OBJECTIVETo study the possible relationship between tumor necrosis factor (TNF)-alpha-238G/A gene polymorphism and the susceptibility to intrauterine HBV infection.

METHODSTwo hundred and fifty-six children, including 130 infants born to HBsAg positive mothers were divided into two groups: forty-five children with intrauterine HBV infection (group I) and 85 children without intrauterine HBV infection (group II), with a control group of 126. TNF-alpha-238G/A gene polymorphism was examined in all 256 children, by means of real-time quantitative fluorescent PCR.

RESULTSA significant difference of TNF-alpha-238A allele frequency was found between group I and group II (x2=6.797, P=0.009), and between group I and the controls group (x2=0.047, P=0.002), but there was no significant difference between group II and the control groups (x2=0.047, p=0.828).

CONCLUSIONThis study found that genetic polymorphism of tumor necrosis factor-a was associated with intrauterine HBV infection

Adult ; Child ; Disease Susceptibility ; Female ; Hepatitis B ; transmission ; Humans ; Infant ; Infectious Disease Transmission, Vertical ; Polymorphism, Genetic ; Tumor Necrosis Factor-alpha ; Tumor Necrosis Factors ; genetics

OBJECTIVETo explore polarization of T lymphocyte and its relationship with apoptosis of marrow cells in patients with myelodysplastic syndromes (MDS).

METHODSMeasurements of Th1, Th2, Tc1, Tc2 subsets in bone marrows from 34 patients with MDS and 13 normal controls were performed by flow cytometry. INF-gamma and TNF-alpha in marrow serum were determined by ELISA (Enzyme-linked immunosorbent assay). Apoptosis index of marrow cells was detected by TUNEL (TdT-mediated dUTP nick end labeling). Correlations between Th1, Th2, Tc1, Tc2 subsets and INF-gamma, TNF-alpha levels as well as apoptosis index were analyzed, and relationship between TNF-alpha, INF-gamma levels and apoptosis index was also investigated.

RESULTS(1) The percentage of Th1 cells [(10.1 +/- 1.6)%], Tc1 cells [(24.0 +/- 3.6)%] and Tc1/Tc2 ratio (50.0 +/- 11.1) was significantly increased in patients with MDS than in normal controls [(4.0 +/- 0.5)%, (5.8 +/- 0.6)% and 13.4 +/- 2.7, respectively]. Levels of INF-gamma [(58.6 +/- 21.7) microg/L] and TNF-alpha [(15.7 +/- 3.8) microg/L] in marrow serum of MDS patients was markedly elevated compared to normal controls [0 and (0.3 +/- 0.2) microg/L, respectively]. An increased apoptosis index of nucleated cells was observed in MDS patients [(7.8 +/- 1.5)%] as compared to controls [(2.1 +/- 0.3)%, P < 0.05]. The Th1 cell percentage showed a positive correlation with the levels of INF-gamma and TNF-alpha (r = 0.38, P < 0.05 and r = 0.39, P < 0.05, respectively), and with apoptotic index of nucleated marrow cells in MDS patients (r = 0.33, P < 0.05). Furthermore, a positive correlation was observed between INF-gamma, TNF-alpha levels and apoptotic index of marrow cells (r = 0.74, P < 0.01 and r = 0.73, P < 0.01, respectively). (2) Th1, Tc1 cells and Tc1/Tc2 ratio in MDS-RCMD patients was markedly elevated (P < 0.01) but did not in RCMD-RS, RAEB-1 and RAEB-2 patients as compared to normal controls. (3) An elevation in the percentages of Th1, Tcl and Tc1/ Tc2 ratio was detected in patients with IPSS lower-risk but did not in higher-risk group as compared to controls. (4) Increased Th1 and Tc1 percentages and Th1/Th2 and Tc1/Tc2 ratios were observed in RCMD patients with normal karyotype, but did not in those with abnormal karyotype. Conclusions Th1/Th2 and Tc1/Tc2 in bone marrow of MDS patients were unbalanced, polarizing to type I reaction especially in patients with RCMD subtype, IPSS lower-risk and normal karyotype. The increased Th1 cells in bone marrow may account for the increased apoptosis of nucleated marrow cells in MDS, through proapoptotic cytokines such as INF-gamma and TNF-alpha.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Apoptosis ; immunology ; Bone Marrow ; immunology ; metabolism ; pathology ; Female ; Hematopoietic System ; immunology ; Humans ; Interferon-gamma ; metabolism ; Male ; Middle Aged ; Myelodysplastic Syndromes ; immunology ; T-Lymphocytes ; immunology ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the biological difference of clonal cells between myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

METHODBone marrow (BM) clonal cells (which had cytogenetic markers detected by FISH assay) and blasts were quantitatively analysed in 51 MDS and 11 AML patients. The clonal cell percentage in orthochromatic normoblasts, granulocytes and megakaryocytes were assayed. The biological functions for phagocytosis and oxidation of MDS peripheral blood (PB) neutrophils were compared with that of normal controls.

RESULTSAlmost all MDS patients BM had a higher clonal cell percentage (mean 48.2%) than blasts percentage (mean 6.7%) (P < 0.01), but with the subtype of MDS advancing this percentage gap was closing up, and in 11 AML patients no such gap was observed. This gap in MDS patients with + 8 abnormality was smaller than in those with 5q -. In MDS BM, clonal cells were detected in segmented granulocytes (mean 45.9%), orthochromatic normoblasts (mean 46.0%) and mature megakaryocytes (mean 38.0%). In Addition, an approximate amount of clonal cells with the same karyotype abnormality in BM were detected in MDS PB (mean 37.3% in blood vs 48.6% in marrow). Functional analysis showed that the neutrophils in MDS PB could exert nearly normal physiological functions (P > 0.05), but those from AML could not as compared to healthy donors (P < 0.01).

CONCLUSIONThere is a significant difference in the biological features between MDS and AML clonal cells.

Adult ; Aged ; Aged, 80 and over ; Bone Marrow Cells ; pathology ; Cell Differentiation ; Clone Cells ; Female ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute ; pathology ; Male ; Middle Aged ; Myelodysplastic Syndromes ; pathology

OBJECTIVETo investigate the apoptotic situation of CD(34) positive cells in myelodysplastic syndromes (MDS).

METHODIn 36 MDS patients, immunocytochemical technique was used for the detection of the expression of CD(34) antigen and DNA in situ end labelling (ISEL) (fluorescein) for the apoptotic signals. Fourteen cases of iron deficiency anemias (IDA) were used as controls.

RESULTS(1) CD(34) expression in MDS group was much higher than that in controls (49.2 +/- 38.5 vs 10.2 +/- 9.7, P < 0.01), and MDS cases had an obviously higher apoptotic rate than control did (69.1 +/- 28.2 vs 17.8 +/- 11.2, P < 0.01). (2) Expression of CD(34) was higher in transforming group (P < 0.05) than in non-transforming and post-transforming groups. Apoptotic rates in both non-transforming/transforming group were higher than in post-transforming group (P < 0.02 and < 0.05 respectively). (3) No apoptosis was found in CD(34) positive cells in MDS; (4) Both CD(34) positive cells and apoptotic cells formed into small or large clusters but did not co-distributed in a given area.

CONCLUSIONThere is overexpression of CD(34) antigen on hematopoietic cells in MDS. High CD(34) expression accompanied high apoptosis coexisted in the process of transformation from MDS to AML. Apoptosis-resistance of these CD(34) positive cells suggested that they came from malignant hematopoietic cell clones.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; metabolism ; Apoptosis ; Bone Marrow Cells ; immunology ; pathology ; Child ; Female ; Humans ; Immunoenzyme Techniques ; In Situ Nick-End Labeling ; Male ; Middle Aged ; Myelodysplastic Syndromes ; immunology ; pathology

OBJECTIVETo observe the relationship between macrophage proliferation and cell apoptosis in patients with myelodysplastic syndromes (MDS).

METHODSA double labelling method of immunohistochemistry (alkaline phosphatase anti-alkaline phosphatase, APAAP) and ISEL (DNA in situ end labelling) was used to detect the positive CD68 expression (macrophages) and apoptosis on cold plastic embedded bone marrow biopsy sections in 30 MDS cases. 12 cases of iron deficient diseases (IDA) were used as the control.

RESULTS(1) The number of CD68 positive cells in MDS were higher than that in controls (29.2 +/- 33.0/mm(2) bone marrow tissue vs 21.2 +/- 16.7/mm(2)) (P > 0.05); (2) The number of apoptotic cells in MDS group was much higher than that in the controls (71.5 +/- 70.9/mm(2) vs 37.3 +/- 23.0/mm(2), P < 0.05); (3) The number of CD68 expression (35.5 +/- 37.0/mm(2)) and apoptosis (90.7 +/- 74.6/mm(2)) in less advanced MDS were much higher than that in advanced MDS group (14.6 +/- 11.7/mm(2) and 26.8 +/- 33.1/mm(2), P < 0.05 and < 0.01 respectively); (4) CD68 expression showed an obvious positive correlation to apoptosis in MDS cases (r = 0.83, P < 0.001); (5) CD68 positive cells did not show location correlation to apoptotic cells; (6) CD 68 positive cells in MDS showed simultaneous apoptosis.

CONCLUSIONSOver-apoptosis existed in MDS. Less advanced group has a higher ratio of apoptosis than in advanced group. The correlation between macrophages and apoptosis indicates the participation of TNFalpha in apoptosis-induction during MDS development.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; Apoptosis ; Child ; Female ; Humans ; Macrophages ; pathology ; Male ; Middle Aged ; Myelodysplastic Syndromes ; pathology ; Tumor Necrosis Factor-alpha ; biosynthesis

OBJECTIVETo investigate the clinical therapeutic results of allograft tendon for anatomical reconstruction of medial patellofemoral ligament (MPFL) for the treatment of patellar dislocations.

METHODSFrom September 2008 to June 2013, 16 patients with patellar dislocation underwent MPFL reconstructions. There were 2 males and 14 females, aged 11 to 27 years old (16 years old on average). Patellar dislocations occurred in 11 left and 5 right knees. The disease course ranged from 3 to 10 years. The frequency of dislocation ranged from 9 to 33 times (19 times on average). Affected knee joints showed patellar instability; the range of action for patella obviously increased. The X-ray films showed patellar dislocation. The preoperative Q angle was (36 ± 9)°, and the congruence angle was (63 ± 18)°. Reconstruction was performed via allograft tendon. Allograft tendon was fixed through the superomedial pole of the patella, and the other end was fixed at the natural MPFL insertion site near the medial femoral condyle with an interference screw in a bone tunnel. All the patients were evaluated postoperatively; Kujala patellofemoral scores, objective knee function, complications, and reoperations were assessed.

RESULTSPrimary healing was achieved in all cases. No infection or necrosis and absorption of grafts was observed. All the patients were followed up for an average of 16.4 months (ranged, 10 to 24 months) postoperatively. At the latest follow-up, all the patients had no pain, swelling and patellar instability; neither patella redislocation nor fracture occurred. The X-ray films showed good position of tunnel 6 months after operation, and the congruence angle was (5 ± 9)°, showing statistically significant difference when compared with preoperation (P < 0.05). The postoperative Q angle was (17 ± 8)°, the Kujala knee function score improved significantly from 45.20 ± 9.20 to 89.30 ± 6.40 at the latest follow-up, showing statistically significant difference (P < 0.05).

CONCLUSIONMPFL reconstruction improves clinical symptoms. Anatomical MPFL reconstruction is effective for patellar dislocation, and it offers good recovery of the premorbid patella mechanics. The interference screw provides firm fixation. Allograft can avoid the graft harvest site morbidity, but it increases the cost of the surgery.

Adolescent ; Adult ; Allografts ; Child ; Female ; Humans ; Ligaments, Articular ; surgery ; Male ; Patellar Dislocation ; surgery ; Patellofemoral Joint ; surgery ; Reconstructive Surgical Procedures ; methods ; Tendons ; transplantation

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.