Research Progress of Risk Factors Associated with Gestational Diabetes Mellitus.

Gestational Diabetes Mellitus (GDM) is a common endocrine condition associated with adverse pregnancy outcomes. In recent years, a growing number of risk factors associated with gestational diabetes mellitus have been defined. GDM poses a serious threat to maternal health. The etiology is complex and multifactorial and can be divided into inherent and modifiable factors. The inherent factors have been described in other literature, while the modifiable factors are mainly the risk of lifestyle habits. In this study, we performed a narrative review of the progress of risk factors associated with gestational diabetes mellitus.

Establishment of a Prognostic Nomogram for Cancer-Specific Survival in Patients With Base-of-Tongue Squamous Cell Carcinoma: A Retrospective Study Based on the SEER Database.

BACKGROUND: The aim of this retrospective study was to construct and clinically apply a nomogram for cancer-specific survival (CSS) in patients diagnosed with base-of-tongue squamous cell carcinoma (BOTSCC) to predict their survival prognosis. METHODS: We collected 8448 patients diagnosed with BOTSCC during 2004-2015 from the Surveillance, Epidemiology, and End Results (SEER) database and divided 30% and 70% of them into validation and training cohorts, respectively. We utilized backward stepwise regression in the Cox model to select variables. Predictive variables were subsequently identified from the variables selected above by using multivariate Cox regression. The new survival model was compared with the American Joint Committee on Cancer (AJCC) prognosis model using the following variables: calibration curve, time-dependent area under the receiver operating characteristic curve (AUC), concordance index (C-index), integrated discrimination improvement (IDI), decision-curve analysis (DCA), and net reclassification improvement (NRI). RESULTS: A nomogram was established for predicting the CSS probability in patients with BOTSCC. Factors including sex, race, age at diagnosis, marital status, radiotherapy status, chemotherapy status, TNM AJCC stage, surgery status, tumor size, and months from diagnosis to treatment were selected through multivariate Cox regression as independent predictors of CSS. Calibration plots indicated that the model we established had satisfactory calibration ability. The AUC, C-index, IDI, DCA, and NRI results illustrated that the nomogram performed explicit prognoses more accurately than did the AJCC system alone. CONCLUSION: We identified the relevant factors affecting the survival of BOTSCC patients and analyzed the data on patients suffering from BOTSCC in the SEER database. These factors were used to construct a new nomogram to give clinical staff a more-visual prediction model for the 3-, 5-, and 8-year probabilities of CSS for patients newly diagnosed with BOTSCC, thereby aiding clinical decision making.

The Effect of Bicycle Saddle Widths on Saddle Pressure in Female Cyclists.

Choosing an unsuitable bicycle saddle increases the saddle pressure and discomfort during cycling. Women contract sports injuries more easily than men during cycling owing to their anatomy. To investigate the effect of saddle widths on the saddle pressure in female cyclists. Ten healthy women with an average age of 20.7 ± 1.3 years, height of 162 ± and 5.9 cm, weight of 56.1 ± 7.5 kg, and a sciatic bone width of 15.5 ± 1.4 cm were recruited for this study. The distributions of saddle pressure for four different saddle widths (i.e., narrow, moderate, wide, and self-chosen) were recorded using a saddle pressure mat. Participants were instructed to pedal steadily with a frequency of 90 RPM and a load of 150 watts. Thirty seconds of riding data was randomly retrieved for analysis. The trials were conducted with a counter-balanced design to minimize random errors. One-way repeated measures ANOVA was used to compare the saddle pressure of different saddle widths, and the significance level was set at α = 0.05. When wide saddles were used, the maximum and average pressure on the right surface of the posterior ischium were lower than those with narrow (p = 0.001, p = 0.012) and moderate (p = 0.016, p = 0.019) saddles. The area of pressure on the pubic bone was smaller when using a wide saddle than when using narrow (p = 0.005) and moderate (p = 0.018) saddles, and the area of pressure on the right posterior sciatic bone was larger under the wide saddle than under the narrow (p = 0.017) and moderate (p = 0.036) saddles. The average force was greater with the moderate saddle than with the wide (p = 0.008) and self-chosen (p = 0.025) saddles. Using a saddle with a width that is longer than the width of the cyclist's ischium by 1 cm can effectively improve the distribution of saddle pressure during riding, while providing better comfort.

α-Viniferin-Induced Apoptosis through Downregulation of SIRT1 in Non-Small Cell Lung Cancer Cells.

α-Viniferin, a natural stilbene compound found in plants and a polymer of resveratrol, had demonstrated potential anti-cancer and anti-inflammatory effects. However, the specific mechanisms underlying its anti-cancer activity were not yet fully understood and required further investigation. This study evaluated the effectiveness of α-viniferin and ε-viniferin using MTT assay. Results showed that α-viniferin was more effective than ε-viniferin in reducing the viability of NCI-H460 cells, a type of non-small cell lung cancer. Annexin V/7AAD assay results provided further evidence that the decrease in cell viability observed in response to α-viniferin treatment was due to the induction of apoptosis in NCI-H460 cells. The present findings indicated that treatment with α-viniferin could stimulate apoptosis in cells by cleaving caspase 3 and PARP. Moreover, the treatment reduced the expression of SIRT1, vimentin, and phosphorylated AKT, and also induced AIF nuclear translocation. Furthermore, this research provided additional evidence for the effectiveness of α-viniferin as an anti-tumor agent in nude mice with NCI-H460 cell xenografts. As demonstrated by the TUNEL assay results, α-viniferin promoted apoptosis in NCI-H460 cells in nude mice.

Lower Limb Biomechanics during the Golf Downswing in Individuals with and without a History of Knee Joint Injury.

Although prevention is better than treatment, after a knee injury occurs, the adjustment of the movement technique back to the posture before the injury and the restoration of accuracy is very important for professional and amateur players. This study aimed to compare the differences in lower limb mechanics during the golf downswing between those with and without a history of knee joint injury. A total of 20 professional golfers with single-digit handicaps were recruited for this study, 10 of whom had a knee injury history (KIH+), while another 10 players were without a knee injury history (KIH-). From the 3D analysis, selected kinematic and kinetic parameters during the downswing were analyzed using an independent samples t-test with a significance level of α = 0.05. During the downswing, individuals with KIH+ exhibited a smaller hip flexion angle, smaller ankle abduction angle, and larger ankle adduction/abduction range of motion (ROM). Moreover, there was no significant difference found in the knee joint moment. Athletes with a history of knee injury can adjust the motion angles of their hip and ankle joints (e.g., by avoiding excessive forward leaning of the trunk and maintaining stable foot posture without inward or outward rotation) to minimize the impact of changes in their movement patterns resulting from the injury.

Essential trace elements in patients with dyslipidemia: A meta-analysis.

BACKGROUND: Lipid metabolism is a complex process that includes lipid uptake, transport, synthesis, and degradation. Trace elements are vital in maintaining normal lipid metabolism in the human body. This study explores the relationship between serum trace elements and lipid metabolism Methods: In this study, we reviewed articles on the relationship between alterations in somatic levels of zinc, iron, calcium, copper, chrome, manganese, selenium, and lipid metabolism. In this systematic review and mate-analysis, databases such as PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI), Wanfang was searched for articles on the relationship published between January 1, 1900, and July 12, 2022. The meta-analysis was performed using Review Manager5.3 (Cochrane Collaboration). RESULTS: No significant association was found between serum zinc and dyslipidemia, while other serum trace elements (Iron, selenium, copper, chromium, and manganese) were associated with hyperlipidemia. CONCLUSION: The present study suggested that the human body's zinc, copper, and calcium content may be related to lipid metabolism. However, findings on lipid metabolism and Iron, Manganese have not been conclusive. In addition, the relationship between lipid metabolism disorders and selenium levels still needs to be further studied. Further research is needed on treating lipid metabolism diseases by changing trace elements.

Different nutrient compositions in diet and taking hypoglycemic drugs can modulate gut microbial flora.

The diet structure of diabetic patients is different from that of normal people. Diabetic patients also need to take hypoglycemic drugs to regulate blood sugar. Both dieting and drugs affect the gut microbiota of diabetic patients. In this letter, we discuss that different dietary patterns and the use of hypoglycemic agents may have an impact on changes in gut microbiota in diabetic patients.

α-Viniferin and ε-Viniferin Inhibited TGF-ß1-Induced Epithelial-Mesenchymal Transition, Migration and Invasion in Lung Cancer Cells through Downregulation of Vimentin Expression.

Resveratrol has well-known anticancer properties; however, its oligomers, including α-viniferin, ε-viniferin, and kobophenol A, have not yet been well investigated. This is the first study examining the anti-epithelial-mesenchymal transition (EMT) effects of α-viniferin and ε-viniferin on A549, NCI-H460, NCI-H520, MCF-7, HOS, and U2OS cells. The results showed that α-viniferin and ε-viniferin significantly inhibited EMT, invasion and migration in TGF-ß1- or IL-1ß-induced non-small cell lung cancer. α-Viniferin and ε-viniferin also reversed TGF-ß1-induced reactive oxygen species (ROS), MMP2, vimentin, Zeb1, Snail, p-SMAD2, p-SMAD3, and ABCG2 expression in A549 cells. Furthermore, ε-viniferin was found to significantly inhibit lung metastasis in A549 cell xenograft metastatic mouse models. In view of these findings, α-viniferin and ε-viniferin may play an important role in the prevention of EMT and cancer metastasis in lung cancer.

Skinny people serum factors promote the differentiation of multipotent stem cells into brown adipose tissue.

The original study by Alessio et al reported that skinny people (SP) serum can promote the formation of brown adipocytes, but not the differentiation of white adipocytes. This finding may explain why SP do not often become obese, despite consuming more calories than the body needs. More importantly, they demonstrated that circulating factors in SP serum can promote the expression of UCP-1 protein, thereby reducing fat accumulation. In this study, only male serum samples were evaluated to avoid the interference of sex hormones in experiments, but adult males also synthesize estrogen, which is produced by the cells of the testes. At the same time, adult females secrete androgens, and females synthesize androgens that are mainly produced by the adrenal cortex. We believe that the approach of excluding sex hormone interference by sex selection alone may be flawed, so we comment on the article and debate the statistical analysis of the article.

Comment "Asymptomatic small intestinal ulcerative lesions: Obesity and Helicobacter pylori are likely to be risk factors".

There are many causes of anemia. It is unreasonable to simply associate anemia with asymptomatic ulcers in the small intestine.

Jolkinolide B sensitizes bladder cancer to mTOR inhibitors via dual inhibition of Akt signaling and autophagy.

The monotherapy of mTOR inhibitors (mTORi) in cancer clinical practice has achieved limited success due to the concomitant activation of compensatory pathways, such as Akt signaling and cytoprotective autophagy. Thus, the combination of mTORi and the inhibitors of these pro-survival pathways has been considered a promising therapeutic strategy. Herein, we report the synergistic effects of a natural anti-cancer agent Jolkinolide B (JB) and mTORi (temsirolimus, rapamycin, and everolimus) for the effective treatment of bladder cancer. A mechanistic study revealed that JB induced a dual inhibition of Akt feedback activation and cytoprotective autophagy, potentiating the anti-proliferative efficacy of mTORi in both PTEN-deficient and cisplatin-resistant bladder cancer cells. Meanwhile, mTORi augmented the pro-apoptotic and pro-paraptotic effects of JB by reinforcing JB-activated endoplasmic reticulum stress and MAPK pathways. These synergistic mechanisms were related to cellular reactive oxygen species accumulation. Our study suggests that dual inhibition of Akt feedback activation and cytoprotective autophagy is an effective strategy in mTORi-based therapy, and JB + mTORi combination associated with multiple anti-cancer mechanisms and good tolerance in mouse models may serve as a promising treatment for bladder cancer.

ε-Viniferin and α-viniferin alone or in combination induced apoptosis and necrosis in osteosarcoma and non-small cell lung cancer cells.

This study investigated the effects and molecular mechanisms of ε-viniferin and α-viniferin in non-small cell lung cancer cell line A549, melanoma cell line A2058, and osteosarcoma cell lines HOS and U2OS. Results showed ε-viniferin having antiproliferative effects on HOS, U2OS, and A549 cells. Compared with ε-viniferin at the same concentration, α-viniferin had higher antiproliferative effects on HOS cells, but not the same effect on U2OS and A549 cells. Lower dose combination of α-viniferin and ε-viniferin had more synergistic effects on A549 cells than either drug alone. α-Viniferin induced apoptosis in HOS cells by decreasing expression of phospho-c-Jun-N-terminal kinase 1/2 (p-JNK1/2) and increasing expression of cleaved Poly (ADP-ribose) polymerase (PARP), whereas α-viniferin in combination with ε-viniferin induced apoptosis in A549 cells by decreasing expression of phospho-protein kinase B (p-AKT) and increasing expression of cleaved PARP and cleaved caspase-3. ε-Viniferin and α-viniferin have not been studied using in vivo tumor models for cancer. This research is the first showing that ε-viniferin treatment resulted in significant inhibition of tumor growth in A549-cell xenograft-bearing nude mice compared with the control group. Consequently, ε-viniferin and α-viniferin may prove to be new approaches and effective therapeutic agents for osteosarcoma and lung cancer treatment.

Opportunistic bacteria use quorum sensing to disturb coral symbiotic communities and mediate the occurrence of coral bleaching.

Coral associated microorganisms, especially some opportunistic pathogens can utilize quorum-sensing (QS) signals to affect population structure and host health. However, direct evidence about the link between coral bleaching and dysbiotic microbiomes under QS regulation was lacking. Here, using 11 opportunistic bacteria and their QS products (AHLs, acyl-homoserine-lactones), we exposed Pocillopora damicornis to three different treatments: test groups (A and B: mixture of AHLs-producing bacteria and cocktail of AHLs signals respectively); control groups (C and D: group A and B with furanone added respectively); and a blank control (group E: only seawater) for 21 days. The results showed that remarkable bleaching phenomenon was observed in groups A and B. The operational taxonomic units-sequencing analysis shown that the bacterial network interactions and communities composition were significantly changed, becoming especially enhanced in the relative abundances of Vibrio, Edwardsiella, Enterobacter, Pseudomonas, and Aeromonas. Interestingly, the control groups (C and D) were found to have a limited influence upon host microbial composition and reduced bleaching susceptibility of P. damicornis. These results indicate bleaching's initiation and progression may be caused by opportunistic bacteria of resident microbes in a process under regulation by AHLs. These findings add a new dimension to our understanding of the complexity of bleaching mechanisms from a chemoecological perspective.

YWHAZ amplification/overexpression defines aggressive bladder cancer and contributes to chemo-/radio-resistance by suppressing caspase-mediated apoptosis.

The objective of this study was to characterize the oncogenic actions of a recently identified cancer-associated gene YWHAZ (also named as 14-3-3 ζ/δ) in urothelial carcinomas of the urinary bladder (UCUB). A genome-wide study revealed YWHAZ to be involved in the amplicon at 8q22.3, and its genetic amplification was detected predominantly in muscle-invasive bladder cancer (MIBC). Immunohistochemical staining confirmed the association of YWHAZ overexpression with higher tumor stages, lymph node/vascular invasion, and mitotic activity. Univariate and multivariate analyses further indicated the prognostic potential of YWHAZ for more aggressive cancer types. Both gene set enrichment analysis and STRING network studies suggested involvement of YWHAZ in regulating caspase-mediated apoptosis. Ectopic expression of YWHAZ in bladder cells with low endogenous YWHAZ levels boosted cell resistance to doxorubicin and cisplatin, as well as to ionizing radiation. Conversely, YWHAZ-knockdown using specific shRNA in cells with high endogenous YWHAZ levels diminished survival activity, suppressing cell growth and increasing cell death. Our findings confirm the essential role played by YWHAZ in sustaining cell proliferation during chemo/radiotherapy. Treatments based on anti-YWHAZ strategies may thus be beneficial for UCUB patients overexpressing YWHAZ. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

(-)-Epigallocatechin-3-gallate inhibits entry of hepatitis B virus into hepatocytes.

Hepatitis B virus (HBV) is a major cause of liver disease and hepatocellular carcinoma. Chronic HBV infection is currently managed with either nucleoside/nucleotide-based or interferon-based therapies, but fails to clear infection in a substantial proportion of cases, and antiviral strategies targeting the early stages of infection are therefore required for the prevention of HBV infection. In this study, we examined some common phytochemicals and identified epigallocatechin-3-gallate (EGCG) as a new inhibitor of HBV entry. EGCG, a flavonoid present in green tea extract, belongs to the subclass of catechins. We demonstrated that EGCG at a concentration of 50µM inhibited HBV entry into immortalized human primary hepatocytes by more than 80%, whereas the other four catechins tested had much weaker inhibitory effects. DMSO-differentiated HuS-E/2 cells expressed sodium taurocholate cotransporting polypeptide (NTCP), which is a receptor for HBV. Application of EGCG during HBV inoculation markedly inhibited infection in both DMSO-differentiated HuS-E/2 cells and HA-NTCP-expressing Huh7 cells. Interestingly, EGCG induced clathrin-dependent endocytosis of NTCP from the plasma membrane followed by protein degradation. In addition, EGCG inhibited the clathrin-mediated endocytosis of transferrin. Treatment of cells with EGCG had no effect on HBV genome replication or virion secretion. Moreover, the characteristic of HBV virion and the expression of known HBV entry factors were unaltered by EGCG. Finally, the antiviral activity of EGCG on HBV entry was observed using four different genotypes, A to D. These results show that the green tea-derived molecule EGCG potently inhibits HBV entry and could be used in prevention of HBV reinfection.

A new scenario for negative functional magnetic resonance imaging signals: endogenous neurotransmission.

Functional magnetic resonance imaging (fMRI) has revolutionized investigations of brain functions. Increases in fMRI signals are usually correlated with neuronal activation, but diverse explanations have been proposed for negative fMRI responses, including decreases in neuronal activity, the vascular-steal effect, and large increases in oxygen consumption. These possible scenarios, although encompassing a wide range of potential neurovascular responses, cannot yet be used to interpret certain types of negative fMRI signals. Recent studies have found that intravenous injection of dopamine D(2) receptor (D2DR) agonist reduced the hemodynamic responses in the caudate-putamen (CPu); however, whether endogenous dopaminergic neurotransmission contributes to fMRI signals remains obscure. Since it has been suggested that the D2DR is involved in pain modulation, and the CPu shows equivocal fMRI signals during noxious stimulation, the present study established an animal model based on graded electrical stimulation to elicit different levels of nociception, and aimed to determine whether nociception-induced endogenous dopaminergic neurotransmission is sufficient to generate negative fMRI responses. Our results from cerebral blood volume (CBV)-weighted fMRI, Fos immunohistochemistry, and electrophysiological recording demonstrated a salient bilateral CBV decreases associated with heightened neuronal activity in the CPu induced by unilateral noxious electrical stimulation. In addition, preinjection of D2DR antagonist reduced the observed CBV decreases. Our findings reveal the role of the D2DR in regulating striatal vascular responses and suggest that endogenous neurotransmission-induced CBV decreases underlie negative fMRI signals. Hence, the influence of endogenous neurotransmission should be considered when interpreting fMRI data, especially in an area involved in strong vasoactive neurotransmission.