ObjectiveTo analyze the pharmacodynamic activity of Bupleuri Radix processed with Trionyx sinensis blood in the treatment of Yin deficiency and study the spectrum-effect relationship of this medicine. MethodsHigh performance liquid chromatography was employed to establish the fingerprints of 15 batches of Bupleuri Radix processed with Trionyx sinensis blood， and the similarity was evaluated according to the SOP of Similarity Evaluation System of Chromatographic Fingerprint of TCM （version 2012）. A mouse model of Yin deficiency induced by thyroxine was established. The relationship between the active components and the effect on Yin deficiency was explored by grey correlation analysis and partial least squares method based on the changes in the serum levels of triiodothyronine （T3）， thyroxine （T4）， cyclic adenosine phosphate （cAMP）， and cyclic guanosine phosphate （cGMP）. The components screened out based on the spectrum-effect relationship were used for retrieval of the targets from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database （TCMSP）， The Encyclopedia of Traditional Chinese Medicine （ETCM）， and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Furthermore， the Online Mendelian Inheritance in Man （OMIM）， GeneCards， TTD， DisGeNET， and Drugbank were employed to establish the active component-target against Yin deficiency network of Bupleuri Radix processed with Trionyx sinensis blood. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were carried out for the core targets. Real-time PCR was conducted to verify the predicted key pathways and mechanisms. ResultsThe fingerprints of the 15 batches of Bupleuri Radix processed with Trionyx sinensis blood showed the similarities of 0.976-0.999 with the control fingerprint. Compared with the model group， the drug administration group showed elevated levels of T3 and T4 and lowered levels of cAMP， cGMP and cAMP/cGMP. The results of grey correlation analysis showed that active components in terms of the correlations followed the trend of saikosaponin B₁ > saikosaponin B₂ > saikosaponin C > saikosaponin D > saikosaponin A. The partial least squares analysis showed that saikosaponins A， D， B₁， and B₂ had higher VIP values. Network pharmacology predicted a total of 30 common targets， which were enriched in 276 GO terns and 115 KEGG pathways. The results of Real-time PCR showed that the model group had lower mRNA levels of Caspase-9， kinase insert domain receptor （KDR）， and mammalian target of rapamycin （mTOR） and higher mRNA level of mouse double minute 2 homolog （MDM2） than the blank group and the drug administration group. ConclusionBupleuri Radix processed with Trionyx sinensis blood has therapeutic effect on Yin deficiency syndrome， which provides a new idea for studying Bupleuri Radix processed with Trionyx sinensis blood.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Objective To investigate the imaging features of intestinal schwannoma(IS)in order to improve the diagnostic ability of the disease.Methods The clinical and imaging data of 14 patients with surgically and pathologically confirmed IS were retrospectively analyzed,including the location,size,morphology,nature,growth pattern,CT density,MRI signal,PET/CT metabolism and other characteristics of the tumors.Results Of the 14 IS cases,the lesions of 3 cases were located in the duodenum,2 cases in the cecum,8 cases in the colon and 1 case in the rectum.The lesions were all round or oval,with an average maximum diameter of(2.4±1.1)cm.The lesions were solid in 13 cases,extraluminal growth in 10 cases,cystic degeneration in 1 case and myxoid degeneration in 1 case.Chronic inflammatory lymph nodes were seen around the diseased intestines in 9 cases,and the short diameter of lymph nodes was greater than 5 mm in 6 cases.All 14 cases of IS showed low attenuation on plain CT scan,and progressive enhancement after contrast injection,including 1 case of mild enhancement,2 cases of moderate enhancement,and 11 cases of obvious enhancement.Two cases of IS showed low signal intensity on T1WI,slightly high signal intensity on T2WI,significantly high signal intensity on DWI,and obvious progressive enhancement after contrast injection on MRI.Two cases of IS showed high metabolism on 18F-FDG-PET/CT,and the SUVmax was 9.4 and 8.8,respectively.Conclusion The imaging findings of IS were characteristic to a certain extent.They mainly manifested as solid nodules or masses derived from the intestinal submucosa,with uniform attenuation or signal intensity,obvious progressive enhancement after contrast injection,obvious hypermetabolism on 18F-FDG-PET/CT,and slightly larger homogeneous lymph nodes were common around the lesions.

BACKGROUND:Cerebral ischemic stroke is one of the main fatal and disabling diseases in the clinic,but only a few patients benefit from vascular recanalization in time,so it is urgent to explore new and effective therapy.As one of the critical pathological changes of ischemic stroke,the glial scar formed mainly by astrocytes is one major cause that hinders axonal regeneration and neurological recovery at the late stage of stroke. OBJECTIVE:To elucidate the pathological process and crucial signal regulatory mechanism of astrocytes in the formation of glial scar after ischemic stroke,as well as the potential therapeutic targets,to provide a theoretical reference for intervening astrocytic scar formation against ischemic stroke effectively,and novel strategies for promoting post-stroke rehabilitation. METHODS:The relevant articles published in CNKI,PubMed and Web of Science databases from 2010 to 2022 were retrieved.The search terms were"Ischemic stroke,Brain ischemi*,Cerebral ischemi*,Astrocyt*,Astroglia*,Glial scar,Gliosis,Astrogliosis"in Chinese and English.Finally,78 articles were included after screening and summarized. RESULTS AND CONCLUSION:(1)Astrocytes play an important role in the maintenance of central nervous system homeostasis.After ischemic stroke,astrocytes change from a resting state to an active state.According to the different severities of cerebral ischemic injury,astrocyte activation changes dynamically from swelling and proliferation to glial scar formation.(2)Mature astrocytes are stimulated to restart the cell cycle,then proliferate and migrate to lesions,which is the main source of the glial scar.Neural stem cells in the subventricular zone,neuron-glial antigen 2 precursor cells and ependymal precursor cells in the brain parenchyma can also differentiate into astrocytes.Endothelin-1,aquaporin 4,ciliary neurotrophic factor and connexins are involved in this process.In addition,chondroitin sulfate proteoglycan,as the main component of the extracellular matrix,forms the dense glial scar barrier with proliferated astrocytes,which hinders the polarization and extension of axons.(3)Activation or inhibition of crucial signal molecules involved in astrocyte activation,proliferation,migration and pro-inflammation functions regulate the glial scar formation.Transforming growth factor beta 1/Smad and Janus kinase/signal transducer and activator of transcription 3 are classical pathways related to astrogliosis,while receptor-interacting protein 1 kinase and glycogen synthase kinase 3β are significant molecules regulating the inflammatory response.However,there are relatively few studies on Smad ubiquitination regulatory factor 2 and Interleukin-17 and their downstream signaling pathways in glial scar formation,which are worthy of further exploration.(4)Drugs targeting astrogliosis-related signaling pathways,cell proliferation regulatory proteins and inflammatory factors effectively inhibit the formation of glial scar after cerebral ischemic stroke.Among them,the role of commonly used clinical drugs such as melatonin and valproic acid in regulating glial scar formation has been verified,which makes it possible to use drugs that inhibit glial scar formation to promote the recovery of neurological function in patients with stroke.(5)Considering the protective effects of glial scar in the acute phase,how to choose the appropriate intervention chance of drugs to maintain the protective effect of the glial scar while promoting nerve regeneration and repair in the local microenvironment is the direction of future efforts.

Objective To summarize the pathological morphological features, diagnosis, and differential diagnosis of adult-onset Still disease (AOSD), and to improve clinical understanding of the disease. Methods A retrospective analysis was conducted on the morphological characteristics, immunophenotypes, and molecular detection results of lymph node biopsies from three AOSD patients. Results Case 1: lymph node biopsy tissue showed significant lymphoid follicular hyperplasia, accompanied by parafollicular hyperplasia; the germinal centers exhibited a starry-sky phenomenon, with no obvious histiocyte proliferation foci, plasma cells, or neutrophils; immunohistochemical staining showed that CD3 and CD5 T lymphocyte were positive in the paracortical area, CD20 and CD79α markers showed that B lymphocytes were mainly located in the follicular area, CD21 follicular dendritic cells and CD68 histiocytes were positive. Case 2: lymph node puncture tissue showed paracortical hyperplasia, a decrease in the number of follicles, and a reduction of follicular volume; there were no obvious histiocyte proliferation foci, plasma cells, or neutrophils; immunohistochemical staining showed positive CD3, CD5 T lymphocytes in the paracortical area, and CD20, CD79α B lymphocytes in the follicular region. Case 3: lymph node puncture tissue showed partial preservation of the normal lymph node structure, the paracortical area was diffusely proliferated, and the histiocyte hyperplasia was patchy with partial necrosis, and obvious nuclear debris, scattered plasma cells and eosinophils can be seen and no obvious neutrophil infiltration in the necrotic area; immunohistochemical staining of case 3 showed that CD21 and CD23 follicular dendritic cells were positive, and Bcl-2, Bcl-6, CD3, CD5, CD20, CD79α, and multiple myeloma protein 1 (MUM1) were positively expressed in some lymphocytes; the Ki-67 proliferation index was high, approximately 70%; a few plasma cells were positive for CD138, with individual cells positive for CD1α; CD10 and CyclinD1 were negative; histiocytes were positive for myeloperoxidase (MPO); and EBER was negative for in situ hybridization. The results of TCR gene rearrangement and IG gene rearrangement in the three cases were negative. Conclusion The immunophenotype of AOSD is diversity, and its dignosis depends on the clinical and pathological morphological features and immunophenotype, excluding infectious diseases, malignant tumors and lymphoma, etc.

Glioma is the most common malignancy of the central nervous system, originating mainly from glial cells. Because of its highly aggressive nature, glioma has one of the highest rates of death among all types of cancer. Therefore, it is very important to develop new therapeutic approaches and drugs for glioma treatment. Instead of activate the telomerase, approximately 30% of glioma use alternative lenthening of telomere (ALT) to maintain telomere length. The mechanism of ALT development is poorly understood, however, some genetic mutations have been reported to induce the development of ALT glioma, such as ATRX, IDH1, p53, etc. The lack of ALT glioma cell lines and preclinical ALT glioma models has limited the mechanistic studies of ALT glioma. Therefore, this review listed ALT glioma cell lines that derived from primary culture or gene editing in the last decade, as well as the xenografted animal models established by ALT glioma cell lines, and discussed the role and significance these cell and animal models play in preclinical studies.

Objective To explore the mechanism of somatostatin in improving acute lung injury associated with acute pancreatitis.Methods Wistar rats were randomly divided into sham operation group(injection of normal saline),model group(puncture of common bile duct and injection of 5％sodium taurocholate with wire ligation),somatostatin group(injection of somatostatin into tail vein of model group),somatostatin+miR-146a-5p inhibitor group(on the basis of somatostatin group,tail vein injection of miR-146a-5p inhibitor and somatostatin+oe-angiogenin-like protein 4(ANGPTL4)group(on the basis of somatostatin group,tail vein injection of oe-ANGPTL4 plasmid).Hematoxylin-eosin(HE)staining was used to observe the pathological changes of pancreatic and lung tissues;pathological score and tissue wet-dry weight ratio were determined,real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect miR-146a-5p and ANGPTL4 mRNA expression and Western blot was used to detect the expression of related proteins in lung tissues of rats.Tumor necrosis factor-α(TNF-α)was detected by enzyme-linked immunosorbent assay(ELISA).Results In sham operation group,model group and somatostatin group,the damage degree of pancreas tissue(based on modified computed tomography severity index)were 1.25±0.28,3.20±0.34,2.15±0.31,respectively;the damage degree of lung tissue(based on the Smith lung injury score system)were 1.40±0.13,5.10±0.58,3.10±0.38,respectively.The relative expression levels of ANGPTL4 mRNA in sham operation group,model group,somatostatin group and somatostatin+miR-146a-5p inhibitor group were 1.00±0.17,1.63±0.20,1.21±0.18 and 1.73±0.28.The levels of TNF-α in sham operation group,model group,somatostatin group,somatostatin+miR-146a-5p inhibitor group and somatostatin+oe-ANGPTL4 group were(76.33±7.25),(125.05±13.56),(80.11±10.68),(118.62±14.32)and(105.32±13.52)pg·mL-1,respectively;the relative expression levels of nuclear factor E2-related factor 2(Nrf2)protein were 1.00±0.27,0.51±0.07,0.88±0.14,0.68±0.12,0.51±0.09,respectively;the relative expression levels of heme oxygenase-1(HO-1)protein were 1.00±0.25,0.58±0.11,0.79±0.18,0.48±0.07 and 0.50±0.08,respectively.The above indexes of the model group were compared with those of the sham operation group,and the above indexes of the somatostatin group were compared with those of the model group,somatostatin+miR-146a-5p inhibitor group and somatostatin+oe-ANGPTL4 group,and the differences were statistically significant(all P＜0.05).Conclusion Somatostatin has antioxidant and anti-inflammatory effects and can ameliorate acute lung injury associated with acute pancreatitis.The mechanism may be related to Nrf2/HO-1 pathway mediated by miR-146a-5p/ANGPTL4.