Efficacy and safety of EGFR-TKIs in combination with angiogenesis inhibitors as first-line therapy for advanced EGFR-mutant non-small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: For patients with advanced non-small-cell lung cancer (NSCLC) with EGFR mutations, the suggested course of action is epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Even with a high disease control rate, a majority of patients develop acquired EGFR-TKIs resistance and eventually advance. To increase the benefits of treatment, clinical trials are increasingly exploring the value of EGFR-TKIs combined with angiogenesis inhibitors as a first-line treatment in advanced NSCLC carrying EGFR mutations. METHOD: Using PubMed, EMBASE and Cochrane Library, to locate published full-text articles in print or online, a thorough literature search was done from the database's inception to February 2021. Additionally, oral presentation RCTs from ESMO and ASCO were obtained. We sifted out RCTs that used EGFR-TKIs along with angiogenesis inhibitors as first-line therapy for advanced EGFR-mutant NSCLC. ORR, AEs, OS, and PFS were the endpoints. Review Manager version 5.4.1 was used for data analysis. RESULTS: One thousand eight hundred twenty-one patients were involved in 9 RCTs. According to the results, combining EGFR-TKIs with angiogenesis inhibitors therapy prolonged PFS of advanced EGFR-mutation NSCLC patients on the whole [HR:0.65 (95%CI: 0.59~0.73, P<0.00001)]. No significant statistical difference was identified between the combination group and single drug group in OS(P=0.20) and ORR (P=0.11). There are more adverse effects when EGFR-TKIs are used in combination with angiogenesis inhibitors than when used alone. CONCLUSION: The combination of EGFR-TKIs and angiogenesis inhibitors prolonged PFS in patients with EGFR-mutant advanced NSCLC, but the OS and ORR benefit was not significant, and the risk of adverse events was higher, more pronounced with hypertension and proteinuria; PFS in subgroups suggested that the combination was associated with better PFS in the smoking, liver metastasis, and no brain metastasis groups, and the included studies suggested that the smoking group , liver metastasis group, and brain metastasis group may have a potential OS benefit.

Global trends in polycystic ovary syndrome research: A 10-year bibliometric analysis.

Background: Polycystic ovary syndrome (PCOS) is one of the most common reproductive metabolic disorders in women, significantly affecting the biological functionalities of ovaries. This disease has garnered enormous interest from researchers. However, there is a lack of a comprehensive research concerning assessing the current status and future trends in PCOS field. This study uses bibliometric tools to comprehensively analyze the PCOS-related research progress based on the literature in the past decade. Methods: The reported PCOS literature in the past decade is downloaded from the Web of Science database. The bibliometric software is applied to analyze the co-authorship, co-citation, and co-occurrence status. Results: A total of 9936 publications imported into bibliometric tools for analysis show a sharp increase in the annual citations. The USA is dominant in terms of contribution in the field of PCOS, while China is making a significant contribution to the advancement of this field. Monash University is the most prolific institution with the highest H-index value. The contribution of University of Adelaide must be acknowledged. Legro RS and Teede HJ are the most active and influential authors in recent times, while Azziz R is the most contributed pioneer in this field. The Journal of Clinical Endocrinology & Metabolism is the most active journal with the highest number of publications and citations. The pathogenesis of PCOS had been a long-term forefront of research. In recent years, the health management in PCOS prevention and long-term complications was attracting more and more attention. The keywords like "gut microbiota", "microRNAs", "apoptosis", "Myo-inositol", "TNF-alpha", "androgen receptor", and "Vitamin D-deficient" are considered the latest research topics. Conclusion: The study comprehensively analyzes the current status and global trends in the PCOS field, providing a significant reference for researchers to explore this field effectively.

Design, synthesis, and biological evaluation of benzo[b]thiophene 1,1-dioxide derivatives as potent STAT3 inhibitors.

As a member of the signal transducer and activator of transcription (STAT) family, STAT3 plays a critical role in several biological pathways such as cell proliferation, migration, survival, and differentiation. Due to abnormal continuous activation in tumors, inhibition of STAT3 has emerged as an attractive approach for the treatment of various cancer cells. Herein, we report a series of novel STAT3 inhibitors based on benzo[b]thiophene 1,1-dioxide scaffold and evaluated their anticancer potency. Among them, compound 8b exhibited the best activity against cancer cells. Compound 8b induced apoptosis and blocked the cell cycle. Meanwhile, 8b reduced intracellular ROS content and caused the loss of mitochondrial membrane potential. Further research revealed that 8b significantly blocked STAT3 phosphorylation and STAT3-dependent dual-luciferase reporter gene experiments showed that compound 8b has a marked inhibition of STAT3-mediated Firefly luciferase activity. Molecular modeling studies revealed compound 8b occupied the pocket well with the SH2 domain in a favorable conformation.

Untargeted metabolomics approach (UPLC-Q-TOF-MS) explores the biomarkers of serum and urine in overweight/obese young men.

BACKGROUND AND OBJECTIVES: Obesity is linked to metabolic diseases characterized by insulin resistance, such as diabetes and cardiovascular disease. In this study, we investigated the metabolic disorders of uncomplicated obesity to identify early alterations in biological systems. METHODS AND STUDY DESIGN: Metabolic differences between overweight/obese (n=36) and normal-weight (n=35) young Chinese men without known metabolic disorders were assessed. Metabolic profiling of the serum and urine was performed using ultra-performance liquidchromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Partial least squares discriminant analysis (PLS-DA) was undertaken to reveal and classify the differences between the two groups. RESULTS: Compared to normal-weight men, obese men had higher levels of the serum metabolites phenylalanine, Phe-Phe, and L-tryptophan, whereas those of p-cresol sulfate and p-cresol were less in obesity. Urinary metabolites phenylacetamide, L-glutamine, phenylacetylglutamine, indoxyl sulfate, p-cresol, and p-cresol sulfate were greater in obese men. CONCLUSIONS: These findings indicate that disorders involving aromatic amino acids and the tricarboxylic acid cycle (TCA) have microbiomic involvement in the uncomplicated phase of obesity.

The Screening of Genes Sensitive to Long-Term, Low-Level Microwave Exposure and Bioinformatic Analysis of Potential Correlations to Learning and Memory.

OBJECTIVE: To gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfunction. METHODS: Mice were exposed to whole body 2100 MHz microwaves with specific absorption rates (SARs) of 0.45 W/kg, 1.8 W/kg, and 3.6 W/kg for 1 hour daily for 8 weeks. Differentially expressing genes in the brains were screened using high-density oligonucleotide arrays, with genes showing more significant differences further confirmed by RT-PCR. RESULTS: The gene chip results demonstrated that 41 genes (0.45 W/kg group), 29 genes (1.8 W/kg group), and 219 genes (3.6 W/kg group) were differentially expressed. GO analysis revealed that these differentially expressed genes were primarily involved in metabolic processes, cellular metabolic processes, regulation of biological processes, macromolecular metabolic processes, biosynthetic processes, cellular protein metabolic processes, transport, developmental processes, cellular component organization, etc. KEGG pathway analysis showed that these genes are mainly involved in pathways related to ribosome, Alzheimer's disease, Parkinson's disease, long-term potentiation, Huntington's disease, and Neurotrophin signaling. Construction of a protein interaction network identified several important regulatory genes including synbindin (sbdn), Crystallin (CryaB), PPP1CA, Ywhaq, Psap, Psmb1, Pcbp2, etc., which play important roles in the processes of learning and memorye. CONCLUSION: Long-term, low-level microwave exposure may inhibit learning and memory by affecting protein and energy metabolic processes and signaling pathways relating to neurological functions or diseases.

Dynamic changes of early-stage aortic lipid deposition in chronic renal failure rats and effects of decorin gene therapy.

The aim of the present study was to clarify the association between lipid metabolism and the atherosclerosis in early-stage chronic renal failure at the molecular level and to explore the efficacy of decorin on chronic renal failure. Sprague Dawley rats receiving 5/6 nephrectomy and Sham surgery were divided into control and experimental groups. Sprague Dawley rats receiving 5/6 nephrectomy were divided into control and experimental groups, and the experimental group was further subdivided into rats receiving treatment with fibroblasts (FBs) transfected either with empty vector and with a decorin (DCN) gene. The dynamic levels of triglyceride (TG), total cholesterol (T-Ch) and total phospholipid (T-PL) were detected on the 10th, 30th and 60th days. The body weight, blood lipid levels, renal function and renal tissue were observed after four weeks, and transforming growth factor-ßl and protein expression was detected by immunohistochemistry. In total, 4 weeks after treatment, the DCN expression in the renal tissue of rats treated with DCN-transfected FBs was significantly increased compared to that in the control rats. The results showed that the levels of the three lipids in the aortic arches were slightly elevated on the 10th day compared with those in the control group, and the TG level was significantly increased on the 30th day. The levels of T-Ch, TG and T-PL in the aortic arches were significantly elevated on the 60th day. The TG and T-Ch levels in the plasma and aortic tissues of Sprague Dawley rats receiving 5/6 nephrectomy without any treatment and after receiving treatment with FBs transfected with empty vector were significantly increased compared with those in the control group. The increased T-Ch and decreased T-PL levels in the erythrocyte membrane increased the rigidity of the erythrocyte and decreased erythrocyte deformability. In conclusion, highly expressed DCN mitigated renal fibrosis and thus delayed renal failure as well as mitigating the abnormal lipid metabolism of the chronic renal failure.

[A literature review on Chinese medicine syndrome and syndrome elements of chronic fatigue syndrome].

OBJECTIVE: To research the distribution characteristics of Chinese medicine (CM) syndrome and syndrome elements of chronic fatigue syndrome (CFS) by analyzing literature in recent 20 years. METHODS: Relevant literature on treating CFS by syndrome differentiation of CM at home were retrieved by computer and manual ways. Database were established by using EpiData 3.1 to conduct frequency analysis of syndrome and syndrome elements. RESULTS: The most common clinical syndromes were Xin-Pi deficiency syndrome, Gan stagnation Pi deficiency syndrome, Gan-Shen yin deficiency syndrome, Gan qi stagnation syndrome, and Pi-Wei qi deficiency syndrome. Disease locations were sequenced as Pi, Gan, Shen, and Xin. The clinical pathogenesis of CFS was characterized by deficiency of vital energy, complicated with intermingled excess and deficiency. Asthenia of healthy energy was mainly manifested as qi deficiency, blood deficiency, and yin deficiency, while excess of sthenia was mainly manifested as qi stagnation, phlegm dampness, and static blood. CONCLUSIONS: Research of CM syndrome starting from syndrome elements can better unify and standardize clinical syndrome differentiation. Results of literature analysis can provide reference for further studies.

Association between MDM2 promoter SNP309 T/G polymorphism and liver cancer risk - a meta-analysis.

BACKGROUND: Many studies have investigated the association between the MDM2 promoter SNP309 T/G polymorphism and liver cancer risk, but inconsistencies make drawwing definitive conclusions difficult. METHODS: We therefore searched main databases for articles relating MDM2 SNP309 T/G polymorphism to risk of liver cancer in humans and estimated summary odds ratio (OR) with 95% confidence intervals (95% CI) to assess the possible association in a meta-analysis. RESULTS: The main analysis revealed no significant heterogeneity, and the pooled ORs of fixed-effects were all significant (for G versus T, OR = 1.59, 95% CI 1.42-1.78; for GG versus TT, OR = 2.45, 95% CI 1.93-3.12; for GT versus TT, OR = 1.70, 95% CI 1.38-2.09; for GG versus GT, OR = 1.49, 95% CI 1.24-1.79; for GG and GT versus TT, OR = 1.95, 95% CI 1.61-2.38; for GG versus TT and GT, OR = 1.73, 95% CI 1.46-2.07). Subgroup analyses by ethnicity and sensitivity analyses both showed associations to remain significant. CONCLUSION: The present meta-analysis of available data showed a significant association between the MDM2 SNP309 T/G polymorphism and liver cancer risk, the MDM2 SNP309 G allele contributing to increased risk in both Asians and Caucasians in a graded, dose-dependent fashion.

[Effects of long-term fertilization on pH buffer system of sandy loam calcareous fluvor-aquic soil].

Soil samples (0-80 cm) were collected from a 30-year fertilization experimental site in Xuzhou, Jiangsu Province of East China to study the variations of the pH, calcium carbonate and active calcium carbonate contents, and pH buffer capacity of sandy loam calcareous fluvor-aquic soil under different fertilization treatments. Thirty-year continuous application of different fertilizers accelerated the acidification of topsoil (0-20 cm), with the soil pH decreased by 0.41-0.70. Under different fertilization, the soil pH buffer capacity (pHBC) varied from 15.82 to 21.96 cmol x kg(-1). As compared with no fertilization, single N fertilization decreased the pHBC significantly, but N fertilization combined with organic fertilization could significantly increase the pHBC. The soil pHBC had significant positive correlations with soil calcium carbonate and active calcium carbonate contents, but less correlation with soil organic matter content and soil cation exchange capacity, suggesting that after a long-term fertilization, the sandy loam calcareous fluvor-aquic soil was still of an elementary calcium carbonate buffer system, and soil organic matter and cation exchange capacity contributed little to the buffer system. The soil calcium carbonate and active calcium carbonate contents were greater in 0-40 cm than in 40-80 cm soil layer. Comparing with soil calcium carbonate, soil active calcium carbonate was more sensitive to reflect the changes of soil physical and chemical properties, suggesting that the calcium carbonate buffer system could be further classified as soil active calcium carbonate buffer system.

Bis{2-[2-(isopropyl-ammonio)ethyl-imino-meth-yl]-6-methoxy-phenolato}nickel(II) dithio-cyanate.

The title complex, [Ni(C(13)H(20)N(2)O(2))(2)](NCS)(2), consists of a centrosymmetric mononuclear four-coordinate nickel(II) complex cation and two thio-cyanate anions. The Ni atom is located on an inversion center and is coordinated by two phenol O atoms and two imine N atoms from two equivalent Schiff base ligands, in a square-planar geometry. In the crystal structure, the amino H atoms are involved in N-H⋯O hydrogen bonds with the phenol and meth-oxy O atoms of the ligand, and in N-H⋯N hydrogen bonds with the N atoms of the thio-cyanate anions, which sit above and below the Ni atom.

3,4-Dihydr-oxy-N'-(2-hydroxy-benzyl-idene)benzohydrazide-methanol-water (2/1/3).

The asymmetric unit of the title compound, C(14)H(12)N(2)O(4)·0.5CH(4)O·1.5H(2)O, consists of two Schiff base mol-ecules, three water mol-ecules and one methanol mol-ecule. The dihedral angle between the two benzene rings is 7.8 (2)° in one of the mol-ecules and 4.0 (2)° in the other. Intra-molecular O-H⋯O and O-H⋯N hydrogen bonds are observed. Mol-ecules are linked into a three-dimensional network by O-H⋯O and N-H⋯O inter-molecular hydrogen bonds.

Combined human growth hormone and lactulose for prevention and treatment of multiple organ dysfunction in patients with severe chronic hepatitis B.

AIM: To evaluate the efficiency and safety of combined recombinant human growth hormone (rhGH) and lactulose for treatment and/or prevention of multiple organ dysfunction in patients with chronic severe hepatitis B. METHODS: Forty-eight inpatients with chronic severe hepatitis B were randomly divided into rhGH group (n=28) and control group (n=20). In rhGH group, 4-4.5 IU of rhGH was injected intramuscularly once daily for 2-4 wk, and 100 mL of enema containing 30 mL of lactulose, 2 g of metronidazole and 0.9% saline was administered every 2 d for 2-4 wk. Their symptoms and complications were noted. Liver and kidney functions were analyzed by an Olympus analyzer. Serum GH, IGF-1, IGFBP1 and IGFBP3 were measured by ELISA. RESULTS: Clinical symptoms of 90% of these patients in rhGH group were obviously improved. The total effectiveness in rhGH group was better than that in control group (75% vs 40%, P<0.05). After 2- and 4-wk treatment of rhGH respectively, serum albumin (26.1+/-4.1 vs 30.2+/-5.3, 31.9+/-5.1 g/L), prealbumin (79.6+/-28.0 vs 106.6+/-54.4, 108.4+/-55.0 g/L), cholesterol (76.3+/-16.7 vs 85.6+/-32.3, 96.1+/-38.7 mg/dL), and IGFBP1 (56.8+/-47.2 vs 89.7+/-50.3 ng/mL after 2 wk) were significantly increased compared to control group (P<0.05). However, serum GH was decreased. The increase of serum IGF1 and IGFBP3 after rhGH treatment was also observed. CONCLUSION: rhGH in combination with lactulose may be beneficial to the prevention and treatment of multiple organ dysfunction in patients with chronic severe hepatitis.

[Effects of 2450 MHz microwave on long-term potentiation of hippocampus and lipofuscin contents in rat brain].

OBJECTIVE: To study the mechanism of the effects of microwave on learning and memory. METHOD: Long-term potentiation (LTP) of hippocampus induced potential and lipofuscin content in rat brain were studied. After irradiated by a 2450 MHz microwave, rats hippocampus induced potential in vivo was recorded and lipofuscin content in the brain was measured by fluorospectrophotometry. RESULT: Continuous microwave with 10-25 mW/cm2 intensity could inhibit the amplitude of the population spike (PS) of weak and strong stimuli induced LTP with an intensity-effect relationship. At 25 mW/cm2, lipofuscin content was significantly higher than control and 10 mW/cm2 group (P<0.05). CONCLUSION: Continuous microwave with 10-25 mW/cm2 intensity impairs learning and memory by restraining hippocampus LTP and brain lipofuscin content.

[Effects of microwave irradiation on ATPase activity and voltage dependent ion channel of rat hippocampus cell membrane].

OBJECTIVE: To study the effect of microwave irradiation on hippocampus cell. METHOD: Changes of ATPase activity and voltage dependent ion channel of hippocampus cell membrane were observed in mice exposed to 2 450 MHz microwave irradiation of 10 mW/cm2 from a physical therapy machine. Histochemical method and patch clamp method were used to determine the activity of Na+, K(+)-ATPase, Ca2+, Mg(2+)-ATPase and voltage dependent Na+, K+, Ca2+ channels respectively. RESULT: 1) Na+, K(+)-ATPase activity of microwave irradiated mice showed no significant change as compared with the control, but the activity of Ca2+, Mg(2+)-ATPase decreased significantly (P< 0.05); 2) In microwave irradiated mice, Na+, K+, Ca2+, current inducement rate in hippocampus neuron decreased significantly, the membrane voltage of Na+ current peak shifted to depolarization, and the attenuation rate of Na+ current and current A inducement rate decreased significantly as compared with control mice. CONCLUSION: Irradiation of 2 450 MHz microwave at a doze of 10 mW/cm2 was not fatal to mice hippocampus cell. But Ca2+, Mg(2+)-ATPase activity of hippocampal cell membrane and voltage dependent Na+, K+, Ca2+ ion channel of hippocampal nervous were affected which would affect study and memory.