Autopsy ; Female ; Humans ; Reye Syndrome ; pathology ; physiopathology ; Young Adult

OBJECTIVE: To construct a W203X-mutant mouse model of cblC type methylmalonic acidemia based on the CRISPR/Cas9 technology. METHODS: At first, BLAST was used to compare the conservative nature of the cblC gene and protein sequences in humans and mice, and then, the CRISPR/Cas9 technology was used for microinjection of mouse fertilized eggs to obtain heterozygous F1 mice. Hybridization was performed for these mice to obtain homozygous W203X-mutant mice. The blood level of the metabolite propionyl carnitine (C3) was measured for homozygous mutant mice, heterozygous littermates, and wild-type mice. RESULTS: The gene and protein sequences of MMACHC, the pathogenic gene for cblC type methylmalonic acidemia, were highly conserved in humans and mice. The homozygous W203X-mutant mice were successfully obtained by the CRISPR/Cas9 technology, and there was a significant increase in C3 in these mice at 24 hours after birth (P<0.001). CONCLUSIONS A W203X-mutant mouse model of cblC type methylmalonic acidemia is successfully constructed by the CRISPR/Cas9 technology.
Amino Acid Metabolism, Inborn Errors ; Animals ; CRISPR-Cas Systems ; Carrier Proteins ; Heterozygote ; Mice ; Mutation

Objective To construct recombinant adeno-associated virus and lentivirus carrying siRNA of TIMP-1 and to investigate the efficiency of infection and short-term inhibitory effect of TIMP-1 gene expres-sion on rat hepatic stellate cells. Methods One pair of siRNA which could effectively inhibit expression of the TIMP-1 gene in HSC-T6 was screened and cloned into AAV vector and lentiviral vector to construct the recombinant AAV/siRNA-TIMP-1/GFP and Lenti/siRNA-TIMP-1/GFP. AAV/GFP and Lenti/GFP as neg-ative control were also obtained. Experiments were assigned to five groups: AAV/siRNA-TIMP-1/GFP, AAV/GFP, Lenti/siRNA-TIMP-1/GFP, Lenti/GFP group and mock group. Rat HSC-T6 cells were infected by these recombinant viruses at a concentration of MOI by 10. To monitor the efficiency of infection, fluores-cence microscope and flow cytometer were used. After 7 d post-infection, Western blot was used to detect the TIMP-1 protein expression. Results HSC-T6 had no significant changes after infection. The efficiency of infection in AAV/GFP and Lenti/GFP group were 72.7% and 70.0%, AAV/siRNA-TIMP-1/GFP and Lenti/siRNA-TIMP-1/GFP group were 64.58% and 61.86%. The protein expression levels of TIMP-1 in HSC-T6 cells at 7 d post-infection by the recombinant AAV and Lentivirus were decreased 40.0% compared with those in mock control and normal HSC-T6 (P<0.05). Conclusion Recombinant AAV/siRNA-TIMP-1/GFP and Lenti/siRNA-TIMP-1/GFP could effectively infect HSC-T6 with similar efficiency and suppress the expression of TIMP-1 in rat HSC-T6 remarkably.

BACKGROUNDNon-valvular atrial fibrillation is associated with an increased risk of ischemic stroke; however, the appropriate intensity of anticoagulation therapy for Chinese patients has not been determined. The purpose of this study was to compare the safety and the efficacy of standard-intensity warfarin therapy, low-intensity warfarin therapy, and aspirin therapy for the prevention of ischemic events in Chinese patients with non-valvular atrial fibrillation (NVAF).

METHODSA total of 786 patients from 75 Chinese hospitals were enrolled in this study and randomized into three therapy groups: standard-intensity warfarin (international normalized ratio (INR) 2.1 to 2.5) group, low-intensity warfarin (INR 1.6 to 2.0) group and aspirin (200 mg per day) group. All patients were evaluated by physicians at 1, 3, 6, 9, 12, 15, 18, 21 and 24 months after randomization to obtain a patient questionnaire, physical examination and related laboratory tests.

RESULTSThe annual event rates of ischemic stroke, transient ischemic attack (TIA) or systemic thromboembolism were 2.6%, 3.1% and 6.9% in the standard-intensity warfarin, low-intensity warfarin and aspirin groups, respectively (P = 0.027). Thromboembolic event rates in both warfarin groups were significantly lower than that in the aspirin group (P = 0.018, P = 0.044), and there was no significant difference between the two warfarin groups. Severe hemorrhagic events occurred in 15 patients, 7 (2.6%) in the standard-intensity warfarin group, 7 (2.4%) in the low-intensity warfarin group and 1 (0.4%) in the aspirin group. The severe hemorrhagic event rates in the warfarin groups were higher than that in the aspirin group, but the difference did not reach statistical significance (P = 0.101). The mild hemorrhagic and total hemorrhagic event rates in the warfarin groups (whether in the standard-intensity warfarin group or low-intensity warfarin group) were much higher than that in the aspirin group with the annual event rates of total hemorrhages of 10.2%, 7.6% and 2.2%, respectively, in the 3 groups (P = 0.001). Furthermore, there was no significant difference in all cause mortality among the three study groups.

CONCLUSIONIn Chinese patients with NVAF, the warfarin therapy (INR 1.6 - 2.5) for the prevention of thromboembolic events was superior to aspirin.

Aged ; Aged, 80 and over ; Anticoagulants ; administration & dosage ; therapeutic use ; Aspirin ; administration & dosage ; therapeutic use ; Atrial Fibrillation ; drug therapy ; Female ; Humans ; Male ; Middle Aged ; Warfarin ; administration & dosage ; therapeutic use

Clinical blood transfusion is one of the most important supportive therapy for patients with tumor. The blood transfusion has dual effects for patients with tumor. First, blood transfusion can rectify anemia and improve oxygen saturation, accelerate oxidation and necrosis for tumor cells; the second, blood transfusion can induce immunosuppression, tumor recurrence and postoperative infection for tumor patients. Filtering white blood cells (WBC) before blood transfusion can decrease the incidence of the adverse reactions. The rational perioperative autotransfusion for patients with tumors is focus to which the world medical sciences pay close attention. In this article, the support effect of blood transfusion for treatment of tumor patients, blood transfusion and immunosuppression, blood transfusion and postoperative infection and relapse of tumor patients, depleted leukocyte blood transfusion and autologous transfusion of tumor patients are reviewed.
Blood Transfusion ; Humans ; Immunosuppression ; Neoplasms ; therapy

Objective To explore the influence of comprehensive nursing intervention on treatment compliance and re-currence for patients with chronic obstructive pulmonary disease. Methods 90 cases of chronic obstructive pulmonary disease From 2012 December to 2014 December in our hospital, exclude those with serious cardiovascular and cere-brovascular disease,severe liver and kidney dysfunction and the severity of heart failure,the language barrier. All pa-tients were divided into intervention group and control group with 45 cases in each group, the control group received the routine nursing care intervention group randomly, focusing on the implementation of comprehensive nursing inter-vention, compare treatment compliance rate and quality of life score, disease activity and total score before and after treatment. Compare the average hospitalization time and recurrence rate of two groups. Results The full compliance of the intervention group was 91.11%, significantly higher than control group's 77.78%,the difference was significant(P<0.05). Before treatment,the quality of life symptom score,activity,disease influence, the total score between the two groups,the difference was not significant(P>0.05). After the intervention,quality of life symptom score,activity,dis-ease influence and total scores of two groups were significantly lower than those before treatment, and quality of life scores, activity, disease influence and total scores the intervention group were significantly lower than control group,the difference was significant (P<0.05). The average length of stay of intervention group was significantly shorter than the control group,the difference was significant(P<0.05). The intervention group half year relapse rate was significantly lower than the control group,the difference was significant (P<0.05). Conclusion The implementation of psychological nursing intervention, including health education, medication guide, comprehensive nursing intervention in the treat-ment of patients with chronic obstructive pulmonary disease,improve patient adherence to treatment,to actively coop-erate with the treatment and care, and at the same time, shorten the hospitalization time, reduce the recurrence rate,so as to improve the quality of life of patients.

OBJECTIVETo evaluate visual inspection with Lugol's iodine (VILI) in cervical cancer screening program and to provide evidence for designing a cervical cancer screening algorithm in high risk areas of existing low-resource settings to reduce the incidence and mortality of cervical cancer.

METHODSWomen in Yangcheng county, Shanxi province were screened with VILI, colposcopy, liquid-based cytology test and human papilloma virus (HPV) DNA test. The efficacy of different screening tests was compared by Youden's index based on the pathology as the gold standard.

RESULTSIn the population being screened, the mean age was 40.80 +/- 10.75 years old. Based on pathological findings, 4.35% (32/735) of the subjects had >or= CIN (cervical intraepithelial neoplasia) II. The sensitivity and specificity for the VILI test (>or= positive) were 53.13 and 82.19, while 56.25 and 79.09 were for colposcopy (>or= low grade dysplasia) respectively. Comparing by the Youden's indexs, there was no statistically significant difference (P > 0.05) between VILI and colposcopy. However, statistical significant difference (P < 0.05) was found between VILI and liquid-based cytology test and HPV DNA test. In addition, there was no statistically significant difference (P > 0.05) found between the experienced doctors and the newly-trained doctors working in the field station.

CONCLUSIONWith low sensitivity when using microscope but low cost of equipments, VILI can be one of the primary screening tests in China's rural area with low-resource settings if the screening frequency is to be increased.

Adult ; Cervical Intraepithelial Neoplasia ; diagnosis ; epidemiology ; China ; epidemiology ; Early Detection of Cancer ; economics ; methods ; Female ; Health Resources ; Humans ; Incidence ; Iodides ; Program Evaluation ; Rural Health ; Sensitivity and Specificity ; Socioeconomic Factors ; Uterine Cervical Neoplasms ; diagnosis ; epidemiology

OBJECTIVETo introduce the clinical method of blocking screws and rooting technique in the treatment of distal tibial fracture with interlocking intramedullary nails.

METHODSFrom June 2006 to March 2011, 26 patients with distal tibial fracture were treated with interlocking intramedullary nails using blocking screws and rooting technique, included 18 males and 8 females with an average age of 46.2 years old ranging from 24 to 64 years. According to AO classification: 10 cases of type A1, 4 cases of type A2, 8 cases of type B1, 4 cases of type B2. The average distance of the fractures end to the ankle joint was 85 mm ranging from 55 to 125 mm, the mean time between injured and operation was 4.5 days. The patients were evaluated with pain, range of motion, walking.

RESULTSAll cases were followed-up for 6 to 22 months (averaged 15 months). According to Iowa ankle joint grading system,the score was improved from preoperative (66.8 +/- 8.2) to postoperative (94.6 +/- 4.8). All fractures had united, and got satisfactory reduction and stable fixation with no complications had happen such as breakage of screw.

CONCLUSIONFixation with interlocking intramedullary nail using blocking screws and rooting technique in treating distal tibial fracture, is a safe and effective technique for the improvement of stability.

Adult ; Bone Screws ; Female ; Follow-Up Studies ; Fracture Fixation, Intramedullary ; methods ; Humans ; Male ; Middle Aged ; Recovery of Function ; Retrospective Studies ; Tibial Fractures ; diagnostic imaging ; physiopathology ; surgery ; Tomography, X-Ray Computed ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the lymph nodes distribution and metastatic pattern of the ultra-low rectal cancer after neoadjuvant therapy.

METHODSA total of 21 rectal cancer gross specimen after neoadjuvant therapy and 23 rectal cancer gross specimen without neoadjuvant therapy were investigated by whole mount section and tissue microarray techniques with CK20. All the patients were treated by abdominoperineal resection.

RESULTSThere were 138 lymph nodes retrieved from the mesorectum in the neoadjuvant group including 39 metastatic lymph nodes and 12 micro-metastatic lymph nodes. Among these nodes, there were 7 rectal cancer cases with lymph nodes and 2 cases with micro-metastatic lymph nodes, and 6 cases had pathological complete remission. There were 415 lymph nodes retrieved from the mesorectum in the group without neoadjuvant therapy including 169 metastatic lymph nodes and 59 micro-metastatic lymph nodes. Among these nodes, there were 12 rectal cancer cases with lymph nodes and 4 cases with micro-metastatic lymph nodes. The proportions of metastatic lymph nodes in outer zone between the two groups were 21.5% and 29.0%, and those in pre-zone were 17.6% and 17.2% respectively. The ratio of metastatic lymph nodes in ischiorectal fossa between the two groups were 25.0% vs. 22.2% respectively. The rate of metastatic or micro-metastatic lymph nodes cases between the two groups were 4.8% vs. 13.0% respectively.

CONCLUSIONSThe lymph nodes distribution and metastatic pattern of the ultra-low rectal cancer are affected by neoadjuvant therapy. The proportions of the anal sphincter invasion and metastatic or micro-metastatic lymph nodes in ischiorectal fossa are lower after neoadjuvant therapy. Abdominoperineal resection as the standard treatment of the ultra-low rectal cancer after neoadjuvant therapy should be re-evaluated.

Biopsy ; Digestive System Surgical Procedures ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Neoadjuvant Therapy ; Rectal Neoplasms ; pathology ; therapy

OBJECTIVETo analyze the association of variants of hepatocyte nuclear factor-1alpha (HNF-1alpha) gene with type 2 diabetes in Chinese population.

METHODSIn 152 unrelated type 2 diabetes patients and 93 unrelated controls, eleven single nucleotide polymorphisms (SNPs) were identified and genotyped. Statistical analyses were performed to investigate whether these SNPs were associated with diabetes status in our samples.

RESULTSIn the individual SNP study, no SNP differed significantly in frequency between type 2 diabetes patients and controls. In the haplotype analysis, two haplotype blocks were identified. In haplotype block 1, no evidence was found between common HNF-1alpha haplotypes and type 2 diabetes. However, in haplotype block 2, a common haplotype GCGC formed by four tagging SNPs (tSNPs) was found to be associated with decreased risk of type 2 diabetes (odds ratio [OR] 0.6011, 95% confidence interval [CI] 0.4138-0.8732, P = 0.0073, empirical P = 0.0511, permutation test). A similar trend was also observed in the diplotype analysis, indicating that the increasing copy number of the haplotype GCGC was associated with the decreased frequency of diabetes (P = 0.0193).

CONCLUSIONThe results of this study provide evidence that the haplotype of HNF-1alpha decreases the risk of type 2 diabetes in Chinese individuals.

Adult ; Aged ; Case-Control Studies ; China ; epidemiology ; Diabetes Mellitus, Type 2 ; epidemiology ; genetics ; Genetic Predisposition to Disease ; Haplotypes ; Hepatocyte Nuclear Factor 1-alpha ; genetics ; Humans ; Middle Aged ; Polymorphism, Single Nucleotide