[Effects of ascites derived exosomes on the stemness and invasion ability of ovarian cancer stem-like cell].

Objective: To investigate the effects of ovarian cancer ascites-derived exosomes on the stem cell properties and invasion ability of ovarian cancer stem-like cell (OCS-LC). Methods: (1) A2780 cells were induced into OCS-LC in serum-free medium, and authenticating their stem-like properties by sphere-forming test, differentiation test and CD133 marker detection. (2) Exosomes from ascites and A2780 cell were extracted by ultracentrifugation, then authenticating them. The morphology of exosomes was observed by the transmission electron microscope, exosome particle size was measured by nanoparticle tracking analysis (NTA). The expressions of heat shock protein 70 (HSP-70), CD63 and CD9 were detected by western blot. (3) The exosomes from ovarian cancer ascites and tumor cell supernate were co-cultured with OCS-LC. The groups were divided into control group, ascites-derived exosomes (ADE) group (ADE+OCS-LC group), and cells-derived exosomes (CDE) group (CDE+OCS-LC group). The sphere-forming ability was evaluated by sphere-forming cycle, maximum sphere diameter and sphere-forming rate of each group; the expression of CD133 was detected by immunofluorescence staining under microscope; quantitative real-time (qRT)-PCR was used to detected the expression levels of octamer-4 (Oct-4), Nanog mRNA of the signature genes in the stem cells of each group; the metastasis ability of each group was measured by transwell assay. Results: (1) Identification of OCS-LC: sphere-forming experiment showed that the suspension of OCSC single cells was grown in serum-free medium in secondary sphere-forming. Differentiation function experiment showed that OCS-LC were differentiated into adherent A2780 cells by changing the growth mode in serum containing medium. Flow cytometry showed that the proportion of CD133 positive (CD133+) cells in OCS-LC group was (18.9±0.9)%, significantly higher than that of control group (0.6±0.5)% (t=38.570, P<0.01). (2) Under transmission electron microscope, clear lipid bilayer structure was observed in ADE and CDE, and one side presented a concave hemispheric or cup like structure. NTA showed that the diameter of exosomes mainly ranged from 30 to 100 nm, with an average diameter of 67.2 nm. Western blot analysis showed that the specific protein molecules HSP-70, CD63 and CD9 were positive. (3) Three groups' OCS-LC could continue to grow into spheres, and the group of ADE+OCS-LC showed two growth modes, most of the cells continued to grow into spheres, while a small part of cells grew in adherent differentiation. The sphere-forming rate of OCS-LC in the control group, ADE+OCS-LC group, and CDE+OCS-LC group were (1.05±0.20)%, (4.15±0.10)%, and (10.45±0.25)%, the sphere-forming cycle of OCS-LC in the three groups were (15.3±1.5), (10.3±0.6), and (6.7±0.6) days, and the maximum diameters of OCS-LC were (100.3±3.2), (145.2±5.1) and (170.0±2.1) µm, respectively. And the differences were statistically significant (all P<0.05). After co-culture of exosomes with OCS-LC, the sphere-forming ability of cells in the group of CDE+OCS-LC was prior to ADE+OCS-LC group (all P<0.05). Immunofluorescence staining showed that the number of CD133 green fluorescent chromophore cells in OCS-LC groups [(46.2±2.1)%, (58.4±2.2)%] was significantly higher than that in the control group [(26.6±1.5)%] after the addition of exosomes in co-culture, the positive rate of CD133 was higher than that in the control group(F=187.588, P<0.05). The qRT-PCR results showed that the expression levels of Oct-4 mRNA in ADE+OCS-LC and CDE+OCS-LC groups were 3.46±0.24, 4.03±0.31, compared with that in control group (1.04±0.12), the differences were statistically significant (F=134.932, P<0.05). The mRNA expression levels of Nanog were 1.57±0.32, 2.66±0.15, which were significantly higher than that in the control group (1.00±0.07), and the differences were statistically significant (F=49.329, P<0.05). And the expression of both in CDE+OCS-LC group increased more significantly than ADE+OCS-LC group (all P<0.05). The number of invasive cells in the three groups of OCS-LC were: control group 30±5, ADE+OCS-LC group 102±4, CDE+OCS-LC group 210±7, and there were statistically significant differences among three groups (F=820.800, P<0.05). Compared with the control group, the number of invaded cells in the co-culture group were significantly increased (P<0.05), and the CDE+OCS-LC group had the higher cell invasion ability then the ADE+OCS-LC group (t=23.202, P<0.05). Conclusions: Exosomes derived from ovarian cancer ascites could enhance and maintain the stemness of OSC-LC, and promote the invasion of tumor cells. Moreover, CDE is superior to ADE.

[Comparison on short-term safety outcomes between off-pump and on-pump coronary artery bypass grafting by experienced surgeons: a single center study with 31 075 cases].

Objective: To compare the short-term outcomes between off-pump and on-pump coronary artery bypass graft (CABG) by experienced surgeons with similar surgical team in a single large-volume cardiac surgery center. Methods: A total of 31 075 patients with multivessel coronary disease who underwent isolated off-pump or on-pump CABG between January 1, 2009 and December 31, 2019 by experienced surgeons in Fuwai hospital were enrolled in this retrospective study. Patients was divided into on-pump CABG group and on-pump CABG group on an intention-to treat basis. Short term safety endpoints, including 30 days mortality, composite endpoint of major morbidity or mortality, prolonged postoperative length of stay (PLOS), and prolonged ICU length of stay (PICULOS), and distal anastomosis were compared between the two groups. Mortality was evaluated on 30 days post operation, other endpoints were collected before discharge. After 1∶1 propensity-score matching of baseline characteristics for on-pump and off-pump CABG, postoperative endpoints were compared with use of McNemar's test and further adjusted with the use of a logistic regression model. Results: After propensity-score matching, 10 243 matched pairs of patients were included in the final analysis, there were 4 605(22.5%) females and mean age was (60.7±8.6) years. The standardized differences were less than 5% for all baseline variables in matched cohort. Univariate analysis indicated lower risk of 30 days mortality (0.2% vs. 0.7%, P<0.001), major morbidity or mortality (5.7% vs. 8.8%, P<0.001), PLOS (3.2% vs. 4.9%, P<0.001), PICULOS (9.4% vs. 12.2, P<0.001), and lower number of distal anastomosis ((3.3±0.8) vs. (3.6±0.8), P<0.001) in off-pump CABG group than in on-pump CABG group. After adjustment of cofounders, multivariate analysis showed that off-pump CABG was still associated with a lower risk of 30 days mortality (OR=0.29, 95%CI: 0.09-0.87, P=0.027), composite endpoint of major morbidity or mortality (OR=0.60, 95%CI: 0.53-0.68, P<0.001), PLOS (OR=0.64, 95%CI 0.54-0.75, P<0.001), PICULOS (OR=0.76, 95%CI: 0.69-0.84, P<0.001). Conclusions: Off-pump CABG is related with superior short-term safety outcomes than on-pump CABG by experienced surgeons in our center.

[Cathepsin L mediates glomerular endothelial cell injury by cleavaging complement C3 in trichloroethylene-sensitized mice].

Objective: To observe the expressions of complement 3 (C3) and endothelial cell injury-associated proteins before and after cathepsin L (CTSL) blockade in renal injury of trichloroethylene (TCE) -sensitized mice. Methods: In June 2018, 41 SPF female BALB/c mice were divided respectively into blank control group (n=5) , vehicle control group (n=5) , TCE group (n=15) and TCE+CTSLi group (n=16) to establish trichloroethylene-sensitized mice model by pretreating the mice with intraperitoneal injection of CTSL inhibitor (CTSLi) and using TCE for the first and last challenge. According to the skin sensitization score, the mice were divided into positive group and negative group. 72 hours after the last challenge, the renal function indexes of the mice were detected, the pathological changes of mice kidneys were observed, and the glomerular C3 and endothelial cell damage-related proteins [vascular cell adhesion molecule 1 (VCAM-1) , tight junction protein 5 (Claudin-5) and Syndecan-1] expression levels were detected. Results: The sensitization rates of mice in TCE group and TCE+CTSLi group were 53.3% (8/15) and 50.0% (8/16) , respectively, and there was no significant difference between the two groups (P>0.05) . Compared with vehicle control group and the corresponding TCE negative group, the serum creatinine (CRE) and blood urea nitrogen (BUN) levels of mice in the TCE positive group was increased, while the TCE positive group were higher than the TCE+CTSLi positive group (P<0.05) . Pathological examination showed obvious vacuolar degeneration and cellular edema in the mice kidney of the TCE positive group. In the TCE+CTSLi positive group, the above pathological damage was significantly improved. Immunohistochemical results showed that the expression of glomerular C3 fragment and VCAM-1 in TCE positive group were significantly higher than that of the vehicle control and TCE negative group (P<0.05) , while TCE+CTSLi positive group was significantly lower than that of TCE positive group (P<0.05) . Western blot test results showed that the relative expression levels of Claudin-5 and Syndecan-1 protein in the mice glomeruli of TCE positive group were significantly lower than those in the vehicle control group and TCE negative group (P<0.05) . Compared with the TCE positive group, the Claudin-5 protein was increased in the kidney of the TCE+CTSLi positive group, but the difference was not statistically significant (P>0.05) , while the Syndecan-1 protein was significantly increased in the TCE+CTSLi positive group (P<0.05) . Conclusion: CTSL may mediate the glomerular structural damage by cutting complement C3, activating the complement system, damaging endothelial cell structural protein Syndecan-1 and overexpressing adhesion molecule VCAM-1 in TCE-sensitized mice. Inhibiting the expression of CTSL may be an effective way to protect the glomerular integrity of structure and function in pharmacology.

Survey on common reference intervals for general chemistry analytes in Hong Kong.

INTRODUCTION: Reference intervals (RIs) are essential tool for proper interpretation of results. There is a global trend towards implementing common RIs to avoid confusion and enhance patient management across different laboratories. However, local practices with respect to RIs lack harmonisation. METHODS: We have conducted the first local survey regarding RIs for 14 general chemistry analytes in 10 chemical pathology laboratories that employ four different analytical platforms (Abbott Architect, Beckman Coulter AU, Roche Cobas, and Siemens Dimension EXL). Analytical bias was assessed by an inter-laboratory results comparison of external quality assurance programmes. RESULTS: Sufficient inter-laboratory and inter-platform agreement regarding the 10 analytes (albumin, alanine aminotransferase, aspartate aminotransferase, chloride, gamma-glutamyl transferase, phosphate, potassium, sodium, total protein, and urea) were demonstrated. However, the RIs were heterogeneous across all laboratories, with percentage differences of the upper RI value of up to 47% for aspartate aminotransferase (absolute difference of 16 U/L), 29% for urea (1.8 mmol/L), and 18% for potassium (0.8 mmol/L). The percentage difference between lower RI values was up to 24% for urea (0.6 mmol/L), 22% for phosphate (0.16 mmol/L), and 8% for total protein (5 g/L). The coefficients of variation of the upper RI values of potassium and sodium were 1.2 times and 1.0 times of their corresponding between-subject biological variation, respectively, representing unnecessary variations that are overlooked and unchecked in current practice. CONCLUSIONS: We recommend the use of common RIs for general chemistry analytes in Hong Kong to prevent interpreter confusion, improve electronic data transfer, and unite laboratory practice. This is the first local study on this topic, and our data can lay the groundwork for increasing harmonisation of RIs across more laboratory tests.

Sudden arrhythmia death syndrome in young victims: a five-year retrospective review and two-year prospective molecular autopsy study by next-generation sequencing and clinical evaluation of their first-degree relatives.

OBJECTIVE: Sudden arrhythmia death syndrome (SADS) accounts for about 30% of causes of sudden cardiac death (SCD) in young people. In Hong Kong, there are scarce data on SADS and a lack of experience in molecular autopsy. We aimed to investigate the value of molecular autopsy techniques for detecting SADS in an East Asian population. METHODS: This was a two-part study. First, we conducted a retrospective 5-year review of autopsies performed in public mortuaries on young SCD victims. Second, we conducted a prospective 2-year study combining conventional autopsy investigations, molecular autopsy, and cardiac evaluation of the first-degree relatives of SCD victims. A panel of 35 genes implicated in SADS was analysed by next-generation sequencing. RESULTS: There were 289 SCD victims included in the 5-year review. Coronary artery disease was the major cause of death (35%); 40% were structural heart diseases and 25% were unexplained. These unexplained cases could include SADS-related conditions. In the 2-year prospective study, 21 SCD victims were examined: 10% had arrhythmogenic right ventricular cardiomyopathy, 5% had hypertrophic cardiomyopathy, and 85% had negative autopsy. Genetic analysis showed 29% with positive heterozygous genetic variants; six variants were novel. One third of victims had history of syncope, and 14% had family history of SCD. More than half of the 11 first-degree relatives who underwent genetic testing carried related genetic variants, and 10% had SADS-related clinical features. CONCLUSION: This pilot feasibility study shows the value of incorporating cardiac evaluation of surviving relatives and next-generation sequencing molecular autopsy into conventional forensic investigations in diagnosing young SCD victims in East Asian populations. The interpretation of genetic variants in the context of SCD is complicated and we recommend its analysis and reporting by qualified pathologists.

Prevalence of Ureaplasma urealyticum, Chlamydia trachomatis, Neisseria gonorrhoeae and herpes simplex virus in Beijing, China.

The prevalence of sexually transmitted infection (STI) pathogens in Beijing, China, is rarely reported. In this study, 34 911 symptomatic outpatients with suspected genital infections who attended outpatient clinics in a tertiary care hospital were included to investigate the updated prevalence of Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and herpes simplex virus (HSV) from 1 January 2013 to 31 December 2016 in Beijing, China. Results indicated that a decrease trend (UU, CT, NG and HSV) in male and an increase trend (UU, CT and NG) in female were observed during the period. Patients aged 20-39 years old were mostly affected by these pathogens, while the prevalence in patients aged 20-29 years old was the highest, The prevalence of UU in male was significantly lower than in female (31.5% vs. 49.3%, P < 0.05), while the prevalence of NG in male was significantly higher than in female (2.5% vs. 0.8%, P < 0.05). In patients with co-infections, 60.6% of male and 71.4% of female were co-infected by UU + CT. In total, 11.9% and 88.1% of patients with HSV infections were confirmed to be infected by HSV-1 and HSV-2. This study could contribute to a better understanding of the current epidemiological features of UU, NG, CT and HSV among symptomatic patients attending an outpatient clinic in Beijing, China, and thus facilitate to develop more effective intervention, prevention and treatment of STI.

[Mode of median nerve irritation under different wrist forcing postures observed by ultrasonography and foot pressure measurement system].

Objective: To analyze the influence of simulation mouse use motion under different wrist forcing postures on median nerve, tendons and ligaments in the carpal tunnel. Methods: From June to November in 2017, a total of 49 healthy volunteers [aged from 18 to 27 years, 24 males (48 cases of hands) and 25 females (50 cases of hands)] were selected in the Institute of Digitized Medicine and First Affiliated Hospital of Wenzhou Medical University.Three hand postures of the volunteers were simultaneously and continuously measured by using LOGIQ E9 ultrasonic diagnostic apparatus and Zebris foot pressure distribution measurement system.Seventeen parameters of nerves, tendons and ligaments in carpal tunnel were observed under natural (0 N), and two forced (25 and 50 N) states.Double factor variance analysis was performed with generalized estimating equation (GEE). Results: With increasing pressure (0, 25 and 50 N) of hand postures, the distance between median nerve and transverse carpal ligament were all less than 0.2 cm.The differences in both the distance between median nerve and flexor pollicis longus under the hand pressure changes or under the hand posture changes and the top angle of a triangle composed of median nerve, flexor pollicis longus and flexor digitorum superficialis group under the hand pressure changes or under the hand posture changes were all significant under the GEE analysis (all P<0.01). There were no significant changes in all other structural parameters in the carpal tunnel with the increasing of hand pressure (all P>0.05). Conclusions: The influence of the transverse carpal ligament to the median nerve belongs to the mechanism of pressure-induced irritation damage.The influence of flexor pollicis longus to median nerve belongs to the mechanism of tension-induced irritation damage.The influence of flexor digitorum superficialis to median nerve belongs to the mechanism of mixed shear irritation damage.

Flunarizine versus topiramate for chronic migraine prophylaxis: a randomized trial.

OBJECTIVES: Chronic migraine (CM) is a prevalent and devastating disorder with limited therapeutic options. This study explored the efficacy of 10 mg/d flunarizine for CM prophylaxis as compared with 50 mg/d topiramate. METHODS: We conducted a prospective, randomized, open-label, blinded-endpoint trial. Patients with CM were randomized to flunarizine and topiramate treatment. The primary outcomes assessed were the reductions in the total numbers of headache days and migraine days after 8 weeks of treatment. Secondary outcomes were reductions in the numbers of days of acute abortive medication intake and acute abortive medication tablets taken, and the 50% responder rate. RESULTS: Sixty-two subjects were randomized (n=31/group). Patients treated with flunarizine showed significant reductions in the numbers of total headache days (-4.9 vs -2.3, P=.012) and migraine days (-4.3 vs -1.4, P=.001) compared with those treated with topiramate. Patients treated with flunarizine also showed significant reductions in the numbers of days of acute abortive medication intake (-2.3 vs -0.2, P=.005) and acute abortive medication tablets taken (-4.6 vs -0.5, P=.005) and had a higher 50% responder rate in terms of total headache days (58.6% vs 25.9%, P=.013) and migraine days (75.9% vs 29.6%, P=.001), compared with topiramate-treated patients. Flunarizine was generally well tolerated and had a safety profile comparable to that of topiramate. CONCLUSIONS: Our results suggest that, in an 8-week study, 10 mg/d flunarizine is more effective than 50 mg/d topiramate for CM prophylaxis.

crAssphage is not associated with diarrhoea and has high genetic diversity.

crAssphage is a newly discovered gut bacteriophage. However, its pathogenicity and molecular epidemiology in humans are as yet unclear. In this study, we investigated the association between crAssphage and diarrhoea, as well as the molecular epidemiology of crAssphage in Chinese patients from our hospital. Our results indicated that there were no significant differences in the crAssphage-positive ratio and viral loads in faecal supernatants between adults with diarrhoea and healthy adults. Of infants and children with diarrhoea, 2·8% were found to be crAssphage-positive, including two infants aged <1 month. Markedly, of all confirmed crAssphage-positive strains, 100% had the ORF00039 deletion and 77·8% had low identity of ORF00018 compared to crAssphage (GenBank accession no. NC_024711, designated genotype 1). Thus, crAssphage was not associated with diarrhoea and most strains of crAssphage in Chinese patients (designated genotype 2) were characterized by the ORF00039 deletion and low identity of ORF00018.

[Predictive value of deubiquitination enzymes USP37 in the prognosis of breast cancer].

OBJECTIVE: To explore the expression of Ubiquitin-specific processing enzyme 37(USP 37)in breast cancer and its association with the prognosis of breast cancer. METHODS: In this study, the method of Western blot was utilized to examine the expression of USP37 protein in breast cancer fresh tissue. Immunohistochemistry (IHC) was used to determine the expression of USP37 in 533 cases of breast cancer. Receive operating characteristic (ROC) curve analysis was employed to determine a cut-off score for USP37 expression. For validation, the ROC-derived cut-off score was subjected to analysis the association of USP37 expression with cancer patient outcome and clinical characteristics. RESULTS: USP37 protein was mainly located in cytoplasm of the cell, occasionally in nucleus by immunohistochemistry. In the normal breast tissue, USP37 was not expressed or with low expression level, while in the 533 cases of breast cancer, the high USP37 expression was detected in 50.7% samples (270/533) with corresponding low or negative expression rate 49.3% (263/533). We found that USP37 was highly expressed in primary breast cancer tissues compared to paired adjacent non-cancerous tissues. High expression of USP37 was associated with breast cancer node classification, molecular classification and proliferation biomarker Ki67. Both univariate and multivariate analyses further revealed that USP37 expression was an independent poor prognostic parameter for overall survival (OS), recurrence-free survival (RFS) and metastasis-free survival (MFS) in breast cancer. Furthermore, USP37 expressions divided the luminal and triple negative breast cancer into different prognosis subgroups. CONCLUSION: Our findings first provide evidences that high expression of USP37 served as an independent molecular biomarker for poor prognosis in breast cancer.

Genetics of Apparently Sporadic Pheochromocytoma and Paraganglioma in a Chinese Population.

Identification of germline mutation in patients with apparently sporadic pheochromocytomas and paragangliomas is crucial. Clinical indicators, which include young age, bilateral or multifocal, extra-adrenal, malignant, or recurrent tumors, predict the likelihood of harboring germline mutation in Caucasian subjects. However, data on the prevalence of germline mutation, as well as the applicability of these clinical indicators in Chinese, are lacking. We conducted a cross-sectional study at a single endocrine tertiary referral center in Hong Kong. Subjects with pheochromocytomas and paragangliomas were evaluated for the presence of germline mutations involving 10 susceptibility genes, which included NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, TMEM 127, MAX, and FH genes. Clinical indicators were assessed for their association with the presence of germline mutations. Germline mutations, 2 being novel, were found in 24.4% of the 41 Chinese subjects recruited and 11.4% among those with apparently sporadic presentation. The increasing number of the afore-mentioned clinical indicators significantly correlated with the likelihood of harboring germline mutation in one of the 10 susceptibility genes. (r=0.757, p=0.026). The presence of 2 or more clinical indicators should prompt genetic testing for germline mutations in Chinese subjects. In conclusion, our study confirmed that a significant proportion of Chinese subjects with apparently sporadic pheochromocytoma and paraganglioma harbored germline mutations and these clinical indicators identified from Caucasians series were also applicable in Chinese subjects. This information will be of clinical relevance in the design of appropriate genetic screening strategies in Chinese populations.

Evolutionary history of Ebola virus.

SUMMARY: Since Ebola virus was discovered in 1970s, the virus has persisted in Africa and sporadic fatal outbreaks in humans and non-human primates have been reported. However, the evolutionary history of Ebola virus remains unclear. In this study, 27 Ebola virus strains with complete glycoprotein genes, including five species (Zaire, Sudan, Reston, Tai Forest, Bundibugyo), were analysed. Here, we propose a hypothesis of the evolutionary history of Ebola virus which will be helpful to investigate the molecular evolution of these viruses.

Molecular evolution and epidemiology of four serotypes of dengue virus in Thailand from 1973 to 2007.

Thailand was a hyper-endemic country for dengue with co-circulation of four serotypes and tens of thousands of infected cases annually. Taking into consideration the large number of local dengue virus (DENV) sequences available in GenBank, Thailand was the most ideal locality to study co-evolution of DENV. Therefore, we undertook a large-scale molecular epidemiological analysis of all DENV strains isolated in Thailand. In this study, we demonstrated that DENV strains of four serotypes post-1990 grouped into distinct clades, and that specific mutations in the envelope protein were first confirmed in these clades. Compared to the DENV1, DENV2 and DENV3 clades, the DENV4 clade evolved markedly more slowly (6·4 × 10-5 substitutions/site per year). Our results also showed that the genetic diversity of the predominant genotype of each serotype tended to slightly increase over time with fluctuating changes, followed by a stationary phase after 2000. This suggests that the four DENV clades became the predominant strains due to DENV possessing improved fitness after long-term selection.

Molecular phylogenetic and evolutionary analysis of Japanese encephalitis virus in China.

We elucidated the molecular epidemiology and evolution of Japanese encephalitis virus (JEV) strains isolated from 1949 to 2009 in China in this study. Three genotypes (I, III, V) were confirmed to be co-circulating in China in both high- and low-prevalence areas. Genotype III consisted of two clades (mainland clade and Taiwan clade). Compared to the mainland clade, genotype I and the Taiwan clade were newly introduced and evolved more rapidly. We also demonstrated that JEV strains in China, especially those in the mainland clade, were not only under purifying selection, but also probably under positive selection (aa 227 and 408 in the envelope protein).

Detection of two HLA-A alleles, A*31:30 and A*26:20, in two Taiwanese volunteer bone marrow donors by sequence-based typing.

We here report detection of a novel sequence of HLA-A*31:30 and a confirmatory sequence of HLA*26:20 from two Taiwanese individuals. The sequence of A*31:30 is identical to that of A*31:01:02 in exons 2 and 3, except one nucleotide (n.t.) substitution c.539T > G resulting in p.Leu180Trp. The sequence of A*26:20 is identical to A*26:01:01 in exons 2 and 3, except a segment of the sequence from n.t. 78 to n.t.102. The mismatched sequence segment is identical to a sequence segment of A*02:03:01, suggesting that the formation of A*26:20 was resulted from a DNA recombination event between A*26:01:01 and A*02:03:01 sequences. A*26:20 differs from A*26:01:01 with c.98A > T resulting in p.Tyr33Phe.

RYR1-related central core myopathy in a Chinese adolescent boy.

Central core myopathy is a rare, inherited neuromuscular disorder with a wide spectrum of phenotypic presentations. It is also considered an allelic disease of malignant hyperthermia. We report a case of central core myopathy in a Chinese adolescent boy presenting with atypical clinical features and a moderately elevated serum creatine kinase level. The diagnosis was made from the histopathological findings of central cores on muscle biopsy, and confirmed by the molecular genetic testing for the RYR1 gene mutation. This is the first case of central core myopathy confirmed by molecular study in our locality.

Elevated Serum FGG Levels Prognosticate and Promote the Disease Progression in Prostate Cancer.

Castration-resistant prostate cancer (CRPC) threatens the health of men in general and no effective therapeutics currently exists for the treatment of CRPC. It is therefore of great importance to find a novel molecule that can be a biomarker and a therapeutic target for CRPC. First, we found that the serum fibrinogen gamma (FGG) levels in patients with CRPC were significantly higher than those with localized prostate cancer (PCa) through iTRAQ proteomics and ELISA experiments. Immunohistochemistry, quantitative real-time polymerase chain reaction and western blot also showed an increase of FGG expression in CRPC tissues and cells. Then we proved the proliferation, invasion and migration ability of CRPC cells were significantly reduced after FGG knockdown. The number of apoptotic cells increased at least sixfold after FGG silencing, and was observed in conjunction with an upregulation of p53, caspase 3, clea-caspase 3, and Bax, and a downregulation of Bcl2 and survivin. FGG knockdown in DU145 cells resulted in smaller xenografts than control cells in a mouse model. and we established that FGG is modulated by IL-6 which was increased in CRPC patients via phosphorylation of STAT3. The data suggests that FGG may be a potential therapeutic target and prognostic marker for CRPC.