The effectiveness and safety of liraglutide in treating overweight/obese patients with polycystic ovary syndrome: a meta-analysis.

PURPOSE: The purpose of this study is to evaluate the effectiveness and safety of liraglutide/liraglutide + metformin in overweight/obese women with polycystic ovary syndrome (PCOS). METHODS: The related literatures published until April 2021 were searched in PubMed, Cochrane Library, MEDLINE and EmBase. RESULTS: Six randomized controlled trials of 127 related articles were obtained through searching. Three articles compared liraglutide with metformin, and four articles compared liraglutide combined with metformin with metformin. Our meta-analysis suggests that liraglutide was superior to metformin only in weight loss [MD = - 2.74, 95% CI (- 4.29, - 1.18), P = 0.0006]. Compared with metformin group, the combination group had significant advantages in weight loss [MD = - 3.81, 95% CI (- 5.16, - 2.46), P < 0.001], BMI [MD = - 2.59, 95% CI (- 3.12, - 2.07), P < 0.001], waist circumference [MD = - 6.26, 95% CI (- 7.79, - 4.72), P < 0.001], fasting blood glucose [MD = - 0.59, 95% CI (- 0.74, - 0.44), P < 0.001] and fasting insulin [MD = - 1.52, 95% CI (- 2.69, - 0.35), P = 0.01], while the incidence of adverse reactions was relatively high [RR = 2.91, 95% CI (1.55, 5.46), P = 0.00009]. CONCLUSION: The present results indicate that liraglutide and metformin have the similar effects in the treatment of overweight/obese PCOS patients. Liraglutide combined with metformin is more effective than metformin in improving PCOS, but it is necessary to master the correct medication method to reduce the occurrence of adverse reactions.

[Legal liability of stomatological institutions in responding to state public health emergencies].

Crisis management in emergent public health event is a global difficult problem for researchers worldwide, which is highlighted by World Health Organization for its vital importance to public sanitation and health, life quality and survival. This article briefly analyzes and summarizes the relevant legal issues faced by stomatological institutions and workers after the emergent crisis caused by COVID-19 virus breakout in China since December 2019, so as to provide legal advises and guidance to stomatological institutions for responding public health emergencies.

MiR-296-3p may affect the proliferation and migration of non-small cell lung cancer cells via regulating RABL3.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The pathogenesis of NSCLC has not yet been fully understood, and the therapeutic efficacy of current anti-NSCLC medication remains unsatisfactory. Previous studies indicated that miR-296-3p was down-regulated in NSCLC, suggesting that miR-296-3p may participate in the pathogenesis of NSCLC; however, the specific mechanisms still need to be further explored. The aim of this work is to investigate the roles of miR-296-3p in NSCLC and the related mechanism. PATIENTS AND METHODS: Thirty NSCLC tissue and paired adjacent tissue were collected, and Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to examine the expression of miR-296-3p in cancer tissue and the adjacent tissue. Next, A549 cells were cultured and transfected with miR-296-3p mimics, and cell migration and invasion were determined using scratch wound-healing and transwell assays. Moreover, Western blot assay was performed to determine the effect of miR-296-3p on the expression of Rab-like 3 (RABL3), Matrix metallopeptidase (MMP)-2, Janus kinase (JAK) and Signal transducer and activator of transcription 3 (STAT3); next, Dual-Luciferase reporter assay has been conducted to prove the direct targeting relationship between miR-296-3p and RABL3. Finally, the cells of different treatments were subcutaneously implanted into nude mice to investigate the effect of miR-296-3p mimics in the xenograft mice tumor models. RESULTS: Our data indicated that miR-296-3p was significantly down-regulated and RABL3 was markedly up-regulated in NSCLC tissue compared with the adjacent tissue. Moreover, transient over-expression of miR-296-3p in A549 cells induced a significant decrease in the proliferation and invasion ability of A549 cells, as well as decreased expression of RABL3, MMP-2, JAK and STAT3. Furthermore, the Dual-Luciferase reporter assay confirmed that RABL3 is a direct target of miR-296-3p. Finally, the results of animal studies indicated that miR-296-3p can regulate the tumorigenesis of A549 cells in vivo. CONCLUSIONS: Our findings proved that miR-296-3p may play a role as a tumor suppressor in NSCLC both in vitro and in vivo, and we first reported that miR-296-3p can regulate the migration and invasion of A549 cells via targeting RABL3. Our data suggested that miR-296-3p may serve as a potential therapeutic target for treating NSCLC.

[Adrenal androgen measurement for assessing the selectivity of adrenal venous sampling in primary aldosteronism].

Objective: To investigate the usefulness of adrenal androgens for assessing the selectivity of adrenal venous sampling (AVS). Methods: Between January 2010 and December 2016, 37 consecutive patients [with an average age of (47±14) years, 16 males and 21 females] with primary aldosteronism (PA) who underwent AVS were enrolled. AVS procedures were performed with the bilateral simultaneous technique without cosyntropin stimulation. Cortisol, androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS) concentrations were measured in adrenal venous (AV) and peripheral venous (PV) samples, respectively. Results: The selectivity index (SI) based on androstenedione and DHEA was higher than that of cortisol (SI-left: 13.9, 13.1 vs 6.05, P=0.006, 0.035; SI-right: 30.4, 18.5 vs 11.6, P=0.028, 0.051). However, the SI based on DHEAS was lower than that of cortisol (SI-left: 1.3 vs 6.0, P=0.002; SI-right: 1.5 vs 11.6, P=0.038). Plasma androstenedione and DHEA concentrations were positively correlated with cortisol and aldosterone in AV samples (all P<0.001). Compared to cortisol, the variation ratio of AV androstenedione and DHEA was lower from t(-15) to t(0) (0.23, 0.43 vs 0.52, both P<0.05). Using the receiver operating characteristic curve, a SI ≥ 3.0 for androstenedione or DHEA provided optimal sensitivity(97.7%, 91.9%) and specificity (93.8%, 93.8%) in AVS. Conclusion: Given the greater AV/PV ratios and reduced variability compared to cortisol, the adrenal androgens androstenedione and DHEA are useful for assessing the selectivity of AVS without cosyntropin stimulation and may be superior analytes in conditions with marked variability of cortisol levels or with adrenocortical tumors co-secreting cortisol and aldosterone.

[Role of adrenal vein sampling in differential diagnosis of primary aldosteronism subtypes].

Objective: To investigate the role of adrenal vein sampling (AVS) in identifying the subtype of primary aldosteronism (PA). Methods: AVS was performed in 50 patients who were confirmed as PA between September 2010 and September 2016 in Nanjing Drum Tower Hospital. Clinical, biochemical and follow-up data were reviewed retrospectively. Bilaterally simultaneous catheterization without cosyntropin stimulation and contemporaneous cortisol measurement during AVS were used. Selectivity index (SI)≥1.5 suggested that the sample was from the adrenal vein.Lateralization index (LI) ≥2 suggested unilateral disease.Clinical data was further compared and the AVS findings were analyzed. Results: AVS was successful performed in 41 cases of 50 patients, and the success rate was 82%. According to the results of AVS and postoperative pathology, 41 cases were divided into aldosterone-producing adenoma (APA)/unilateral adrenal hyperplasia (UAH) group (24 cases) and idiopathic hyperaldosteronism (IHA) group (17 cases). Compared with IHA group, patients with APA/UAH showed longer duration of hypertension[10.0 (5.0, 13.0) y vs 4.0 (2.0, 8.0) y, P=0.046], higher proportion of hypokalemia (95.8% vs 64.7%, P=0.009). Furthermore, patients with APA/UAH demonstrated lower plasma renin activity (P=0.089), higher plasma aldosterone concentration and aldosterone to renin ratio (ARR) (both P<0.05). The diagnostic concordance between CT and adrenal vein sampling was only 48.8%(20/41). Conclusions: The application of bilaterally simultaneous catheterization and contemporaneous cortisol measurement improves success rate and diagnostic accuracy of AVS. AVS is useful in subtype diagnosis of PA with equivocal imaging findings.

ANP32B deficiency impairs proliferation and suppresses tumor progression by regulating AKT phosphorylation.

The acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) is reported to impact normal development, with Anp32b-knockout mice exhibiting smaller size and premature aging. However, its cellular and molecular mechanisms, especially its potential roles in tumorigenesis, remain largely unclear. Here, we utilize 'knockout' models, RNAi silencing and clinical cohorts to more closely investigate the role of this enigmatic factor in cell proliferation and cancer phenotypes. We report that, compared with Anp32b wild-type (Anp32b(+/+)) littermates, a broad panel of tissues in Anp32b-deficient (Anp32b(-/-)) mice are demonstrated hypoplasia. Anp32b(-/-) mouse embryo fibroblast cell has a slower proliferation, even after oncogenic immortalization. ANP32B knockdown also significantly inhibits in vitro and in vivo growth of cancer cells by inducing G1 arrest. In line with this, ANP32B protein has higher expression in malignant tissues than adjacent normal tissues from a cohort of breast cancer patients, and its expression level positively correlates with their histopathological grades. Moreover, ANP32B deficiency downregulates AKT phosphorylation, which involves its regulating effect on cell growth. Collectively, our findings suggest that ANP32B is an oncogene and a potential therapeutic target for breast cancer treatment.

Deformation and fracture of K3 rotary nickel-titanium endodontic instruments after clinical use.

AIM: The aim was to evaluate the incidence and type of defects that occurred with K3 rotary nickel-titanium instruments during routine clinical use. METHODOLOGY: A total of 2397 K3 (G-PACKS, SybronEndo, West Collins, Orange, CA, USA) instruments were collected from a graduate endodontic clinic over 21 months. All the instruments were limited to a maximum use of 30 canal preparations. The collected instruments were measured by a digital caliper to determine whether any fractures had occurred and then were visually inspected for deformation and fracture under a stereomicroscope. The surfaces of fractured instruments were further evaluated under a scanning electron microscope. Data were analysed using chi-square test and Kruskal-Wallis test. RESULTS: The incidence of instrument defect was 5.63%, consisting of 3.59% fractures and 2.05% deformations. The defect rates of 0.04 and 0.06 files were statistically higher than the other taper groups (P < 0.003) except for 0.08 files (P > 0.05). For the fractured instruments, 63.95% failed from flexural fatigue, whilst 36.05% failed from torsion. CONCLUSION: Flexural fracture was the major mode of fracture for instruments with larger taper. A routine check for instrument integrity particularly for 0.04 and 0.06 files at high magnification is recommended after each clinical use.

Cytotoxicity of ammonium hexafluorosilicate on human gingival fibroblasts.

Ammonium hexafluorosilicate (SiF), which is claimed to significantly improve occlusion of dentinal tubules, was proposed as a novel desensitizer for dentine hypersensitivity (DH). However, the cytotoxicity of SiF on oral cells is lacking. The purpose of this study was to investigate the cytotoxicity of SiF on human gingival fibroblasts (hGFs) under different dosages (0.001%, 0.01%, 0.1%, and 1%) and treatment durations (1, 5, 10, and 30min). Cell proliferation, mitochondrial membrane potential (MMP) and cell cycle were tested by MTT assay, JC-1 staining and flow cytometry, respectively. Glutathione (GSH) depletion was analyzed to further investigate the underlying mechanism of SiF-induced cytotoxicity. MTT assay showed that there was significantly lower number of viable cells when the hGFs were treated with 0.01% (10min), 0.1% (10 and 30min) and 1% (5, 10, and 30min) SiF than the control group (p<0.05). MMP decreased and GSH depletion increased dramatically along with higher concentrations (0.1% and 1% SiF) and prolonged times (10 and 30min). DNA synthesis [S (%)] of cells treated with 0.1% and 1% SiF (5, 10, and 30min) was significantly lower than the control group (p<0.05). Our results indicate exposure to up to 0.01% SiF for less than 5min causes low or no cytotoxicity in vitro.

The (TTTA)n polymorphism in intron 4 of CYP19 and the polycystic ovary syndrome risk in a Chinese population.

Polycystic ovary syndrome (PCOS) is a heterogeneous disease with a strong genetic origin, but the specific determinants are still unknown. The aim of this study was to investigate the association between the (TTTA) n polymorphism in intron 4 of CYP19 and the PCOS risk in a Chinese population. We performed a case-control study which involved 222 PCOS patients and 281 controls. The fluorescent-labeled target DNA fragments containing the (TTTA)n short tandem repeats were obtained by PCR, thereafter genotyped via capillary electrophoresis. Representative alleles were directly sequenced to confirm their repeat numbers. Genotype analysis revealed seven different alleles including 7-3(∆)-, 7-, 8-, 10-, 11-, 12- and 13-TTTA-repeats. The most common allele in a Chinese population is (TTTA) 11 in our study (0.354 for PCOS and 0.390 for controls). PCOS patients showed a higher frequency of short alleles compared with controls (0.47 vs. 0.41, OR=1.245, 95% CI 0.97-1.60). The overall allelic distributions of this polymorphism did not show any significant differences between PCOS patients and the control group. No statistical differences were found in the clinical parameters or serum steroid hormone levels among PCOS patients with different genotypes. In conclusion, PCOS patients had a higher frequency of short alleles, albeit this might not strongly affect the risk of PCOS.

Occurrence and distribution of Naegleria species from thermal spring environments in Taiwan.

UNLABELLED: Naegleria spp. is a free-living amoeba that can be found in the natural environment. A number of Naegleria spp. can cause fatal infections in the central nervous system in humans and animals, and the most important source of infection is through direct water contact. In this study, water samples from various thermal springs were taken from four thermal spring areas. Naegleria spp. was detected via culture confirmation and molecular taxonomic identification. Among the 60 samples obtained, Naegleria spp. was identified in 26 (43·3%) samples. The identified species included Naegleria australiensis, Naegleria gruberi, Naegleria lovaniensis and Naegleria mexicana. The presence of living Naegleria spp. was significantly associated with elevated pH value in the water sample. SIGNIFICANCE AND IMPACT OF STUDY: In this study, we examined the presence of living Naegleria spp. in thermal spring waters in south-eastern Taiwan. Naegleria spp. was isolated and culture-confirmed from thermal spring water. Naegleria fowleri was not found in all water samples, and Naegleria australiensis was the most common Naegleria genotype.

Correlated increase of omentin-1 and adiponectin by exenatide, avandamet and dietary change in diet-induced obese rats.

Adipokines omentin-1 and adiponectin have been reported to improve insulin resistance. It is known that insulin sensitizers exenatide, avandamet, or diet change from high-fat to normal chow ameliorate metabolic disorders. However, whether these treatments increase omentin-1 levels in high fat-diet animals and the relationship between omentin- 1 and adiponectin remain largely unknown. We investigated the effect of insulin sensitizers exenatide and avandamet, and of dietary change on these adipokine levels, body weight, and insulin sensitivity in diet-induced obese rats. Obesity was induced in rats by high-fat diet feeding for 8 weeks, and then the rats were given exenatide, avandamet and diet change to normal chow, respectively, for additional 8 weeks. Compared to the high-fat control group, exenatide and avandamet treatment significantly induced adipose gene expression and elevated the circulation levels of omentin-1 and adiponectin, whereas they decreased the leptin gene expression and circulation level, which is associated with improvement of systemic insulin sensitivity and the glucose and lipid profile. Notably, there was a significant positive correlation between omentin-1 and adiponectin in the above regimens, suggesting that omentin-1 and adiponectin may contribute to the insulin-sensitizing effect of exenatide and avandamet.

SLC30A8 polymorphism and type 2 diabetes risk: evidence from 27 study groups.

BACKGROUND AND AIMS: Intense research has been performed to identify the genetic risk factors in type 2 diabetes, and a single nucleotide polymorphism (SNP) in SLC30A8 (rs13266634) was reported to be associated with type 2 diabetes mellitus. However, published data on the association between SLC30A8 polymorphism and the risk of type 2 diabetes were inconsistent. Therefore, we conducted this meta-analysis to derive a more precise estimation of the relationship. METHODS AND RESULTS: We searched PubMed through October 2009 to identify all relevant papers. Odds ratios (ORs) and 95% confidence intervals (CIs) were extracted under an additive genetic model. In the current meta-analysis, we identified a total of 27 groups including 42,609 cases and 69,564 controls. In analyses of the case-control studies by ethnicity, the results indicated that SLC30A8 polymorphism was related to elevate risks of type 2 diabetes both in Europeans (OR=1.15, 95% CI 1.11-1.18, P<0.001) and Asians (OR=1.15, 95% CI 1.11-1.19, P<0.001). Next, we separated hospital-based case-control studies from population-based case-control studies, however, there was no apparent difference between population-based case-control study groups (OR=1.15, 95% CI 1.12-1.17, P<0.001) and hospital-based case-control study groups (OR=1.16, 95% CI 1.07-1.25, P<0.001). CONCLUSION: Our present meta-analysis provided evidence that SLC30A8 (rs13266634) C allele carriers could elevate the risk of type 2 diabetes, especially in Europeans and Asians.

[Purification of soluble egg antigen (SEA) 38 kDa molecule of Schistosoma japonicum and preliminary evaluation of its immunodiagnostic efficacy].

OBJECTIVE: To study the applicability of soluble egg antigen (SEA) 38 kDa molecule of Schistosoma japonicum in the immunodiagnosis of schistosomiasis. METHODS: The target immunodiagnositic antigen SEA 38 kDa molecule was separated and purified by SDS-PAGE and electroelution technique and evaluated by SDS-PAGE and Western blotting. To compare their immunodiagnostic efficacy, the purified SEA 38 kDa and SEA were used to examine the sera from 182 cases including 31 acute schistosomiasis patients, 31 chronic schistosomiasis patients, 60 normal human controls, 30 paragonimiasis patients and 30 clonorchiasis patients. RESULTS: The positive rates of purified SEA 38 kDa and SEA for acute schistosomiasis patients, chronic schistosomiasis patients, normal human controls, paragonimiasis patients and clonorchiasis patients were 90.3%, 90.3%, 1.7%, 0, 0 and 90.3%, 83.9%, 3.3%, 0, 0, respectively. The P/N ratio of purified SEA 38 kDa and SEA in immunodiagnosis of schistosomiasis by ELISA had been compared by two-sample t-test. It was demonstrated that there existed significant differences between purified SEA 38 kDa and SEA in the three groups of acute and chronic schistosomiasis patients and normal persons(P < 0.001). The P/N ratio of SEA 38 kDa in detecting the sera from schistosomiasis patients was obviously higher than that of SEA, but when SEA 38 kDa was used to examine normal human sera, the result was converse. CONCLUSION: The purified SEA 38 kDa has higher sensitivity and specificity and immunodiagnostic potential.

Baculovirus expression of the major surface antigen of Toxoplasma gondii and the immune response of mice injected with the recombinant P30.

The major surface antigen (P30) of the Toxoplasma gondii was expressed by an insect cell culture system infected with recombinant baculovirus. About 750 microg of purified (95% purity) P30 was obtained from a culture of 10(8) insect Sf21 cells. The recombinant P30 was used to immunize mice to induce immune response. Mice injected with the recombinant protein produced specific humoral and cellular immune responses. Immunization with P30 also prolonged the period of survival of mice infected by Toxoplasma. The average survival time of control group is 13.25+/-1.16 days, but are 16.13+/-2.1 days, 19.50+/-3.21 days, 20.38+/-3.38 days in different immunized groups, respectively.

[Studies on antifertility constituents of Siegesbeckia glabrescens Mak].

Three diterpenes including a new compound were isolated from the whole plant of Siegesbeckia glabrescens Mak. The new one was named as neodarutoside and its structure was elucidated as ent-3 alpha, 15,16-trihydroxy pimarane 3,15-bis-(beta-glucopyranoside) based on the spectral evidence and chemical transformation. The other two were darutigenol and darutoside. Darutoside possesses the activity of termination of early pregnancy in experimental rats at a dosage of 20-40 mg/kg.

Effects of endotoxin in cortisone-treated rabbits with a hereditary deficiency of the sixth component of complement (C6 deficiency).

Endotoxin was infused into normal rabbits and C6 deficient rabbits prepared with cortisone for the generalized Shwartzman reaction. Endotoxin produced profound granulocytopenia and moderate thrombocytopenia in both normal and C6 deficient rabbits. In normal rabbits endotoxin consistently produced extensive intravascular clotting. In C6 deficient animals endotoxin resulted in intravascular clotting of variable extent. In one group of eight C6 deficient rabbits mean fibrinogen levels fell 0.67 g per 1 over 6 hrs after endotoxin and four of eight animals developed a generalized Shwartzman reaction. In a second group of seven C6 deficient rabbits mean fibrinogen level fell only 0.17 g per 1 over 6 hrs and one animal developed a generalized Shwartzman reaction. Values for mean fibrinogen consumption, calculated from plasma fibrinogen levels and rate of disappearance of 25I-fibrinogen, were as follows: normal animals infused with saline, 10 mg per kg; C6 deficient animals infused with endotoxin, 58 mg per kg. Fibrinogen consumption after endotoxin was found to be related to granulocyte levels prior to endotoxin, which determined the number of granulocytes disappearing from the blood after endotoxin. The data indicate that C6 deficiency in the rabbit does not prevent intravascular clotting and the generalized Shwartzman reaction.

The effects of infusion of thrombin or endotoxin in rabbits treated with cortisone.

Rabbits treated for 4 days with cortisone to prepare for the generalized Shwartzman reaction (GSR) were infused with thrombin or endotoxin. Whereas endotoxin induced the GSR, infusion of from 120--400 U/kg of thrombin over 1 to 2 1/2 hr failed to induce the GSR. Mean values for fibrinogen consumption after thrombin or endotoxin, calculated from changes in plasma fibrinogen concentration and plasma 125I-fibrinogen radioactivity, were as follows: for rabbits infused with thrombin, from 43 to 61 mg/kg over a 3 hr period; for rabbits infused with endotoxin, 58.5 mg/kg over a 6 hr period. A small peak of non-clottable protein radioactivity, indicative of secondary fibrinolysis, was found in animals infused with thrombin but not in animals infused with endotoxin. A striking late rise in plasma fibrinogen levels was noted in animals infused with endotoxin. It was not noted in animals infused with thrombin. This observation provides further evidence that endotoxin stimulates fibrinogen synthesis by mechanisms independent of intravascular clotting or fibrinolysis. The failure to produce the GSR with thrombin in cortisone-treated rabbits leads us to conclude that depression of reticuloendothelial cell clearance of fibrin can not account for the preparatory effect of cortisone for the GSR after endotoxin.