Objective:To explore the related factors of thrombocytopenia (TCP) occurrence in patients with cirrhosis.Methods:A cross-sectional study was conducted. Inpatients with an initial diagnosis of cirrhosis at Peking University First Hospital from January 1, 2010 to December 31, 2020 were included. Clinical data such as demographic characteristics, etiology of cirrhosis, complications of cirrhosis, laboratory indicators, Child-Pugh grade, invasive procedures, and mortality during hospitalization were collected. A logistic regression model was used to explore the related factors of TCP occurrence in patients with cirrhosis. Categorical variables were compared by the χ2 test. The inter-group comparison was performed using continuous variables, a t-test, one-way analysis of variance (ANOVA), or a nonparametric test. Results:There were a total of 2 592 cases of cirrhosis. 75 cases with incomplete clinical data were excluded. 2 517 cases were included for analysis. The median age was 58 (50, 67) years. Males accounted for 64%. 1 435 cases (57.0%) developed TCP, and 434 cases (17.2%) had grade 3-4 TCP. Gender, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and concomitant esophagogastric varices (EGV) were the major factors associated with TCP. Females were more prone to combine with TCP ( OR=1.32, 95% CI: 1.12-1.56, P=0.001). Patients combined with EGV ( OR=3.09, 95% CI: 2.63-3.65, P<0.001) were more prone to develop TCP, which was associated with the increased incidence of hypersplenism ( P<0.001). Patients with PBC ( OR=0.64, 95% CI: 0.50-0.82, P<0.001) and PSC ( OR=0.23, 95% CI: 0.06-0.65, P=0.010) were less prone to develop TCP, which was due to the shorter prothrombin time and better coagulation function of PBC patients ( P<0.001), and the lower proportion of hypersplenism in combined PSC patients ( P=0.004). Patients with TCP and grade 3-4 TCP had a higher rate of hemostatic procedures ( P<0.05), but a lower rate of liver biopsy ( P<0.05). Patients with grade 3-4 TCP had a higher nosocomial mortality rate compared to those without ( P=0.004). Conclusion:TCP is common in patients with cirrhosis. However, TCP occurrence is higher in female patients with EGV and lower in patients combined with PBC and PSC. TCP affects invasive procedures and is associated with adverse outcomes.

Objective To analyze and summarize the clinical presentation of spontaneous and secondary intracranial hypotension syndrome(IHS).Methods Patients diagnosed with spontaneous or secondary IHS from September 2022 to May 2023 were retrospectively analyzed.The clinical data,imaging features,treatment methods and prognosis were collected.The correlation between intracranial pressure values and clinical characteristics of the patients was statistically analyzed.Results A total of 30 patients were enrolled,and the proportion of spontaneous and secondary IHS was 63%(19 cases)and 37%(11 cases),respectively.In terms of clinical features,orthostatic headache was the most common type(29 cases,96.7%)and most commonly involved occipital region(12 cases,40.0%),followed by frontoparietal region(9 cases,30.0%).Among the brain imaging features,dural enhancement was the most common(17 cases,56.7%).According to CT angiography of spinal cord findings,cerebrospinal fluid leakage is one of the most common location of cervical spine segments(10 cases),and on the thoracic segments(9 cases),followed by the thoracic segments(4 cases)and lumbar segments(4 cases).After conservative treatment and surgical treatment,the total effective rate was 90%.Conclusion Orthostatic headache and cranial MRI"dural enhancement"have strong indication on the definitive diagnosis of IHS.CT myelography is helpful to precisely localize the site of cerebrospinal fluid leakage.Targeted epidural blood patch therapy is an effective method to cure IHS when conservative treatment is ineffective.

OBJECTIVE To analyze the hotspots， progress and frontiers of the therapy of recurrent high-grade gliomas， and to provide a reference for the research in this field. METHODS The relevant literature were retrieved from the Web of Science and CNKI during Jan. 1st， 2005-Mar. 14th， 2022. CiteSpace 6.1.R3 software was used to quantitatively analyze the countries， authors， institutions and keywords of the included literature to form visual network maps and generate data. RESULTS A total of 1 019 English papers and 308 Chinese papers were included. The number of international publications kept growing and the number of domestic publications remained stable. Institutions and authors cooperated extensively. The United States featured a large centrality （0.38） and the largest number of publications （442）， with major research institutions such as the University of California San Francisco， University Texas MD Anderson Cancer Center， Dana-Farber Cancer Institute， and important researchers such as Wen， Cloughesy， Reardon， and so on. Domestic research groups were relatively fixed and closed. Internationally， the mechanism of tumorigenesis and drug resistance were the focus of basic research， while there was less basic research in China. Radiotherapy， chemotherapy， targeted therapy and combination therapy were studied the most internationally. Immunotherapy and photodynamic therapy were emerging therapies in recent years. In China， temozolomide and radiotherapy were the main research directions. CONCLUSIONS International attention and investment in the treatment of recurrent high-grade glioma are increasing. The United States has a high influence in this field. Currently， radiotherapy， traditional chemotherapeutic agents and bevacizumab are still the main treatment for recurrent high-grade glioma. Novel therapeutic approaches， including immunotherapy and photodynamic therapy， warrant more attempts and research.

In order to investigate the molecular mechanism of silk/threonine protein kinase (STK)-mediated blue light response in the algal Chlamydomonas reinhardtii, phenotype identification and transcriptome analysis were conducted for C. reinhardtii STK mutant strain crstk11 (with an AphvIII box reverse insertion in stk11 gene coding region) under blue light stress. Phenotypic examination showed that under normal light (white light), there was a slight difference in growth and pigment contents between the wild-type strain CC5325 and the mutant strain crstk11. Blue light inhibited the growth and chlorophyll synthesis in crstk11 cells, but significantly promoted the accumulation of carotenoids in crstk11. Transcriptome analysis showed that 860 differential expression genes (DEG) (559 up-regulated and 301 down-regulated) were detected in mutant (STK4) vs. wild type (WT4) upon treatment under high intensity blue light for 4 days. After being treated under high intensity blue light for 8 days, a total of 1 088 DEGs (468 upregulated and 620 downregulated) were obtained in STK8 vs. WT8. KEGG enrichment analysis revealed that compared to CC5325, the crstk11 blue light responsive genes were mainly involved in catalytic activity of intracellular photosynthesis, carbon metabolism, and pigment synthesis. Among them, upregulated genes included psaA, psaB, and psaC, psbA, psbB, psbC, psbD, psbH, and L, petA, petB, and petD, as well as genes encoding ATP synthase α, β and c subunits. Downregulated genes included petF and petJ. The present study uncovered that the protein kinase CrSTK11 of C. reinhardtii may participate in the blue light response of algal cells by mediating photosynthesis as well as pigment and carbon metabolism, providing new knowledge for in-depth analysis of the mechanism of light stress resistance in the algae.
Chlamydomonas reinhardtii/genetics* ; Photosynthesis/genetics* ; Plants/metabolism* ; Protein Kinases ; Threonine/metabolism* ; Carbon/metabolism* ; Serine/metabolism*

Objective:To understand the clinical characteristics of hospitalized patients with liver cirrhosis, so as to provide theoretical basis for disease diagnosis and treatment, formulation of intervention measures, and improve the level of disease diagnosis and treatment.Methods:Hospitalized patients who were initially diagnosed with liver cirrhosis at Peking University First Hospital from August 2017 to December 2018 were selected retrospectively as the research objects. Liver cirrhosis demographic data, etiology, severity classification, incidence of complications, diagnosis and prognosis were recorded. Statistical analysis was performed using SPSS software.Results:Among all liver cirrhosis cases, there were 291 males and 209 females, with a male-to-female ratio of 1.4:1 and an age of 59.5±12.9 years as at August 2017 to December 2018. HBV infection, alcoholic liver disease, and autoimmune liver diseases were the most common etiology of liver cirrhosis. HBV infection alone, HBV infection combined with other factors, alcoholic liver disease alone, alcoholic liver disease combined with other factors, autoimmune liver disease alone, and autoimmune liver disease combined with other factors were presented in 163 (32.6%), 57 (11.4%), 47 (9.4%), 63 (12.6%), 85 (17.0%), and 22 (4.4.0%) cases, respectively. Ascites (221 cases, 44.2%), followed by esophagogastric varices (214 cases, 42.8%), and other including hypersplenism (137 cases), liver cancer (126 cases), upper digestive system tract hemorrhage (66 cases), hepatic encephalopathy (40 cases), infection (37 cases), portal vein thrombosis (23 cases), hepatorenal syndrome (20 cases) were the most common complications. The most common site of infection was the abdominal cavity (20 cases), accounting for 54.1%; followed by respiratory tract infection (8 cases), accounting for 21.6% in patients with liver cirrhosis with concurrent infection. Among them, there were 32 cases of bacterial infection alone, one case of bacterial infection combined with fungal infection, one case of bacterial infection combined with viral infection, and three cases of unknown pathogens. There were 69 cases in Child Pugh grade C, and the average hospitalization times were 12.6 days in terms of prognosis. There were total seven cases of death, of which five cases were due to upper gastrointestinal hemorrhage and two due to hepatic encephalopathy.Conclusion:HBV infection, ascites, and upper gastrointestinal bleeding were the most common etiologies, complications, and causes of death in patients with liver cirrhosis at our hospital.

WRKY is a superfamily of plant-specific transcription factors, playing a critical regulatory role in multiple biological processes such as plant growth and development, metabolism, and responses to biotic and abiotic stresses. Although WRKY genes have been characterized in a variety of higher plants, little is known about them in eukaryotic algae, which are close to higher plants in evolution. To fully characterize algal WRKY family members, we carried out multiple sequence alignment, phylogenetic analysis, and conserved domain prediction to identify the WRKY genes in the genomes of 30 algal species. A total of 24 WRKY members were identified in Chlorophyta, whereas no WRKY member was detected in Rhodophyta, Glaucophyta, or Bacillariophyta. The 24 WRKY members were classified into Ⅰ, Ⅱa, Ⅱb and R groups, with a conserved heptapeptide domain WRKYGQ(E/A/H/N)K and a zinc finger motif C-X4-5-C-X22-23-H-X-H. Haematococcus pluvialis, a high producer of natural astaxanthin, contained two WRKY members (HaeWRKY-1 and HaeWRKY-2). Furthermore, the coding sequences of HaeWRKY-1 and HaeWRKY-2 genes were cloned and then inserted into prokaryotic expression vector. The recombinant vectors were induced to express in Escherichia coli BL21(DE3) cells and the fusion proteins were purified by Ni-NTA affinity chromatography. HaeWRKY-1 had significantly higher expression level than HaeWRKY-2 in H. pluvialis cultured under normal conditions. High light stress significantly up-regulated the expression of HaeWRKY-1 while down-regulated that of HaeWRKY-2. The promoters of HaeWRKY genes contained multiple cis-elements responsive to light, ethylene, ABA, and stresses. Particularly, the promoter of HaeWRKY-2 contained no W-box specific for WRKY binding. However, the W-box was detected in the promoters of HaeWRKY-1 and the key enzyme genes HaeBKT (β-carotene ketolase) and HaePSY (phytoene synthase) responsible for astaxanthin biosynthesis. Considering these findings and the research progress in the related fields, we hypothesized that the low expression of HaeWRKY-2 under high light stress may lead to the up-regulation of HaeWRKY-1 expression. HaeWRKY-1 may then up-regulate the expression of the key genes (HaeBKT, HaePSY, etc.) for astaxanthin biosynthesis, consequently promoting astaxanthin enrichment in algal cells. The findings provide new insights into further analysis of the regulatory mechanism of astaxanthin biosynthesis and high light stress response of H. pluvialis.
Eukaryota ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/metabolism* ; Plants/metabolism* ; Stress, Physiological/genetics* ; Transcription Factors/metabolism*

ObjectiveTo investigate the features of liver injury and related influencing factors in adolescents and adults with infectious mononucleosis (IM). MethodsA retrospective analysis was performed to investigate the features of liver injury in adolescents and adults with IM who were hospitalized in Peking University First Hospital from January 2005 to December 31 2018, and the patients were divided into subgroups based on age, Epstein-Barr virus (EBV) DNA level, and presence or absence of jaundice or infection with cytomegalovirus or hepatitis E virus (HEV). The t-test was used for comparison of continuous data meeting analytical conditions between two groups, and the Mann-Whitney U test was used for comparison of continuous data which did not meet analytical conditions between two groups; the chi-square test was used for comparison of categorical data between two groups, and the Fisher’s exact test was used for comparison of categorical data which did not meet the analytical conditions of the chi-square test. A logistic regression analysis was used for multivariate analysis. ResultsA total of 274 patients were enrolled, with 154 male patients (56.2%) and 120 female patients (43.8%), and the mean age of onset was 22.3±67 years. The incidence rate of liver injury ［defined as alanine aminotransferase (ALT) ＞50 U/L and/or aspartate aminotransferase (AST)＞40 U/L］ was 97.4% (267/274), and that of jaundice was 27.6% (74/268). The patients, aged ≥20 years, tended to have a higher level of gamma-glutamyl transpeptidase (GGT) (Z=2.070, P=0.038). Serum EBV DNA was measured for 167 patients, among whom 90 had positive results and 77 had negative results. The positive serum EBV DNA group had significantly higher levels of GGT (Z=3.005, P=0.003) and lactate dehydrogenase (Z=2.162, P=0.031) than the negative serum EBV DNA group. The patients with cytomegalovirus infection tended to have a higher level of alkaline phosphatase (Z=2.351, P=0.019), and the patients with HEV infection presented with a higher level of GGT (Z=1.988, P=0.047). AST (odds ratio ［OR］=1.006, 95% confidence interval ［CI］: 1.002-1.010, P=0.005) and ALP (OR=1.012, 95%CI: 1.005-1.020, P=0.001) were independent risk factors for jaundice. ConclusionThere is a high incidence rate of liver injury in adolescents and adults with IM, and the patients with an older age or positive serum EBV DNA tend to have more severe liver injury.

Objective:To explore the risk factors of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis.Methods:A retrospective study was designed. Patients with liver cirrhosis combined with /without OHE who were hospitalized to our hospital during the same period were selected as the case/control group. Clinical and laboratory data of both groups of patients were compared to analyze the risk factors affecting the occurrence of OHE. SPSS software was used for statistical analysis. A t-test or rank-sum test was used to compare the measurement data. Chi-square test or Fisher’s exact probability method was used to compare the count data. Logistic regression was used for multivariate analysis.Results:A total of 500 patients with liver cirrhosis diagnosed in our hospital from August 2017 to December 2018 were selected as the case group, and 40 cases with cirrhosis without OHE who were hospitalized during the same period were randomly selected as the control group. The gender composition and age of the case and control group were comparable. Viral hepatitis (mainly hepatitis B) was the main etiology of liver cirrhosis in both groups. There were 52.5% patients in the case group and 57.5% patients in the control group, respectively. Alcoholic liver disease, autoimmune liver disease and so on were the other included causes. With regard to blood biochemical indicators, the serum creatinine levels of both groups were comparable, but in the case group, the serum total bilirubin level was higher (34.30 μmol / L vs. 18.65 μ mol/L, Z = -3.185, P < 0.05), while the serum sodium level was lower (137.00 mmol/L vs. 140.08 mmol/L, Z = -2.348, P < 0.05), and the prothrombin time was longer (14.60 s vs. 12.20 s) s. 078, P < 0.05), and international normalized ratio (1.33 vs. 1.07, Z = - 5.632, P < 0.05), and serum albumin level (30.6 g/L vs. 35.6 g/L, t = 3.386, P < 0.05) was lower. In terms of complications, patients in the case group had a higher proportion of combined gastrointestinal bleeding (30.0% vs. 10.0%, χ 2 = 5.000, P < 0.05), ascites (87.5% vs. 30.0%, χ 2 = 27.286, P < 0.05) and secondary infection (32.5% vs. 10.0%, χ 2 = 7.813, P < 0.05). In terms of severity classification, the proportion of Child-Pugh C in the case group was higher (62.5% vs. 10.0%, χ 2 =26.593, P < 0.05). In terms of outcome, there were 3 deaths in the case group and no deaths in the control group. Multivariate analysis showed that Child-Pugh class C ( OR = 12.696), and combined ascites ( OR = 10.655) were an independent risk factor for OHE in patients with liver cirrhosis. Conclusion:Our single-center retrospective clinical study shows that patients with cirrhosis combined with OHE are more critical and have more complications. In order to promptly diagnose and treat OHE, more attention should be paid to patients with combined ascites and Child-Pugh class C.

Objective: The active components and potential targets were predicted and confirmed to explore the possible mechanism of Wenpi decoction on ulcer colitis. Methods: The traditional Chinese medicine integrated pharmacology platform (TCMIP) was used to construct the decoction-target-disease target network, and the key nodes were analyzed and screened. The function and pathway enrichment analysis were conducted to explore the biological processes, which Wenpi decoction may be involved in the treatment of ulcerative colitis. Results: The study showed that there were 455 active ingredients and 3044 targets in Wenpi decoction. The 434 targets and multiple biological processes and metabolic pathways were involved, such as chemokine signaling pathways, estrogen signaling pathway, thyroid hormone signaling pathway, MAPK signaling pathway, and PI3K/Akt signaling pathway. These targets and pathways were consistent with the pathogenesis of ulcerative colitis reported in the literature. In addition, Wenpi decoction was potential to be applied in the treatment of tumor, endocrine and metabolic diseases. Conclusions This study provided a scientific basis for further studies on the mechanism of Wenpi decoction in the treatment for ulcer colitis.

Objective To study the relationship between the expression of sonic hedgehog (Shh) and vascular endothelial growth factor (VEGF) in hypoxic human retinal pigment epithelial (hRPE) cells.Methods Cultured hRPE-19 cells (3rd-6th generations) were used in this experiment.hRPE-19 cells were divided into three groups including the control group,the hypoxia experimental group (100 μmol/L CoCl2) and the inhibition group (pretreatment with 20 μmol/L cyclopamine 1 hour before hypoxia).After culturing for 4,8,12 and 24 hours,the mRNA level of Shh and VEGF genes in these cells were measured by fluorescence quantitative polymerase chain reaction,and the protein level of Shh and VEGF in the supematants were measure by enzymelinked immunosorbent assay.The relationship between the expression of Shh and VEGF was analyzed by Pearson correlation analysis.Results The control group expressed low levels of Shh and VEGF mRNA/protein.The expression of Shh and VEGF mRNA/protein in the hypoxia experimental group was significantly higher than that in the control group (F=178.364,183.732,77.456,91.572;P＜0.01).The expression of Shh and VEGF mRNA in the inhibition group was significantly lower than that in the hypoxia experimental group (F=68.745,121.834;P＜0.01).In the hypoxia experimental group,the expression of VEGF protein was positively correlated with the expression of Shh protein (r=0.942,P＜ 0.05);and the expression of VEGF and Shh mRNA was positively correlated (r=0.970,P＜0.01).However,there was no significant correlation in the expression of VEGF and Shh mRNA in the inhibition group (r=0.915,P＞ 0.05).Conclusion There is a positive correlation between the expression of Shh and VEGF in hypoxic hRPE cells.