Objective: To investigate the factors associated with the patient's adherence to screening in the five years before the diagnosis of hepatocellular carcinoma (HCC) related to chronic hepatitis B ( CHB ), so as to provide reference for improving the screening rate. Methods: From June 2016 to April 2018, the patients with newly diagnosed HCC and a history of CHB for more than five years in Southwest Hospital in Chongqing were interviewed. The information about socio-demographic characteristics, health status, medical care and HCC screening in the past five years were collected. A multivariate logistic regression model was used to analyze the factors associated with adherence to screening. Results: Among 420 participants, 140 ( 33.33% ) adhered to HCC screening, 124 ( 29.53% ) had irregular/incomplete screening, while 156 ( 37.14% ) never had screening. The proportion of early-stage HCC at diagnosis was significantly higher in patients who adhered to screening ( 77.14% ) than that in patients who had irregular/incomplete screening (35.48%) or no screening ( 12.82% ) and the differences were statistically significant ( P<0.05 ). The multivariate analysis demonstrated that five factors were significantly associated with patient's adherence to screening, including education level of high school and above ( OR=2.346, 95%CI: 1.370-4.017), family history of HCC ( OR=2.795, 95%CI: 1.457-5.362 ), history of chronic diseases ( OR=3.860, 95%CI: 2.052-7.262), acceptance of antiviral therapy ( OR=17.816, 95%CI: 9.702-32.716 ) and specialized clinic visits ( OR=8.332, 95%CI: 1.588-43.710 ). Conclusions Adherence to screening is conducive to the early detection of HCC, but the screening rate is low in the patients with CHB. Education level, history of HCC, health status and medical status are significantly related to screening adherence.

OBJECTIVETo develop a TaqMan real-time PCR for the detection of Aeromonas hydrophila.

METHODSThe conserved region of major adhesion gene of Aeromonas hydrophila (aha) was used to design primers and TaqMan probe. A total of six concentration gradients for forward and reverse primers ranging from 200 -700 nmol/L were chosen, and four concentration gradients for probe ranging from 100 - 400 nmol/L were chosen. And then the concentration of primers and probe were optimized by ANOVA of completely randomized design respectively. The specificity of the established method was evaluated by using bacteria as contrast, including 45 strains Vibrio cholerae, 20 strains Vibrio parahaemolyticus, 10 strains Vibrio fluvialis, 4 strains Vibrio mimicus, 5 strains Vibrio vulnificus, 1 strain Vibrio alginolyticus, 1 strain Vibrio furnissii, 5 strains Salmonella, 10 strains Shigella and 2 strains Plesiomonas shigelloides. The sensitivity, bacterial sensitivity and DNA sensitivity included,were evaluated. The stool of healthy people was contaminated by Aeromonas hydrophila artificially, and the ability of the established TaqMan real-time PCR system for detection of Aeromonas hydrophila was also evaluated.

RESULTSThe cycle threshold (Ct) value deserved from 6 groups of primers concentration gradient was (x +/- s):20.69 +/- 0.33, 20.72 +/- 0.21, 20.81 +/- 0.12, 20.74 +/- 0.12, 20.51 +/- 0.16 and 20.69 +/- 0.11, respectively, and the concentration of forward primer and reverse primer was determined to be 200 nmol/L (F = 1.33, P = 0.28). The Ct value deserved from 4 groups of probe concentration gradient was (x +/- s):20.56 +/- 0.08, 20.82 +/- 0.05, 20.82 +/- 0.11 and 20.93 +/- 0.09, respectively, and the concentration of probe was determined to be 100 nmol/L (F = 5.26, P = 0.01). The bacterial sensitivity and DNA sensitivity were 80 CFU/ml and 100 fg/microl respectively, and the sensitivity to detect Aeromonas hydrophila from stool was 8 x 10(3) CFU/ml, which might be 8 CFU/ml after 8 hours' enrichment. No amplification was observed in the templates of other bacterial.

CONCLUSIONThe TaqMan real-time PCR method targeting the aha gene of Aeromonas hydrophila had a high sensitivity and specificity and might be used to detect Aeromonas hydrophila from pure bacterial and stool rapidly.

Aeromonas hydrophila ; genetics ; DNA Primers ; Genes, Bacterial ; Molecular Probes ; Polymerase Chain Reaction ; methods ; Sensitivity and Specificity ; Species Specificity

Objective To evaluate the diagnostic value of brain SPECT imaging with a novel Aβ plaque probe,131 I-2-(4'-dimethylaminophenyl) -6-iodoimidazo[ 1,2-α ] pyridine ( 131 I-IMPY) in early AD.Methods Thirteen patients with AD (3 males,10 females,age ranged 52 - 79 y),11 with mild cognitive impairment (MCI,4 males,7 females,age ranged 48 - 67 y) and 14 normal controls (6 males,8 females,age ranged 42 - 67 y) were enrolled in this study.131I-IMPY SPECT imaging was acquired in 2 -3 h after the agent injection.ROIs were drawn on cerebral lobes and cerebellum.The ratios of mean radioactivity of cerebral lobes over cerebellum (Rcl/cb) were calculated.The t-test was used for data analysis.Results In patients with MCI,Rcl/cb ratios were increased in parietal gyrus,temporal gyrus and frontal gyrus (right:1.15±0.18,1.18±0.12,1.14±0.14; left:1.16±0.11,1.19±0.18,1.15±0.09)compared with those in normal control group ( right:1.02 ± 0.12,1.05 ± 0.14,1.01 ± 0.12 ; left:1.03 ±0.13,1.05 ±0.13,1.01 ±0.14; t:2.1642 to 2.8757,all P ＜0.05).Rcl/cb ratios of basel ganglia and occipital gyms in MCI group (right:0.92 ±0.18,1.12 ±0.15; left:0.94 ±0.15,1.13 ±0.17) showed no statistical difference compared with those in normal control group (right:0.82 ±0.15,1.06 ±0.18;left:0.85 ±0.16,1.08 ±0.15; t:0.7805 to 1.4344,all P＞0.05).In patients with AD,Rcl/cb ratios were increased in parietal,temporal,basal ganglia and occipital lobes (right:1.16 ±0.19,1.24 ±0.17,1.16 ±0.13,1.14±0.11,1.23±0.10; left:1.17±0.21,1.25±0.15,1.18±0.08,1.17±0.16,1.25±0.11)compared with those in normal control group( t:2.1001 to 6.2789,all P ＜0.05).Rcl/cb ratios of parietal,temporal and frontal lobes in AD group showed no statistical difference compared with those in MCI group (t:0.1316 to 0.9806,all P ＞ 0.05 ),while Rcl/cb ratios of basal ganglia and occipital lobes in AD group were increased compared with those in MCI group ( t:2.0850 to 3.6772,all P ＜ 0.05 ).Conclusion 131 I-IMPY as a β- amyloid plaque probe for brain SPECT imaging may be potentially helpful for early diagnosis of AD.

This study was aimed to explore the frequency of PTPN11 mutation in children with leukemia and its clinical significance. Genomic DNAs were extracted from peripheral leukocytes of 131 patients with leukemia, including 101 cases of ALL, 26 cases of AML, 3 cases of CML and 1 case of juvenil myelomonocytic leukemia (JMML). The sequences of PTPN11 exons 3, 8, 13 were amplified by polymerase chain reaction (PCR), and the clinical characteristics of positive patients were analyzed. The results indicated that the PTPN11 mutation was found in 10 cases (9.9%) from newly diagnosed 101 cases of ALL. Grouping the newly diagnosed ALL children by various clinical features, it was found that the PTPN11 mutation did not show associations with sex, age, white blood cell (WBC) count, prednisone test sensitivity, clinical risk and disease recurrences at the first visit (P > 0.05). PTPN11 mutations were found in 2 cases out of 26 AML patients, including one AML-M(2) and one AML-M(4). No PTPN11 mutation in 3 CML patients was found. Exon 13 mutation of PTPN11 gene was found in 1 case of JMML. It is concluded that the E76 of exon 3 is the hot spot of PTPN11 mutation in children leukemia. The novel G503E (1508G > A) mutation is detected in one JMML patient. The PTPN11 mutation does not associate with the sex, age, WBC count, prednisone sensitive test and early recurrence.
Adolescent ; Base Sequence ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Leukemia ; genetics ; Male ; Mutation ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; genetics

OBJECTIVETo study therapeutic effects of capsulitis of little toe treated with minimal incisional osteotomy and manipulations procedures.

METHODSFrom 2003.7 to 2008.6, 90 patients (160 feet) with capsulitis of little toe including 3 male (5 foot) and 87 female (155 foot) ranging in age from 17 to 76 years(average of 49.2 years).The average medical history was 10.1 years ranging from 1 to 32 years. All patients with capsulitis of little toe were treated with minimal incisional osteotomy and manipulations procedures adopting the modified Coughlin standard to evaluation.

RESULTSAll patients were followed up, the duration of follow-up raunged from 3 to 36 months with averagement of 15.7 months. According to the modified Coughlin standard, 80 cases obtained an excellent result, 8 good, 2 fair and 0 poor, the effective rate was 97.8%. However,two patients were found delayed union after operation, the distal fragments healed following the time of fixation were delayed.

CONCLUSIONThe treatment of capsulitis of little toe with minimal incisional osteotomy and manipulations procedures is easy to operate and its therapeutic effect is convincing.

Adolescent ; Adult ; Aged ; Bunion, Tailor's ; surgery ; Female ; Humans ; Male ; Manipulation, Orthopedic ; methods ; Middle Aged ; Minimally Invasive Surgical Procedures ; Osteotomy ; methods ; Toes ; surgery

Benzene is an established leukotoxin and leukemogen in humans. We have previously reported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to mediate the cellular response to DNA double strand break (DSB) caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026), as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phosphorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apoptosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.
Apoptosis ; drug effects ; physiology ; Benzene ; toxicity ; Catalysis ; Chromones ; pharmacology ; DNA Damage ; drug effects ; genetics ; DNA Repair ; drug effects ; physiology ; DNA-Activated Protein Kinase ; antagonists & inhibitors ; metabolism ; Humans ; K562 Cells ; Morpholines ; pharmacology ; Protein Subunits

OBJECTIVETo evaluate the epidemiological and serological efficacy after 10 years of vaccination against hemorrhagic fever with renal syndrome (HFRS) vaccines in Zhejiang province.

METHODSOne county was randomly chosen as the research unit with all the healthy people between 16 and 60 years old were equally divided into study and control groups. The study group was vaccinated. Immunofluorescent antibody assay was used to test specific IgG antibody and Mcro-CPE method was used to test the titer of neutralizing antibody.

RESULTSTwo weeks after the full-course immunization, the seroconversion rate became 100% (67/67, with 95% CI as 96.3%-100%) by immunofluorescent antibody test (IgG) and 44.4% (8/18 with 95% CI as 22.0%-69.0%) by neutralization test with GMT titers as 72.1 and 4.6 respectively. Booster immunization was provided one year later. Time span as two weeks prior to, one year, one and half years, two years, three years and five years after booster immunization, the rates of seroconversion on immunofluorescent antibody using IFAT method, were 28.6%, 83.3%, 75.0%, 53.1%, 22.6%, 10.0% and 55.0% respectively, and rates of seroconversion of neutralizing antibody by Mcro-CPE method were 14.8%, 55.6%, 35.0%, 31.3%, 26.0%, 10.0% and 50.0% respectively. Nine years after the reinforcement, the rates of seroconversion of immunofluorescent antibody by IFAT method was only 7.1%. The vaccinated group had no patient seen but the control group appeared 34 patients including 3 deaths. According to the ten-year observation, the vaccine seemed effective with the protection rate in population reached 100%.

CONCLUSIONHFRS vaccine was effective on epidemiological, social and economical efficacy.

Adolescent ; Adult ; Animals ; Female ; Hemorrhagic Fever with Renal Syndrome ; epidemiology ; immunology ; prevention & control ; Humans ; Immunization, Secondary ; methods ; Male ; Middle Aged ; Rats ; Vaccination ; methods ; Viral Vaccines ; administration & dosage ; therapeutic use ; Young Adult

OBJECTIVEWiskott-Aldrich syndrome (WAS) is a primary immunodeficiency diseases. The patients with classical WAS have poor prognosis. The hematopoietic stem cell transplantation is the most effective method to cure WAS at present. In this report, a patient with WAS was cured with HLA identical sibling bone marrow transplantation (BMT).

METHODSWiskott-Aldrich syndrome protein (WASP) was detected using flow cytometry and WASP were analyzed for the diagnosis. The bone marrow was collected from the elder sister who was the HLA identical sibling donor. A total of 4.38x10(8)/kg mononuclear cell (MNC) and 3.78x10(6)/kg CD34+ cells were collected and transfused into the patient after the conditioning regimen with busulfan/cyclophosphamide. Cyclosporine only was used for graft-versus-host disease prophylaxis. WASP and short tandem repeats (STR) were detected as the evidence of engraftment.

RESULTSThe diagnosis was WAS: WASP (-IVS9+2T>C, WASP-negative). The patient received busulfan/cyclophosphamide 9 days before the transplantation. WBC decreased to 0.1x10(9)/L in d+4; The absolute number of neutrophils (ANC) was 0.8x10(9)/L in d+13, and exceeded 1.0x10(9)/L later on. From d(-9)-d+14 the patient was dependent on platelet transfusion. From d+15 the patient's PLT>50x10(9)/L and returned to normal after d+30. In d+9-d+10 mild GVHD (I degree) occurred but subsided after the steroid treatment. From d+50, WASP was detected positive and STR showed full donor DNA chimera. Follow-up for 510 d post-transplant, the patient suffered only from mild cold twice, no eczema, no bleeding occurred. The PLT is normal and no chronic GVHD occurred. The levels of IgG, IgM and IgA of the patient were approximately normal.

CONCLUSIONThe HLA-identical sibling's BMT seems to be the periorit treatment of choice for the WAS patient.

Child, Preschool ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Treatment Outcome ; Wiskott-Aldrich Syndrome ; surgery

Alzheimer's disease（AD） is an incipient aging neurodegenerative disease， which increases rapidly along with the development trend of social aging and seriously threatens the health of the people. In the absence of effective preventive measures， it will have an enormous impact on the socio-economic and healthcare system. The study found that abnormal cell signal transduction is a key link in many diseases. Cell signal transduction theory has been widely used to clarify the essence of traditional Chinese medicine visceral image and the mechanism of traditional Chinese medicine. 'Correlation of Liver and Kidney' is one of the core plates of the theory of 'Correlation of Five Organs'， which is suitable for explaining the pathogenesis of complex diseases and the correlation of multiple syndromes， and guiding the prescription of clinical syndrome. Hei Xiaoyaosan， as the first choice compound for the prevention and treatment of AD based on the theory of "Correlation of Liver and Kidney' in our team， can play the effects of prevention and treatment by soothing liver and nourishing blood， strengthening spleen and tonifying kidney， and promoting brain collaterals and dredging viscerab spirit. Based on the theory of 'Correlation of Liver and Kidney'， this paper expounds the pathogenesis of AD from the perspective of traditional Chinese medicine， and puts forward the methods and ideas of the preventing and treating of AD from Ca²⁺-calcium/calmodulin dependent protein （CaM）/calcium/calmodulin dependent protein kinaseⅡ（CaMKⅡ）-cyclic adenosine phosphate reactive element binding protein （CREB） cell signal transduction pathway by consulting literatures and previous studies.

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Apoptosis ; China ; Disease-Free Survival ; East Asian People ; Immunotherapy ; Interferon-alpha/therapeutic use* ; Lymphatic Metastasis ; Melanoma/pathology* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Skin Neoplasms/pathology* ; Melanoma, Cutaneous Malignant