Objective To analyze the distribution of B-cell subtypes and IgG subclasses in pa-tients with non-small cell lung cancer ( NSCLC) and to investigate their potential functions in the progress of NSCLC.Methods Flow cytometry analysis was used to detect the distribution of immature B cells, memory B cells and mature B cells in 25 healthy subjects and 55 patients who were at different clinical stages of NSCLC.Enzyme-linked immune-sorbent assay ( ELASA) was performed to measure the concentrations of IgG1, IgG2, IgG3, IgG4 and total IgG, as well as the ratio of each IgG subclass in total IgG.Results The percentages of immature and memory B cells in CD19+B cells were positively correlated with the progress of NSCLC.The ratio of IgG4/IgG gradually increased along with the development of NSCLC, while that of the other three IgG subclasses showed no significant changes as compared with that of the control group.Conclu-sion The imbalanced distribution of B-cell subtypes and the up-regulated ratio of IgG4/IgG were closely as-sociated with the development of NSCLC.This study paved the way for further investigation on more effective immune therapy strategies targeting NSCLC.

Depending on the meaning and function of the liver in traditional Chinese medicine and modern medicine,this paper explores the important role of liver in the pathogenesis of DM (Diabetes Mellitus,DM).Combined with treatment based on syndrome differentiation and specific case report study,this paper has stressed the importance of treating DM from liver and so to set a sound basis for the systemic treatment based on syndrome differentiation from internal organs for DM.

Streptomycetes produce many antibiotics and are important model microorgansims for scientific research and antibiotic production. Metabolomics is an emerging technological platform to analyze low molecular weight metabolites in a given organism qualitatively and quantitatively. Compared to other Omics platform, metabolomics has greater advantage in monitoring metabolic flux distribution and thus identifying key metabolites related to target metabolic pathway. The present work aims at establishing a rapid, accurate sample preparation protocol for metabolomics analysis in streptomycetes. In the present work, several sample preparation steps, including cell quenching time, cell separation method, conditions for metabolite extraction and metabolite derivatization were optimized. Then, the metabolic profiles of Streptomyces coelicolor during different growth stages were analyzed by GC-MS. The optimal sample preparation conditions were as follows: time of low-temperature quenching 4 min, cell separation by fast filtration, time of freeze-thaw 45 s/3 min and the conditions of metabolite derivatization at 40 degrees C for 90 min. By using this optimized protocol, 103 metabolites were finally identified from a sample of S. coelicolor, which distribute in central metabolic pathways (glycolysis, pentose phosphate pathway and citrate cycle), amino acid, fatty acid, nucleotide metabolic pathways, etc. By comparing the temporal profiles of these metabolites, the amino acid and fatty acid metabolic pathways were found to stay at a high level during stationary phase, therefore, these pathways may play an important role during the transition between the primary and secondary metabolism. An optimized protocol of sample preparation was established and applied for metabolomics analysis of S. coelicolor, 103 metabolites were identified. The temporal profiles of metabolites reveal amino acid and fatty acid metabolic pathways may play an important role in the transition from primary to secondary metabolism in S. coelicolor.
Gas Chromatography-Mass Spectrometry ; Metabolic Networks and Pathways ; Metabolome ; Metabolomics ; methods ; Streptomyces coelicolor ; metabolism

ObjectiveIn this study， based on ultra-high performance liquid chromatography-mass spectrometry（UHPLC-MS/MS） and high-throughput transcriptome sequencing technology（RNA-seq）， we investigated the mechanism of Yishen Huashi granules in regulating serum metabolites and renal messenger ribonucleic acid（mRNA） expression to improve diabetic kidney disease（DKD）. MethodSD rats were randomly divided into normal group ， model group and Yishen Huashi granules group， with 8 rats in each group. The rat model of DKD was established by intraperitoneal injection of streptozotocin. Yishen Huashi granules group was given 5.54 g·kg^-1·d^-1 of Yishen Huashi granules by gavage， and the normal group and the model group were given the same amount of normal saline for 6 weeks. During the experiment， the body weight and blood glucose of rats were monitored， and the rats were anesthetized 24 hours after the last administration， blood was collected from the inferior vena cava， serum was separated， and renal function， blood lipid， and inflammatory indicators were detected. Kidney tissue of rats was fixed in neutral paraformaldehyde， and stained with hematoxylin-eosin（HE）， Masson and periodic acid-Schiff（PAS） to observe the renal pathological changes. UHPLC-MS/MS and RNA-seq were used to identify the changes of serum metabolism and the differences of renal mRNA expression， and real time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the differential mRNA and protein expression in renal tissue to explore the common expression mechanism. ResultCompared with the normal group， rats in the model group showed a decrease in body weight， a significant increase in blood glucose， urinary microalbumin to urinary creatinine ratio（UACR）， blood urea nitrogen（BUN）， cystatin-C（Cys-C）， β₂-microglobulin（β₂-MG）， interleukin-6（IL-6）， triglyceride（TG） and total cholesterol（TC）， and a significant decrease in total superoxide dismutase（T-SOD）（P<0.01）. After the intervention of Yishen Huashi granules， all the indexes were improved to different degrees in rats（P<0.05， P<0.01）. Compared with the normal group， the model group showed renal mesangial stromal hyperplasia， fibrous tissue hyperplasia and tubular vacuolar degeneration. Compared with the model group， the renal pathology of rats in Yishen Huashi granules group was improved to a certain extent. A total of 14 target metabolites and 96 target mRNAs were identified， the target metabolites were mainly enriched in 20 metabolic pathways， including sphingolipid metabolism， glycerophospholipid metabolism， and the biosynthesis of phenylalanine， tyrosine and tryptophan. The target mRNAs were enriched to obtain a total of 21 differential mRNAs involved in the TOP20 pathways closely related to glycolipid metabolism. A total of 6 pathways， glycerophospholipid metabolism， arachidonic acid metabolism， purine metabolism， primary bile acid biosynthesis， ascorbic acid and uronic acid metabolism， and galactose metabolism， were enriched by serum differential metabolites and renal differential mRNAs， among them， there were 7 differential metabolites such as phosphatidylethanolamine（PE） and 7 differential mRNAs such as recombinant adenylate cyclase 3（ADCY3）. Seven differential metabolites had high predictive accuracy as verified by receiver operating characteristic（ROC） curve， and the results of Real-time PCR and Western blot were highly consistent with the sequencing results. ConclusionYishen Huashi granules can reduce UACR， BUN and other biochemical indexes， correct the disorder of glucose and lipid metabolism， and improve renal function of DKD rats. And its mechanism may be related to the regulation of the level of PE and other blood metabolites， and expression of Phospho1 and other mRNAs in the kidney， of which six pathways， including glycerophospholipid metabolism， may play an important role.

BACKGROUND: Improving and maintaining the health of mothers and newborns is indisputably a global priority, especially during a pandemic. This study intends to examine the factors associated with cesarean section (CS) during lockdown time. METHODS: A total of 678 women who just gave birth within 7 days were enrolled from maternal and children hospitals in nine cities of China from April to May 2020. The delivery modes and potential influencing factors were investigated. The subgroup analysis and sensitivity analysis were used to examine the association of CS and risk factors among populations with different characteristics and to control for possible confounding, respectively. RESULTS: The overall rate of cesarean delivery was 37.3%. In multi-variant model, maternal age > 30 years (OR, 95% CI = 1.71, 1.21-2.41), higher pre-gestational BMI (OR, 95% CI = 1.16, 1.10-1.23), living in regions with confirmed COVID-19 cases > 500 (OR, 95% CI = 2.45, 1.74-3.45), and excess gestational weight gain (OR, 95% CI = 1.73, 1.17-2.55) were associated with cesarean delivery. These trends of associations were not changes in sensitivity analysis and subgroup analysis. Cesarean delivery occurred more in women who got more nutrition instruction during the pandemic period in the univariant model; however, this association showed insignificance in the multiple-variant analysis. CONCLUSION A high cesarean delivery rate was found in uninfected women who experienced lockdown in their third trimester. During the COVID-19 pandemic, more medical support should be provided in severely affected regions to ensure and promote health in pregnancy.

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.
Chromatin ; Chromosomes ; Genome ; Humans ; Lamin Type B/genetics*

ObjectiveTo explore the compatibility advantage of Scutellariae Radix-Coptidis Rhizoma in the prevention and treatment of neuroinflammation， and to elucidate the action characteristics and mechanism of the compatibility advantage based on Toll like receptor （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappaB （NF-κB） pathway. MethodRepresentative mouse microglia cells （BV2） in vitro were selected and divided into 8 groups： control group， model group， Scutellariae Radix-Coptidis Rhizoma group， Piracetam group， Scutellariae Radix group and Coptidis Rhizoma group. The BV2 cell inflammatory model was established by lipopolysaccharide （LPS）， and the cell activity was detected by cell counting kit-8 （CCK-8）. Cell morphology was observed under bright field. The production and release of pro-inflammatory factors in BV2 cells were determined by enzyme-linked immunosorbent assay （ELISA） and immunofluorescence assay， and the mRNA expressions of TLR4， MyD88 and NF-κB were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The nuclear translocation of NF-κB p65 was detected by immunofluorescence， and TLR4 signal transduction inhibitor （CLI-095） and NF-κB inhibitor （PDTC） were used to confirm the anti-neuroinflammation targets of Scutellariae Radix-Coptidis Rhizoma. ResultCompared with the conditions in the control group， most cells in LPS-induced model group were activated， and the contents of IL-6， TNF-α and IL-1β in culture medium and cells and the mRNA expressions of TLR4， MyD88， NF-κB p50 and NF-κB p65 were increased （P<0.01）， with obvious nuclear entry of NF-κB p65. Compared with the conditions in the model group， BV2 cell morphology was mostly recovered after pretreatment in Scutellariae Radix-Coptidis Rhizoma and Piracetam groups， and the levels of IL-6， TNF-α and IL-1β and the mRNA expressions of TLR4， MyD88， NF-κB p50 and NF-κB p65 were decreased （P<0.05， P<0.01）， with NF-κB p65 mostly observed in cytoplasm. Compared with the conditions in the model group， cell morphology was slightly recovered in Scutellariae Radix group and Coptidis Rhizoma group， and the levels of pro-inflammatory factors and mRNA expressions of TLR4， MyD88， NF-κB p50 and NF-κB p65 were reduced. In terms of inhibitory effect on pro-inflammatory factors， Scutellariae Radix group and Coptidis Rhizoma group were lower than Scutellariae Radix-Coptidis Rhizoma group （P<0.05）. Compared with the model group， the "Scutellariae Radix-Coptidis Rhizoma+CLI-095" group and "Scutellariae Radix-Coptidis Rhizoma+PDTC" group had lowered mRNA expressions of TLR4， MyD88， NF-κB p50 and NF-κB p65 （P<0.05， P<0.01）， and the transfer of NF-κB p65 into nucleus was obviously inhibited. ConclusionThe anti-neuroinflammation effect of Scutellariae Radix-Coptidis Rhizoma was significantly better than Scutellariae Radix or Coptidis Rhizom alone， and the anti-neuroinflammation advantage was closely related to the inhibition of activation of TLR4/MyD88/NF-κB signaling pathway in microglial cells. It was confirmed that TLR4， MyD88 and NF-κB were potential targets for Scutellariae Radix-Coptidis Rhizoma to exert the compatibility advantage.