[Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis].

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

[Preliminary exploration of the metabolic profile and metabolic pathways in newly diagnosed multiple myeloma].

Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.

[A study on the status and problem countermeasures of key occupational disease monitoring in Shandong, China, from 2015 to 2017].

Objective: To analyze the completion status, monitoring results, and existing problems of key occupational disease monitoring in Shandong, China, from 2015 to 2017, and to provide reference materials for improving monitoring quality and carrying out occupational disease prevention and control. Methods: The monitoring situation including project coverage, data collection, monitoring results, and monitoring quality of key occupational diseases in Shandong from 2015 to 2017 were described and comparatively analyzed. Results: In the past three years, the uncoverage rate of monitored counties (38.69% in 2015, 10.95% in 2016, and 5.11% in 2017) , the non-work rate of occupational health examination institutions (41.67% in 2015, 18.02% in 2016, and 8.72% in 2017) , and the non-work rate of occupational disease diagnosis institutions (42.31% in 2015, 38.46% in 2016, and 38.46% in 2017) in Shandong decreased year by year. The number of institutions with key occupational hazard factors reported to the safety supervision and management department increased year by year (it was 24140 in 2017, with an increase of 40.50% compared with 2016 and an increase of 114.62% compared with 2015) ; the key occupational hazard factors in enterprises were mainly noise (72.76%) , followed by benzene, silica dust, and coal dust. The number of workers exposed to key occupational hazard factors reported to the safety supervision and management department increased year by year; in 2017, it was 729245, with an increase of 39.78% compared with 2016 and an increase of 84.81% compared with 2015. The ratio of people exposed to key occupational hazard factors identified by the medical examination to the total people in the safety supervision system in a year decreased year by year (40.87% in 2015, 23.86% in 2016, and 17.95% in 2017) . Conclusion: In Shandong, the supervision of enterprises with key occupational hazard factors and the responsibility of enterprise protection should be strengthened. The occupational health examination rate of workers should be improved. It is suggested that we should carry out the special investigations and occupational health risk assessment for key enterprises and key populations.

[Epidemiological characteristics on temporal-spatial distribution of varicella in Guangxi Zhuang Autonomous Region, 2014-2016].

Objective: To analyze the epidemiological characteristics of temporal-spatial distribution on varicella in Guangxi Zhuang Autonomous Region (Guangxi) during 2014 to 2016. Methods: Incidence data on varicella was collected from the National Notifiable Infectious Disease Reporting Information System (NNIDRIS) of the Center for Disease Control and Prevention (CDC) while geographic information data was from the national CDC. ArcGIS 10.2 software was used to analyze global and local spatial auto correlation on spatial clusters. SaTScan v9.1.1 was used to conduct temporal-spatial scan for exploring the areas of temporal-spatial clusters. Results: The overall incidence rates of varicella during 2014 to 2016 were 32.48/100 000, 43.56/100 000 and 61.56/100 000 respectively. Incidence of varicella showed a positive spatial auto correlation at the county level (the value of Moran's I was between 0.24 to 0.35, P<0.01), with consistent high morbidity. High-high cluster areas were seen and mainly concentrated in the north-western areas of Guangxi. Result from the temporal-spatial scan showed that temporal cluster of varicella occurred mainly between October and next January while the type Ⅰ cluster area was mainly distributed in all of the counties in Hechi city and most counties of Baise city, with most counties being covered in the north-western areas of Guangxi, during 2014-2016. When comparing to data from the last two years, two type Ⅱ cluster areas with larger scales were formed in the north-eastern area of Guanyang county and Haicheng county of southern area in Guangxi, in 2016. Conclusions: Incidence on Varicella seemed on the rise, and the distribution of cases showed clustered features, both on time and space. Strategies regarding control and prevention on Varicella should focus on high-high clustered areas, namely north-western areas of the province, including surrounding areas during the high onset season.

[A prospective multi-center trial of non-interventional and observational study of lenalidomide in Chinese patients with multiple myeloma].

Objective: To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM). Methods: It was a prospective, multi-center, observational study. A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015. Relevant information was recorded, such as baseline clinical data, cytogenetic abnormalities, treatment regimens, and duration of treatment, safety, and survival. Results: (1)There were 126 relapsed and refractory MM (RRMM) patients, 25 newly diagnosed patients and 19 maintenance patients. The evaluable RRMM patients accounted for 120 cases, among which 74 cases(61.7%) reached the partial response (PR) or above, and a very good partial response (VGPR) in 16 patients (13.3%), a complete response (CR) in 14 cases (11.7%), a strictly complete response (sCR) in 4 cases (3.3%). Thus, a VGPR or above in 34 patients accounted for 28.3%. (2)The median follow-up was 13 months, the median time to progression 12 months. The median survival after receiving lenalidomide was 19 months, and the median overall survival (OS) was 62 months. (3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype, international staging system (ISS) Ⅰ-Ⅱ, t(4; 14) negative (detected by fluorescence in situ hybridization), non-bortezomib resistance and response to previous regimens. As to OS, non-bortezomib resistance, response to previous regimens and non-primary refractoriness were positive factors. Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival(PFS), non-bortezomib resistance and non-primary refractoriness for OS. (4) Grade 3 or 4 adverse events that occurred in more than 10% of all enrolled patients were neutropenia (12.7%), leukocytosis(11.5%) and thrombocytopenia (12.7%). Owing to intolerance of toxic side effects, 7 cases withdrew lenalidomide. Conclusions: No matter what combination, regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7%, a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable. In addition, the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS, non-bortezomib resistance and non-primary refractoriness for OS. Clinical trail registration: Clinicaltrials.gov, NCT01947309.

Correlation of cadherin-17 protein expression with clinicopathological features and prognosis of patients with sporadic gastric cancer

This study aimed to explore the correlations between cadherin-17 (CDH17) protein expression and the clinicopathological features and prognosis of patients with sporadic gastric cancer (GC). Nine relevant studies of 1,960 patients were identified using electronic database searches supplemented with a manual search in strict accordance with inclusion and exclusion criteria. Statistical analyses were conducted using STATA 12.0 statistical software. Relative risks and 95% confidence intervals were determined, and Z test was used to measure the significance of the overall effect size. A total of nine eligible cohort studies were included in this meta-analysis. The expression of CDH17 in patients with diffuse GC was significantly higher than in those with intestinal-type GC. Moreover, the tumor depth of invasion differed significantly between patients with positive CDH17 (CDH17+) and negative CDH17 (CDH17-) GC. However, there were no significant differences between CDH17+ and CDH17- GC patients with respect to tumor node metastasis clinical stages, histological grades, or lymph node metastasis. Despite the differences in invasive depth, there was no significant difference in 5-year survival rates between CDH17+ and CDH17- GC patients. Our meta-analysis provides evidence that CDH17 protein expression may be associated with the development of GC, suggesting that CDH17 is an important biomarker that could be useful for the early diagnosis of GC. However, CDH17 levels do not appear to impact overall survival.

Correlation of cadherin-17 protein expression with clinicopathological features and prognosis of patients with sporadic gastric cancer.

This study aimed to explore the correlations between cadherin-17 (CDH17) protein expression and the clinicopathological features and prognosis of patients with sporadic gastric cancer (GC). Nine relevant studies of 1,960 patients were identified using electronic database searches supplemented with a manual search in strict accordance with inclusion and exclusion criteria. Statistical analyses were conducted using STATA 12.0 statistical software. Relative risks and 95% confidence intervals were determined, and Z test was used to measure the significance of the overall effect size. A total of nine eligible cohort studies were included in this meta-analysis. The expression of CDH17 in patients with diffuse GC was significantly higher than in those with intestinal-type GC. Moreover, the tumor depth of invasion differed significantly between patients with positive CDH17 (CDH17+) and negative CDH17 (CDH17-) GC. However, there were no significant differences between CDH17+ and CDH17- GC patients with respect to tumor node metastasis clinical stages, histological grades, or lymph node metastasis. Despite the differences in invasive depth, there was no significant difference in 5-year survival rates between CDH17+ and CDH17- GC patients. Our meta-analysis provides evidence that CDH17 protein expression may be associated with the development of GC, suggesting that CDH17 is an important biomarker that could be useful for the early diagnosis of GC. However, CDH17 levels do not appear to impact overall survival.

Clinical three-dimensional conformal radiotherapy research using repeated computed tomography scans for field reduction in older non-small-cell lung cancer patients.

This study investigated the curative and toxic effects of three-dimensional conformal radiotherapy (3D-CRT), using repeated CT scans for field reduction in older non-small-cell lung cancer (NSCLC) patients. 3D-CRT was administered to 36 older patients with NSCLC, and irradiation fields included the primary lesion and metastatic lymph nodes. After CT localization scanning, images were fed into a treatment planning system to delineate the gross tumor volume (GTV)1 and prepare Plan 1. After the DT50 (dose of the tumor is 50 Gy) increased from 50 Gy in 25 fractions to 54 Gy in 27 fractions, secondary CT localization scanning was performed to delineate GTV2 and prepare Plan 2; radiotherapy was administered continuously. When the DT increased to 60-65 Gy, tertiary CT scanning was performed to prepare another plan. The field was reduced to boost irradiation to the residual target volume until the total DT increased to 68-74 Gy. Compared with GTV1, the median absolute volume regression and median relative regression amounts for GTV2 were 68.85 cm(3) and 31.17%, respectively (Z = -2.673, P = 0.021). There were 8 cases of complete remission (22.2%), 20 of partial remission (55.6%), 7 of stable disease (19.4%), and 1 of progressive disease (2.8%). The total effectiveness rate was 77.8% and the 1- and 2-year survival rates were 63.9 and 27.8%, respectively. Radiation esophagitis and radiation pneumonia, the main toxic side effects, were tolerable. 3D-CRT, using repeated CT scans for field reduction in older NSCLC patients, could increase the local control and survival rates and relieve the toxic radiotherapy side effects.

Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study.

We conducted a single-arm prospective study in 50 patients who received the combination of an haploidentical stem cell graft and an unrelated umbilical cord blood unit for the treatment of hematological malignancies. The median time for neutrophil engraftment was 13 days (11-20 days), and for platelets was 15 days (11-180 days). All surviving patients attained complete haploidentical engraftment except three patients who presented a mixed engraftment with increasing cord blood and decreasing haplo mismatch chimerism during the first 4 months after transplantation. The cumulative incidence of grade II-IV acute GVHD was 20%±0.327% at day+100, and the incidence of chronic GVHD was 19.26%±1.0% at 1 year. The 1-year cumulative incidence of relapse was 19.78%±1%, and the TRM was 16.2%±0.54%. At 1 year, overall survival was 78.6%±7.6% and PFS 64.0%±11.0%. The BU/CY-based conditional regimen showed a significant superiority over TBI/CY on PFS (relative risk=5.012, 95% confidence interval, 1.146-21.927, P=0.032). In conclusion, the co-infusion of an unrelated cord blood unit may potentially improve the outcome of haploidentical allogeneic hematopoietic SCT.

EMP1 inhibits nasopharyngeal cancer cell growth and metastasis through induction apoptosis and angiogenesis.

This study aimed to analyze the expression, clinical significance of epithelial membrane protein-1 (EMP1) in nasopharyngeal carcinoma, and the biological effect in its cell line by EMP1 overexpression. Immunohistochemistry and Western blot were used to analyze the EMP1 protein expression in 75 cases of nasopharyngeal cancer and 31 cases of normal tissues to study the relationship between EMP1 expression and clinical factors. Recombinant lentiviral vector was constructed to overexpress EMP1 and then infect nasopharyngeal cancer CNE2 cell line. Quantitative real-time RT-PCR and Western blot were used to detect the mRNA level and protein of EMP1. MTT assay, cell apoptosis, migration, and invasion assays were also conducted to determine the influence of the upregulated expression of EMP1 that might be found on CNE2 cells' biological effect. Immunohistochemistry and Western blot: The level of EMP1 protein expression was found to be significantly lower in nasopharyngeal cancer tissue than in the normal tissues (P < 0.05). Decreased expression of EMP1 was significantly correlated with T stages, lymph node metastasis, clinic stage, and histological grade of patients with nasopharyngeal cancer (P < 0.05). Meanwhile, the loss of EMP1 expression correlated significantly with poor overall survival time by Kaplan-Meier analysis (P < 0.05). The result of biological function has shown that CNE2 cell-transfected EMP1 had a lower survival fraction, higher cell apoptosis, significant decrease in migration and invasion, higher caspase-9, and lower vascular endothelial growth factor C protein expression compared with CNE2 cell-untransfected EMP1 (P < 0.05). EMP1 expression decreased in nasopharyngeal cancer and correlated significantly T stages, lymph node metastasis, clinic stage, histological grade, and poor overall survival, suggesting that EMP1 may play important roles as a negative regulator to nasopharyngeal cancer cell.

Improving strategies for syphilis control in China: selective testing of sexually transmitted disease patients--too little, too late?

SUMMARY: Syphilis testing guidelines in China are usually based on symptomatic criteria, overlooking risk assessment and ultimately opportunities for disease detection and control. We used data from 10,695 sexually transmitted disease (STD) clinic patients in Guangxi, China, to assess the efficacy of a potential screening tool inquiring about behavioural and health risk factors in identifying the STD patients who should not be triaged for syphilis testing under current guidelines, but on the contrary receive such testing. Validity testing of the screening tool was performed and receiver-operating characteristic curves were plotted to determine an optimal total risk score cut-off for testing. About 40.9% of patients with positive toluidine red unheated serum test and Treponema pallidum particle agglutination test did not show hallmark signs of syphilis. The screening tool was more sensitive in detecting infection in non-triaged male versus female patients (highest sensitivity = 90% vs. 55%) and the cut-off score to warrant testing was lower in non-triaged female patients than in non-triaged male patients (cut-off = 1 vs. 2). Most of the cases were missed among female STD patients. In spite of selective testing based on behavioural and health indicators that improve case detection, cases were still missed. Our study supports universal testing for syphilis in the STD population.

Thromboxane/prostacyclin balance in type II diabetes: gliclazide effects.

We studied serum thromboxane (TXB2), the prostacyclin metabolite, 6-keto-PGF1 (6KPGF1) glucose, insulin, and lipid/lipoprotein profiles in 27 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were switched from therapy with glibenclamide (GLB) (with [GLBH] or without phenformin) to gliclazide for 3 months. We found that therapy with gliclazide was followed by a decrease in serum TXB2 (281.8 +/- 128.3 to 149.1 +/- 77.0 mg/L, P less than .001) and an increase in serum 6KPGF1 (60.5 +/- 19.1 to 96.0 +/- 40.3 mg/L, P less than .001). This was accompanied by a decrease in total and low-density lipoprotein (LDL) cholesterol and an increase in high-density lipoprotein (HDL) cholesterol, within the HDL3 cholesterol fraction. These changes were seen despite the fact that neither fasting plasma glucose nor insulin changed with therapy. These findings suggest that gliclazide may have beneficial actions on cardiovascular risk factors in these NIDDM patients.

Familial hyperinsulinemia associated with secretion of an abnormal insulin, and coexistence of insulin resistance in the propositus.

A 45-yr-old muscular nonobese white man who had a 9-yr history of syncopal episodes was studied on several occasions between April 1979 and August 1984. Fasting glucose concentrations ranged between 74-115 mg/dl, and those of insulin ranged between 14-64 microU/ml. Reactive hypoglycemia 3-4 h after ingestion of glucose occurred in the first 2 yr. Glucose tolerance was impaired in 1979, from February 1982 through September 1983, and again in August 1984. The maximum plasma insulin response to glucose ranged between 475-1630 microU/ml. When studied in November 1982, insulin (0.1 U/kg) caused a fall in blood glucose concentration of only 25% (normal, greater than 50%), and maximal glucose utilization during the euglycemic hyperinsulinemic clamp was 7.5 mg/kg . min (normal, greater than 12 mg/kg . min). Plasma counterregulatory hormone concentrations were normal, and antibodies to insulin and the insulin receptor were absent. Binding of exogenous insulin to the patient's cellular receptors (monocytes, red blood cells, and skin fibroblasts) was normal. Insulin was purified from plasma by immunoaffinity and molecular sieve chromatography and was found to elute later than human insulin on reversed phase high performance liquid chromatography. It was more hydrophobic than normal human insulin and had only 10% of the activity of normal insulin in terms of ability to bind to and stimulate glucose metabolism in isolated rat adipocytes. The abnormal insulin was identified in two of three sons and a sister, but not in the mother, brother, or niece. Sensitivity to insulin was normal in the two sons who had abnormal insulin. These results suggest that in this family the abnormal insulin was due to a biosynthetic defect, inherited as an autosomal dominant trait. The hyperinsulinemia was not associated with diabetes in family members who had no insulin resistance.

Characterization of circulating insulin in insulin autoimmune syndrome.

We examined the forms of circulating insulin in three patients with the insulin autoimmune syndrome by a method combining gel filtration and reverse phase high performance liquid chromatography (RP-HPLC). Insulin bound to circulating antibody was dissociated by molecular sieve chromatography at acid pH. The free insulin peak eluted from a Sephadex G-50 column was subsequently chromatographed on a Bio-Gel P-30 column. In all three patients, insulin coeluted with normal human insulin. However, when the partially purified insulins, obtained by gel filtration, were applied to RP-HPLC, an abnormally migrating insulin was found in two of three patients. The insulins were more hydrophobic than normal human, porcine, or bovine insulin, but were different from each other. A third patient had only a single insulin peak on RP-HPLC which corresponded to normal insulin. In contrast, the insulin from insulin-treated diabetic patients with antibodies to exogenous insulin corresponded to either porcine or bovine and normal human insulin. The antibodies in the circulation of these patients with the autoimmune syndrome were of the immunoglobulin G type and contained kappa and lambda-chains in the same proportions as antibodies in insulin-treated patients. Autoantibodies could not be distinguished from those secondary to exogenous insulin treatment on the basis of displacement of binding by human, beef, or pork insulin. These results suggest that in certain patients with the insulin autoimmune syndrome, there may be a molecular abnormality of circulating insulin. Whether this comprises a cause for the syndrome or is a result of posttranslational processing of insulin remains to be determined.

Identification of insulin variants in patients with hyperinsulinemia by reversed-phase, high-performance liquid chromatography.

We have characterized the molecular forms of circulating insulins in patients with hyperinsulinemia of diverse etiology. We have also compared the efficacy of various chromatographic conditions using reversed-phase (RP) HPLC. Using 0.2% trifluoroacetic acid (TFA) and triethylamine (TEA) with acetonitrile as the organic modifier, at an elution rate of 0.17%/min, porcine, bovine, and human insulins could be easily separated as well as abnormal insulins in the plasma of a patient (J.R.) with hyperinsulinemia of unknown etiology. When the reversed-phase C18 column was changed and a gradient of 0.33%/min was used, the abnormal insulin in patient J.R. could not be separated. By changing the solvent system to acetonitrile and isopropanol (vol:vol, 3:1) containing 0.1% TFA, omitting the TEA, and using a gentle gradient of 0.1%/min, various semisynthetic analogues of human insulin could be easily separated and the abnormal insulin could be identified in the plasma of the patient J.R. Abnormal insulin was also found in a patient with MEN-I, but in contrast, the insulins in eight patients with benign sporadic insulinomas appeared to be normal. These results suggest that certain hyperinsulinemic states may be associated with an abnormal insulin and that RP-HPLC is useful for identification of insulin variants in the circulation. However, the conditions of RP-HPLC may be critical if the abnormalities of the insulin are subtle.