Objective To describe the development of nodules of altered hepatocytes (NAH) in chronic hepatitis B and to reveal progression of the nodules to hepatocellular carcinoma (HCC). Methods HCC, NAH and ordinary regenerative nodules (ORN) were identified and compared histologically. Expression levels of hepatitis B virus (HBV) antigens, mitoactivity and p53 accumulation in these lesions were evaluated by immunohistochemistry. Results Multiple foci of altered hepatocytes (FAH) and NAH were identified in the liver parenchyma surrounding HCC in all of the samples examined. Sequential architectural and cellular changes were observed during the progression of FAH to NAH and HCC. Expression levels of HBV surface and core antigens were found to be significantly decreased in ORN, NAH and HCC, with their positive rates being 70 % (35/50), 50 % (25/50), 10 % (5/50) and 60 % (30/50), 40 % (20/50), 6 % (3/50), respectively (P ＜0.05). Ki-67-1abelling indices were determined to be (0.58±0.49) %, (2.46±1.05) % and (40.36±26.27) %in these lesions, respectively (P ＜0.05). Nuclear p53 accumulation was found only in HCC. Its occurrence was associated to a high histological grade, with its frequencies being 13 % (1/8), 41% (11/27) and 73 % (11/15)in grade 1, 2 and 3 lesions, respectively. Conclusion NAH lesions, identified by their morphologic features and mitoactivity elevation, are detectable in resected liver samples with chronic hepatitis B and cirrhosis. They represent a common HCC precursor and can be used as a surrogate marker for the surveillance of high-risk individuals.

Objective Focal nodular hyperplasia(FNH) is composed of multiple hyperplastic liver cell nodules,but its pathogenesis has not been elucidated. Foci (FAH) or nodules of altered hepatocytes (NAH) are precursors of hepatocellular adenoma (HCA) and carcinoma.This study aimed at identifying FAH and NAH from FNH and evaluating their role in FNH development.Methods 6 FNH lesions from 5 patients and 10 HCA from 9 patients were examined histologically,and expression levels of CD_(34) cytokeratin 19(CKl9) and Ki-67 antigen were demonstrated immunohistochemicailly.Proliferative activity was evaluated by Ki-67 antigen-labeling indices(Ki-67 LI).Results Multiple FAH and NAH were identified in all of the 6 FNH lesions. Whiie micmvasculatures were demonstrated by CD_(34) immunoreactivity in both HCA and FNH,their density and distribution were different in these two lesions,being diffuse in HCA and focal or nodular,mainly within NAH.CKl9 expression Was found in FNH,localized in ductal and ductular cells,but not within NAH and HCA.Average Ki.67 LI of 73 NAH(2.8%) was shown to be higher than that of the whole FNH lesions (0.6%),and had no statistieal difference comparable to that of HCA(1.8%).Conclusion Muhiple NAH are present in all classical FNH lesions.Unlike the surrounding parenchyma,NAH lesions are more proliferative and equipped with CD_(34)-positive microvasculatures as in HCA.

Objective To evaluate the effectiveness of Chronic Care Model in hypertension management in community health services.Methods Three hundred patients diagnosed with hypertension participated in this study and were divided into intervention and control groups.In the following 9 months,intervention measures based on the Chronic Care Model were delivered to intervention group,while the conventional measures to control group.Data collected before and after the intervention were analyzed uuing descriptive statistics,t-test,x2-test and analysis of covariance by SPSS16.0 for Windows.Results The intervention group had statistically significant positive effectiveness in drinking habit,daily salt intake(decreased 0.78g),diastolic blood pressure (decreased 2mmHg),BMI(decreased 0.4) and SF-36 physical component summary score(decreased 1.7)(P＜0.05).The intervention group had better improvement in BMI and SF-36 physical component summry score than the control group.Conclusion The health outcomes of patients with hypertension could be improved by applying the Chronic Care Model featured diet,exercise habits and other health related factors management.

Background:Erythrocytosis,a rare paraneoplastic syndrome,generally occurs in patients with clear cell renal cell carcinoma and has never been reported in patients with chromophobe renal cell carcinoma.Case presentation:We report a case of a young man suffering from a giant (22-cm) mass on his left kidney.Because of a history of polycythemia vera,the patient had been treated for the condition for 9 years.Radical nephrectomy was successfully performed,and the postoperative pathologic examination confirmed a diagnosis ofchromophobe renal cell carcinoma.Unexpectedly,the symptom of erythrocytosis disappeared after the surgery.Further examination and analysis were performed,and we finally attributed his erythrocytosis to chromophobe renal cell carcinoma.Conclusions:Chromophobe renal cell carcinoma could cause erythrocytosis,but the clear-cut mechanism needs further research.Secondary erythrocytosis such as those related with renal tumors should be taken into consideration during the diagnosis of polycythemia vera.

Aim TostudytheeffectsofCuO,ZnOand TiO2 nanoparticles on the viability and metastatic po-tential of EC-9706 and EC-109 esophageal squamous carcinomacelllineinvitro.Methods Characteristics of CuO,ZnO and TiO2 nanoparticles were detected u-sing transmission electron microscope (TEM)and dy-namic light scattering (DLS ).EC-9706 and EC-109 cells were treated with different concentrations of CuO, ZnO and TiO2 (5 ~80 mg · L-1 ).The cell prolifera-tion was analyzed by MTT assay.The cell cycle and apoptotic rates were determined by flow cytometry (FCM).The cell invasion was assayed in Transwell chambers.The expression of Bcl-2 and caspase-3 pro-tein in cells was detected by Western blot method.Re-sults CuO,ZnOandTiO2nanoparticleswerespheri-cal with primary particle size 12,20. 6,12 nm.The particles were agglomerated in water and cell culture medium with negative charge.CuO and ZnO nanoparti-cles induced decreases in EC-9706 and EC-109 cell vi-ability dose-dependently.After exposed to increasing concentrations of CuO and ZnO nanoparticles,the cell cycle analysis revealed a decreasing proportion of cells in G2/Mand S phase,and up-regulation of the cells in G0/G1 phase.Apoptotic cells also increased along with decreased cell invasion upon CuO and ZnO treatment. Nanoparticles treatment after 48 h, the activated caspase-3 expression quantity increased significantly and the Bcl-2 expression quantity decreased obviously (P<0. 05 )compared with control group.TiO2 nanop-articles had no obvious effect on the EC-9706 and EC-109 cell proliferation,cell cycle,apoptosis and inva-sion.Conclusion ComparedwithTiO2,CuOand ZnO nanoparticles can inhibit EC-9706 and EC-109 cell viability and metastatic potential,the mechanism of action involves cell cycle arrest in G0/G1 phase and apoptosis.These findings can help the development of nanoparticles as anti-cancer therapeutics for esophageal cancer.

Objective To study the histological classification,clinical stage,histological grade and prognosis of renal cell carcinoma by analyzing the records of the patients in Shanghai Renji hospital. Methods A consecutive series of 435 patients with renal cell carcinoma between 2003 and 2005derived from the renal cancer database were reviewed clinically and pathologically.The 1997 version of WHO histological classification for renal epithelial tumor,the 2002 version of AJCC clinical TNM staging system and the 1982 version of Fuhrmaffs system for nuclear grade were used.By survival analysis of 57 cases with advanced renal cell carcinoma using Kaplan-Meier method prognostic factors were confirmed using logrank test. Results Of a total 435 patients,cases were classified into 10(accounting for 2.4%of renal cell tumors)hereditary renal cancer in VHL disease,372(85.5%)clear cell renal cell carcinoma(CCRCC),13(3.0%)papillary renal cell carcinoma(PRCC),18(4.1%)chromophobe renal cell carcinoma(CRCC),4(0.9%)oncocytoma,4(0.9%)carcinoma of the collecting ducts of Bellini(CCDB),and 14(3.2%)renal cell carcinoma unclassified.There were 335(77%)patients undergone radical nephrectomy,74(17%)nephron sparing surgery and 26(6%)others,such as palliative nephrectomy.The patients with VHL disease come from 5 Chinese kindred and all had bilateral clear cell renal cell carcinomas and multifocal renal cysts.There were 7 paients of stage Ⅰ and 3 cases of stage Ⅱ and 6 cases of grade Ⅰ and 4 cases of grade Ⅱ.Genetic test revealed that all patients had VHL gene mutation.4 patients had recurrence while no evidence of local advance and distant metastasis were found during a mean of 28.6 months.Patients with chromophobe RCC are all of stage Ⅰ and 5 cases of grade Ⅰ and 13 cases of gradeⅡ.All patients are alive without recurrence or metastasis during a mean of 19.8 months.Collecting ducts RCC all presented with stage Ⅰ but grade Ⅲand with the median survival only 11.3 Months.Of clear cell and papillary RCC,260(67.6%),64(16.6%),32(8.3 %),29(7.5%)were stage Ⅰ,Ⅱ,Ⅲand Ⅳ,and of stage Ⅰ patients 147(38.2%),113(29.4%)were T1a and T1b respectively.124(32.2%),219(56.9%),40(10.4)and 2(0.5%)were grade Ⅰ,Ⅱ,Ⅲ,Ⅳ,respectively.Median survival of 57 advanced RCC is 16.0±1.3months,1-year survival is 55%,and 2-year survival is 31%,respectively.By using logrank test,clinical stage(＜0.01),tumor size(＜0.01),lymphadenopathy(＜0.01),metastasis(＜0.01)and tumor grade(＜0.01)were anatomical and histological prognostic factors for advanced RCC. Coneluslons Different RCC subtypes have different clinical course.The RCC patients in VHL disease have VHL gene mutation and the tumors are often multifocal,bilateral,clear cell type with a low stage and grade which often recurrence but without metastasis.Chromophobe RCC may have a favorable prognosis but collecting duct RCC poor prognosis.In anatomical and histological level,clinical stage,tumor size,lymphadenopathy,metastasis and tumor grade are prognostic factors of survival for advanced RCC.

Objective To investigate the role of histone H4 in the polarization of alveolar macrophages (AM) in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) in mice. Methods i) The specific pathogen free male C57BL/6 mice were randomly divided into control group and 2, 4, 6 and 8 mg/kg LPS groups, with six mice in each group. The mice in the LPS groups were intratracheally administered LPS according to their respective doses, while the mice in the control group received an equivalent volume of 0.9% saline. After 12 hours, the arterial blood gas was analyzed, and the pulmonary edema and histopathological changes in lung tissues of mice in each group were observed. The level of histone H4 in bronchoalveolar lavage fluid (BALF) of mice was detected using enzyme-linked immunosorbent assay , and mice AMs of the five group were isolated using adherent method. ii) AMs from normal mice were isolated using adherent method and randomly divided into control group, histone H4 injury group, BALF injury group and anti-histone H4 antibody (anti-H4) intervention group. In the histone H4 injury group, AMs were treated with histone H4 at a final concentration of 20 mg/L. In the BALF injury group and anti-H4 intervention group, AMs were treated with 200 μL BALF supernatant from mice intratracheally administered 6 mg/kg body weight LPS, with the latter group treated with 25 mg/L anti-H4 antibody. The control group AMs were treated with phosphate-buffered saline. iii) After 12 hours of stimulation, the cells were collected, and the relative expression of tumor necrosis factor-α (Tnfa), interleukin-1β (Il1b), differentiation antigen 206 (Cd206) and arginase 1 (Arg1) in AMs was detected using real-time quantitative polymerase chain reaction. Results i) Compared with the control group, mice in all four LPS groups exhibited rapid breathing, inflammatory reaction and lung edema in lung tissues, which were aggravated in a dose-dependent manner. The ratio of partial pressure of arterial oxygen to fraction of inspired oxygen in mice decreased with the increase of LPS dose (P<0.05). The wet/dry weight ratio of lung, the level of histone H4 in BALF and the relative expression of Tnfa and Il1b mRNA in AMs increased with the increase of LPS dose (all P<0.05). The mice in the 6 and 8 mg/kg LPS groups developed ARDS. The level of histone H4 in BALF and the relative expression of Tnfa and Il1b mRNA in AMs of mice in 6 and 8 mg/kg LPS groups were higher than those in the other three groups (all P<0.05). ii) The relative expression of Tnfa and Il1b mRNA increased (both P<0.05), and the relative expression of Cd206 and Arg1 mRNA decreased (both P<0.05) in AMs of histone H4 injury group and BALF injury group compared with the control group. Compared with BALF injury group, the relative mRNA expression of Tnfa and Il1b in AMs of anti-H4 intervention group decreased (both P<0.05), while the relative expression of Arg1 mRNA increased (P<0.05). Conclusion LPS can induce a dose-dependent increase in histone H4 levels in BALF in mice. Histone H4 drives the development of ARDS by activating AMs to M1 polarization. Antagonizing histone H4 to interfere with AM polarization to M1 could be a target for the treatment of ARDS.

Objective:To investigate the feasibility of sentinel lymph node biopsy in breast cancer patients with positive axillary lymph nodes turned to clinical negative after neoadjuvant chemotherapy.Methods:Full-text journal databases such as PubMed, Cochrane Library, Embase, Wanfang, VIP, and CNKI were searched to include research literature on sentinel lymph node biopsy in breast cancer patients who had axillary lymph nodes turned negative after neoadjuvant chemotherapy. The retrieval time was self-established to November 2020. Meta-analysis was performed on the literature that met the inclusion criteria. Heterogeneity among studies was analyzed by I2 test. If I2<30%, the heterogeneity among studies was considered to be small. If the value of I2 was between 30% and 70%, it was considered that there was a certain heterogeneity among the studies. If I2> 70%, it was considered that there was great heterogeneity among the studies. Small heterogeneity was analyzed by fixed effects model, otherwise, random effects model was used. Publication bias was evaluated by funnel plot and Egger′s test. Results:Finally, 14 literatures were included, including 4 Chinese literatures and 10 English literatures. The results of Meta-analysis showed that the sentinel lymph node detection rate was 90.7% and the false negative rate was 12.2%.Conclusions:In breast cancer patients with axillary lymph node turning negative, the detection rate of sentinel lymph node biopsy can meet the acceptable clinical standard for sentinel lymph node biopsy, but the false negative rate is still higher than the clinically acceptable standard. It is necessary to screen suitable patients and apply new techniques to reduce the false negative rate of sentinel lymph node biopsy.

Objective:To translate the Pressure Ulcer Quality of Life Questionnaire (PU-QOL) into Chinese and test its reliability and validity.Methods:The PU-QOL was translated, back translated, cross-cultural debugged and pre-investigated to form the Chinese version of PU-QOL. From August 2020 to November 2021, 405 patients with PU in wound clinics of two third-class hospitals in north and south regions of China were conveniently selected as the research objects.Results:The Chinese version of PU-QOL had 74 items. The content validity of the items was 0.80 to 1.00 and the content validity of the scale level was 0.95. Exploratory factor analysis extracted 7 common factors and the cumulative variance contribution rate was 60.79%. Each problem area is moderately correlated with the 12-Item Short Form Survey (SF-12), and the correlation coefficient between each dimension (0.13-0.28) was less than the correlation coefficient between each dimension and the total score of the scale and the difference was statistically significant( P<0.01). The Cronbach′s α coefficient was 0.84 and the retest reliability was 0.92. Conclusions:The Chinese version of PU-QOL questionnaire was proved to be a good instrument with acceptable reliability and validity, which can be used as a tool for evaluating quality of life of patients with PU in China.

Objective:To establish a LC-MS/MS method for determination of paraquat and diquat in plasma and urine samples.Methods:Plasma is precipitated by acetonitrile then diluent with phosphate buffer (pH=7) , urine is diluent with phosphate buffer (pH=7) , then diluent samples extracted with Oasis WCX solid-phase extraction column. Samples were analyzed using LC-MS/MS in multiple reaction monitoring (MRM) mode. The analytical column was XBridge?BEH-HILIC (100 mm×2.1 mm×2.5 μm) and the mobile phase were 100 mmol ammonium formate add 0.5% formic acid and acetonitrile. Paraquat was quantified by internal standard method and diquat by external standard method.Results:The calibration curves of paraquat and diquat were linear in the concentration range of 10.0~120.0 μg/L, the correlation coefficient (r) were 0.9985~0.9994. The limit of detection of paraquat in plasma and urine were 1.98 μg/L and 1.00 μg/L, respectively, the recovery rate were 100.2%~107.3%, the RSD were 1.6%~3.3%. The limit of detection of diquat in plasma and urine were 1.80 μg/L and 2.77 μg/L, respectively, the recovery rate were 85.3%~93.1%, the RSD were 1.8%~5.5%. Conclusion:This method is sensitive and accurate, and can simultaneously determine paraquat and diquat in plasma and urine.