Pemigatinib, a selective FGFR inhibitor overcomes ABCB1-mediated multidrug resistance in cancer cells.

P: -glycoprotein (P-gp/ABCB1) overexpression is one of the primary causes of multidrug resistance (MDR). Therefore, it is crucial to discover effective pharmaceuticals to combat multidrug resistance mediated by ABCB1. Pemigatinib is a selective the fibroblast growth factor receptor (FGFR) inhibitor that is used to treat a variety of solid tumors, Clinical Trials for Urothelial Carcinoma (NCT02872714) completed its research on Pemigatinib. This study aimed to determine whether Pemigatinib can reverse ABCB1-mediated multidrug resistance, as well as its mechanism of action. Pemigatinib substantially reversed ABCB1-mediated multidrug resistance, as determined by a CCK8 assay, and immunofluorescence experiments revealed that Pemigatinib had no effect on the intracellular localization of ABCB1. Pemigatinib was discovered to increase intracellular drug accumulation, thereby reversing multidrug resistance. In addition, Docking analysis revealed that Pemigatinib and ABCB1 have a high affinity for one another. This study concludes that Pemigatinib is capable of reversing the multidrug resistance mediated by ABCB1, offering ideas and references for the clinical application of Pemigatinib.

Analysis of the clinical characteristics in 18 patients with novel coronavirus pneumonia: Observational study.

The aim of the present study was to analyze the clinical features, treatments, and short-term prognoses of 18 patients with novel coronavirus pneumonia (NCP) in order to provide reference for further clinical prevention and control of the epidemic. From January 29 to February 29, 2020, data from 18 patients with NCP who were positive for the 2019 novel coronavirus nucleic acid test were collected, and their clinical manifestations, laboratory tests, imaging features, and treatment protocols were analyzed retrospectively. From among the 18 patients with NCP, 9 (50%) were imported cases and 9 (50%) had contact histories with confirmed adult patients. Clinical classification was mainly of the normal type (16 cases, 88.9%). Fever and cough were common clinical symptoms, and the main laboratory indices were lymphocytopenia and leukocytopenia. The main imaging findings yielded ground-glass opacity in 12 cases (66.7%) and patchy opacity in 9 cases (50%). All 18 patients were treated with antiviral therapy and targeted treatment in accordance with their symptoms, returned negative nucleic acid tests (9-23 days) after their treatment, and were cured and discharged by March 5, 2020. During the early stages in Deyang, most patients with NCP were input cases; in the later stages, the main route of infection was close contact within the family. Close contact history in epidemiology, nucleic acid detection, and chest imaging were important references for diagnosis. Antiviral therapy resulted in good therapeutic effects. Adopting multi-departmental consultation and remote consultation in combination with traditional Chinese medicine treatment and psychological counseling may result in a good short-term prognosis.

Prevalence and clinical characteristics of hospitalized children with community-acquired Mycoplasma pneumoniae pneumonia during 2017/2018, Chengde, China.

ABSTRACT: Community acquired-pneumonia (CAP) has varying causative pathogens and clinical characteristics. This study investigated the prevalence of Mycoplasma pneumoniae (M pneumoniae) and evaluated the clinical characteristics in infected hospitalized children by disease severity.From throat swabs of hospitalized children (5 months to 14 years) with CAP collected between November 2017 and May 2018, M pneumoniae and other CAP pathogens were identified using polymerase chain reaction (PCR). Differences in clinical and laboratory test data were compared between severe and mild case groups.Of 333 hospitalized children enrolled, 221/333 (66.4%) tested positive for M pneumoniae and 24/221 (10.9%) patients were (n = 9, aged <5 years vs n = 15, ≥5 years) single infection by PCR, however, only 170/333 (51.1%) patients were presented with M pneumoniae IgM-positive. M pneumoniae detection rate by PCR was higher than by immunoglobulin (IgM) serology. In 123/221 (55.7%) M pneumoniae infected patients, coinfection with bacterial pathogens (n = 61, <5 years vs n = 62, ≥5 years) occurred. Children (aged 3-8 years) had most M pneumoniae infection. Severe M pneumoniae pneumonia (MPP) in children occurred mostly in older age (7 [interquartile ranges {IQR}, 6-8] years; P < .0001), with longer cough days (14 [IQR, 10-19.5] days; P = .002) and hospitalization duration (9.5 [IQR, 7-12.3] days; P < .0001), lower lymphocyte ratio (24.1, [IQR, 20.0-31.1] %; P = .001), higher neutrophils ratio (66.0, [IQR, 60.2-70.3]%; P < .0001), and serum C-reactive protein (CRP) level (3.8, [IQR, 1.3-10.9] mg/L; P = .027).M pneumoniae is the most commonly detected pathogen in CAP. High coinfection prevalence increases diagnosis difficulty by clinically nonspecific characteristics. M pneumoniae detection by PCR with IgM may improve precise and reliable diagnosis of community-acquired MPP.

Safety and Efficacy of Placenta-Derived Mesenchymal Stem Cell Treatment for Diabetic Patients with Critical Limb Ischemia: A Pilot Study.

AIM: Diabetic foot has become the main cause of non-traumatic amputation. Stem cell therapy, especially mesenchymal stem cells (MSCs), holds a great promise as a therapy for diabetic foot with ischemia limb arterial disease. The aim of this pilot study is to evaluate the safety and efficacy of placenta-derived MSCs (P-MSCs) treatment for diabetic patients with critical limb ischemia (CLI). METHODS: Four eligible diabetic patients with CLI were consecutively enrolled in this pilot study. On the base of the standard-of-care treatment, these patients accepted P-MSCs treatment by intramuscular injection for successive 3 times at an interval of 4 weeks, and the safety and efficacy of placenta-derived MSCs (P-MSCs) treatment were evaluated. RESULTS: There were no serious adverse events during the period of P-MSCs injection and the 24-weeks follow-up period. The clinical ischemic features of patients were improved 24 weeks after P-MSCs treatment. The scores of resting pain and limb coldness significantly decreased, and pain-free walking distance significantly increased from baseline to 24 weeks after P-MSCs therapy. The resting ankle brachial index increased, but no statistically significant difference was found. The findings of magnetic resonance angiography showed the increase of collateral vessel formation in one patient, but there were no significant changes observed in the other patients. CONCLUSIONS: The data in this pilot study indicated that multiple intramuscular P-MSCs injections may be a safe and effective alternative therapy for diabetic patients with CLI, and larger, placebo-controlled, perspective studies are needed to prove these results.

Metformin improves survival in lung cancer patients with type 2 diabetes mellitus: A meta-analysis / La metformina mejora la supervivencia en pacientes con cáncer de pulmón y diabetes mellitus tipo 2: metaanálisis

Background and objective: In recent years, many studies have investigated metformin and its effects on lung cancer. However, since previous studies have shown that the relationship between metformin and lung cancer is complicated, we performed a meta-analysis to analyze this relationship. Material and methods: An electronic database search was conducted using PubMed, Embase, and Cochrane library. Outcomes were quantified with hazard ratios and 95% confidence intervals to compare lung cancer survival in patients treated with or without metformin. Results: Ten studies, involving 4397 participants, were included. In the pooled analysis, we found that metformin treatment significantly improved the survival of lung cancer patients (hazard ratio = 0.75, 95% confidence interval: 0.70-0.80; P<0.001). Subgroup analysis showed that when stratified by geographic region, the hazard ratios for overall survival were 0.76 (95% confidence interval: 0.71-0.81, P<0.001) and 0.51 (95% confidence interval: 0.25-0.78, P<0.001) for Western and Asian countries, respectively. When stratified by lung cancer subtype, the hazard ratios for overall survival were 0.78 (95% confidence interval: 0.71-0.84, P<0.001), 0.73 (95% confidence interval: 0.66-0.81, P<0.001), and 0.51 (95% confidence interval: 0.25-0.78, P<0.001) for non-divided, non-small cell, and small-cell lung cancer subtypes, respectively. When stratified by study design, the hazard ratios for overall survival were 0.77 (95% confidence interval: 0.71-0.83, P<0.001) and 0.71 (95% confidence interval: 0.63-0.80, P<0.001) for cohort-based and case-controlled studies, respectively

Antecedentes y objetivo: En los últimos años, muchos estudios han investigado los efectos de la metformina sobre el cáncer de pulmón. Sin embargo, dado que estudios previos habían demostrado que la relación entre la metformina y el cáncer de pulmón era complicada, realizamos un metaanálisis para estudiar esta relación. Materiales y métodos: Se realizó una búsqueda en las bases de datos electrónicas PubMed, Embase y Cochrane Library. Los resultados se cuantificaron con cociente de riesgos instantáneos e intervalos de confianza del 95% para comparar la supervivencia del cáncer de pulmón en pacientes tratados con o sin metformina. Resultados: Se incluyeron 10 estudios con un total de 4.397 participantes. En el análisis combinado, el tratamiento con metformina mejoró significativamente la supervivencia de los pacientes con cáncer de pulmón (cociente de riesgos instantáneos=0,75; intervalo de confianza del 95%: 0,70-0,80; p<0,001). El análisis de subgrupos mostró que cuando se estratificó por región geográfica, los cocientes de riesgos para la supervivencia global fueron de 0,76 (intervalo de confianza del 95%: 0,71-0,81; p<0,001) y 0,51 (intervalo de confianza del 95%: 0,25-0,78; p<0,001) para los países occidentales y asiáticos, respectivamente. Cuando se estratificó por subtipo de cáncer de pulmón, los cocientes de riesgo para la supervivencia global fueron de 0,78 (intervalo de confianza del 95%: 0,71-0,84; p<0,001), de 0,73 (intervalo de confianza del 95%: 0,66-0,81; p<0,001) y de 0,51 (intervalo de confianza del 95%: 0,25-0,78; p<0,001) para subtipos de cáncer de pulmón no microcítico, de células no pequeñas y de células pequeñas, respectivamente. Cuando se estratificó según el diseño del estudio, los cocientes de riesgo para la supervivencia global fueron de 0,77 (intervalo de confianza del 95%: 0,71-0,83; p<0,001) y de 0,71 (intervalo de confianza del 95%: 0,63-0,80; p<0,001) para estudios de cohortes y de casos-controles, respectivamente

Metformin improves survival in lung cancer patients with type 2 diabetes mellitus: A meta-analysis.

BACKGROUND AND OBJECTIVE: In recent years, many studies have investigated metformin and its effects on lung cancer. However, since previous studies have shown that the relationship between metformin and lung cancer is complicated, we performed a meta-analysis to analyze this relationship. MATERIAL AND METHODS: An electronic database search was conducted using PubMed, Embase, and Cochrane library. Outcomes were quantified with hazard ratios and 95% confidence intervals to compare lung cancer survival in patients treated with or without metformin. RESULTS: Ten studies, involving 4397 participants, were included. In the pooled analysis, we found that metformin treatment significantly improved the survival of lung cancer patients (hazard ratio=0.75, 95% confidence interval: 0.70-0.80; P<0.001). Subgroup analysis showed that when stratified by geographic region, the hazard ratios for overall survival were 0.76 (95% confidence interval: 0.71-0.81, P<0.001) and 0.51 (95% confidence interval: 0.25-0.78, P<0.001) for Western and Asian countries, respectively. When stratified by lung cancer subtype, the hazard ratios for overall survival were 0.78 (95% confidence interval: 0.71-0.84, P<0.001), 0.73 (95% confidence interval: 0.66-0.81, P<0.001), and 0.51 (95% confidence interval: 0.25-0.78, P<0.001) for non-divided, non-small cell, and small-cell lung cancer subtypes, respectively. When stratified by study design, the hazard ratios for overall survival were 0.77 (95% confidence interval: 0.71-0.83, P<0.001) and 0.71 (95% confidence interval: 0.63-0.80, P<0.001) for cohort-based and case-controlled studies, respectively.

Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis.

Studies have suggested that metformin can potentially decrease the incidence of cancer and improve survival outcomes. However, the association between metformin use and the incidence and survival of endometrial cancer (EC) remains controversial. So, a meta-analysis was performed. An electronic search was conducted using PubMed, EMBASE, and Web of Science. The outcome measures were relative risks (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs) comparing the EC incidence and survival in patients treated with and without metformin. Eleven studies involving 766,926 participants were included in this study. In the pooled analysis of five studies which evaluated the association of metformin use with the incidence of EC, we found that metformin use was associated with a 13% reduction in EC risk among patients with diabetes (RR = 0.87, 95% CI: 0.80-0.95; p = 0.006). In the pooled analysis of six retrospective cohort studies evaluating the effect of metformin on the survival of EC patients, we found that, relative to nonuse, metformin use significantly improved the survival of EC patients (HR = 0.63, 95% CI: 0.45-0.87; p = 0.006). This study showed that metformin use was significantly associated with a decreased incidence of EC in diabetes and a favorable survival outcome of EC patients.

Uric Acid Induces Endothelial Dysfunction by Activating the HMGB1/RAGE Signaling Pathway.

Uric acid (UA) is a risk factor for endothelial dysfunction, a process in which inflammation may play an important role. UA increases high mobility group box chromosomal protein 1 (HMGB1) expression and extracellular release in endothelial cells. HMGB1 is an inflammatory cytokine that interacts with the receptor for advanced glycation end products (RAGE), inducing an oxidative stress and inflammatory response, which leads to endothelial dysfunction. In this study, human umbilical vein endothelial cells (HUVECs) were incubated with a high concentration of UA (20 mg/dL) after which endothelial function and the expression of HMGB1, RAGE, nuclear factor kappa B (NF-κB), inflammatory cytokines, and adhesion molecules were evaluated. UA inhibited endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) production in HUVECs, increased intracellular HMGB1 expression and extracellular HMGB1 secretion, and upregulated RAGE expression. UA also activated NF-κB and increased the level of inflammatory cytokines. Blocking RAGE significantly suppressed the upregulation of RAGE and HMGB1 and prevented the increase in DNA binding activity of NF-κB and the levels of inflammatory cytokines. It also blocked the decrease in eNOS expression and NO production induced by UA. Our results suggest that high concentrations of UA cause endothelial dysfunction via the HMGB1/RAGE signaling pathway.

[Growth adaptability of Zostera marina at different habitats of the Swan Lake in Rongcheng, China]. / é³—è‰åœ¨è£æˆå¤©é¹ æ¹–ä¸åŒç”Ÿå¢ƒä¸­ç”Ÿé•¿çš„é€‚åº”æ€§.

Eelgrass (Zostera marina), a seagrass species widely distributed in the coastal regions of northern hemisphere, has suffered with a great decline due to a variety of anthropogenic and environmental stresses. In order to examine the adaptability of eelgrass to different environmental stresses, studies on the morphology and reproductive capacity of eelgrass had been carried out monthly from November 2014 to October 2015 at four different habitats of the Swan Lake, including patch area inintertidal area and subtidal area, eelgrass meadow edge, and eelgrass meadow area. The results showed significant spatio-temporal variations in the morphological parameters and branch frequency of eelgrass shoots at different habitats of the Swan Lake. The highest values of leaf length, leaf width, aboveground/belowground biomass, and internode length/diameter were observed in the meadow area, i.e., 78.54 cm, 7.93 mm, 7.03 and 3.88, respectively, while the highest branch frequency was observed in the meadow edge (88.4%). The plasticity index for aboveground/belowground biomass was higher (ranging from 0.77 to 0.92) at the four habitats, but those for the leaf width was slightly lower (ranging from 0.41 to 0.64). The number of spathes in each shoot showed no significant difference at different habitats, whereas the number of spathes per unit area was significantly different. Clonal reproduction was more dominant in meadow area than in the patch area where human disturbance was high.

Insulin autoimmune syndrome in a pregnant female: A rare case report.

RATIONALE: Insulin autoimmune syndrome (IAS) is an uncommon disorder characterized by hyperinsulinemic hypoglycemia related to insulin-binding autoantibodies. To the best of our knowledge, we report the first case of a pregnant female with IAS. PATIENT CONCERNS: The 26-year-old patient with Graves disease and 10 weeks pregnant developed IAS after approximately 6 months treatment with methimazole. The patient exhibited recurrent spontaneous hypoglycemia. DIAGNOSES: On evaluation, laboratory findings detected both high fasting insulin (>1000 mIU/L) and insulin autoantibodies. An oral glucose tolerance test showed elevated insulin concentrations with disproportionately elevated C-peptide levels. The imaging study showed nomasslesionsinthepancreas,and the patient was clinically diagnosed with IAS. INTERVENTIONS: The patient had an abortion, discontinued methimazole and switched to oral prednisone (30 mg once daily) and propylth- iouracil (100 mg 3 times daily) for 3 months. OUTCOMES: At the 3-month follow-up visit, hypoglycemic episodes had disappeared and insulin antibody levels were no longer detectable. LESSONS: We have described this case and reviewed the relevant literature concerning diagnosis and treatment of IAS. Importantly, this case indicates that clinicians should view pregnancy as another factor of hypoglycemia in IAS.

Circulating omentin-1 levels in women with polycystic ovary syndrome: a meta-analysis.

To investigate the association between circulating omentin-1 levels and polycystic ovary syndrome (PCOS) in women, a meta-analysis was performed. A systematic literature search using PubMed, Embase and Web of Science was carried out. Ten articles with 13 studies were included in this meta-analysis, which included a total of 1264 subjects (733 patients with PCOS and 531 controls). The pooled standard mean difference (SMD) and 95% confidence interval (CI) were used to estimate the association between omentin-1 levels and PCOS. Circulating omentin-1 levels were lower in PCOS with an SMD (95% CI) of -0.67 (-0.91, -0.43) and p = 0.000 (random-effects). However, significant heterogeneity was detected across studies (I2=73.6% and p = 0.000). The subgroup analysis suggested that omentin-1 levels in PCOS patients were associated with HOMA-IR ratio. Meta-regression analysis indicated region was the main source of heterogeneity (p = 0.048). The results of this meta-analysis suggested that circulating omentin-1 levels are significantly lower in women with PCOS compared with controls, which indicated that omentin-1 may play a role in the pathologic processes of PCOS.

Polymorphism 2184A/G in the AGER gene is not associated with diabetic retinopathy in Han Chinese patients with type 2 diabetes.

OBJECTIVE: To assess the association between the 2184A/G polymorphism in the advanced glycosylation end product-specific receptor (AGER) gene and the susceptibility to diabetic retinopathy (DR) in Han Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional genotyping study included patients with T2DM with and without DR. Genotype and allele frequencies of the 2184A/G polymorphism were detected using polymerase chain reaction-restriction fragment-length polymorphism analysis. RESULTS: This study included 943 patients with T2DM (285 with DR [DR group] and 658 without DR [NDR group]). There were no significant differences in age, sex, body mass index, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, diastolic blood pressure, glycosylated haemoglobin, fasting blood glucose, postprandial 2-hour blood glucose, and triglycerides between the two groups. The duration of T2DM and systolic blood pressure were significantly increased in the DR group compared with the NDR group. No significant differences were found in allele (A and G) and genotype (AA, AG and GG) frequencies of the 2184A/G polymorphism between the two groups. CONCLUSION: The 2184A/G polymorphism in the AGER gene is not associated with DR in Han Chinese patients with T2DM.

Ultrasound elastographic findings of mammary fibromatosis.

Mammary fibromatosis is an uncommon, benign tumor of the breast. It is locally aggressive and has a high rate of recurrence. Its clinical presentation and imaging results always call for suspicion of malignancy. Here we describe a case of mammary fibromatosis with clinical manifestation, radiographic and pathologic results, and imaging findings from ultrasound elastography.

Serum advanced glycation end products are associated with insulin resistance in male nondiabetic patients with obstructive sleep apnea.

PURPOSE: Advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic vascular complications. Recently, growing evidence has shown that AGEs could be involved in the pathogenesis of insulin resistance. It has also been suggested that circulating AGE are associated with insulin resistance in nondiabetic patients. This study investigated whether serum AGEs levels are associated with insulin resistance in nondiabetic patients with obstructive sleep apnea (OSA). METHODS: A total of 139 male nondiabetic patients with OSA were recruited for participation in the study. Serum AGE levels were examined using an enzyme-linked immunosorbent assay. Insulin resistance was determined using the homeostasis model assessment index (HOMA-IR). RESULTS: There was a significant correlation between serum AGEs and the apnea-hypopnea index (AHI) (r = 0.281, p = 0.014), duration of SaO2 < 90% (r = 0.267, p = 0.018), minimum SaO2 (r = -0.188, p = 0.046), high-sensitivity C-reactive protein (hsCRP) (r = 0.274, p = 0.012), and HOMA-IR (r = 0.303, p < 0.001). Multiple regression analysis showed that serum AGEs (p = 0.011), AHI (p = 0.024), waist circumference (p = 0.040), and hsCRP (p = 0.046) were independently associated with HOMA-IR (R(2) = 0.392). In addition, the strength of the correlation between serum AGEs and HOMA-IR was related to the severity of OSA. CONCLUSIONS: The present study indicated that serum AGE levels were associated with insulin resistance in male nondiabetic patients with OSA. These findings suggest that AGEs may play a role in insulin resistance in OSA and may also be a biomarker for patients with OSA with high risk of developing type 2 diabetes.

Association of 2184AG Polymorphism in the RAGE Gene with Diabetic Nephropathy in Chinese Patients with Type 2 Diabetes.

OBJECTIVE: The interaction between advanced glycation end products and their cellular receptor (RAGE) has an important role in the pathogenesis of diabetic microvascular complications. The aim of this study was to investigate the relationship between the 2184A/G polymorphism in the RAGE gene and diabetic nephropathy in Chinese Han patients with type 2 diabetes mellitus. METHODS: A total of 868 patients with type 2 diabetes mellitus (486 without and 382 with diabetic nephropathy) were enrolled in this study. The genotype and allele frequencies of the 2184A/G polymorphism were detected using the polymerase chain reaction-restriction fragment-length polymorphism method. RESULTS: The G allele and AG + GG genotype frequencies in patients with diabetic nephropathy were significantly lower than those in patients without diabetic nephropathy (P = 0.001 and P = 0.005, resp.). After adjustments for possible confounders, multivariate logistic regression analyses showed that the 2184A/G polymorphism was independently associated with diabetic nephropathy (OR = 0.46, 95% CI: 0.22-0.92, P = 0.028). CONCLUSIONS: Our study indicated that the 2184A/G polymorphism in the RAGE gene was significantly associated with diabetic nephropathy in Chinese Han patients with type 2 diabetes.

Girdin correlated with autophagy in invasive ductal breast carcinomas.

AIMS AND BACKGROUND: Increasing evidence claims that autophagy is essential for breast cancer progression. Girdin was found highly expressed in breast cancers. It has been reported that Girdin attenuates autophagy in HeLa cells. We explored the relationship between Girdin expression and autophagic patterns in breast cancer. METHODS AND STUDY DESIGN: In the study, Girdin expression and autophagic activity were investigated in a series of 99 invasive ductal breast carcinomas after immunohistochemical staining for the autophagy-associated proteins LC3-II and Girdin. RESULTS: The level of Girdin expression negatively correlated with LC3-II level, which represents autophagic activity (r = -0.289), and positively correlated with lymph node metastasis (r = 0.472). Girdin level was found no different in the "diffuse cytoplasmic" and "stone-like" patterns of LC3-II. CONCLUSIONS: Up-regulated autophagy was negatively associated with Girdin level. There was a significant correlation between Girdin expression and lymph nodes metastasis in invasive ductal breast carcinoma.