Factor VII Deficiency ; genetics ; Humans

Cardiomyopathy, Dilated ; etiology ; pathology ; therapy ; Humans ; Myocardium ; pathology

Abstract: Objective　To investigate the cause of poisoning leading to multi-organ damage in a patient with an unexplained condition, to confirm the type and exposure amount of the pathogenic factor, to identify the sources of pathogenic factors, and to provide references and bases for the clinical treatment and the prevention of such events. Methods　Starting with the unknown traditional Chinese medicine taken by patients for a long time, the targeted screening strategy was initially used to screen for alkaloid poisoning. Subsequently, a non-targeted screening strategy using Information-dependent Acquisition Mode (IDA) was used to screen the patient's blood, urine, and drug samples. Combining the toxicological effects of suspected compounds with the patient′s clinical manifestations, the main pathogenic factors were determined. Quantitative methods were established according to standard substances to quantify the pathogenic factors in all the samples. An epidemiological investigation was conducted to obtain the patient's medication history, and combined with the examination of the medication's specifications and content, the exposure dose of each pathogenic factor was determined. Finally, a Data data-independent acquisition (DIA) mode termed Sequential Window Acquisition of All Theoretical Fragment-Ion Spectra (SWATH) was used to screen all samples, unbiasedly collecting secondary mass spectrometry information of compounds, thereby verifying and supplementing the confirmed pathogenic factors. Results　Targeted screening ruled out common alkaloid poisoning. Tadalafil was detected in the patient's blood and urine. Tadalafil, sildenafil, chloropretadalafil, acetaminophen, and diclofenac were detected in unknown traditional Chinese medicine. The side effects of these compounds were consistent with the clinical manifestations of the patient. The highest daily average exposure doses of tadalafil, sildenafil, chloropretadalafil, acetaminophen, and diclofenac were 30.5 mg, 15.8 mg, 0.05 mg, 45.6 mg, and 3.2 mg respectively, which were seriously excessive. The SWATH mode also screened out the above five drugs. In addition, palmatine chloride was also detected. Conclusions　Combining the patient's clinical manifestations and epidemiological data, this study integrated targeted screening, untargeted screening, targeted quantitative strategies, data-dependent, and DIA mode to confirm that this case is a drug poisoning event caused by long-term overdose consumption of traditional Chinese medicine adulterated with chemical components. This study provides insights for the diagnosis and investigation of patients with poisoning for unknown causes, offering references for emergency detection and management of related poisoning incidents.

Objective: To investigate the expressions of signal transducer and activators of transcription 3 (STAT3) and suppressor of cytokine signaling 3 (SOCS3) protein in the breast carcinoma tissue and their relationship with tumor differentiation, invasion, and metastasis. Methods: The expression of STAT3, phospho-STAT3 and SOCS3 protein were determined by tissue microarray and immunohistochemistry with EnVision system in 71 cases of archival breast carcinoma tissues and 41 cases of noncancerous tissues. The relationship between their expression and the clinical pathological parameters were analyzed. Results: (1) The positive rates of STAT3, phospho-STAT3, and SOCS3 was 78.9%, 69.0%, and 29.6%, respectively. The difference was significantly different compared with control (P<0.01, P<0.01, and P<0.05). (2) The expressions of STAT3 and phospho-STAT3 were positively related with the histological grade, the axillary lymph node metastasis, and the clinical stage (P<0.01), but not related with the age, the tumor size, and the histological grade of breast carcinoma tissues (P>0.05). The expression of SOCS3 was negatively related with the histopathologic grade and the axillary lymph node metastasis (P<0.05), but was not related with the age, histological type, the tumor size, and the clinical stage (P>0.05). (3) The expression of STAT3 and phospho-STAT3 had negative correlation with the expression of SOCS3 in breast carcinoma tissues (P<0.01). Conclusion: The overexpressions of STAT3 and phospho-STAT3 and the down-regulated expression of SOCS3 closely correlated with the tumor carcinogenesis, progression, invasion, and metastasis of breast carcinoma. Detection of their expression is helpful in accessing the malignant degree and the biological behaviors of breast carcinoma.

OBJECTIVE: To evaluate and compare whole exome sequencing (WES) and targeted panel sequencing in the clinical molecular diagnosis of the Chinese families affected with inherited retinal dystrophies (IRDs). METHODS: The clinical information of 182 probands affected with IRDs was collected, including their family history and the ophthalmic examination results. Blood samples of all probands and their relatives were collected and genomic DNA was extracted by standard protocols. The first 91 cases were subjected to the WES and the other 91 cases were subjected to a specific hereditary eye disease enrichment panel (HEDEP) designed by us. All likely pathogenic and pathogenic variants in the candidate genes were determined by Sanger sequencing and co-segregation analyses were performed in available family members. Copy number variations (CNVs) detected by HEDEP were further validated by multiplex ligation-dependent probe amplification (MLPA). As PRGR ORF15 was difficult to capture by next generation sequencing (NGS), all the samples were subjected to Sanger sequencing for this region. All sequence changes identified by NGS were classified according to the American College of Medical Gene-tics and Genomics and the Association for Molecular Pathology (ACMG/AMP) variant interpretation guidelines. In this study, only variants identified as pathogenic or likely pathogenic were included, while those variants of uncertain significance, likely benign or benign were not included. RESULTS: In 91 cases with WES, pathogenic or likely pathogenic variants were determined in 30 cases, obtaining a detection rate of 33.00% (30/91); While in 91 cases with HEDEP sequencing, pathogenic or likely pathogenic variants were determined in 51 cases, achieving the diagnostic rate of 56.04% (51/91), and totally, the diagnostic rate was 44.51%. HEDEP had better sequencing coverage and read depth than WES, therefore HEDEP had higher detection rate. In addition, HEDEP could detect CNVs. In this study, we detected disease-causing variants in 29 distinct IRD-associated genes, USH2A, ABCA4 and RPGR were the three most common disease-causing genes, and the frequency of these genes in Chinese IRDs population was 11.54% (21/182), 6.59% (12/182) and 3.85% (7/182), respectively. We found 43 novel variants and 6 cases carried variants in RPGR ORF15. CONCLUSION NGS in conjunction with Sanger sequencing offers a reliable and effective approach for the genetic diagnosis of IRDs, and after evaluating the pros and cons of the two sequencing methods, we conclude that HEDEP should be used as a first-tier test for IRDs patients, WES can be used as a supplementary molecular diagnostic method due to its merit of detecting novel IRD-associated genes if HEDEP or other methods could not detect disease-causing va-riants in reported genes. In addition, our results enriched the mutational spectra of IRDs genes, and our methods paves the way of genetic counselling, family planning and up-coming gene-based therapies for these families.
DNA Copy Number Variations ; Humans ; Mutation ; Pedigree ; Retinal Dystrophies/genetics* ; Whole Exome Sequencing

To evaluate the influence of phacoemulsification on corneal endothelium of senile cataract with lupus nephritis (LN).
●METHODS:This clinical trial involved 40 cataract patients with lupus nephritis (40 eyes), and 50 cases (50 eyes) without lupus nephritis. All of them underwent phacoemulsification+lOL implantation. The parameters of corneal endothelial cell including central corneal endothelium cell density ( CED ), average area of endothelial cell ( AVE) and coefficient of variation ( CV) were recorded by corneal endothelial microscope pre -operation and at one month after operation. The data were analyzed by SPSS 13. 0 statistical software.
● RESULTS: Both LN group and control group, the morphology of coneal endothelial was statistical significant differences between pre - operation and 1mo postoperation. The CED was lower, AVE and CV were higher ( P < 0. 05, respectively). A significant decrease in CED was seen in the LN group than did in the control group (P < 0. 05). Compared to control group,the post -operative AVE and CV in LN group was significantly increased (P<0. 05).
● CONCLUSlON: The corneal endothelial cell in lupus nephritis patients is more fragile. Safe and reliable operation should be selected for these patients.

Objective To study the correlation between prognosis of non-small cell lung cancer ( NSCLC) patient and serum levels of HGF and IL-6. Methods Eligible 109 NSCLC patients and preoperative blood samples of each patient in our hospital from March 2013 to May 2014 were collected. Then the levels of HGF and IL-6 of serum samples were detected by using ELISA kit. All patients were followed up for 1 year. The neoplasm staging:67 cases were stagingⅠ-Ⅱ,38 cases were stagingⅢ,2 cases were staging IV. There were 79 cases with ad-enomatous carcinoma( ADC) ,26 cases with squamous carcinoma( SCC) and 4 cases with NSCLC. According to the TNM staging,there were 79 cases in pN( -) group,31 in pN( +) group,77 in pT(T1-T2) group and 28 in pT(T3-T4) group. Results The average concentration of HGF and IL-6 in serum were 860 pg/mL and 2. 7 pg/mL respectively. Analysis of survival indicated that,compared to those patient with lower serum level of HGF and IL-6,the survival rate of patient with high serum level was much lower. The difference was statistically signifi-cant (HGF,P=0. 019;IL-6,P=0. 002). The analysis of the patients with stageⅢdisease separately also indicated that survival rate of pa-tient with lower serum of HGF and IL-6 was higher than others. Conclusion The serum levels of HGF and IL-6 might be a effective indica-tors for predicting prognosis of the NSCLC paitents.

Objective To study the effects and current mechanism of low concentration of lidocaine on evoked-bursting (EB) firing of dorsal root ganglion (DRG) neurons in rat model of chronic compression (CCD) of DRG . Methods Twenty-four SD rats were divided into normal control group (n=12) and CCD model group (n=12). CCD group was treated with chronic oppression on L4 and L5 DRG with L shape bar. Normal control group received no treatment. In vivo intracellu?lar recording was used to record the incidence of EB and the effect of lidocaine on subthreshold membrane potential oscilla?tion (SMPO). Patch clamp recording was used to record the effect of lidocaine on persistent sodium current (INaP). Results The incidence of EB increased in CCD group( 45.97%, 57/124), which was significantly different when compared with nor?mal group (χ2=26.810, P<0.01). The magnitude of SMPO, INaP and EB were inhibited in a reversible way by lidocaine (50μmol/L). Conclusion The low concentration of lidocaine might play an analgesic effect in peripheral nervous system by se?lectively inhibiting INap, which participates in SMPO formation.

Objective To study the effect of melatonin on ultrastructural changes of aorta endothelium of insulin-resistant (IR) rats. Methods Insulin-resistant rat model was established with SD rats (n=20) aged 6-8 weeks by high-glucose diet (70% calories from glucose) for 6 weeks. All the IR rats were divided into 2 groups: with melatonin (MEL group, n=10) and without melatonin (control group, n=10). Rats in MEL group were filled with melatonin (10mg? kg -1?d -1) for 6 weeks. The ultrastructure of aorta endothelium was observed with transmission electron microscope (TEM). Results Systolic blood pressure (SBP), serum triglyceride (TG), low-density lipoprotein (LDL-c), insulin (Ins), and malondialdehyde (MDA) declined while the Serum high-density lipoprotein(HDL-c), superoxide dismutase (SOD) and insulin sensitive index (ISI) elevated in the rats of MEL group than that in control group (P

Child ; Female ; Humans ; Polyendocrinopathies, Autoimmune ; classification ; diagnosis ; therapy ; Treatment Outcome