isolados por microdissecção, e folículos de lã e pedaços de pele foram cultivados em várias concentrações de di-hidrotestosterona (DHT) em meio de cultura. Em seguida, medições diárias de crescimento longitudinal dos folículos capilares foram obtidas usando um micrômetro microscópico. Folículos de lã cultivados de Hetianos foram corados pelo método SACPIC para revelar a estrutura do folículo piloso, enquanto fatias de pele de carneiro foram usadas para observar a proliferação celular por imunocoloração e apoptose celular por meio do método TUNEL. Em âmbito da biologia molecular, a expressão gênica da proteína associada à queratina (Kap) foi estudada usando folículos capilares cultivados por vários dias, in vitro. Os efeitos das concentrações de andrógenos no crescimento e desenvolvimento dos folículos de lã de Hetianos foram estudados experimentalmente. Ensaios de proliferação de EdU revelaram que o andrógeno promoveu a proliferação celular dentro das papilas dérmicas do folículo piloso. A detecção de apoptose por TUNEL demonstrou que o tratamento com andrógeno poderia atrasar a apoptose celular. Os resultados da reação em cadeia da polimerase transcrição reversa quantitativa (qPCR) demonstraram que os padrões de expressão gênica da proteína de enxofre Kap1.1, KIF1.2, Kap2.12 e Kap4.2 foram significativamente maiores no grupo de ovinos Hetianos de montanha. Uma concentração de androgênio de 100 nM pode promover o crescimento de células foliculares de lã de Hetianos in vitro, resultando na superexpressão de alguns genes da família Kap.

Seroprevalence of Toxoplasma gondii infection in people in southeast Hubei province, China

@# Toxoplasma gondii is a world-widely spread zoonotic parasite. However, scarce knowledge is known about the prevalence of T. gondii infection in people in Hubei province, China. This study herein was to perform epidemiological investigation of T. gondii infection in people in this region. A total 12527 blood samples were obtained during 2015-2018, and were assayed for T. gondii antibodies of IgG and IgM, respectively by employing an indirect hemagglutination test (IHA). The results discovered that the prevalence of T. gondii in people was 2.44% and 6.1%, respectively based on antibodies of IgG and IgM, respectively. The prevalence was ranged from 0.3% to 5.4% during 2015-2018 based on IgM antibodies. For genders, the prevalence was 0.7% and 2.6% in males and females, respectively based on IgM antibodies. In different years, the prevalence was ranged from 4.9% to 14.0% based on IgG antibodies. The prevalence of T. gondii was 4.9% and 6.6% in males and femalesy based on IgG antibodies. The current results may be helpful for the implementation of preventive measures against Toxoplasma infection among people living in this region.

Three-dimensional digital visualization of phacoemulsification and intraocular lens implantation

Purpose: To evaluate the feasibility and safety of heads-up three-dimensional (3D) vision system for phacoemulsification and intraocular lens (IOL) implantation surgery. Methods: In this prospective, randomized controlled study, 20 eyes with age-related cataract received phacoemulsification and IOL implantation and were randomly divided into “heads-up” 3D vision group and conventional surgery group. Ocular and surgical parameters such as surgery time, pre and postoperative best-corrected visual acuity (BCVA), and corneal endothelial cells density were recorded and statistically analyzed. Results: The result showed significant postoperative improvement of BCVA in both groups. There was no difference in either mean surgery time or postoperative mean endothelial cell density between the 3D group and the conventional group. No major complication occurred during surgery in either group. Conclusion: The heads-up 3D vision system is suitable and safe for cataract phacoemulsification and IOL implantation. This technique can be of widespread use.

Astragalus polysaccharides improve cardiomyopathy in STZ-induced diabetic mice and heterozygous (SOD2+/-) knockout mice

Oxidative stress plays an important role in the development of diabetic cardiomyopathy. In the present study, we determined whether the effect of astragalus polysaccharides (APS) on diabetic cardiomyopathy was associated with its impact on oxidative stress. Streptozotocin (STZ)-induced diabetic mice and heterozygous superoxide dismutase (SOD2+/-) knockout mice were administered APS. The hemodynamics, cardiac ultrastructure, and the apoptosis, necrosis and proliferation of cardiomyocytes were assessed to evaluate the effect of APS on diabetic and oxidative cardiomyopathy. Furthermore, H2O2 formation, oxidative stress/damage, and SOD activity in cardiomyocytes were evaluated to determine the effects of APS on cardiac oxidative stress. APS therapy improved hemodynamics and myocardial ultrastructure with reduced apoptosis/necrosis, and enhanced proliferation in cardiomyocytes from both STZ-induced diabetic mice and heterozygous SOD2+/- knockout mice. In addition, APS therapy reduced H2O2 formation and oxidative stress/damage, and enhanced SOD activity in both groups of mice. Our findings suggest that APS had benefits in diabetic cardiomyopathy, which may be partly associated with its impact on cardiac oxidative stress.

Comparative efficacy and safety of contact force-sensing catheter and second-generation cryoballoon ablation for atrial fibrillation: a meta-analysis

This meta-analysis compared the efficacy and safety of the contact force (CF)-sensing catheter and second-generation cryoballoon (CB) ablation for treating atrial fibrillation (AF). Six controlled clinical trials comparing ablation for AF using a CF-sensing catheter or second-generation CB were identified from PubMed, EMBASE, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure. The procedure duration was significantly lower in the CB group compared with that in the CF group [mean difference (MD)=29.4; 95%CI=17.84-40.96; P=0.01], whereas there was no difference between the groups for fluoroscopy duration (MD=0.59; 95%CI=-4.48-5.66; P=0.82). Moreover, there was no difference in the incidence of non-lethal complications (embolic event, tamponade, femoral/subclavian hematoma, arteriovenous fistula, pulmonary vein stenosis, phrenic nerve palsy, and esophageal injury) between the CB and the CF groups (8.38 vs 5.35%; RR=0.66; 95%CI=0.37-1.17; P=0.15). Transient phrenic nerve palsy occurred in 17 of 326 patients (5.2%) of the CB group vs none in the CF group (RR=0.12; 95%CI=0.03-0.43; P=0.001). A comparable proportion of patients in CF and CB groups suffered from AF recurrence during the 12-month follow-up after a single ablation procedure [risk ratio (RR)=1.03; 95%CI=0.78-1.35; P=0.84]. AF ablation using CF-sensing catheters and second-generation CB showed comparable fluoroscopy duration and efficacy (during a 12-month follow-up), with shorter procedure duration and different complications in the CB group.

PDK2 promotes chondrogenic differentiation of mesenchymal stem cells by upregulation of Sox6 and activation of JNK/MAPK/ERK pathway

This study was undertaken to clarify the role and mechanism of pyruvate dehydrogenase kinase isoform 2 (PDK2) in chondrogenic differentiation of mesenchymal stem cells (MSCs). MSCs were isolated from femurs and tibias of Sprague-Dawley rats, weighing 300-400 g (5 females and 5 males). Overexpression and knockdown of PDK2 were transfected into MSCs and then cell viability, adhesion and migration were assessed. Additionally, the roles of aberrant PDK2 in chondrogenesis markers SRY-related high mobility group-box 6 (Sox6), type ΙΙ procollagen gene (COL2A1), cartilage oligomeric matrix protein (COMP), aggrecan (AGC1), type ΙX procollagen gene (COL9A2) and collagen type 1 alpha 1 (COL1A1) were measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The expressions of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and extracellular regulated protein kinase (ERK) were measured. Overexpressing PDK2 promoted cell viability, adhesion and inhibited cell migration in MSCs (all P<0.05). qRT-PCR assay showed a potent increase in the mRNA expressions of all chondrogenesis markers in response to overexpressing PDK2 (P<0.01 or P<0.05). PDK2 overexpression also induced a significant accumulation in mRNA and protein expressions of JNK, p38MAPK and ERK in MSCs compared to the control (P<0.01 or P<0.05). Meanwhile, silencing PDK2 exerted the opposite effects on MSCs. This study shows a preliminary positive role and potential mechanisms of PDK2 in chondrogenic differentiation of MSCs. It lays the theoretical groundwork for uncovering the functions of PDK2 and provides a promising basis for repairing cartilage lesions in osteoarthritis.

Efficacy of minimally invasive tonsil surgery for treatment of obstructive sleep apnea-hypopnea syndrome in children

This study aimed to investigate the efficacy of minimally invasive tonsil surgery for the treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS) in children. Tonsil ablation or turbinate reduction was performed on 49 pediatric patients with OSAHS by minimally invasive tonsil surgery. In order to evaluate the efficacy of surgery, a comparison was conducted between pre-operation and post-operation data in terms of the symptoms, signs and polysomnography test. Total effectiveness rate of the surgery was 83.7%. Subgroup analysis was also performed based on the severity of their conditions: mild, moderate, and severe groups had an effectiveness rate of 90.0, 88.9, and 66.7%, respectively (Hc=6.665, P<0.05). Postoperatively, the apnea-hypopnea index, the minimum oxygen saturation (SaO2), and corresponding symptoms improved compared to pre-operation conditions (P<0.05). Minimally invasive tonsil surgery was a safe and effective method for treating OSAHS in children.

Serum microRNA-30c levels are correlated with disease progression in Xinjiang Uygur patients with chronic hepatitis B

We aimed to investigate the potential role and mechanism of microRNA-30c (miR-30c) in the pathological development of chronic hepatitis B (CHB). The serum levels of miR-30c in hepatitis B virus (HBV) carrier Xinjiang Uygur patients with inactive, low-replicative, high-replicative and HBe antigen-positive CHB were investigated. HepG2 cells were co-transfected with pHBV1.3 and miR-30c mimic or inhibitor or scramble RNA. The effects of miR-30c dysregulation on HBV replication and gene expression, cell proliferation and cell cycle were then investigated. miR-30c was down-regulated in Xinjiang Uygur patients with CHB compared to healthy controls and its expression level discriminated HBV carrier patients with inactive, low-replicative, high-replicative and HBe antigen-positive risk for disease progression. Overexpression of miR-30c significantly inhibited HBV replication and the expressions of HBV pgRNA, capsid-associated virus DNA and Hbx in hepatoma cells. Moreover, overexpression of miR-30c significantly inhibited cell proliferation and delayed G1/S phase transition in hepatoma cells. Opposite effects were obtained after suppression of miR-30c. Our results indicate that miR-30c was down-regulated in Xinjiang Uygur patients with CHB, and miR-30c levels could serve as a marker for risk stratification of HBV infection. Down-regulation of miR-30c may result in the progression of CHB via promoting HBV replication and cell proliferation.

Effects of heme oxygenase-1 recombinant Lactococcus lactis on the intestinal barrier of hemorrhagic shock rats

This study aimed to investigate the effects of heme oxygenase-1 recombinant Lactococcus lactis (LL-HO-1) on the intestinal barrier of rats with hemorrhagic shock. One hundred Sprague-Dawley male rats (280–320 g) were randomly divided into healthy control group (N group) and hemorrhagic shock group (H group). Each group was subdivided into HO1t, HO2t, HO3t, PBS and LL groups in which rats were intragastrically injected with LL-HO-1 once, twice and three times, PBS and L. lactis (LL), respectively. The mortality, intestinal myeloperoxidase (MPO) activity, intestinal contents of TNF-α, IL-10 and HO-1, and intestinal Chiu's score were determined. Results showed that in N group, the HO-1 content increased after LL-HO-1 treatment, and significant difference was observed in HO1t group and HO2t group (P<0.05). In H groups, MPO activity and Chiu's score decreased, but IL-10 content increased in LL-HO-1-treated groups when compared with PBS and LL groups (P<0.05). When compared with N group, the MPO activity reduced dramatically in LL-HO-1-treated groups. Thus, in healthy rats (N group), intragastrical LL-HO-1 treatment may increase the intestinal HO-1 expression, but has no influence on the intestinal barrier. In hemorrhagic shock rats, LL-HO-1 may significantly protect the intestinal barrier, and repeating the intragastrical LL-HO-1 treatments twice has the most obvious protection.

Effectiveness of oral and intravenous PPI for peptic ulcer re-bleeding and management after endoscopic therapy.

To explain the effectiveness of different oral and intravenous (IV) Proton Pump Inhibitors (PPI) used in the management of peptic ulcer re-bleeding after successful endoscopic intervention. This article offers the summarization of various articles on PPI which are published in a well-known journals. All the articles used the same method in the management of peptic ulcer re-bleeding. Rockall risk scoring system were used for grading the rate of the bleeding. Pubmed and Embase was used to identify the related articles that assessed the efficacy of PPI and found Six articles matched our criteria. All the results where P <0.05 where considered significant for writing this review article. Neither any alterations or modifications nor any softwares were used in this article. All the results and conclusions were briefed and summarized carefully after a through discussion of the articles included in our review.

Low vaspin levels are related to endothelial dysfunction in patients with ankylosing spondylitis

Vaspin is a novel adipocytokine associated with glucose tolerance and chronic inflammation. Some studies reveal that vaspin may be involved in cardiovascular diseases. Our objective was to investigate the relationship between serum vaspin levels and endothelial function in patients with ankylosing spondylitis. One hundred and twenty patients with newly diagnosed ankylosing spondylitis and 100 healthy subjects were studied. Serum vaspin levels were measured with enzyme-linked immunosorbent assay. High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia (flow-mediated dilation, FMD) and after sublingual glyceryltrinitrate. Serum vaspin level in patients was 1.92±1.03 ng/mL, which was significantly lower than that in healthy subjects (2.88±0.81 ng/mL). By dividing the distribution of serum vaspin levels into quartiles, FMD levels increased gradually with the increase of serum vaspin levels in patients (P<0.01). Univariate analysis showed a correlation between vaspin and FMD (r=0.73, P=0.003), low-density lipoprotein cholesterol (r=-0.45, P=0.033), high-density lipoprotein cholesterol (r=0.63, P=0.025), fasting blood glucose (r=-0.79, P=0.006), triglycerides (TG) (r=-0.68, P=0.036), systolic blood pressure (r=-0.35, P=0.021), C-reactive protein (r=-0.67, P=0.011), homeostatic model assessment of insulin resistance (HOMA-IR) (r=-0.77, P=0.023) and erythrocyte sedimentation rate (r=-0.88, P=0.039) in patients. Multivariate analysis indicated that serum vaspin levels were independently associated with FMD, HOMA-IR and TG in patients. Our study found that serum vaspin levels were decreased in patients with ankylosing spondylitis and were associated with FMD levels. Vaspin may serve as an independent marker for detecting early stage atherosclerosis in patients with ankylosing spondylitis.

Meta-analysis of the efficacy of proton pump inhibitors for the symptoms of laryngopharyngeal reflux

The objective of this study was to perform a systematic review and meta-analysis to assess the effectiveness of proton pump inhibitors (PPI) for reflux disease in adult patients with laryngopharyngeal symptoms. A comprehensive search of Cochrane Library, EMBASE, Ovid EBM Reviews, and PubMed was performed for English-language literature about laryngopharyngeal reflux (LPR), in September 2014. The papers were filtered using pre-defined inclusion and exclusion criteria. Eight papers were identified and included in this meta-analysis. The sample comprised a pooled total of 370 patients, of which 210 and 160 patients took PPIs and placebo, respectively. The difference between PPIs and placebo groups in overall improvement of symptoms in adult patients with LPR was not statistically significant (RR=1.22; 95%CI=0.93-1.58; P=0.149). The difference in cough improvement was also not significant between PPIs and placebo groups (RR=0.65; 95%CI=0.30-1.41; P=0.279).

Intramyocardial implantation of differentiated rat bone marrow mesenchymal stem cells enhanced by TGF-ß1 improves cardiac function in heart failure rats

The present study tested the hypotheses that i) transforming growth factor beta 1 (TGF-β1) enhances differentiation of rat bone marrow mesenchymal stem cells (MSCs) towards the cardiomyogenic phenotype and ii) intramyocardial implantation of the TGF-β1-treated MSCs improves cardiac function in heart failure rats. MSCs were treated with different concentrations of TGF-β1 for 72 h, and then morphological characteristics, surface antigens and mRNA expression of several transcription factors were assessed. Intramyocardial implantation of these TGF-β1-treated MSCs to infarcted heart was also investigated. MSCs were initially spindle-shaped with irregular processes. On day 28 after TGF-β1 treatment, MSCs showed fusiform shape, orientating parallel with one another, and were connected with adjoining cells forming myotube-like structures. Immunofluorescence revealed the expression of cardiomyocyte-specific proteins, α-sarcomeric actin and troponin T, in these cells. The mRNA expression of GATA4 and Nkx2.5 genes was slightly increased on day 7, enhanced on day 14 and decreased on day 28 while α-MHC gene was not expressed on day 7, but expressed slightly on day 14 and enhanced on day 28. Transmission electron microscopy showed that the induced cells had myofilaments, z line-like substances, desmosomes, and gap junctions, in contrast with control cells. Furthermore, intramyocardial implantation of TGF-β1-treated MSCs to infarcted heart reduced scar area and increased the number of muscle cells. This structure regeneration was concomitant with the improvement of cardiac function, evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure and increased maximal positive pressure development rate. Taken together, these results indicate that intramyocardial implantation of differentiated MSCs enhanced by TGF-β1 improved cardiac function in heart failure rats.

A meta‑analysis of lentinan injection combined with chemotherapy in the treatment of nonsmall cell lung cancer.

OBJECTIVE: To systematic review and analysis the clinical efficacy and toxicity of lentinan injection combined with chemotherapy in the treatment of nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: The databases of PubMed and CNKI were electronic searched with the free text word of lung cancer/NSCLC and lentinan. The prospective clinical study reporting the clinical efficacy and safety of lentinan injection combined with chemotherapy in the treatment of NSCLC were reviewed and included in this meta‑analysis. The combined treatment efficacy and toxicity of lentinan injection combined with chemotherapy were pooled by Stata 11.0 software. RESULTS: Twelve clinical studies of lentinan injection combined with chemotherapy in the treatment of NSCLC with 458 controls and 492 NSCLCs patients were finally included in this meta‑analysis. The pooled results indicated that the objective response rate was significant improved in the lentinan injection combined chemotherapy group compared with chemotherapy group only (relative risk [RR] = 1.31, 95% confidence interval [CI]: 1.14–1.52). The chemotherapy‑related toxicity of III/IV gastrointestinal reaction (RR = 0.54, 95% CI: 0.43–0.68) and III/IV granulocytopenia (RR = 0.65, 95% CI: 0.51–0.70) were significant decreased in the combined group. CONCLUSION: Lentinan injection combined chemotherapy significant increase the objective response rate and decreased the chemotherapy‑related toxicity.

Optimization and head-to-head comparison of MISSR-PCR, ERIC-PCR, RAPD and 16S rRNA evolutionary clock for the genotyping of Vibrio cholerae isolated in China.

Purpose: To establish a new genotyping method for Vibrio cholerae and compare it with other methods. Materials and Methods: In the current study, a modified inter simple sequence repeat-polymerase chain reaction (MISSR-PCR) system was developed via several rounds of optimisation. Comparison study was then conducted between MISSR-PCR and three other methods, including enterobacterial repetitive intergenic consensus sequences-based PCR (ERIC-PCR), randomly amplified polymorphic DNA (RAPD) and 16S rRNA evolutionary clock, for the detection and genetic tracing of Vibrio cholerae isolated from seafood in China. Result: The results indicated that the MISSRPCR system could generate the highest polymorphic fingerprinting map in a single round PCR and showed the best discriminatory ability for Vibrio cholerae genotyping by clearly separating toxigenic/nontoxigenic strains, local/foreign strains, and O1/O139/non-O1/non-O139 serogroup strains, comparing to ERIC-PCR, RAPD and 16S rRNA evolutionary clock. Moreover, the MISSR-PCR is superior to previously described traditional simple sequence repeat based PCR method on genotyping by more clearly separating different clusters. Conclusion: To the best of our knowledge, this is the first head-to-head comparison of four detection and genotyping methods for Vibrio cholerae. The MISSRPCR system established here could serve as a simple, quick, reliable and cost-effective tool for the genotyping and epidemiological study.

Evaluation of a father and son with atypical chronic myeloid leukemia with SETBP1 mutations and a review of the literature

We report the case of a father and son diagnosed with atypical chronic myeloid leukemia (aCML). Both patients harbored SETBP1 mutations, which are present in 24.3% of aCML patients. Moreover, both shared the variant encoding p.Pro737His, but the aCML severity was greater in the son because of the presence of two other missense mutations causing p.Asp868Asn and p.Ser885Arg alterations. SETBP1 mutations may be associated with an adverse prognosis, so their detection would help in the diagnosis of aCML and the determination of a patient's prognosis.

Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.

Erythromycin-resistant genes in group A β-haemolytic Streptococci in Chengdu, Southwestern China.

Context: The management of Group A β‑haemolytic Streptococci (Streptococcus pyogenes or GAS) infection include the use of penicillins, cephalosporins or macrolides for treatment. A general increase in macrolides resistance in GAS has been observed in recent years. Differences in rates of resistance to these agents have existed according to geographical location and investigators. Aims: To investigate the antibiotic pattern and erythromycin‑resistant genes of GAS isolates associated with acute tonsillitis and scarlet fever in Chengdu, southwestern China. Settings and Design: To assess the macrolide resistance, phenotype, and genotypic characterization of GAS isolated from throat swabs of children suffering from different acute tonsillitis or scarlet fever between 2004 and 2011 in the city of Chengdu, located in the southwestern region of China. Materials and Methods: Minimal inhibitory concentration with seven antibiotics was performed on 127 GAS isolates. Resistance phenotypes of erythromycin‑resistant GAS isolates were determined by the double‑disk test. Their macrolide‑resistant genes (mefA, ermB and ermTR) were amplified by PCR. Results: A total of 98.4% (125/127) of the isolates exhibited resistance to erythromycin, clindamycin and tetracycline. All isolates were sensitive to penicillin G and cefotaxime. Moreover, 113 ermB‑positive isolates demonstrating the cMLS phenotype of erythromycin resistance were predominant (90.4%) and these isolates showed high‑level resistance to both erythromycin and clindamycin (MIC90 > 256 μg/ml); 12 (9.6%) isolates demonstrating the MLS phenotype of erythromycin resistance carried the mefA gene, which showed low‑level resistance to both erythromycin (MIC90 = 8 μg/ml) and clindamycin (MIC90 = 0.5 μg/ml); and none of the isolates exhibited the M phenotype. Conclusions: The main phenotype is cMLS, and the ermB gene code is the main resistance mechanism against macrolides in GAS. Penicillin is the most beneficial for treating GAS infection, and is still used as first‑line treatment. And macrolide antibiotics are not recommended for treatment of GAS infection in children because of the high rates of antimicrobial resistance in mainland China.