Objective To observe the effect of pre-hospital and intra-hospital collaborative ther-apeutic model in the treatment of patients with acute cerebral infarction.Methods A total of 67 pa-tients with acute cerebral infarction were selected as the research objects,and they were divided into observation group(n=37)and control group(n=30)according to the therapeutic model.The con-trol group was conducted with the traditional therapeutic model,while the observation group was con-ducted with the pre-hospital and intra-hospital collaborative therapeutic model.The time efficiency of intravenous thrombolysis,early recovery of nerve function and oxidative stress indexes were compared between the two groups.Results There was no significant difference in the time from onset to visit between the two groups(P＞0.05);the time from seeing a doctor to thrombolysis and the time from seeing a doctor to signing the informed consent for intravenous thrombolysis in the observation group were significantly shorter than those in the control group(P＜0.05).On the hospital admission,there was no significant difference in the National Institutes of Health Stroke Scale(NIHSS)score be-tween the two groups(P＞0.05);at the time points of 7 days after admission and 90 days after thrombolysis,the NIHSS scores of patients in the observation group were significantly lower than that in the control group(P＜0.05).There were no significant differences in the levels of serum glutathione peroxidase(GSH-Px)and malonaldehyde(MDA)between the two groups(P＞0.05);the level of serum superoxide dismutase(SOD)in the observation group was significantly higher than that in the control group(P＜0.05).One patient died in the control group,with a mortality rate of 3.33％;no patient died in the observation group.Conclusion Pre-hospital and intra-hospital collaborative therapeutic model can effectively improve the time efficiency of intravenous thrombolysis for patients with acute cerebral infarction,alleviate the neurological damage,and reduce degree of oxidative stress reaction and death risk.

Objective To observe the effect of pre-hospital and intra-hospital collaborative ther-apeutic model in the treatment of patients with acute cerebral infarction.Methods A total of 67 pa-tients with acute cerebral infarction were selected as the research objects,and they were divided into observation group(n=37)and control group(n=30)according to the therapeutic model.The con-trol group was conducted with the traditional therapeutic model,while the observation group was con-ducted with the pre-hospital and intra-hospital collaborative therapeutic model.The time efficiency of intravenous thrombolysis,early recovery of nerve function and oxidative stress indexes were compared between the two groups.Results There was no significant difference in the time from onset to visit between the two groups(P＞0.05);the time from seeing a doctor to thrombolysis and the time from seeing a doctor to signing the informed consent for intravenous thrombolysis in the observation group were significantly shorter than those in the control group(P＜0.05).On the hospital admission,there was no significant difference in the National Institutes of Health Stroke Scale(NIHSS)score be-tween the two groups(P＞0.05);at the time points of 7 days after admission and 90 days after thrombolysis,the NIHSS scores of patients in the observation group were significantly lower than that in the control group(P＜0.05).There were no significant differences in the levels of serum glutathione peroxidase(GSH-Px)and malonaldehyde(MDA)between the two groups(P＞0.05);the level of serum superoxide dismutase(SOD)in the observation group was significantly higher than that in the control group(P＜0.05).One patient died in the control group,with a mortality rate of 3.33％;no patient died in the observation group.Conclusion Pre-hospital and intra-hospital collaborative therapeutic model can effectively improve the time efficiency of intravenous thrombolysis for patients with acute cerebral infarction,alleviate the neurological damage,and reduce degree of oxidative stress reaction and death risk.

Objective:To compare results of four glycosylated hemoglobin A1c (HbA1c) detection methods and to evaluate the uncertainty of HbA1C results in clinical laboratory, and to provide method for clinical laboratory on the evaluation of uncertainty.Methods:According to the four uncertainty evaluation methods, which were recommended by "CNAS-TRL-001, the evaluation and expression of measurement uncertainty in medical laboratory", the relative and absolute uncertainty of low, medium and high HbA1c in 33 clinical laboratories measured in 2019 and 35 clinical laboratories measured in 2020 was evaluated by more than 6 months of internal quality control (IQC) data, trueness verification and external quality assessment (EQA) data. The four uncertainty evaluation methods were: IQC data and trueness verification data (method 1), only trueness verification data (method 2), IQC and EQA data (method 3) and only EQA data (method 4). The related statistical methods used in this analysis were Friedman and Wilcoxon signed rank test.Results:For method 1, the median range of relative and absolute uncertainty of low, medium and high HbA1c detection in 2019 and 2020 ranged from 4.21% to 9.24% and from 0.27% to 0.64%, respectively. Compared to method 1, the relative and absolute uncertainties obtained by method 2 were smaller, and the differences were statistically significant ( P<0.016 7, P<0.05). Compared to method 1, the relative uncertainties obtained by method 3 and method 4 were smaller, except for the high concentration of HbA1c level in 2020. Among the 6 pairs of comparisons (low, medium and high HbA1c in 2019 and 2020), there were 3 pairs (high HbA1c in 2019, low and medium HbA1c in 2020) and 2 pairs (low and high HbA1c in 2020) of differences with statistical significance (all P<0.016 7). Conclusion:The uncertainty evaluation of HbA1c detection in clinical laboratory should be evaluated based on IQC and trueness verification data.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

Objective:To investigate the role of basic fibroblast growth factor (bFGF) in decreasing intracranial pressure in rats after intra-abdominal hypertension (IAH).Methods:A total of 60 healthy SD rats were selected for the experiment. Secondary IAH rat models were established by hemorrhagic shock/resuscitation, followed by injecting nitrogen into the peritoneal cavity of the rats to maintain an intra-abdominal pressure of 12mmHg and above. According to the random number table, the rats were divided into control group, IAH group, IAH+ bFGF group (bFGF group) and IAH+ bFGF+ PD173074 group (antagonist group), with 15 rats per group. Indicators were measured 4 hours after injury, including intracranial pressure, brain morphological observation, apparent diffusion coefficient (ADC) value, lactic acid content of brain MRI, brain water content and Evans blue exudation. Immunofluorescence staining, Western blotting and PCR were used to detect the expressions of phosphorylate-fibroblast growth factor receptor 1, 2 (p-FGFR1, 2), Zonula occludens-1 (ZO-1), β-catenin, matrix metalloproteinases 9 (MMP9), interleukin-1β (IL-1β) in brain microvascular endothelial cells (BMECs).Results:The intracranial pressure in IAH group [(5.52±0.45)mmHg] gradually increased 4 hours after injury compared control group [(3.36±0.30)mmHg]. Compared with IAH group, the intracranial pressurein bFGF group [(4.46±0.41)mmHg] was decreased ( P<0.05). Compared with bFGF group, the intracranial pressure in antagonist group [(5.36±0.44)mmHg] was enhanced ( P<0.05). Brain morphological observations in IAH group showed swelling and obvious cerebral edema, accompanied with a small amount of subarachnoid hemorrhage. Compared with IAH group, cerebral edema and brain swelling were relieved in bFGF group, while the antagonist group still showed cerebral edema and obvious brain swelling. At 4 hours after injury, MRI examination showed that the relative ADC value in IAH group (cortex: 0.82±0.11, corpus callosum: 1.26±0.17) was lower than that in control group (cortex: 1.00±0.13, corpus callosum: 1.43±0.15)( P<0.05). Compared with IAH group, the relative ADC value in bFGF group (cortex: 0.94±0.16, corpus callosum: 1.36±0.16) was increased ( P<0.05). Compared with bFGF group, the relative ADC value in antagonist group (cortex: 0.87±0.13, corpus callosum: 1.30±0.14) was decreased ( P<0.05). Relative lactic acid content in IAH group (cortex: 15.50±2.14, corpus callosum: 10.82±1.90)was higher than that in control group (cortex: 1.00±0.23, corpus callosum: 0.70±0.20)( P<0.05). Compared with IAH group, the relative lactic acid content in bFGF group (cortex: 10.85±1.42, corpus callosum: 6.96±1.30) was decreased ( P<0.05). Compared withbFGF group, the relative lactic acid content in antagonist group (cortex: 13.71±1.61, corpus callosum: 9.12±1.52) was increased ( P<0.05). The brain water content in IAH group [(87.9±0.8)%] was higher than that in control group [(76.3±0.9)%]. Compared with IAH group, the brain water content in bFGF group [(83.2±1.0)%] was decreased( P<0.05). Compared with bFGF group, the brain water content in antagonist group[(85.4±0.8)%] was increased ( P<0.05). Evans blue exudation in IAH group [(3.22±0.29)μg/ml] was greater than that in control group [(0.42±0.22)μg/ml]( P<0.05). Compared with IAH group, the Evans blue exudation in bFGF group [(2.04±0.25)μg/ml] was decreased ( P<0.05). Compared with bFGF group, the Evans blue exudation in antagonist group [(2.92±0.20)μg/ml] was increased ( P<0.05). Compared with control group, the expression of p-FGFR1 in BMECs in IAH group was weakened 4 hours after injury, but p-FGFR2 remained unchanged, the expressions of ZO-1, β-catenin protein and mRNA were weakened, and the expressions of MMP9, IL-1β protein and mRNA were enhanced ( P<0.05). Compared with IAH group, the expressions of p-FGFR1, ZO-1, β-catenin protein and mRNA were enhancedin bFGF group, and the expressions of MMP9, IL-1β protein and mRNA were weakened as well ( P<0.05). However, the expressions of p-FGFR1, ZO-1 and β-catenin protein and mRNA in antagonist group were weaker than those in bFGF group, and the expressions of MMP9 and IL-1β protein and mRNA were stronger than those in the bFGF group ( P<0.05). Conclusion:After IAH, the rat model presents damaged blood-brain barrier, increased cerebral edema, and increased intracranial pressure, and the use of bFGF can improve these symptoms. FGFR1 of BMECs is a key receptor for bFGF to play a protective role, and its receptor inhibitor PD173074 can attenuate the protective effect of bFGF.

OBJECTIVE: To detect potential variant in an ethical Han Chinese pedigree affected with breast cancer. METHODS: The proband and her relatives were subjected to next-generation sequencing using a target capture sequencing kit containing 121 cancer-related genes. Candidate variants were selected by analysis of their type, frequency in population, and segregation with the phenotype. Candidate variant was verified by Sanger sequencing and TA cloning. RESULTS: A c.2013_2014ins GT variant was detected in the BRCA1 gene among all breast cancer patients from this pedigree but not among healthy females. The variant was not recorded in the 1000 Genome Project database or the Exome Aggregation Consortium (ExAC) database. The frameshifting insertion was predicted to form an premature stop codon in gene transcript and can give rise to a truncated protein. CONCLUSION The BRCA1 c.2013_2014ins GT variant probably underlies the pathogenesis of breast cancer in this Chinese pedigree.
Asian Continental Ancestry Group ; BRCA1 Protein ; genetics ; Breast Neoplasms ; genetics ; Exome ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Pedigree ; Phenotype

Objective To investigate the target achievement of serum trough concentration of vancomycin in elderly patients routinely treated with vancomycin,and to analyze the influencing factors for vancomycin-associated acute kidney injury(VA-AKI).Methods A single-center retrospective study was conducted by collecting clinical data of elderly inpatients from January 2016 to July 2017 who received intravenous vancomycin therapy and serum vancomycin trough concentration test.Logistic regression was used to analyze the risk factors for VA-AKI.Results A total of 141 patients were enrolled,including 74 males (52.5 ％) and 67 females (47.5 ％).The median (interquartile range)age was 77.0(13.5) years old.Patients with serum vancomycin trough concentrations within 10～ 20 mg/L accounted for 48.9 ％ (69 cases),while those lower than the target value accounted for 23.4 ％ (33 cases),and those higher than the target value accounted for 27.7％ (39 cases).Patients were divided into three groups according to the vancomycin serum trough concentration:＜10 mg/L group,10～20 mg/L group,and ＞20 mg/L group.There were statistically significant differences among the three groups in median(interquartile range) age[74.0 (14.0) years old,76.0 (11.5) years old vs.80.0 (14.0) years old,H =9.506,P =0.009] and the median (interquartile range) vancomycin daily dose [1.5(0.5) g/d,1.5 (0.8) g/d vs.1.5 (0.5) g/d,H =6.131,P =0.047].VA-AKI occurred in 23 patients(16.3 ％).Logistic regression analysis showed that the baseline serum creatinine levels (OR =1.022,95 ％CI:1.001 ～ 1.042,P =0.035)and vancomycin trough concentration(OR =1.058,95 ％CI:1.011～1.106,P=0.015)were influencing factors for VA-AKI.Conclusions The elderly patients with infection who received clinical vancomycin therapy have a low target achievement rate of serum trough concentration.Baseline serum creatinine level and serum vancomycin trough concentration are influencing factors for VA-AKI.

Objective To compare and study the two kinds of quality control methodologies related to intelligent quality management system ( iQM) and traditional quality control , and the quality control performance of iQM equivalent to traditional quality control were evaluated , ensuring the accuracy of the results of blood gas testing.Methods Beijing Chaoyang Hospital of Capital Medical University , Beijing Tiantan Hospital of Capital Medical University , Shanghai Longhua Hospital of Shanghai University of Chinese Medicine, and Sichuan Provincial People′s Hospital, these 4 medical institutions were selected to implement this study.During the period from June 2016 to December 2016, in the routine detection of total 3 712 specimen, the iQM and traditional quality control modes were used simultaneously to calculate the mean values of all blood gas parameters quality controls , SD, CV (%) and Sigma values, to evaluate the quality control performance and difference of the two quality control modes .Results During the process of testing blood gas samples from 3 712 specimen in 4 hospitals, iQM process control solution ( PCS) A, B, C ran 1 089, 7 678 and 154 quality control samples respectively , and 732 external quality control samples were run by traditional quality control mode .Considering the most sensitive parameters of blood gas testing pO 2, iQM PCS A, B, C′s Sigma value are higher than 8, however, the traditional quality control′s Sigma value are less than 6; For parameters pCO2, pO2and Na+, there exists significant difference between two quality control methods (P＝0.004 8,P＝0.000 1,P＝0.004 4,P＜0.01), other parameters pH, K+, Ca ++, Glu, Lac and Hct, there exists no significant difference between two quality control methods (P＝0.250 6, P＝0.062 3,P＝0.034 0,P＝0.346 9,P＝0.186 3,P＝0.823 1,P＞0.01).Totally 22 errors detected by iQM, includes 14 micro-clots and 8 interferences samples, which were not detected by traditional quality control .Conclusions The error in blood gas analysis mainly comes from the pre-analytical phase.iQM enhanced specimen inspection capabilities and make up for the inability of traditional quality control to monitor the quality of specimens , enabling full-scale, real-time, and dynamic monitoring of each specimen , powerful error detection capabilities , and automatic error correction capabilities . Besides, automatic documentation saves staff much time.The system can effectively ensure the accuracy of blood gas test results, meet the quality requirements of related laws and regulations and related industry standards , and also can meet the clinical intended use , providing new ideas for POCT quality management and improvement.

Eccrine spiradenoma usually occurs as solitary tender nodules. However, it rarely occurs as multifocal localized tumors or has zosteriform distribution. We report the case of a 32-year-old woman with a 20-year history of itchy lesions on the left side of the back and forearm with a zosteriform distribution. Before disease onset, almost no patients have inducing factors, but our patient received an injection beforehand; however, whether this was coincidental or causative remains unknown. The lesions became very itchy after perspiration or eating spicy food, which has never been reported. A literature search revealed 22 cases of multiple segmental eccrine spiradenoma; we summarized the clinical characteristic in order to aid diagnosis and treatment selection.
Adult ; Diagnosis ; Eating ; Female ; Forearm ; Humans

Objective There is a lack of information on the effect of hypoxia on the virulence of Cryptococcus neoformans . This study was to construct a Cryptococcus neoformans bilfilm model in vitro and observe the influence of hypoxia on the biofilm forma-tion. Methods We constructed a Cryptococcus neoformans biofilm model in vitro in 24-well and 96-well microculture plates using DMEM culture medium at the oxygen concentrations of 21%( normoxia ) and 1% ( hypoxia ) .We collected the Cryptococcus neofor-mans biofilms at 2, 4, 8, 12, 24, 48, and 72 hours after culturing and observed their thickness , structure, and growth activity in the two different oxygen conditions by light microscopy , confocal laser scanning microscopy , and MTT assay . Results The Cryptococcus neoformans biofilm model was successfully constructed in the conditions of both hypoxia and normoxia .The processes of biofilm forma-tion in the two conditions were similar , involving adhesion , aggregation , micro-colony formation , and biofilm maturation , with the ulti-mate biofilm thickness of about 16 μm.The cell density and growth activity of the biofilms increased with the extension of incubation time, gradually stabilized with their maturity , and both were relatively higher at 1%than at 21%oxygen concentration . Conclusion The abilities of Cryptococcus neoformans biofilm formation vary with different oxygen concentrations , and hypoxia can promote the for-mation of Cryptococcus neoformans biofilms .