Objective To explore the intrinsic relationship between circadian clock and cell cycle in osteoarthritis(OA)chondrocytes,especially the regulation of cell cycle-related genes by the clock gene Bmal1.Methods The chondroid ATDC5 cells induced by insulin-transfering-selenium(ITS)were divided into control group,OA group and LV-Bmal1 group.The cell viability of each group was detected by CCK8 method.The expression of Bmal1,Per1,Wee1,Cdk1,Ccnb1 and Mmp13 mRNA in each group was detected by RT-qPCR.The expression of BMAL1,PER1,WEE1,CDK1,CCNB1 and MMP13 protein in each group was detected by Western blot.The effects of Bmal1 on different stages of cell cycle and apoptosis was analyzed by flow cytometry.The regulation of Bmal1 on Per1,Wee1,Cdk1,Ccnb1 and Mmp13 and their roles in OA were analyzed.Results Compared with the normal group,the cell viability of the OA group was increased,the relative mRNA expression of Bmal1 and Wee1 in the OA group decreased,and the relative mRNA expression of Per1,Cdk1,Ccnb1 and Mmp13 increased signif-icantly.The cell viability of LV-Bmal1 group decreased,the relative expression of Bmal1 and Wee1 mRNA in-creased,and the relative expression of Per1,Cdk1,Ccnb1 and Mmp13 mRNA decreased(P＜0.05).Correlation analysis showed that Bmal1 was positively correlated with Wee1 and they were negatively correlated with Per1,Cdk1,Ccnb1 or Mmp13.The results of Western blot showed that protein expression in different groups were con-sistent with the trend of PCR.The results of cell cycle and apoptosis showed that compared with the normal group,the S phase and G2/M phase of the OA group were shortened,the proportion of cells decreased significantly,and the proportion of early and late apoptosis increased.The S phase and G2/M phase of the LV-Bmal1 group were prolonged,the proportion of cells was increased,and the proportion of early and late apoptosis was decreased.Conclusions Circadian clock gene Bmal1 in inflammatory chondrocytes might regulate the expression of cell cycle-related genes.

Objective To retrospectively analyze the clinical data of 47 young NSCLC patients mutation style of EGFR and PD-L1 expression in tumor cells, to understand their clinicopathological and molecular characteristics. Methods We enrolled 47 young (≤40 years old) patients confirmed as NSCLC who underwent surgical resection, and 94 old patients (≥60 years old) were matched as 1:2 by R language. EGFR mutation status was detected by ARMS-PCR, and the expression of PD-L1 was detected by immunohistochemistry. Results The median age of 47 young patients with NSCLC was 37 years old. The disease was more common in women and the majority type was adenocarcinoma. In youth group, the 19del and 20ins were more frequent, but the exon 21 L858R point mutation proportion was higher in elder group. The expression of PD-L1 was significantly increased in the solid predominant histological subtype. The PD-L1 expression in 19del patients was higher than that in the patients with L858R mutation in youth group. Conclusion The majority of young NSCLC patients are female, nonsmokers and suffered from adenocarcinoma cancer. The proportion of EGFR alteration in 19del and 20ins in youth group is higher than that in elder group. The positive rate of PD-L1 expression in solid predominant histological subtype is higher than that with other subtypes. The expression of PD-L1 in young patients with EGFR 19del is higher than that with L858R.

Objective:To evaluate the quality of the current foreign clinical practice guidelines (CPG) on obstetric venous thromboembolism (VTE), providing reference for standardizing the prevention and treatment of domestic VTE clinical practice.Methods:The GPGs for the management of obstetric VTE published abroad from inception to July 2020 were electronically searched. Two researchers independently evaluated the quality of the included guidelines in accordance with the internationally recognized guideline evaluation tool, AGREE Ⅱ.Results:A total of 12 guidelines, 2 recommendations and 1 consensus for obstetric VTE were included, covering 3 continents and 9 countries, and the published time span was 2009-2020. The standardized scores of the six domain (scope & purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability and editorial independence) included in the guidelines were: 99.44%, 62.78%, 70.35%, 95.74%, 68.80% and 76.94% respectively, and the scores in each domain were ≥ 50.00%, indicating that the included CPGs were of good quality. Except for the domain scope & purpose, the ranges of the other five domains were ≥ 50.00%, suggesting that the quality of the CPGs differed significantly. Among the 15 included CPGs, 4 CPGs were level A (recommended), 11 CPGs were level B (recommended after being revised), and there was no CPG in level C (not recommended). The difference in the recommended content of obstetric VTE management mainly focused on the risk assessment, drug type, dosage and period.Conclusions:The overall quality of the CPGs for obstetric VTE management is high, while the quality of the CPGs varies greatly. In addition, there are differences in the recommended content of obstetric VTE management. More high-quality researches are required to provide evidence-based support for the improvement of the CPGs.

BACKGROUND: Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid growth, early metastasis and acquired therapeutic resistance, and the prognosis is extremely poor. Studies have proved that the stem cell marker CD44 is correlated with tumor recurrence and treatment resistance, however, there are limited reports yet concerning on the CD44 expression and its clinical prognostic significance in SCLC patients. The purpose of this study is to investigate the expression of CD44 in tumor tissues as well as serum of SCLC patients and explore its correlation with the clinical characteristics, therapeutic effect and prognosis. METHODS: The tumor tissues and serum samples of 47 newly diagnosed SCLC patients were collected. Immunohistochemistry and enzyme-linked immunosorbent assay were applied to detect CD44. The relationship between CD44 level and the clinical characteristics as well as prognosis of the patients was analyzed. RESULTS: The stem cell marker CD44 was detectable both in serum sample and tumor tissue of SCLC patients. The positive rate of CD44 in tumor tissue was significantly higher in patients with performance status (PS) 2 than that of patients with PS 0-1 (85.71% vs 30%, P=0.017). Patients were divided in to different groups according to the treatment efficacy. The CD44 immunohistochemical score and serum level in the disease progression group were significantly higher than those in the disease control group, and the differences were statistically significant (P=0.006, P=0.034), Univariate analysis depicted that the progression-free survival (PFS) of CD44 positive patients was significantly shorter than that of CD44 negative patients (5.23 mon vs 9.03 mon, P=0.036). CONCLUSIONS The positive expression of CD44 in tumor tissues of pre-treatment SCLC patients is correlated with poor PFS. The clinical significance of CD44 is worthy to be further studied.

With the development of precise medicine, targeted therapy has greatly improved the survival and prognosis of patients in advanced non-small cell lung cancer (NSCLC) with oncogenic drivers. However, no matter which kinds of targeted therapy are inevitable to develop therapeutic resistance, treatment options upon exhaustion of targeted therapies are limited. Immune checkpoint inhibitors (ICIs) can bring long-term survival to some patients with advanced NSCLC because of its unique long tailing effect. More and more studies have shown that ICIs can also benefit NSCLC patients with oncogenic drivers. However, the timing of ICIs intervention, the therapeutic regimen and the predictive biomarkers are actually debated, underscoring the need to explore the potential interest of ICIs in these populations.
.

The facultative anaerobic and strict anaerobic microorganisms enriched and acclimated during the anaerobic digestion process are crucial for the efficiency of the anaerobic digestion system. Most of the problems encountered during running anaerobic digestion processes could be effectively improved via stimulation of microbial metabolic activity. Benefited from the rapid development of microbiome techniques, deeper insights into the microbial diversity in anaerobic digestion systems, e.g. the microbe-microbe interactions and microbe-environment interactions, have been gained. A complex and intricate metabolic network exists in the anaerobic digestion system of solid organic wastes. However, little is known about these interactions and the underlying mechanisms. This review briefly summarized the representative interactions between microbial communities during anaerobic digestion process discovered to date. In addition, typical issues encountered during the anaerobic digestion of solid organic wastes and how microbes can tackle and alleviate these issues were discussed. Finally, future priorities on microbiome research were proposed based on present contribution of microbiome analysis in anaerobic digestion system.
Anaerobiosis ; Bioreactors ; Methane ; Microbial Interactions ; Microbiota ; Solid Waste

Objective To analyze the effects of different supplements on anemia related indexes in rural children. Methods A stratified method was adopted, and six villages (towns) in and around Qinghai Province were selected as intervention sits for the present study. A total of 304 children from 2 to 6 years old at each intervention site meeting the inclusion criteria were screened and divided into three groups (A, B, and C), who were intervened for 3 months. Serum vitamin A, vitamin D and hemoglobin levels were measured before and after the intervention. Results The hemoglobin level of 304 children before intervention was (118.65±16.07) g /L, and the prevalence of anemia was 9.54%. The vitamin A value, vitamin D value and hemoglobin value were increased after three months of the intervention. The changes of vitamin A value, vitamin D value and hemoglobin value in rural children in group C were significantly higher than those in groups A and B. The increase in vitamin A value in rural children aged 3 years was significantly higher than that in other age groups, and the increase in hemoglobin in rural children of 1 year old was significantly higher than that in other age groups. The increase in vitamin A value of rural children of other ethnic groups (mainly Tibetans) was significantly higher than that of Han and Hui nationalities, and the increase of hemoglobin value in Hui rural children was significantly higher than that in Han and other ethnic groups. Conclusion Vitamin A combined with iron dextran tablets was effective in preventing anemia in rural children.

Objective:To investigate the correlation between serum bilirubin level and the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus of different sexes.Methods:A total of 1 304 patients with type 2 diabetes mellitus were included in this study. The clinical data were collected and fundus examination was performed. According to the results of fundus examination, the patients were divided into DR group and Non-DR (NDR) group. The correlation between the levels of serum total bilirubin, direct bilirubin, indirect bilirubin, and the occurrence of DR was analyzed.Results:The levels of total bilirubin, direct bilirubin, and indirect bilirubin in DR group were significantly lower than those in NDR group. Univariate analysis showed that the levels of total bilirubin and indirect bilirubin were negatively correlated with the occurrence of DR ( P<0.01). There was no significant correlation between the level of direct bilirubin and the occurrence of DR. Smooth curve fitting showed that there was a U-shaped relationship between the levels of total bilirubin and indirect bilirubin and the risk of DR in women, while a negative correlation between total bilirubin, indirect bilirubin and the risk of DR in men. The results of multiple regression analysis showed that in men total bilirubin increased by 1 μmol/L, the risk of DR decreased by 8% ( OR=0.92, 95% CI 0.88-0.98, P<0.01). Indirect bilirubin increased by 1 μmol/L, and the risk of DR decreased by 9% ( OR=0.91, 95% CI 0.84-0.96, P<0.01). In women, when total bilirubin<12.8 μmol/L, for every 1 μmol/L increase in total bilirubin, the risk of DR decreased by 17%( OR=0.83, 95% CI 0.72-0.95, P<0.01); When total bilirubin≥12.8 umol/L, for every 1 μmol/L increase in total bilirubin, the risk of DR increased by 10%( OR=1.10, 95% CI 1.01-1.20, P<0.05); When indirect bilirubin<9.8 μmol/L, for every 1 μmol/L increase in indirect bilirubin, the risk of DR decreased by 20%( OR=0.80, 95% CI 0.68-0.94, P<0.01); When indirect bilirubin≥9.8 μmol/L, for every 1 μmol/L increase in indirect bilirubin, the risk of DR increased by 13%( OR=1.13, 95% CI 1.01-1.25, P<0.05). Conclusion:This study shows that there is a U-shaped relationship between the levels of total bilirubin and indirect bilirubin and the risk of DR in female patients with type 2 diabetes mellitus, and there is a negative correlation between total bilirubin, indirect bilirubin and the risk of DR in male patients. However, there was no significant correlation between direct bilirubin and DR risk.

Objective:To investigate the association between single nucleotide polymorphism (SNP) of eukaryotic translation initiation factor 2-α kinase 3 (EIF2AK3) gene in growth hormone deficiency (GHD), and to determine whether the polymorphisms in the EIF2AK3 of children with GHD associate with the efficacy of recombinant human growth hormone (rhGH) therapy.Methods:Five SNPs of EIF2AK3 gene, including rs1805165 (G>T), rs13045 (A>G), rs867529 (C>G), rs11684404 (T>C), rs6547787(T>G) were selected and genotyped by a TaqMan probe method in 104 children with GHD and 269 normal height control children. Among them, 55 children with GHD were treated with rhGH. The height and weight of each patient with GHD after rhGH treatment were collected. Finally, to investigate whether there were differences between the efficacy of rhGH in children with GHD and different genotypes of EIF2AK3 gene polymorphism.Results:(1) The polymorphisms rs13045 and rs867529 of EIF2AK3 gene were associated with the occurrence of GHD ( P<0.05). (2) The haplotypes GACTG and GAGTT composed of SNPs rs1805165, rs13045, rs867529, rs11684404, and rs6547787 of EIF2AK3 gene increased the risk of GHD with OR (95% CI) of 2.05 (1.33-3.17) and 2.62 (1.48-4.65), respectively. The haplotypes GACTT and TGCCG reduced the risk of GHD, with OR (95% CI) of 0.68 (0.48-0.97) and 0.36 (0.23-0.57), respectively. (3) After determination the relationship between different genotypes and efficacy of rhGH with rs13045 and rs867529, it was found that there was no significant difference in height gain between rs13045 genotypes after rhGH treatment ( P>0.05). Compared with CC genotype, there was a less height gain of CG genotype at rs867529 by 0.099 cm for every 30 d( β=-0.099, 95% CI -0.162--0.018, P=0.016). Conclusions:The EIF2AK3 gene polymorphism (rs13045, rs867529) was associated with the occurrence of GHD. The height gain of CG genotype of rs867529 was lower than that of CC genotype in children with GHD treated with rhGH. The EIF2AK3 locus rs867529 genotype was associated with rhGH efficacy.

Objective The aim of this study was to evaluate the relationship between hemoglobin ( Hb ) levels and diabetic retinopathy( DR) risk in Chinese patients with type 2 diabetes mellitus( T2DM) . Methods A total of 629 patients who were hospitalized and diagnosed as T2DM were enrolled in the study. The clinical data were collected;All participants underwent an ophthalmic examination, including fundus photographs. They were divided into DR and non-diabetic retinopathy( NDR) groups based on the results of fundus examination. Anemia was defined according to Chinese anemia criteria. The analyses were performed to evaluate the relationships between Hb levels and DR risks. Results The patients with DR had lower hemoglobin levels and a higher prevalence of anemia compared to those without DR. A univariate analysis displayed a significant negative correlation between Hb levels and the rates of DR( P<0.01) . In multivariate linear regression, a 29％ decrease in DR risk was found with a 1 g/dl increase in Hb level(OR=0.713, 95％CI 0.598-0.850, P<0.01). Presence of anemia increased the risk of DR with OR=4.123(95％CI 1.793-9.478, P<0.01) times compared to those who did not have anemia. Conclusion The study indicates a negatire relationship letween Hb levels and DR risk, and a higher Hb levels may reduce the development of DR in T2DM.