The aberrant activities or overexpression of kinases have been closely linked to the development of many diseases, including liver fibrosis, and kinases have become important therapeutic targets for these diseases. Protein kinases, including tyrosine kinases and serine/threonines protein kinases, and phosphoinositide 3-kinase(PI3K)are involved in the development of liver fibrosis through direct and indirect mechanisms, such as regulating the activation of hepatic stellate cells and intrahepatic angiogenesis. Recent studies have shown that small molecule kinase inhibitors(SMKIs)manifest great potential for treating liver fibrosis by inhibiting cell proliferation and angiogenesis. The present review summarizes the activities of tyrosine kinase, serine/threonine kinase and PI3K in liver fibrosis, as well as the pathway they involved in during the development of liver fibrosis, and the recently reported antifibrotic effects of various SMKIs both on preclinical animal models and on patients with liver fibrosis in clinical trials.
10.11665/j.issn.1000-5048.20180203

Osteoporosis is a global public health problem. The kidney, especially the Na-Cl co-trans-porter ( NCC) located in the renal distal tubular cells, which is an important transporter for urinary calcium reg-ulation, plays an important role in calcium homeostasis and bone metabolism. This review summarized recent re-searches on effects and mechanisms of NCC on calcium and bone metabolism.

Objective:To observe the clinical features in Gitelman syndrome (GS) patients with different urinary calcium excretion, and investigate the value of urinary calcium excretion in the clinical classification for GS.Methods:GS cases from the National Rare Diseases Registry System of China (NRSC) (2016-2018) with SLC12A3 gene screened in Peking Union Medical College Hospital were collected. The features of urinary calcium excretion were analyzed, and the phenotypes of patients with hypocalciuria were compared to those without. Hydrochlorothiazide (HCT) test was performed according to the standard process, and the maximal increment of chloride excretion fraction (ΔFECl) was calculated. Results:A total of 83 GS patients were included, among whom 53 (63.86%) patients had hypocalciuria. The ratio of urinary calcium/creatine was significantly lower in patients with hypocalciuria compared to those without [(0.085±0.058) mmol/mmol vs (0.471±0.284) mmol/mmol, t=7.349, P<0.001]. Age, gender, estimated glomerular filtration rate, blood pressure, serum and urinary electrolytes, and alkalosis were all comparable between groups. Fatigue ( χ2=4.595, P=0.032) and polyuria ( χ2=5.778, P=0.016) were less frequently reported in hypocalciuria patients, while all the other clinical symptoms were comparable. Sixteen patients in each group underwent HCT test, and the median value of ΔFECl was comparable between patients with and without hypocalciuria [0.539%(0.430%, 1.283%) vs 0.829% (0.119%,1.298%), U=130.000, P=0.956], both of which indicated no response to HCT. Conclusions:The proportion of low urinary calcium in GS patients is 63.86%. There is no definite relationship between urinary calcium excretion, phenotype and the extent of NCC dysfunction.

Objective:To analyze the clinical features and mutation of myeloid differentiation factor 88 (MYD88) L265P in patients with diffuse large B-cell lymphoma (DLBCL) of central nervous system (CNS).Methods:The clinicopathological materials of 45 cases of DLBCL of CNS were retrospectively collected in Xuanwu Hospital, Capital Medical University from September 2014 to February 2017. The clinicopathological data were retrospectively analyzed, combined with immunohistochemistry, EB virus in situ hybridization, imaging and medical history. The mutation of MYD88 L265P gene was detected by pyrosequencing and its clinical significance was analyzed. Results:The age of the patients ranged from 42 to 82 years [(57.6±8.8) years], including 24 males and 21 females. Totally 93.3% (42/45) of the patients had supratentorial tumours, which were single or multiple. The cerebral hemisphere (31/45, 68.9%) was the most common involved site, and 21 cases (21/45, 46.7%) had multiple lesions. Histologically, DLBCL in the CNS showed diffuse infiltration of tumor tissue, some of which grew around blood vessels in a "sleeve" arrangement. CD 20 and CD 79a were diffusely and strongly positive. Thirty-nine cases (39/45, 86.7%) were non-germinal center B cell (non-GCB) subtype and 6 cases (6/45, 13.3%) were germinal center B cell (GCB) subtype. MYD88 L265P mutation was found in 64.4% (29/45) patients. There was statistically significant difference between non-GCB type (71.8%, 28/39) and GCB type DLBCL (1/6, P=0.017). Compared with the operation/biopsy group without chemotherapy, operation+chemotherapy, biopsy+chemotherapy, operation/biopsy+chemotherapy+stem cell transplantation can improve the survival and prognosis ( HR=0.05, 95% CI 0.01-0.33 , P=0.002; HR=0.04, 95% CI 0.01-0.36 , P=0.004; HR=0.01, 95% CI 0.00-0.17 , P=0.001; respectively). Conclusions:DLBCL of the CNS is aggressive tumor with poor prognosis, the clinical manifestations are complex and diverse, and the diagnosis is challenging. MYD88 L265P is a common and specific gene mutation in primary CNS lymphoma(PCNSL), which is of great significance in the diagnosis and treatment of lymphoma. The MYD88 L265P mutation was more frequently detected in non-GCB than GCB subtype. Chemotherapy can improve the survival rate of PCNSL patients. If chemotherapy achieves complete remission and autologous hematopoietic stem cell transplantation is performed, there may be a chance of long-term survival.

In recent years,with the development of gene testing and new drug research,the diagnosis and treatment of inherited diseases have made rapid progress,corresponding to higher requirements for genetics education.As a teacher of medical genetics,the author joined the course remodeling during last 10 years from a web-based study of genetic disorders to a"case-based learning"supported by flipped classroom in order to optimize teaching effects and learning outcomes.The result of this remodeling project proposes a new strategy to guide perspectives course de-sign in future.

Objective:To investigate the genetic characteristics of pancreatic cancer-associated diabetes mellitus (PCDM) and screen out the possible molecular markers for PCDM.Methods:The clinical data of pancreatic cancer (PC) cohort from The Cancer Genome Atlas (TCGA) were selected and collected, and the patients were divided into PCDM( n=11) and PC groups( n=109) according to whether the patients were diagnosed as diabetes within 2 years of PC diagnosis. Then, the mRNA microarray data of genome expression were extracted from TCGA PC cohort, and the differentially expressed genes (DEGs) were screened out by the " limma" package of R software based on (|log2 fold change|>2 and P<0.05). The functions of DEGs were revealed with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, a protein-protein interaction (PPI) network was constructed with the STRING database, and the hub genes were identified by the molecular complex detection (MCODE) module of Cytoscape software. Results:The analysis showed that among 20 531 genes, 47 genes were significantly upregulated, and 60 genes were significantly downregulated in the PCDM group. GO analyses revealed that 107 DEGs were mainly involved in the positive regulation of secretory function in terms of biological function (gene number=9, P<0.01); in the regulation of receptor function of molecular function (gene number=10, P<0.01); and in the intracavitary components of cytoplasmic microtubules of cellular components (gene number=8, P<0.01). The results of KEGG pathway enrichments revealed that DEGs mainly affected PCDM via cytokine interactions (gene number=8, P<0.01). Finally, five hub genes, including GNG8, CNR2, GALR2, CXCL13, and NPY2R, were identified for PCDM in PPI network analysis. Conclusions:The feature genes of PCDM are mainly different from PC in terms of secretion function, receptor function, cytoplasmic microtubule composition, and cytokine interaction. Five genes including GNG8, CNR2, GALR2, CXCL13, and NPY2R may become potential molecular markers for PCDM.

Background::Patients who undergo coronary artery bypass grafting (CABG) are known to be at a significant risk of experiencing long-term adverse events, emphasizing the importance of regular assessments. Evaluating health-related quality of life (HRQoL) serves as a direct method to gauge prognosis. Our objective is to ascertain the prognostic significance of consecutive HRQoL assessments using the Physical Component Summary (PCS) and Mental Component Summary (MCS) derived from the Short-Form 36 (SF-36) health survey in CABG patients.Methods::The study population consisted of 433 patients who underwent isolated elective CABG at Fuwai Hospital between 2012 and 2013. SF-36 assessments were conducted during both the hospitalization period and follow-up. The primary endpoint of the study was all-cause mortality, while the secondary outcome was a composite measure including death, myocardial infarction, stroke, and repeat revascularization. We assessed the relationships between the PCS and MCS at baseline, as well as their changes during the first 6 months after the surgery (referred to as ΔPCS and ΔMCS, respectively), and the observed outcomes.Results::The patients were followed for an average of 6.28 years, during which 35 individuals (35/433, 8.1%) died. After adjusting for clinical variables, it was observed that baseline MCS scores (hazard ratio [HR] for a 1-standard deviation [SD] decrease, 1.57; 95% confidence interval [CI], 1.07–2.30) and ΔMCS (HR for a 1-SD decrease, 1.67; 95% CI, 1.09–2.56) were associated with all-cause mortality. However, baseline PCS scores and ΔPCS did not exhibit a significant relationship with all-cause mortality. Notably, there was a dose-response relationship observed between ΔMCS and the likelihood of all-cause mortality (HRs for the 2nd, 3rd and 4th quartiles compared to the 1st quartile, 0.33, 0.45 and 0.11, respectively).Conclusions::Baseline MCS and changes in MCS were independent predictors for long-term mortality of CABG. Better mental health status and recovery indicated better prognosis.

Objective To understand the types, proportions, and radiation dose levels of pediatric cardiac interventional procedures. Methods A retrospective analysis was conducted using the basic information and radiation dose data from all cases of pediatric cardiac interventional procedures performed at two tertiary medical institutions in Beijing from July 2023 to August 2024. The data included air kerma-area product, reference point air kerma, and fluoroscopy time. Descriptive statistical analysis was conducted to evaluate the basic information and dosimetric indicators of the procedures. Non-parametric tests were employed to examine the differences between variables, and Spearman’s correlation coefficient was utilized to investigate the relationships among various factors. All cases were categorized into the diagnostic group and the therapeutic group. In the diagnostic group, the majority of procedures involved catheter examinations and angiography for identifying the type of disease. In the therapeutic group, the primary procedures included patent ductus arteriosus, atrial septal defect, ventricular septal defect, patent foramen ovale, pulmonary stenosis, radiofrequency catheter ablation, major aortopulmonary collateral arteries, complex congenital heart diseases, and other interventional procedures. Results The survey comprised 1008 cardiac interventional procedures involving 476 males and 532 females. The ages of the participants ranged from 0 to 15 years and the body weights from 4.5 to 105 kg. Among these participants, 92 and 916 were classified in the diagnostic and therapeutic groups, respectively. The proportions of interventional procedures were in the order of atrial septal defect (36.9%), radiofrequency catheter ablation (22.3%), patent ductus arteriosus (15.1%), complex congenital heart disease (4.8%), patent foramen ovale (3.1%), pulmonary stenosis (3.1%), ventricular septal defect (2.2%), other procedures (2.0%), and major aortopulmonary collateral arteries (1.5%). The radiation doses of different interventional procedures were statistically different (P < 0.05), with air kerma-area product ranging from 0.02 to 658.4 Gy·cm², reference point air kerma from 0.1 to 2524 mGy, and fluoroscopy time from 0.2 to 62 min. Conclusion In pediatric cardiac interventional procedures, there is considerable variability in radiation doses for the same type of procedure. Additionally, radiation doses for identical procedures vary between different medical institutions, and a few cases carry a risk of deterministic effects.

Schimke immuno-osseous dysplasia (SIOD)caused by SMARCAL1 gene mutations is a rare genetic disorder characterized by multi-system involvement, including T-cell dysfunction, skeletal dysplasia, disproportionate short stature, nephrotic syndrome, and kidney failure. This multidisciplinary consultation involved a 9-year-old boy with intrauterine growth retardation, presenting with short stature, T-cell lymphopenia, proteinuria, and degenerative bone and joint disease. Treatment primarily focused on symptomatic and supportive care. Through the multidisciplinary rare disease consultation, holistic support was provided to the patient, offering comprehensive care from various specialtiesx.We also aim to use this case report to enhance clinicians′ under-standing of SIOD and improve the management and treatment of rare diseases.

A young female patient presented with fever, arthralgia, and rash was diagnosed with adults still's disease. When treated with glucocorticoid steroid, the above patient progressed to anuria, sudden, and confusion. After a teamwork involving different departments, the patient was finally diagnosed with atypical hemolytic uremic syndrome (aHUS) and treated with good outcome. aHUS is a rare disease, while Eculizumab is an orphan drug. The diagnosis and treatment of the patient reveals the importance of multidisciplinary team on the diagnosis and treatment of rare and difficult diseases.