Gut Microbiome and Metabolome Alterations in Overweight or Obese Adult Population after Weight-Loss Bifidobacterium breve BBr60 Intervention: A Randomized Controlled Trial.

Probiotics, known for regulating gut microbiota, may aid those with overweight or obesity, but their mechanisms require more research. This study involved 75 overweight or obese young adults, randomly assigned to either a Bifidobacterium breve BBr60 (BBr60) group or a placebo group. Both groups received diet guidance and took either BBr60 (1 × 1010 CFU/day) or a placebo for 12 weeks. Researchers analyzed body composition, serum glucose, lipids, liver and kidney function, comprehensive metabolome, and intestinal homeostasis before and after the intervention. After 12 weeks, BBr60 significantly reduced weight and BMI compared to pretreatment levels and outperformed the placebo. The BBr60 group also showed improved blood biochemistry, with notably lower fasting blood glucose (FBG) levels than the placebo group (p < 0.05). Additionally, BBr60 influenced vital serum and fecal metabolites related to three amino acid metabolic pathways and regulated the bacteria Dialister, Klebsiella, and Bacteroides, which correlated strongly with serum metabolites. These findings indicate that BBr60 can safely and effectively regulate BMI, body weight, serum glucose, lipids, and liver function markers, which may involve BBr60's impact on key gut bacteria, which influence metabolites related to the valine, leucine, and isoleucine biosynthesis; glycine, serine, and threonine metabolism; and alanine, aspartate, and glutamate metabolism.

Rutaecarpine induces the differentiation of triple-negative breast cancer cells through inhibiting fumarate hydratase.

BACKGROUND: Triple-negative breast cancer (TNBC) is one of the most aggressive human cancers and has poor prognosis. Approximately 80% of TNBC cases belong to the molecular basal-like subtype, which can be exploited therapeutically by inducing differentiation. However, the strategies for inducing the differentiation of TNBC remain underexplored. METHODS: A three-dimensional (3D) morphological screening model based on a natural compound library was used to identify possible candidate compounds that can induce TNBC cell differentiation. The efficacy of rutaecarpine was verified using assays: RT-qPCR, RNA-seq, flow cytometry, immunofluorescence, SCENITH and label-free LC-MS/MS. The direct targets of rutaecarpine were identified through drug affinity responsive target stability (DARTS) assay. A xenograft mice model was also constructed to confirm the effect of rutaecarpine in vivo. RESULTS: We identified that rutaecarpine, an indolopyridoquinazolinone, induces luminal differentiation of basal TNBC cells in both 3D spheroids and in vivo mice models. Mechanistically, rutaecarpine treatment leads to global metabolic stress and elevated ROS in 3D cultured TNBC cells. Moreover, NAC, a scavenger of ROS, impedes rutaecarpine-induced differentiation of TNBC cells in 3D culture. Finally, we identified fumarate hydratase (FH) as the direct interacting target of rutaecarpine. The inhibition of FH and the knockdown of FH consistently induced the differentiation of TNBC cells in 3D culture. CONCLUSIONS: Our results provide a platform for differentiation therapy drug discovery using 3D culture models and identify rutaecarpine as a potential compound for TNBC treatment.

Enhanced Biogenic Sulfidation of Zero-Valent Iron in Columns: Implications for Promoting Dechlorination in Permeable Reactive Barriers.

Biogenic sulfidation of zero-valent iron (ZVI) using sulfate reducing bacteria (SRB) has shown enhanced dechlorination rates comparable to those produced by chemical sulfidation. However, controlling and sustaining biogenic sulfidation to enhance in situ dechlorination are poorly understood. Detailed interactions between SRB and ZVI were examined for 4 months in column experiments under enhanced biogenic sulfidation conditions. SRB proliferation and changes in ZVI surface properties were characterized along the flow paths. The results show that ZVI can stimulate SRB activity by removing excessive free sulfide (S2-), in addition to lowering reduction potential. ZVI also hinders downgradient movement of SRB via electrostatic repulsion, restricting SRB presence near the upgradient interface. Dissolved organic carbon (e.g., >2.2 mM) was essential for intense biogenic sulfidation in ZVI columns. The presence of SRB in the upgradient zone appeared to promote the formation of iron polysulfides. Biogenic FeSx deposition increased the S content on ZVI surfaces ∼3-fold, corresponding to 3-fold and 2-fold improvements in the trichloroethylene degradation rate and electron efficiency in batch tests. Elucidation of SRB and ZVI interactions enhances sustained sulfidation in ZVI permeable reactive barrier.

All-optically controlled beam splitting through asymmetric polarization-based holography.

All-optically controlled beam splitting is demonstrated by a tunable split ratio through polarization modulation. The beam splitters are essentially holographic gratings recorded by means of the interference of two 532 nm beams with asymmetric polarization states in an azobenzene liquid crystal film. It is found that the intensity ratio between zero and the first diffraction order is adjustable through the polarization manipulation of the recording light. An arbitrary split ratio from 0 to 1 is obtained with the photoinduced birefringence of the film being set to an appropriate value, which is independent on the polarization state of the probe light. Furthermore, the formation processes of the recorded beam splitters are contributed to the dual-grating coupling, and the tunable split ratio under various polarization conditions is discussed in terms of the Fresnel theory and Jones matrices.

Long Non-Coding MALAT1 Functions as a Competing Endogenous RNA to Regulate Vimentin Expression by Sponging miR-30a-5p in Hepatocellular Carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) has a high morbidity as well as mortality and is believed to be one of the most prevalent cancers worldwide. The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in numerous cancers, including HCC. This study aimed to explore the role of MALAT1 in HCC progression. METHODS: The expression levels of MALAT1 and Vimentin in HCC tissues and relative pair-matched adjacent normal liver tissues were analyzed by RT-PCR, and immunohistochemistry. Using bioinformatics analysis and dual-luciferase assay, we examined the correlation between MALAT1 and miR-30a-5p. Dual-luciferase assay and western blotting suggested that Vimentin was a target of miR-30a-5p. A wound healing assay and transwell assays were employed to determine the effect of MALAT1 and miR-30a-5p on cell migration and invasion in HCC. RESULTS: Our data demonstrated that the levels of MALAT1 and Vimentin were upregulated in HCC tissues and that miR-30a-5p was a direct target of MALAT1. Silenced MALAT1 and overexpressed miR-30a-5p each inhibited cell migration and invasion. Additionally, dual-luciferase assay and western blotting demonstrated that MALAT1 could competitively sponge miR-30a-5p and thereby regulate Vimentin. CONCLUSION: Our data suggest that MALAT1 acts as an oncogenic lncRNA that promotes HCC migration and invasion. Therefore, the MALAT1-miR-30a-5p-Vimentin axis is a potential therapeutic target and molecular biomarker in HCC.

Polarization modulation by means of tunable polarization gratings in an azobenzene side-chain liquid-crystalline polymer film.

Polarization modulation was achieved by means of a new type of grating recorded with two 532 nm beams at varying polarization angles in an azobenzene side-chain liquid-crystalline polymer film through light regulation instead of voltage control. In contrast to conventional polarization holographic gratings, the polarization state of the ± first-order diffracted beams of the recorded gratings depended strongly on angles between polarization directions of two recording beams, while the polarization state of the second-order diffraction remained unchanged. With the polarization angle changing from 0 to 90 deg, the ± first-order diffraction efficiency increased from 5.15% to 10.53%. Diffraction properties of the recorded gratings were attributed to the combination of polarization holographic gratings and amplitude gratings based on the calculation of Jones matrices and polarization holographic theory.

RUVBL1-ITFG1 interaction is required for collective invasion in breast cancer.

BACKGROUND: The mechanisms of breast cancer collective invasion are poorly understood limiting the metastasis therapy. The ATPase RUVBL1 is frequently overexpressed in various cancers and plays a crucial role in oncogenic process. We further investigated the role of RUVBL1 in promoting collective invasion and uncovered that targeting RUVBL1 could inhibit metastatic progression. METHODS: The expression levels of RUVBL1 and ITFG1 were examined by Western blot and qRT-PCR. Co-localization and interaction of RUVBL1 and ITFG1 were determined by immunofluorescence and co-immunoprecipitation. The invasive ability was examined by transwell assay and microfluidic assay. The metastatic and tumorigenic abilities of breast cancer cells were revealed in BALB/c nude mice by xenograft and tail vein injection. RESULTS: ATPase RUVBL1 is highly expressed in breast cancer and predicts the poor prognosis. Elevated expression of RUVBL1 is found in high metastatic breast cancer cells. Silencing RUVBL1 suppresses cancer cell expansion and invasion in vitro and in vivo. RUVBL1 interacts with a conserved transmembrane protein ITFG1 in cytoplasm and plasma membrane to promote the collective invasion. Using a microfluidic model, we demonstrated that silencing RUVBL1 or ITFG1 individually compromises collective invasion of breast cancer cells. CONCLUSION: RUVBL1 is a vital regulator for collective invasion. The interaction between RUVBL1 and ITFG1 is required for breast cancer cell collective invasion and progression. GENERAL SIGNIFICANCE: Targeting collective invasion promoted by RUVBL1-ITFG1 complex provides a novel therapeutic strategy to improve the prognosis of invasive breast cancer.

Enhanced diffraction properties of photoinduced gratings in nematic liquid crystals doped with Disperse Red 1.

Diffraction properties of photoinduced gratings recorded by overlapping two coherent beams at 532 nm in nematic liquid crystals doped with Disperse Red 1 were investigated with a probe beam at 632.8 nm. The grating was formed due to the alignment of dye molecules that leaded to the reorientation of the liquid crystal phase. The diffraction efficiency of the photoinduced grating was found to increase rapidly when the sample temperature was close to the clearing point in the nematic phase and a nearly 30-fold enhancement of the first-order diffraction efficiency was obtained. The pretransitional enhancement of the diffraction efficiency was discussed in terms of the reorientation of liquid crystals, optical nonlinearity effects and the onset of critical opalescence near the nematic-isotropic phase transition. Moreover, a peak shift of diffraction efficiency towards the lower temperature was observed with the increase of recording light intensity, which was attributed to laser induced photochemical disordering.

Effect of Endometrial Stem Cell-derived Cytokine Cocktail on a Mouse Model of Myocardial Reperfusion Injury.

Objective To study the effect of endometrial stem cells (EnSCs) derived cytokine cocktail (EdCC) on myocardial ischemic reperfusion injury (I/R) in a mouse model. Methods EdCC was concentrated from the culture medium of EnSCs with Millipore ultra-filtration technology and was administrated to a myocardial I/R mouse models through tail vein injection. The infarct area was determined by TTC/Evans Blue staining. The apoptotic cells were counted by TUNEL assay and the protein level of cleaved caspase 3 was evaluated by Western blotting. Results The EdCC extraction efficiency was (222.4±29.3) Μg/10(6) cells in every 24 h,but the protein gradually degraded under-80 ℃ storage. As compared with I/R group,100 Μg fresh EdCC decreased infarct area (P=0.001),reduced apoptotic nuclei in the infarct border (P=0.019),and inhibited cleaved caspase 3 expression (P=0.002). Increasing EdCC dosage did not further reduce the infarct area. The myocardial protective effect of EdCC diminished after 90 days' storage under-80 ℃. Conclusion EdCC reduces myocardial I/R injury through protecting cardiomyocytes from apoptosis within 30 days storage under-80 ℃.

Pinpointing Functionally Relevant miRNAs in Classical Hodgkin Lymphoma Pathogenesis.

Classical Hodgkin lymphoma (cHL) is a hematological malignancy of B-cell origin. The tumor cells in cHL are referred to as Hodgkin and Reed-Sternberg (HRS) cells. This review provides an overview of the currently known miRNA-target gene interactions. In addition, we pinpointed other potential regulatory roles of microRNAs (miRNAs) by focusing on genes related to processes relevant for cHL pathogenesis, i.e., loss of B-cell phenotypes, immune evasion, and growth support. A cHL-specific miRNA signature was generated based on the available profiling studies. The interactions relevant for cHL were extracted by comprehensively reviewing the existing studies on validated miRNA-target gene interactions. The miRNAs with potential critical roles included miR-155-5p, miR-148a-3p, miR-181a-5p, miR-200, miR-23a-3p, miR-125a/b, miR-130a-3p, miR-138, and miR-143-3p, which target, amongst others, PU.1, ETS1, HLA-I, PD-L1, and NF-κB component genes. Overall, we provide a comprehensive perspective on the relevant miRNA-target gene interactions which can also serve as a foundation for future functional studies into the specific roles of the selected miRNAs in cHL pathogenesis.

Prognostic impact of gamma-glutamyl transpeptidase to platelets ratio on hepatocellular carcinoma patients who have undergone surgery: a meta-analysis and systematic review.

Gamma-glutamyl transpeptidase to platelet ratio (GPR) is an inflammatory index and has been used as a prognostic index for a variety of tumors. However, the association between GPR and hepatocellular carcinoma (HCC) still remained controversial. Therefore, we performed a meta-analysis to determine the prognostic impact of GPR on HCC patients. PubMed, Embase, Cochrane Library, Web of Science, the Chinese National Knowledge Infrastructure, Wanfang Database, Chinese VIP Database, the US Clinical Trials Registry, and the Chinese Clinical Trials Registry were searched from inception to December 2022. A hazard ratio (HR) with a 95% confidence interval (CI) was used to evaluate the association between preoperative GPR and the prognosis of HCC patients. Ten cohort studies including 4706 HCC patients were identified. This meta-analysis showed that higher GPRs were closely related to worse overall survival (HR: 1.79; 95% CI: 1.35-2.39; P < 0.001; I2 = 82.7%), recurrence-free survival (HR: 1.30; 95% CI: 1.16-1.46; P < 0.001; I2 = 0%), and disease-free survival (HR: 1.84; 95% CI: 1.58-2.15; P < 0.001; I2 = 25.4%) in patients with HCC. This meta-analysis suggests that preoperative GPR appears to be significantly associated with the prognosis of HCC patients who have undergone surgery and may be an effective prognostic marker. Trial registration: PROSPERO: CRD42021296219.

Effect of Fe Content on Microstructure and Properties of Laser Cladding Inconel 625 Alloy.

Dilution rate is one of most important factors influencing the microstructure and performance of the laser cladding layer. In order to obtain a reasonable dilution rate in the laser cladding layer of Inconel 625 alloy, the laser cladding layers with different Fe content were prepared on the surface of 20# steel by the laser cladding technique. The influence of Fe content on the microstructure and performance of Inconel 625 alloy cladding layer was investigated. The results indicate that with the increase in Fe content in the alloy, the grain size of the cladding layer becomes coarser, the grain orientation difference increases first and then decreases, and the grain boundary angle decreases first and then increases. The hardness, high temperature wear resistance, and high temperature corrosion resistance gradually decreased. It is concluded that the dilution rate of Fe in laser cladding Inconel 625 alloy should be under 5 wt.%.

The Efficacy and Safety of Dingkun Pill in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: Dingkun Pill (DKP) is a proprietary Chinese medicine that has been utilized for patients with gynecological diseases, and its clinical application has been widely accepted in China. However, the effects of DKP on reproduction and metabolism in women with polycystic ovary syndrome (PCOS) have never been systematically evaluated. Our objective was to evaluate the efficacy and safety of DKP in treating reproductive and metabolic abnormalities with PCOS. Methods: We searched in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and Chinese Biomedical Literature Database up until January 2022 to identify randomized controlled trials (RCTs). The methodological quality of the included RCTs was estimated using the Cochrane collaboration risk-of-bias instrument, and the meta-analysis was performed using RevMan. Results: A total of 22 RCTs (including 1994 participants) were identified. DKP, combined with ovulation-inducing drugs (OID) or combined oral contraceptives (COC) was superior to OID or COC alone in improving the pregnancy rate (relative risk (RR) 1.84, 95% CI 1.62 to 2.11 and RR 1.38, 95% CI 1.16 to 1.64, respectively), ovulation rate (RR 1.38, 95% CI 1.03 to 1.84 and RR 1.23, 95% CI 1.11 to 1.37, respectively), endometrial thickness (weighted mean difference (WMD) 2.50, 95% CI 1.91 to 3.09 and WMD 0.62, 95% CI 0.08 to 1.16, respectively), luteinizing hormone (WMD -1.93, 95% CI -2.80 to-.07 and WMD -1.79, 95% CI -2.66 to-0.92, respectively), and testosterone (standardized mean difference (SMD) -2.12, 95% CI -3.01 to-1.24 and SMD -1.21, 95% CI -1.64 to-0.78, respectively). DKP combined with COC led to a greater improvement in homeostasis model assessment-ß (WMD 20.42, 95% CI 16.85 to 23.98) when compared with COC alone. There was a significant difference between DKP and COC in terms of decreasing total cholesterol (WMD -0.37, 95% CI -0.72 to-0.02), triacylglycerol (WMD -0.85, 95% CI -1.50 to-0.20), and free fatty acid (WMD -130.00, 95% CI -217.56 to-42.22). However, DKP did not affect the follicle stimulating hormone, fasting blood glucose, fasting insulin, body mass index, waist-to-hip ratio, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. Adverse reactions were more common in COC alone compared to DKP and COC in combination (RR 0.22, 95% CI 0.07 to 0.63). Conclusion: DKP shows promise in modifying reproductive and metabolic parameters in patients with PCOS and may be used as a primary choice in conventional or complementary therapies for PCOS. The quality of the evidence analyzed was suboptimal, and therefore, our results should be interpreted cautiously. More prospective large-scale and well-designed RCTs, as well as longer intervention durations are required in the future to draw more reliable conclusions.

Chinese herbal medicine for the treatment of chronic fatigue syndrome: A systematic review and meta-analysis.

Objectives: This meta-analysis aimed to assess the effectiveness and safety of Chinese herbal medicine (CHM) in treating chronic fatigue syndrome (CFS). Methods: Nine electronic databases were searched from inception to May 2022. Two reviewers screened studies, extracted the data, and assessed the risk of bias independently. The meta-analysis was performed using the Stata 12.0 software. Results: Eighty-four RCTs that explored the efficacy of 69 kinds of Chinese herbal formulas with various dosage forms (decoction, granule, oral liquid, pill, ointment, capsule, and herbal porridge), involving 6,944 participants were identified. This meta-analysis showed that the application of CHM for CFS can decrease Fatigue Scale scores (WMD: -1.77; 95%CI: -1.96 to -1.57; p < 0.001), Fatigue Assessment Instrument scores (WMD: -15.75; 95%CI: -26.89 to -4.61; p < 0.01), Self-Rating Scale of mental state scores (WMD: -9.72; 95%CI:-12.26 to -7.18; p < 0.001), Self-Rating Anxiety Scale scores (WMD: -7.07; 95%CI: -9.96 to -4.19; p < 0.001), Self-Rating Depression Scale scores (WMD: -5.45; 95%CI: -6.82 to -4.08; p < 0.001), and clinical symptom scores (WMD: -5.37; 95%CI: -6.13 to -4.60; p < 0.001) and improve IGA (WMD: 0.30; 95%CI: 0.20-0.41; p < 0.001), IGG (WMD: 1.74; 95%CI: 0.87-2.62; p < 0.001), IGM (WMD: 0.21; 95%CI: 0.14-0.29; p < 0.001), and the effective rate (RR = 1.41; 95%CI: 1.33-1.49; p < 0.001). However, natural killer cell levels did not change significantly. The included studies did not report any serious adverse events. In addition, the methodology quality of the included RCTs was generally not high. Conclusion: Our study showed that CHM seems to be effective and safe in the treatment of CFS. However, given the poor quality of reports from these studies, the results should be interpreted cautiously. More international multi-centered, double-blinded, well-designed, randomized controlled trials are needed in future research. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022319680], identifier [CRD42022319680].

Therapeutic effect and safety of curcumin in women with PCOS: A systematic review and meta-analysis.

Background: Polycystic ovary syndrome (PCOS) is a multi-factorial heterogeneous syndrome that has both adverse reproductive and metabolic implications for affected women and its management is a challenging clinical problem. Curcumin, as a phenolic compound with potent anti-inflammatory and antioxidant properties exerting positive effects on the lipid profile and insulin resistance, appears to be a valuable treatment regimen for patients with PCOS. Objective: This study aimed to evaluate the efficacy and safety of curcumin in the treatment of PCOS. Methods: Chinese databases (Chinese National Knowledge Infrastructure, China Biology Medicine Databases, VIP database, Wanfang Database, and Chinese Clinical Trial Registry) and English databases (PubMed, Web of Science, Embase, Cochrane Library, Scopus and Clinical trials) were thoroughly investigated through screening randomized controlled trials on curcumin in PCOS published from the date of inception to May 2022. Standardized data search and abstraction were conducted following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. Quantitative and qualitative analyses were performed. Heterogeneity was assessed using I2 statistics. Results: A total of 447 patients from seven randomized controlled trials were included in the meta-analysis. Results showed that the ingestion of curcumin decreased body mass index (WMD -0.267, 95% CI -0.450 to -0.084, P = 0.004, I2 = 0.0%), fasting plasma glucose (WMD -3.618, 95% CI -5.165 to -2.071, P < 0.001, I2 = 20.4%), insulin (WMD -1.834, 95% CI -2.701 to -0.968, P < 0.001, I2 = 8.4%), homeostatic model assessment for insulin resistance (WMD -0.565, 95% CI -0.779 to -0.351, P < 0.001, I2 = 0.0%), total cholesterol (WMD -15.591, 95% CI -27.908 to -3.273, P = 0.013, I2 = 68.9%), C-reactive protein (WMD -0.785, 95% CI -1.553 to -0.017, P = 0.045, I2 = 23.9%), and increased the quantitative insulin sensitivity check index (WMD 0.011, 95% CI 0.005 to 0.017, P = 0.001, I2 = 39.6%). As for safety, the treatment group did not cause significant adverse reactions than that in the control group. Conclusion: In light of presented findings, curcumin has beneficial effects on serum markers of inflammation, weight loss and glucose and lipid metabolism in patients with PCOS. The incidence of adverse reactions does not increase with the application of curcumin. However, a larger, more definitive study is needed to further investigate these results. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022332394.

Nuclear Aurora kinase A switches m6A reader YTHDC1 to enhance an oncogenic RNA splicing of tumor suppressor RBM4.

Aberrant RNA splicing produces alternative isoforms of genes to facilitate tumor progression, yet how this process is regulated by oncogenic signal remains largely unknown. Here, we unveil that non-canonical activation of nuclear AURKA promotes an oncogenic RNA splicing of tumor suppressor RBM4 directed by m6A reader YTHDC1 in lung cancer. Nuclear translocation of AURKA is a prerequisite for RNA aberrant splicing, specifically triggering RBM4 splicing from the full isoform (RBM4-FL) to the short isoform (RBM4-S) in a kinase-independent manner. RBM4-S functions as a tumor promoter by abolishing RBM4-FL-mediated inhibition of the activity of the SRSF1-mTORC1 signaling pathway. Mechanistically, AURKA disrupts the binding of SRSF3 to YTHDC1, resulting in the inhibition of RBM4-FL production induced by the m6A-YTHDC1-SRSF3 complex. In turn, AURKA recruits hnRNP K to YTHDC1, leading to an m6A-YTHDC1-hnRNP K-dependent exon skipping to produce RBM4-S. Importantly, the small molecules that block AURKA nuclear translocation, reverse the oncogenic splicing of RBM4 and significantly suppress lung tumor progression. Together, our study unveils a previously unappreciated role of nuclear AURKA in m6A reader YTHDC1-dependent oncogenic RNA splicing switch, providing a novel therapeutic route to target nuclear oncogenic events.

Prognostic Value of the Glasgow Prognostic Score on Overall Survival in patients with Advanced Non-Small Cell Lung Cancer.

Background: Findings from previous studies regarding the association between the Glasgow Prognostic Score (GPS) and overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) were limited. This study aimed to investigate the prognostic value of GPS in patients with advanced NSCLC after adjusting for potential confounding factors. Methods: A retrospective cohort study was conducted in 494 patients with advanced NSCLC between 2009 and 2019. Clinicopathological characteristics (including GPS) were analyzed to determine predictors of OS using univariate and multivariate Cox proportional hazards models. Survival curves were estimated using the Kaplan-Meier method. Results: Of the enrolled patients with advanced NSCLC, 66.46% were men and 53.85% were aged <60 years. The percentages of GPS scores of 0, 1, and 2 were 36.44%, 36.03%, and 27.53%, respectively. The median OS of the GPS 0, 1, and 2 groups were 23.27, 14.37, and 10.27 months, respectively (log-rank P <0.0001). A higher GPS was independently associated with an increased risk of death (P for trend = 0.0004) after full adjustment for potential confounders. The risk of death increased by 77% in the GPS 1 group (hazard ratio [HR]=1.77, 95% confidence interval [CI]=1.22-2.57, P=0.0027) and 109% in the GPS 2 group (HR=2.09, 95%CI=1.36-3.22, P=0.0008) compared with the GPS 0 group after adjustment. We did not find significant heterogeneity among the analyzed subgroups apart from sex (P interaction=0.017). Conclusion: High pretreatment GPS is independently associated with worse OS in patients with advanced NSCLC. GPS should be considered in patient counseling and decision-making and needs to be further validated by large-cohort and prospective studies.

The Effects of Traditional Chinese Medicine-Associated Complementary and Alternative Medicine on Women with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a touchy clinical and public health problem worldwide, which adversely affects women's health and health-related comorbidities for lifetime, and represents a tremendous burden for both the family of the patient and for society. According to the diagnostic criteria used and the population studied, the prevalence rate of PCOS is between 6% and 21%. However, current conventional modern medicines for PCOS are only moderately effective at controlling the signs and symptoms, while they are not thoroughly able to prevent complications. Therefore, many patients have turned to complementary and alternative medical (CAM) treatments. CAM use is wide spread among patients with PCOS, and more than 70% of patients use CAM at one point during their diseases. The patients' primary motivations include dissatisfaction with available medications, perceive higher risk of drug side effects and crushing health burden and economic costs, desire for symptom relief, pursuit of shortening the course of disease, and the belief that CAM therapy is in accordance with the patients' values and beliefs. At present, several CAM methods have been used in women with PCOS, which has achieved obvious effects. However, biologically plausible mechanisms of the action of traditional Chinese medicine- (TCM-) associated CAM for PCOS have not been systematically reviewed. This review briefly summarizes the current progress of the impact of herbal medicine on the outcomes of PCOS and introduces the mechanisms.

Effects of Tea Consumption on Anthropometric Parameters, Metabolic Indexes and Hormone Levels of Women with Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: Our aim was to conduct a systematic review and meta-analysis to assess the effectiveness and safety of tea supplements for patients with polycystic ovary syndrome (PCOS). Methods: We conducted searches of the published literature in PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure (CNKI), VIP database, and Wanfang Database in 1985 to September 2021. Data from randomized controlled trials (RCTs) were obtained to assess the effects of tea versus placebo in women with PCOS. Weighted mean differences (WMDs) were pooled using a random-effects model or risks ratios (RRs) using a random-effects model. Results: Six RCTs (235 participants) were included in our systematic review. Tea supplements as adjuvant therapy led to greater improvement in body weight (WMD -2.71, 95% CI -4.95 to -0.46, P = 0.02, I2 = 0%), fasting blood glucose (FBG: WMD -0.40, 95% CI -0.59 to -0.20, P < 0.0001, I2 = 0%) and fasting insulin (FINS: WMD -3.40, 95% CI -4.76 to -2.03, P < 0.00001, I2 = 0%) when compared with placebo. There were no significant differences of body mass index, waist circumference, hip circumference, waist-to-hip ratio (WHR), body fat rate, total testosterone, free testosterone (FT), dehydroepiandrosterone, luteinizing hormone or follicular-stimulating hormone (FSH) between the two groups. In addition, subgroup analysis suggested that green tea was effective on body weight, FINS, FBG, FT, and FSH, and herbal tea can also reduce FT levels, tea supplements had a significant impact on FBG and FSH in trials with intervention duration ≥ 3 months, and intervention lasting less than 3 months can improve FINS. Tea had significant effect on reducing WHR, FBG and FSH in Asian PCOS patients, but not in Caucasians. And there was no statistically significant effect of tea on weight and FINS in Asians, but it was effective for Caucasian participants. Compared with placebo, tea supplements did not cause significant adverse reactions (RR 1.45, 95% CI 0.30 to 6.90, P = 0.65, I2 = 0%). Conclusion: This meta-analysis suggests that consumption of tea supplementation in women with PCOS could significantly decrease the levels of FBG and FINS as well as reduce body weight. Especially green tea, not only has the above effects, but also has a significant effect on improving a variety of reproductive hormone indexes. Furthermore, tea supplementation is a relatively safe therapy for PCOS patients. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=212755, identifier CRD42021249196.

Downregulation of miR-146b-5p via iodine involvement repressed papillary thyroid carcinoma cell proliferation.

miR-146b-5p is overexpressed in papillary thyroid carcinoma (PTC) and is thought to be a related diagnostic marker. Previous studies have indicated the effects of iodine on oncogenic activation. However, the effect of iodine on the proliferation of PTC cells and the associated underlying mechanisms remain unclear. We found that miR-146b-5p was downregulated and smad4 was upregulated in patients exposed to high iodine concentration by in situ hybridisation (ISH) and immunohistochemical (IHC). NaI (10-3 M) treatment downregulated miR-146b-5p and upregulated Smad4 in PTC cell lines. Luciferase assay was used to confirm that Smad4 is a target of miR-146b-5p. Furthermore, MTT assay and cell cycle analysis indicated that 10-3 M NaI suppressed cell proliferation and caused G0/G1 phase arrest. Real-time PCR and Western blotting demonstrated that 10-3 M NaI increased p21, p27, and p57 levels and reduced cyclin D1 levels in PTC cells. Our findings suggest that 10-3 M NaI increases Smad4 levels through repression of miR-146b-5p expression, curbing the proliferation in PTC.