[Comparison of therapeutic effect of metformin hydrochloride/vildagliptin and liraglutide on type 2 diabetes mellitus in obese patients].

OBJECTIVE: To evaluate the therapeutic effects of two therapeutic strategies based on metformin hydrochloride/vildagliptin and liraglutide on type 2 diabetes mellitus (T2DM) in obese patients. METHODS: We retrospectively collected the clinical data of 107 obese patients (BMI>25 kg/m2) with T2DM treated in Second Affiliated Hospital of Wannan Medical College (Wuhu, China) during 2019-2021, including 53 patients treated continuously with metformin hydrochloride/vildagliptin and 54 with liraglutide for 3 months. The changes in BMI, waist circumference, fasting blood glucose (FBG), postprandial blood glucose, HbA1C, fasting C-peptide, postprandial C-peptide, fasting insulin and postprandial insulin of the patients after treatment were compared between the two groups. RESULTS: In both of the groups, the patients all showed significant reductions of BMI, waist circumference, FBG, postprandial blood glucose and HbA1C (all P < 0.05) with improved fasting and postprandial C-peptide levels after the treatments (P < 0.05). The two treatment regimens showed comparable blood glucoselowering effects, but liraglutide produced better effect in reducing waist circumference (P < 0.01). Neither of two regimens obviously affected insulin level of the patients (P>0.05). CONCLUSION: Both metformin hydrochloride/vildagliptin and liraglutide have good therapeutic effects on T2DM in obese patients and can achieve good blood glucose and weight control, but liraglutide has a better effect for weight control.

Cold Plasma Treatment Promotes Full-thickness Healing of Skin Wounds in Murine Models.

Cold plasma can be beneficial for promoting skin wound healing and has a high potential of being effectively used in treating various wounds. Our aim was to verify the effect of cold plasma in accelerating wound healing and investigate its underlying mechanism in vitro and in vivo. For the in vivo experiments, 2 full-thickness dermal wounds were created in each mouse (n = 30). While one wound was exposed to 2 daily plasma treatments for 3 min, the other wound served as a control. The wounds were evaluated by imaging and histological analyses at 4, 7, and 11 days post the wound infliction process. Immunohistochemical studies were also performed at the same time points. In vitro proliferation and scratch assay using HaCaT keratinocytes and fibroblasts were performed. The expression levels of wound healing-related genes were analyzed by real-time polymerase chain reaction and western blot analysis. On day 7, the wound healing rates were 53.94% and 63.58% for the control group and the plasma-treated group, respectively. On day 11, these rates were 76.05% and 93.44% for the control and plasma-treated groups, respectively, and the difference between them was significant (P = .039). Histological analysis demonstrated that plasma treatment promotes the formation of epidermal keratin and granular layers. Immunohistochemical studies also revealed that collagen 1, collagen 3, and alpha-smooth muscle actin appeared more abundantly in the plasma-treated group than in the control group. In vitro, the proliferation of keratinocytes was promoted by plasma exposure. Scratch assay showed that fibroblast exposure to plasma increased their migration. The expression levels of collagen 1, collagen 3, and alpha-smooth muscle actin were elevated upon plasma treatment. In conclusion, cold plasma can accelerate skin wound healing and is well tolerated.

Differentiation of multiple visceral artery aneurysm rupture from major bleeding after coronary artery bypass grafting.

BACKGROUND: Visceral artery aneurysm is a very rare disease, but it is clinically important because of the high risk of rupture involved. These ruptures must be differentiated from those that occur during hospitalization after extra-abdominal surgery. METHODS: During hospitalization after off-pump coronary artery bypass grafting, a 77-year-old woman developed hypovolemic symptoms and had decreased hemoglobin. There was no obvious bleeding, but while screening for possible complications after cardiac surgery, abdominal computed tomographic angiography showed multiple visceral artery aneurysms of the gastroduodenal and pancreaticoduodenal arteries along with hemoperitoneum. RESULTS: The patient underwent coil embolization of the visceral artery aneurysm and was discharged without any complications. CONCLUSIONS: In patients with coronary artery disease with risk factors for atherosclerosis, if anemia occurs without apparent bleeding after surgery, visceral artery aneurysm should be considered as a differential diagnosis.

Acute biological mitral valve thrombosis after the left atrial venting in a patient with a venoarterial extracorporeal membrane oxygenator.

BACKGROUND: Left atrial venting through atrial septotomy in patients with decreased left ventricular (LV) contractility after venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a simple and effective method for treating LV decompression. MATERIALS & METHODS: We report a case of prosthetic mitral valve thrombosis after left atrial venting in a patient with VA-ECMO. RESULTS: In patients undergoing mitral valve replacement, left atrial venting reduces the flow through the mitral valve and forms a prosthetic thrombosis. DISCUSSION: Therefore, excessive left atrial venting should be avoided. Other venting methods that can maintain the flow through the mitral valve should be considered after mitral valve replacement.

Intraoperative Neuromonitoring Using a Single Transcartilage Needle Electrode During Thyroidectomy.

OBJECTIVES: Application of transcartilage needle electrode for intraoperative neuromonitoring (IONM) during thyroidectomy has been considered an alternative method of electromyography (EMG) tube recording. However, needle electrodes must be inserted into both sides of the thyroid cartilage with exposure of the cartilage lamina. We sought to evaluate the feasibility of applying a single ipsilateral transcartilage needle electrode for IONM during unilateral hemithyroidectomy. METHODS: Thirty-four patients underwent IONM during unilateral thyroidectomy. A dual disposable needle electrode was inserted obliquely into the inferior lower third of the ipsilateral lamina of the thyroid cartilage. Patients were classified as deep (≥ 5 mm) or superficial (< 5 mm) by the depth of the needle electrode inserted into the thyroid cartilage. Without using an EMG tube, IONM was done according to the standardized procedure using a single needle electrode only. RESULTS: IONM was successful in all nerves at risk. Amplitude of the EMG signal was stable during the surgery, with no cases presenting loss of signal. Amplitude of the signal from vagal and recurrent laryngeal nerve stimulation was significantly lower when needle insertion was superficial (< 5 mm). None of the patients showed postoperative vocal cord paralysis, and complications related to needle electrode were not identified. CONCLUSION: IONM using a single ipsilateral transcartilage needle electrode during unilateral hemithyroidectomy was feasible with no significant complications. It may serve as an alternative method of IONM with the advantage of minimal exposure of the thyroid cartilage lamina. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:448-452, 2021.

Aflatoxins in Food and Feed: An Overview on Prevalence, Detection and Control Strategies.

Aflatoxins produced by the Aspergillus species are highly toxic, carcinogenic, and cause severe contamination to food sources, leading to serious health consequences. Contaminations by aflatoxins have been reported in food and feed, such as groundnuts, millet, sesame seeds, maize, wheat, rice, fig, spices and cocoa due to fungal infection during pre- and post-harvest conditions. Besides these food products, commercial products like peanut butter, cooking oil and cosmetics have also been reported to be contaminated by aflatoxins. Even a low concentration of aflatoxins is hazardous for human and livestock. The identification and quantification of aflatoxins in food and feed is a major challenge to guarantee food safety. Therefore, developing feasible, sensitive and robust analytical methods is paramount for the identification and quantification of aflatoxins present in low concentrations in food and feed. There are various chromatographic and sensor-based methods used for the detection of aflatoxins. The current review provides insight into the sources of contamination, occurrence, detection techniques, and masked mycotoxin, in addition to management strategies of aflatoxins to ensure food safety and security.

Fumonisins: Impact on Agriculture, Food, and Human Health and their Management Strategies.

The fumonisins producing fungi, Fusarium spp., are ubiquitous in nature and contaminate several food matrices that pose detrimental health hazards on humans as well as on animals. This has necessitated profound research for the control and management of the toxins to guarantee better health of consumers. This review highlights the chemistry and biosynthesis process of the fumonisins, their occurrence, effect on agriculture and food, along with their associated health issues. In addition, the focus has been put on the detection and management of fumonisins to ensure safe and healthy food. The main focus of the review is to provide insights to the readers regarding their health-associated food consumption and possible outbreaks. Furthermore, the consumers' knowledge and an attempt will ensure food safety and security and the farmers' knowledge for healthy agricultural practices, processing, and management, important to reduce the mycotoxin outbreaks due to fumonisins.

Clinicopathologic characteristics of double primary endometrial and colorectal cancers in a single institution.

AIM: To investigate the clinicopathologic and genetic correlations between double primary endometrial and colorectal cancer related to Lynch syndrome and to analyze germline mutations in mismatch repair genes in endometrial cancer patients in Korea. METHODS: Thirteen patients diagnosed with pathologically endometrial and colorectal cancer between January 2005 and November 2016 in a single institution were enrolled in the study. The medical records were retrospectively analyzed. The genetic mutational information of endometrial cancer in Korea was retrieved from the literature review. RESULTS: Endometrial cancer was diagnosed first in eight (62%) patients, and one patient was diagnosed with colorectal cancer first. Endometrioid adenocarcinoma was reported in 10 of 13 (77%) endometrial cancer patients. Endometrial cancer was found at the low uterine segment in three patients. Three of four patients had high microsatellite instability. The loss of mismatch repair proteins was confirmed in 7 of 11 cases using immunohistochemistry. Four patients fulfilled clinical criteria based on a family history of cancer. Overall, the incidence of suspected Lynch syndrome was 77% (10/13). Four of them underwent genetic testing and three were found to have a pathogenic germline mutation. A possible founder mutation, c.1757_1758insC in MLH1, was observed in 21 germline mutation information from literature review. CONCLUSION: The present study describes the clinicopathologic data of double primary endometrial and colorectal cancer patients and supports that these patients should undergo closed approach for Lynch syndrome. Moreover, a possible founder mutation in Korean endometrial cancer patients was identified.

miR-15a-5p suppresses endometrial cancer cell growth via Wnt/ß-catenin signaling pathway by inhibiting WNT3A.

OBJECTIVE: Endometrial cancer is one of the three most common types of gynecologic cancer. The global incidence has increased in recent years. microRNAs (miRNAs) regulate numerous biological processes by binding to the 3'UTR of target mRNA to down-regulate protein synthesis. PATIENTS AND METHODS: Endometrial cancer patients received surgeries in our hospital were enrolled. MiR-15a-5p mimic or miR-15a-5p inhibitor was transfected into HEC-1-A cells by lentivirus. Colony formation assay was applied for detecting cell proliferation. Real-time PCR was performed to test miRNA and mRNA expression. Western blot was used to detect protein level. ChIP was adopted to test transcription activation. TOP/FOP was tested to determine Wnt signaling pathway activity. A dual-luciferase reporter assay was used to confirm miRNA target. RESULTS: miR-15a-5p was decreased in endometrial cancer cells and tissues. miR-15a-5p overexpression restrained HEC-1-A cell proliferation and stemness. miR-15a-5p mimic transfection reduced mRNA and protein levels of the proteins which are related to cell proliferation and Wnt signaling pathway. MiR-15a-5p targeted a putative binding site in the 3'-UTR of Wnt3a gene, thus regulating Wnt signaling pathway. miR-15a-5p overexpression decreased Wnt3a protein expression. Wnt3a presented significant negative correlation with the miR-15a-5p level in endometrial cancer patients. CONCLUSIONS: miR-15a-5p is a regulator of endometrial cancer cell proliferation by directly targeting Wnt3a to block Wnt signaling pathway.

A Randomized, Multi-Center, Open-Label Study to Evaluate the Efficacy of Carvedilol vs. Propranolol to Reduce Portal Pressure in Patients With Liver Cirrhosis.

OBJECTIVES: Propranolol has been used as prophylaxis for variceal bleeding in patients with cirrhosis. More recent data suggest that carvedilol may be more effective for reducing the hepatic venous pressure gradient (HVPG) than propranolol. The primary aim of this study was to evaluate the hemodynamic response to carvedilol compared with propranolol. METHODS: A total of 110 patients with a baseline HVPG value >12 mm Hg were allocated randomly to receive either carvedilol or propranolol. The HVPG measurement was repeated after 6 weeks of daily medication. The primary end point was a ≥20% fall in HVPG compared with baseline or <12 mm Hg. RESULTS: The difference in the proportion of responders in the carvedilol (49.1%) vs. propranolol (30.9%) groups did not reach statistical significance in the intention-to-treat analysis (P=0.08). However, among patients with a model for end-stage liver disease (MELD) score ≥15, carvedilol resulted in a significantly greater response than that of propranolol (7/12, 58.3% vs. 0/10, 0%; P=0.005). Similarly, carvedilol was superior to propranolol in patients with Child-Pugh score ≥9 (46.2 vs. 0%; P=0.046). The presence of ascites also had a significant influence on the response rate (51.5 vs. 24.2%; P=0.042). A MELD score ≥15 was the only significant predictor of response among these post hoc groups after adjusting for multiple comparisons (P=0.005). Severe adverse events were higher in the carvedilol group although drug-associated adverse events were not different. CONCLUSIONS: Overall, carvedilol offered no clear advantage over propranolol but it may be more effective in advanced cirrhotic patients with a MELD score≥15 in reducing the portal pressure gradient. However, this potential benefit may come with a cost of increased risk of side-effects and outcome data over a longer term is needed to understand the relative risk benefit.

Aflatoxins: A Global Concern for Food Safety, Human Health and Their Management.

The aflatoxin producing fungi, Aspergillus spp., are widely spread in nature and have severely contaminated food supplies of humans and animals, resulting in health hazards and even death. Therefore, there is great demand for aflatoxins research to develop suitable methods for their quantification, precise detection and control to ensure the safety of consumers' health. Here, the chemistry and biosynthesis process of the mycotoxins is discussed in brief along with their occurrence, and the health hazards to humans and livestock. This review focuses on resources, production, detection and control measures of aflatoxins to ensure food and feed safety. The review is informative for health-conscious consumers and research experts in the fields. Furthermore, providing knowledge on aflatoxins toxicity will help in ensure food safety and meet the future demands of the increasing population by decreasing the incidence of outbreaks due to aflatoxins.

Postural Re-Education of Scoliosis - State of the Art (Mini-review).

UNLABELLED: A new development of correcting exercises has been derived from the original Schroth program in 2010 and the preliminary results have been published that year. Since then the program has been applied in some centers worldwide. As the original Schroth program was the only program so far to improve many signs and symptoms of scoliosis besides the angle of curvature (Cobb angle) it was interesting to look for the preliminary results of the recent development of scoliosis pattern specific corrective exercises derived from the original program, to see if similar effects can be achieved with this less complicated method. METHODS: A manual search in Pubmed was conducted, using the key words, Schroth, rehabilitation, and idiopathic scoliosis. Three papers have been found describing the short-term results of this new development today called Schroth Best Practice program (SBP). The papers were reviewed and analyzed with respect to the outcome parameters used. RESULTS: Outcome parameters were Angle of Trunk Rotation (ATR), Vital Capacity (VC), surface topography, electromyography, stabilometry and Cobb angle before and after a course of treatment. There was a significant improvement of all parameters after the application of this new program in all the three papers in the short- to mid-term. CONCLUSIONS: Scoliosis corrective exercises are supported by two randomized controlled trials (RCT) and should regularly be applied in mild scoliosis at risk for progression. Unspecific exercises such as Yoga, Dobomed cannot be regarded as effective as exercises using a well defined scoliosis pattern specific corrective routine.

Luteolin suppresses UVB-induced photoageing by targeting JNK1 and p90 RSK2.

Multiple lines of evidence suggest that natural compounds can prevent skin ageing induced by ultraviolet light. Luteolin, a bioactive compound found in chilli, onion, broccoli, celery and carrot, has been reported to exhibit anti-photoageing effects in vitro. However, the molecular targets and mechanisms of luteolin are still poorly understood. In this study, we sought to investigate the effects of luteolin on UVB-induced photoageing and the molecular mechanisms involved, using HaCaT human keratinocytes and SKH-1 hairless mice. Luteolin was found to inhibit UVB-induced MMP-1 expression in HaCaT cells, as well as UVB-induced activation of AP-1, a well-known transcription factor targeting the MMP-1 promoter region, as well as c-Fos and c-Jun, which comprise the AP-1 complex. In contrast, Western blot data showed that UVB-induced phosphorylation of JNK, ERK and p90RSK was not inhibited by luteolin. In vitro kinase assay data revealed that luteolin significantly suppressed JNK1 and p90RSK activity, but not that of JNK2 and ERK2. Pull-down assays showed that luteolin binds JNK1 in an ATP-competitive manner and p90RSK2 in an ATP-independent manner. Luteolin also inhibited UVB-induced wrinkle formation and MMP-13 expression, a rodent interstitial collagenase in mouse skin, in vivo. Taken together, our observations suggest that luteolin exhibits anti-photoageing effects in vitro and in vivo and may have potential as a treatment for the prevention of skin ageing.

Prognostic significance of Notch 3 gene expression in ovarian serous carcinoma.

The Notch signaling pathway is an important cell signaling system, which regulates cell differentiation, proliferation, and apoptosis, and is aberrantly activated in a wide range of cancer, including ovarian cancers. However, it remains unclear as to whether Notch signaling plays a role in the progression and prognosis of ovarian cancer. We examined the mRNA and protein expression of Notch 3, Jagged 1, and Jagged 2 in 98 ovarian epithelial tumors via real-time PCR and in 175 tumors with immunohistochemical analysis, and then correlated their expression levels with clinicopathological parameters and patient survival. In this study, we detected high levels of Notch3 mRNA and protein expression especially in serous ovarian carcinomas compared to their benign counterparts, accompanied by a positive correlation with the expressions of Jagged 1 and Jagged 2. High levels of Notch 3 mRNA expression (>2-fold than that of benign tumor) were noted in 63% of the serous carcinomas (mean level: 17-fold, P = 0.032). Additionally, Notch 3 protein overexpression was significantly associated with advanced stage (P = 0.0008), lymph node (P = 0.001), and distant metastasis (P = 0.003). Notably, high Notch 3 mRNA and protein expressions were correlated with chemoresistance (P = 0.033) and poor overall survival (P = 0.027, P = 0.042) in these patients. Our results indicate that the Notch 3 signaling pathway is involved in the tumor progression of ovarian serous carcinoma, and higher Notch 3 expression may be an independent poor prognostic factor in this subset of tumors.

Polymyxin B, scavenger of endotoxin, enhances isolation yield and in vivo function of islets.

Collagenase purified from bacteria has been used to isolate islets for transplantation. However, collagenase is contaminated with small amounts of endotoxin, which induces dysfunction or apoptosis of islets. In this study, we investigated the effects of polymyxin B, endotoxin scavenger, on the yield and quality of isolated islets. It is revealed that polymyxin B neutralized endotoxin in vitro and inhibited endotoxin-mediated decreases of the glucose stimulation index. Additionally, adenosine triphosphate (ATP) quantitation, islet regression assay, and caspase-3 activation assay demonstrated that polymyxin B efficiently blocked the toxic effects induced by endotoxin. Thereafter, we isolated mouse islets both with and without polymyxin B and compared total islet equivalents (IEQs), glucose-stimulated insulin release, and ATP content. Polymyxin B enhanced islet recovery, and ATP content of islets, and glucose stimulation index, and reduced TNF-alpha expression of islets. Marginal transplantation (200 IEQs/mouse) under the kidney capsule of diabetic mice induced normoglycemia in 30% of the polymyxin B group, but not in any mouse of control group. This result suggests that islets isolated with polymyxin B more effectively lower blood glucose levels as compared with control islets. Thus, polymyxin B could serve as a useful agent in the protection of islets from endotoxin-induced inflammation and apoptosis.

Linfoma testicular primario: estudio descriptivo: Instituto Especializado de Enfermedades Neoplásicas: Lima - Perú: 2006 / Primary testicular lymphoma: descriptive study: Instituto Especializado de Enfermedades Neoplásicas: Lima - Perú

El linfoma testicular es una enfermedad poco frecuente con características peculiares y un pronóstico pobre. Evaluamos en forma retrospectiva 32 pacientes con este diagnóstico estudiando sus características epidemiológicas, valores hematológicos, tipo histológico, lugares de metástasis, tratamiento recibido y tiempo de sobrevida. Así mismo comparamos nuestros resultados con los reportes internacionales, haciendo énfasis en la necesidad de estudios prospectivos para obtener mejores conclusiones.

Testicular lymphoma is a rare illness with peculiar characteristics but with a poor prognosis. We evaluated 32 patients retrospectively studying their epidemiologic characteristics, hematologic values, histological type, metastasis sites, the treatment given and the survival. We compared our results with international reports and we think that prospective studies are needed for better conclusions.

Effects of E. Coli lipopolysaccharide on the pharmacokinetics of ipriflavone and its metabolites, M1 and M5, after intravenous and oral administration of ipriflavone to rats: decreased metabolism of ipriflavone due to decreased expression of hepatic CYP1A2 and 2C11.

It was reported that ipriflavone was primarily metabolized via hepatic CYP1A1/2 and 2C11 in rats. In the present study, the expression of CYP1A2 and 2C11 decreased in the liver, but increased in the intestine in rats pretreated with E. coli lipopolysaccharide (ECLPS; an animal model of inflammation). Thus, pharmacokinetic parameters of ipriflavone and its metabolites, M1 and M5, were evaluated in ECLPS rats. After intravenous administration (20 mg/kg) to ECLPS rats, the AUC of ipriflavone was significantly greater (26.7% increase) and CL(NR) of ipriflavone was significantly slower (19.9% decrease) than in the controls. This could have been due to decreased expression of hepatic CYP1A2 and 2C11 compared to the controls. After oral administration (200 mg/kg) to ECLPS rats, the AUC of ipriflavone was also significantly greater (130% increase) than in the controls. Although the expression of intestinal CYP1A2 and 2C11 increased in ECLPS rats, contribution of this increase to the significantly greater AUC of ipriflavone after oral administration of ipriflavone to ECLPS rats was not considerable. This could have also been due to a significantly decreased expression of hepatic CYP1A2 and 2C11 in ECLPS rats. The formation of M1 and M5 could be mediated via CYP1A2 and/or 2C11 in rats.

Predictive factors for lymph node metastasis and endoscopic treatment strategies for undifferentiated early gastric cancer.

BACKGROUND AND AIM: Although more than 80% of undifferentiated early gastric cancers (EGC) are not associated with lymph node metastasis, endoscopic mucosal resection is not generally accepted as a means of curative treatment because of an abundance of conflicting data concerning clinicopathological characteristics and prognoses. The aim of this study was to define a subgroup of undifferentiated EGC that could be cured by endoscopic treatment without the risk of lymph node metastasis. METHOD: A total of 591 patients surgically resected for undifferentiated EGC between January 1999 and March 2005 were reviewed. Associations between various clinicopathological factors and the presence of lymph node metastasis were analyzed to identify the risk factors of lymph node metastasis. RESULTS: Lymph node metastasis was found in 79 patients (13.4%). By multivariate logistic regression analysis, a tumor diameter 2.5 cm or larger, invasion into the middle third of the submucosal layer or deeper, and lymphatic involvement were identified as independent risk factors of lymph node metastasis (P < 0.001, respectively). Lymph node metastasis was not found in any patient with undifferentiated EGC smaller than 2.5 cm confined to the mucosa or upper third of the submucosal layer without lymphatic involvement. CONCLUSIONS: Undifferentiated intramucosal EGC smaller than 2.5 cm without lymphatic involvement was not associated with lymph node metastasis. Thus, we propose in this circumstance that endoscopic mucosal resection could be considered a definitive treatment without compromising the possibility of cure.