The value of intravoxel incoherent motion diffusion-weighted imaging in predicting perineural invasion for resectable gastric cancer: a prospective study.

AIM: To investigate the potential of intravoxel incoherent motion (IVIM) diffusion-weighted imaging to predict perineural invasion (PNI) preoperatively in resectable gastric cancer (GC). MATERIALS AND METHODS: This study prospectively recruited 85 surgically resected GC patients (58 men, 27 women) aged 60.87 ± 10.17 (39-81) years, who underwent IVIM sequence within 1 week before surgery. According to histopathological PNI diagnoses, patients were divided into PNI positive and negative groups. Conventional apparent diffusion coefficient (ADC) and the IVIM parameters, including true diffusion coefficient (D), pseudodiffusion coefficient (D∗), and pseudodiffusion fraction (f), were compared between the two groups. Morphological MRI features were also analysed. Multivariate logistic regression was used to screen independent predictors of PNI. Receiver-operating characteristic curve analyses were preformed to evaluate the efficacy. Spearman's correlation test was performed to analyse the relationship between MRI parameters and PNI. RESULTS: Tumour thickness and f in PNI-positive group were higher, whereas the ADC, D were lower than those in PNI-negative group (p<0.05). These four parameters correlated with PNI (p<0.05). The D, f, and tumour thickness were independent predictors of PNI. The area under the curve of ADC, D, f, thickness, and the combined parameter (D + f + thickness) were 0.648, 0.745, 0.698, 0.725, and 0.869, respectively. The combined parameter demonstrated higher efficacy than any other parameters (p<0.05). CONCLUSION: The ADC, D, and f can effectively distinguish PNI status in GC. The D, f, and thickness were independent predictors of PNI.

[The long-term efficacy of metformin in megestrol acetate-based fertility-sparing treatment for patients with endometrial atypical hyperplasia and endometrioid endometrial cancer].

Objective: To assess the long-term efficacy of metformin in megestrol acetate (MA)-based fertility-sparing treatment for patients with endometrial atypical hyperplasia (EAH) and endometrioid endometrial cancer (EEC). Methods: The randomized controlled trail study was conducted from October 2013 to October 2017 in the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. Patients with EAH or EEC were firstly stratified according to pathology, and randomized to receive MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day) or MA (160 mg orally, daily). Baseline data between two groups of patients were compared. Estimates of time to complete remission (CR) and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method. Cox proportional-hazards regression model was used to estimate hazard ratios (HR) of related factors for recurrence-free survival. Quantitative data were represented by M (Q1, Q3). Results: A total of 150 patients were included, and 76 patients were allocated to receive MA plus metformin with the age of 32.5 (28.0, 36.0), while 74 patients received MA alone with the age of 32.0 (28.0, 36.0). By the end of follow-up period, 96.7% (n=145) of patients achieved complete remission, with a median follow-up time of 57.7 (26.7, 70.5) months. The median CR time for the MA plus metformin group and the MA alone group were 6.3 (3.5, 8.3) months and 6.8 (4.0, 9.3) months, respectively (P=0.193), with 2-year cumulative CR rate of 98.6% and 98.5%, respectively (P=0.879). The median time of RFS was 28.1 (12.5, 57.3) months for the MA plus metformin group and 33.3 (14.1, 62.5) months for the MA alone group (P=0.213), with a cumulative RFS rate of 61.9% and 65.8%, respectively (P=0.560). In the subgroup of non-obese (body mass index<28 kg/m2) patients with EAH, the median RFS times were 25.7 (7.6, 60.3) months and 47.3 (17.5, 64.8) months for the MA plus metformin group and the MA alone group, respectively (P=0.033), with a cumulative RFS rate of 57.5% and 80.6%, respectively (P=0.029). According to Cox proportional hazards regression analysis, undergoing assisted reproductive treatment (HR=2.358, 95%CI: 1.069-5.204, P=0.034) was identified as an independent risk factor for recurrence-free survival after complete remission of endometrial lesions. Conclusion: The long-term follow-up outcome indicates that there is no significant difference in CR time and RFS time between MA plus metformin therapy and MA alone therapy for patients with EAH or EEC.

[The safety and efficacy of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia in children].

To explore the safety and efficacy of blinatumomab in the treatment of CD19 positive (CD19+) B-cell acute lymphoblastic leukemia (B-ALL) in children. A retrospective analysis was conducted on the clinical data of pediatric B-ALL patients who received blinatumomab treatment from Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences from August 2021 to October 2023. Based on their disease status, the patients were divided into refractory/relapsed(RR) group, minimal residual disease clearance (MC) group, and chemotherapy intolerance (IC) group. Clinical data of the children were collected to evaluate the adverse drug reactions, therapeutic efficacy and survival of the children. In total, 35 patients were included, with 20 males and 15 females, aged from 0.6 to 16.4 (9.9±4.2) years old. There were 10 cases in the RR group, 20 cases in the MC group and 5 cases in the IC group. A total of 56 cycles of infusion were completed, with one cycle in 24 cases, two cycles in 5 cases, three cycles in 2 cases and four cycles in 4 cases. The median infusion time [M (Q1, Q3)] from the first to the fourth cycle was 14 (14, 28) days, 28 (28, 28) days, 28 (28, 28) days and 28 (26, 28) days, respectively. In terms of adverse reactions, the incidence of grade 1-2 cytokine release syndrome(CRS) was 57.1% (32/56), with grade 1 CRS accounting for 84.4% (27/32). The incidence rate of immune effector cell-associated neurotoxicity syndrome(ICANS) (grade 4) was 1.8% (1/56). In the RR group, 6 cases were treated effectively, and minimal residual disease(MRD) turned negative, before treatment, MRD levels were all less than 20%. Among them, 3 cases had MRD turning positive again 14 to 42 days after discontinuation of Belintoumab. Four cases were treated ineffectively, with MRD >20% before treatment. All MRD positive cases in MC group turned negative and all MRD negative cases in the IC group remained negative after treatment. The median follow-up time of RR group was 5.7 (3.8, 9.4) months, and 1 year median survival rate and event-free survival rate were 40.0%±21.9% and 33.3%±19.2%, respectively. The median follow-up time for MC and IC group patients was 6.7 (5.2, 12.5) months and 7.1 (5.1, 7.6) months, respectively, with an event free survival rate of 100%. The safety and efficacy of using belintoumab in partial RR, MRD clearance, and chemotherapy intolerance are good.

[Clinical features and prognostic factors of advanced myelodysplastic syndromes in children].

Objective: To investigate the clinical features and prognostic factors of advanced myelodysplastic syndromes (MDS) in children. Methods: Clinical data of children diagnosed with advanced MDS in the Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, between September 2009 and April 2022 were retrospectively collected. Follow-up assessments were performed through telephone interviews and the review of medical records until May 1, 2023. The clinical features of children with advanced MDS were summarized by analyzing chromosomal karyotype tests, second-generation gene sequencing results. Multivariate Cox regression analysis was used to investigate the prognostic factors of advanced MDS in children. Results: A total of 69 children, comprising 49 males and 20 females, aged [M (Q1, Q3)] 8 (5, 10) years, were enrolled in the study. Sixty-seven cases underwent chromosomal karyotype testing, of which 42 cases (62.7%) had abnormal karyotypes, with monosomy 7 the most common in 17 cases (25.4%). Forty-three cases underwent next-generation sequencing, with mutations in the SETBP1, NRAS, PTPN11 and RUNX1 genes more common, identified in 12 cases (27.9%), 9 cases (20.9%), 8 cases(18.6%), and 8 cases(18.6%), respectively. The follow-up time [M (Q1, Q3)] was 26 (13, 56) months and the 5-year overall survival rate was 56%(95%CI: 44.4%-70.5%). The 5-year overall survival rate for children who underwent hematopoietic stem cell transplantation (HSCT) was higher than that of children who did not undergo HSCT (73.9% vs 29.1%, P<0.001). HSCT (HR=0.118, 95%CI: 0.037-0.372, P<0.001) was a protective factor for the overall survival rate of children with advanced MDS. Serum ferritin level>356.3 µg/L (HR=6.497, 95%CI: 2.068-20.415, P=0.001) and moderate to severe splenomegaly (HR=4.075, 95%CI: 1.174-14.141, P=0.027) were risk factors for the overall survival rate of children with advanced MDS. Conclusions: Monosomy 7 was the most common abnormal karyotype and SETBP1 was the gene that had the highest mutation frequency in children with advanced MDS. HSCT, increased ferritin and moderate to severe splenomegaly are prognostic factors influencing the overall survival rate of children with advanced MDS.

[Distribution characteristics of plasma renin concentration in patients with aldosterone-producing adenoma].

Objective: To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis. Methods: In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed. Results: The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 28.2 mU/L) in 8.0% (16/200) of the patients with APA. And PRC was not suppressed in 2.5% (5/200) of the patients with APA, resulting in a primary aldosteronism negative screening outcome. Conclusions: Although most patients with APA have low PRC, there are a small number (8%) of patients whose PRC has not been fully suppressed, which can lead to missed diagnoses during primary aldosteronism screening. While primary aldosteronism is highly suspected, further investigations are required to determine the diagnosis, even if PRC is not fully suppressed at screening.

[The role of DNA methylation in the screening of endometrial cancer in postmenopausal women].

Objective: To explore the application value of cervical exfoliated cell DNA methylation (CDO1m and CELF4m) combined with or without transvaginal sonography (TVS) for screening endometrial cancer in postmenopausal women. Methods: A total of 143 postmenopausal women who underwent hysteroscopy for suspected endometrial lesions in the Department of Obstetrics and Gynecology of Peking Union Medical College Hospital from May 2020 to October 2021 were enrolled in this study. The cervical exfoliated cells were collected for gene methylation before hysteroscopy. Clinical information, tumor biomarkers, and endometrial thickness of TVS were also collected. With endometrial histopathology as the gold standard, multivariate unconditional logistic regression was applied to analyze the risk factors of endometrial cancer. The role of gene methylation with or without TVS were specifically explored. Results: The 143 patients were divided into an endometrial cancer group (n=56) and a control group (n=87), aged (59.27±6.45) and (61.07±8.26) years, respectively (P=0.051). Multivariate logistic regression analysis showed that, CA125≥35 U/ml, postmenopausal bleeding, endometrial thickness≥5 mm, CDO1m ΔCt≤8.4, and CELF4m ΔCt≤8.8 were the risk factors for endometrial cancer, with OR (95%CI) of 33.23 (2.51-1 335.28), 8.41(1.81-39.05), 14.45 (2.35-88.84), 17.34 (3.34-89.98), and 44.01 (6.79-285.25), respectively (all P values<0.05). The sensitivity and specificity of dual-gene methylation (CDO1 or CELF4) in the screening of endometrial carcinoma were both higher than others factors, reaching 87.5% (95%CI: 75.9%-94.8%) and 90.8% (95%CI: 82.7%-95.9%), respectively. TVS combined with DNA methylation detection further improved the sensitivity to 100.0% (95%CI: 93.6%-100.0%), but could not improve the specificity (59.8%, 95%CI: 48.8%-70.1%). Conclusions: In postmenopausal women with suspected endometrial lesions, the accuracy of cervical cytology DNA methylation is better than other noninvasive clinical indicators for the screening of endometrial cancer. DNA methylation combined with TVS can further improve the sensitivity of screening.

[Fertility-preserving treatment outcomes in endometrial cancer and atypical hyperplasia patients with different molecular profiles].

Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.

[Comparison of the effects and safety of dydrogesterone and medroxyprogesterone acetate on endometrial hyperplasia without atypia: a randomized controlled non-inferior phase â ¢ clinical study].

Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.

[Risk factor assessment and adverse outcome prediction of placenta accreta in pregnant women after cesarean section complicated with placenta previa: a national multicenter retrospective study].

Objective: To study the risk factors of adverse pregnancy outcomes for the diagnosis and treatment of pregnancy after cesarean section complicated with placenta previa. Methods: A national multicenter retrospective study was conducted to select a total of 747 pregnant women with the third trimester singleton pregnancy after cesarean section complicated with placenta previa from 12 tertiary hospitals in January 1st to December 31st, 2018. The risk factors of severe adverse outcomes [hysterectomy, intraoperative blood loss ≥1 000 ml, intraoperative diagnosis of placenta accreta spectrum disorders (PAS)] in pregnant women with second pregnancy complicated with placenta previa after cesarean section were investigated by logistic regression analysis. The roles of prenatal ultrasonography and magnetic resonance imaging (MRI) in the prediction of PAS and severe adverse outcomes were observed. According to whether vascular intervention was performed (uterine artery embolization or abdominal aortic balloon occlusion), the pregnant women were divided into the blocked group and the unblocked group, and the maternal and infant perinatal outcomes between the two groups were compared. Results: (1) General information: the hysterectomy rate of 747 pregnant women with second pregnancy complicated with placenta previa after cesarean section was 10.4% (78/747), the intraoperative blood loss ≥1 000 ml in 55.8% (417/747), and PAS was confirmed in 47.5% (355/747). The incidence of uterine rupture was 0.8% (6/747). (2) Analysis of risk factors for severe adverse outcomes: based on binary unconditioned logistic regression univariate and multivariate analysis, the risk factors for hysterectomy were the mode of vascular embolization and intraoperative blood loss. The probability of hysterectomy with uterine artery embolization was 5.319 times higher than that with abdominal aortic balloon occlusion (95%CI: 1.346-21.018). The risk factors of intraoperative blood loss ≥1 000 ml were the number of cesarean section delivery, ultrasonography indicated PAS and suspected PAS, intraoperative PAS and complete placenta previa. The risk factors for intraoperative PAS were uterine scar thickness, ultrasonography indicated PAS and suspected PAS, MRI indicated PAS and suspected PAS, and complete placenta previa. (3) The roles of ultrasonography and MRI in predicting PAS: the sensitivity and specificity of ultrasonography in predicting PAS were 47.5% and 88.4%; the kappa value was 0.279 (P<0.001), with fair agreement. The sensitivity and specificity of MRI to predict PAS were 79.2% and 97.8%, respectively. The kappa value was 0.702 (P<0.001), indicating a good agreement. The intraoperative blood loss and hysterectomy rate of pregnant women with PAS indicated by ultrasonography and MRI were significantly higher than those with PAS only by ultrasonography or MRI. (4) Influence of vascular occlusion on pregnancy outcome: there were no significant differences in intraoperative blood loss and incidence of intraoperative bleeding ≥1 000 ml between the blocked group and the unblocked group (all P>0.05). There was no significant difference in intraoperative blood loss between the pregnant women with abdominal aortic balloon occlusion, uterine artery embolization and those without occlusion (P=0.409). The hysterectomy rate of pregnant women with uterine artery embolization was significantly higher than those with abdominal aortic balloon occlusion [39.3% (22/56) vs 10.0% (5/50), P=0.001]. Conclusions: In the third trimester of pregnancy with placenta previa after cesarean section, MRI examination has better consistency in predicting PAS than ultrasonography examination. Ultrasonography examination combined with MRI examination could effectively predict the hysterectomy rate and intraoperative blood loss. Vascular occlusion could not reduce the amount of intraoperative blood loss. The hysterectomy rate of pregnant women with uterine artery embolization is higher than those with abdominal aortic balloon occlusion.

[Scimitar syndrome with pulmonary sequestration containing carcinoma: a case report].

We reported the manifestations, auxiliary examination, and treatment courses of a case of scimitar syndrome with pulmonary sequestration containing carcinoma. The clinical characteristics of scimitar syndrome with pulmonary sequestration, pulmonary sequestration containing carcinoma were summarized based on the data of this case and the related literatures before January 2022. Scimitar syndrome can coexist with ipsilateral pulmonary sequestration. Because sequestered lung tissue has a risk of malignant transformation, a cancer screening test is useful for early diagnosis and timely treatment.

[Interpretation on Expert systematic review on the choice of conduits for coronary artery bypass grafting endorsed by the European Association for Cardio-Thoracic Surgery and the Society of Thoracic Surgeons in 2023].

Expert systematic review on the choice of conduits for coronary artery bypass grafting: endorsed by the European Association for Cardio-Thoracic Surgery and the Society of Thoracic Surgeons published in 2023 made recommendations for the selection of bypass vessels. The left internal thoracic artery-anterior descending branch anastomosis represents the accepted gold standard. Radial artery could achieve a better long-term patency rate and a reduction in adverse cardiac events compared to the great saphenous vein. Radial artery graft using an open harvesting method should be chosen to graft the target vessel with low competitive coronary flow, with the use of vasodilators for the first year. There was no clear evidence of better patency for the right internal thoracic artery compared to the great saphenous vein. The bilateral internal thoracic artery had better long-term survival compared to great saphenous vein but may be associated with a higher risk of deep sternal wound infection and should be avoided in high-risk patients. The impact of skeletonization of the internal thoracic artery on graft patency and cardiovascular outcomes was unclear. Endoscopic vein harvest reduced the risk of leg wound complications and was associated with reduced long-term patency. The patency of the no-touch great saphenous vein was significantly better than that of conventional great saphenous vein. A significantly higher risk of complications at the harvesting site and no clear evidence of better long-term clinical outcomes were found in the no-touch great saphenous vein compared to the conventional. There was limited data on the use of right gastroepiploic artery and skeletonized harvesting, which should be used to bypass target vessels in patients with low competitive flow.

[Mutational features of immunoglobulin heavy chain variable region gene in patients with chronic lymphocytic leukemia].

Objective: To investigate the mutational features of the immunoglobulin heavy chain variable region (IgHV) gene in patients with chronic lymphocytic leukemia (CLL) using immunophenotypic and molecular genetic methods. Methods: The laboratory results of 266 CLL patients who underwent IgHV gene examination at Sino-US diagnostics laboratory from February 2020 to February 2021 were analyzed for the IgVH mutational status and presence of specific IgVH fragments. In addition, their immunophenotypic, molecular, chromosomal karyotypic, and FISH profiles were investigated and correlated with the IgVH mutational status. Results: Among 266 patients, 172 were male and 94 were female, with a media age of 67 years (20-82 years).There were more patients with mutated IgHV (m-IgHV) than unmutated IgHV (un-IgHV) (69.2%∶30.8%). There was association of VH family and the presence of gene fragments: the overall incidence of VH families including VH3 family (142/266, 53.4%), VH4 family (75/266, 28.2%), and VH1 family (34/266, 12.8%) was about 95%, among which the proportion of VH4-34 (26/266, 9.8%), VH3-23 (25/266, 9.4%), VH3-7 (24/266, 9.0%), and VH4-39 (16/266, 6.0%) was about 35%. VH3-20 and VH3-49 only occurred in un-IgHV (P<0.05). In addition, the expression rates of CD38 (26.3% vs. 3.0%), CD79b (71.1%∶45.5%) and 11q deletion (25.5%∶5.3%) were higher in un-IgHV, and single trisomy 12 (37.9%∶5.6%) were more commonly found in m-IgHV (P<0.05). MYD88 was one of the major mutation genes in m-IgHV, while ATM had the highest mutation rate in un-IgHV. Conclusion: CLL patients have differential expression in terms of IgHV gene mutations, correlating to their immunophenotype and genetics characteristics.

[Characteristics of fusion gene expression in acute lymphoblastic leukemia].

Objective: To analyze the genetic landscape of 52 fusion genes in patients with de novo acute lymphoblastic leukemia (ALL) and to investigate the characteristics of other laboratory results. Methods: The fusion gene expression was retrospectively analyzed in the 1 994 patients with de novo ALL diagnosed from September 2016 to December 2020. In addition, their mutational, immunophenotypical and karyotypical profiles were investigated. Results: In the 1 994 patients with ALL, the median age was 12 years (from 15 days to 89 years). In the panel of targeted genes, 15 different types of fusion genes were detected in 884 patients (44.33%) and demonstrated a Power law distribution. The frequency of detectable fusion genes in B-cell ALL was significantly higher than that in T-cell ALL (48.48% vs 18.71%), and fusion genes were almost exclusively expressed in B-cell ALL or T-cell ALL. The number of fusion genes showed peaks at<1 year, 3-5 years and 35-44 years, respectively. More fusion genes were identified in children than in adults. MLL-FG was most frequently seen in infants and TEL-AML1 was most commonly seen in children, while BCR-ABL1 was dominant in adults. The majority of fusion gene mutations involved signaling pathway and the most frequent mutations were observed in NRAS and KRAS genes. The expression of early-stage B-cell antigens varied in B-cell ALL patients. The complex karyotypes were more common in BCR-ABL1 positive patients than others. Conclusion: The distribution of fusion genes in ALL patients differs by ages and cell lineages. It also corresponds to various gene mutations, immunophenotypes, and karyotypes.

[Occupational health risk assessment for organic solvent in the major posts of printing industry].

Objective: To evaluate the occupational health risk of organic solvents in major posts of printing industry, and to provide technical reference to take targeted risk control measures. Methods: In January 2021, the contact ratio method was used to assess the occupational health risk of organic solvents in the major posts of 84 printing enterprises in Shantou, and Monte Carto method was used to estimate the probability distribution of risk levels in the majorpostsin January 2021. Results: The highest probability of risk assessment in printing and membranecovering post is Level 4 (high risk) , which are 76.2% and 67.6% respectively; the highest probability of simulation evaluation result in oil blending, dispensing and cleaning post is Level 3 (medium risk) ; and the simulation evaluation result in glueing post are mostly Level 3 (medium risk) and Level 4 (high risk) , the probability of which are 45.7% and 54.3% respectively. Conclusion: The occupational health risk of organic solvents in the major posts is generally middle-high risk level, and then the occupational health risk control of organic solvents in major posts of printing industry should be strengthened.

[Effectiveness of different screening strategies for cardiovascular diseases prevention in a community-based Chinese population: A decision-analytic Markov model].

OBJECTIVE: To evaluate the potential effectiveness of different screening strategies for cardiovascular diseases prevention in a community-based Chinese population from economically developed area of China. METHODS: Totally 202 179 adults aged 40 to 74 years without cardiovascular diseases at baseline (January 1, 2010) were enrolled from the Chinese electronic health records research in Yinzhou (CHERRY) study. Three scenarios were considered: the screening strategy based on risk charts recommended by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases in Chinese adults aged 40-74 years (Strategy 1); the screening strategy based on the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) models recommended by the 2019 Guideline on the assessment and management of cardiovascular risk in China in Chinese adults aged 40-74 years (Strategy 2); and the screening strategy based on the China-PAR models in Chinese adults aged 50-74 years (Strategy 3). According to the guidelines, individuals who were classified into medium- or high-risk groups after cardiovascular risk assessment by the corresponding strategies would be introduced to lifestyle intervention, while high-risk population would take medication in addition. Markov model was used to simulate different screening scenarios for 10 years (cycles), using parameters mainly from the CHERRY study, as well as published data, Meta-analyses and systematic reviews for Chinese populations. The life year gained, quality-adjusted life year (QALY) gained, number of cardiovascular disease events/deaths could be prevented and number needed to be screened (NNS) were calculated to compare the effectiveness between the different strategies. One-way sensitivity analysis on uncertainty of cardiovascular disease incidence rate and probabilistic sensitivity analysis on uncertainty of distributions for the hazard ratios were conducted. RESULTS: Compared with non-screening strategy, QALYs gained were 1 433 [95% uncertainty interval (UI): 969-1 831], 1 401 (95%UI: 936-1 807), and 716 (95%UI: 265-1 111) for the Strategies 1, 2, and 3; and the NNS per QALY in the above strategies were 141 (95%UI: 110-209), 144 (95%UI: 112-216), and 198 (95%UI: 127-529), respectively. The Strategies 1 and 2 based on different guidelines showed similar effectiveness, while more benefits were found for screening using China-PAR models in adults aged 40-74 years than those aged 50-74 years. The results were consistent in the sensitivity analyses. CONCLUSION: Screening for cardiovascular diseases in Chinese adults aged above 40 years seems effective in coastal developed areas of China, and the different screening strategies based on risk charts by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases or China-PAR models by the 2019 Guideline on the assessment and management of cardiovascular risk in China may have similar effectiveness.

[Interpretation of the American Association for Thoracic Surgery expert consensus document: coronary artery bypass grafting in patients with ischemic cardiomyopathy and heart failure in 2021].

An expert consensus on coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy (ICM) was released by the American Association for Thoracic Surgery in May 2021, which contains a vast array of perioperative recommendations. During preoperative period, a comprehensive assessment on ICM including myocardial viability and valve function by a multi-disciplinary team (MDT) approach should be performed. In terms of intraoperative period, multiple arterial conduits and on-pump CABG using cold blood cardioplegia should be considered, meanwhile, other aspects involving concomitant management of mitral valve regurgitation and arrythmia, as well as active use of mechanical cardiac assist devices (e.g., intra-aortic balloon pump) should also be achieved. Finally, a range of postoperative interventions which includes standardized MDT management in intensive care unit (ICU), continuous use of cardiac assist devices, cardiac pacing, close follow-up within 90 days and drug treatment strictly guided by the guidelines after discharge from hospital should be conducted. The above-mentioned perioperative bundled care might reduce perioperative complications and operative mortality, and thus improve the prognosis of the patients with ICM.

[Establishment and consistency verification of the standard operation procedure for laboratory detection of immunoglobulin G oligoclonal bands in cerebrospinal fluid].

Objective: To establish the standard operation procedure (SOP) for detection of oligoclonal band (OCB) in cerebrospinal fluid (CSF) and verify consistency by using this SOP in different laboratories. Methods: The SOP for detection of CSF-OCB fluid was successfully established by an expert feedback approach. Neuroimmunology laboratories in 3 representative Chinese three-tier research hospitals were selected for this study, and commercially available protein electrophoresis automation systems and detection SOP were set up. The quality control product was provided by the College of American Pathologists (CAP) and Sebiacompany were used for interior quality and compared to each other, respectively. Seventeen serum and CSF paired samples were tested and compared using the same SOP. Kappa test or Kendall W test were adopted to evaluate the inter-laboratory consistency among different hospitals. Results: The results of repeated testings in a single hospital suggested that the 2-and 4-fold dilution for CSF-OCB were reported as positive, while 64-and 128-fold dilution were reported as negative. Positive or negative inconsistencies were reported in 8-, 16-, and 32-fold dilution. After increasing the number of repetitions, the results showed that both 16-and 32-fold dilution were reported as negative, and 8-fold dilution exhibited negative results (2 positive results for 40 repetitions, coincidence rate=95%).The results of multi-center inter-laboratory quality assessment showed that the detection consistency rate among 3 hospitals was 100% (Kappa value =1). Conclusions: The SOP to detect CSF-OCB established in this study demonstrates a good repeatability and stability. Therefore,such SOP would be a good reference for diagnostic laboratories to detect CSF-OCB in China.

[Evaluation of the diagnosis and treatment of cesarean scar pregnancy induced in the second trimester: a national multicenter retrospective study].

Objective: To study the risk factors of adverse pregnancy outcomes for induced abortion of cesarean scar pregnancy in midtrimester. Methods: A national multicenter retrospective study was conducted. A total of 154 singletons pregnant women with cesarean scar pregnancy during the second trimester induced abortion by various reasons in 12 tertiary A hospitals were selected, their pregnant outcomes were observed and the risk factors of serious adverse outcomes were analyzed with univariate and multivariate logstic regression; the role of ultrasound and MRI in predicting placenta accreta and severe adverse outcomes was evaluated, the effectiveness of uterine artery embolization (UAE) in preventing hemorrhage in pregnant women with and without placenta accreta was compared. Results: Among 154 subjects, the rate of placenta accreta was 42.2% (65/154), the rate of postpartum hemorrhage≥1 000 ml was 39.0% (60/154), the rate of hysterectomy was 14.9% (23/154), the rate of uterine rupture was 0.6% (1/154). The risk factor of postpartum hemorrhage≥1 000 ml and hysterectomy was placenta accreta (P<0.01). For each increase in the number of parity, the risk of placenta accreta increased 2.385 times (95%CI: 1.046-5.439; P=0.039); and the risk of placenta accreta decreased with increasing ultrasound measurement of scar myometrium thickness (OR=0.033, 95%CI: 0.001-0.762; P=0.033). The amount of postpartum hemorrhage and hysterectomy rate in the group with placenta accreta diagnosed by ultrasound combined with MRI were not significantly different from those in the group with placenta accreta diagnosed by ultrasound only or MRI only (all P>0.05). For pregnant women with placenta accreta, there were no significant difference in the amount of bleeding and hysterectomy rate between the UAE group [median: 1 300 ml; 34% (16/47)] and the non-embolization group (all P>0.05); in pregnant women without placenta accreta, the amount of bleeding in the UAE group was lower than that in the non-embolization group (median: 100 vs 600 ml; P<0.01), but there was no significant difference in hysterectomy rate [2% (1/56) vs 9% (3/33); P>0.05]. Conclusions: (1) Placenta accreta is the only risk factor of postpartum hemorrhage≥1 000 ml with hysterectomy for induced abortion of cesarean scar pregnancy in midtrimester; multi-parity and ultrasound measurement of scar myometrium thickness are risk factors for placenta accreta. (2) The technique of using ultrasound and MRI in predicting placenta accreta of cesarean scar pregnancy needs to be improved. (3) It is necessary to discuss of UAE in preventing postpartum hemorrhage for induced abortion of cesarean scar pregnancy in midtrimester.

[Efficacy and safety of segmental radiofrequency ablation for isolation of the superior vena cava in patients with atrial fibrillation].

Objective: To analyze the three-dimensional distribution of functional sinus node, right phrenic nerve and superior vena cava(SVC)-right atrial muscle sleeves by three-dimensional electrophysiological technique in patients with atrial fibrillation (AF), and to investigate the efficacy and safety of segmental radiofrequency catheter ablation (RFCA) for isolation of superior vena cava in these patients. Methods: In this retrospective study, we enrolled 136 AF patients who underwent first RFCA in the First Affiliated Hospital of Zhengzhou University from July 2018 to June 2019 and all patients underwent SVC isolation under sinus rhythm. Baseline clinical data of patients were collected. The functional sinus node was defined by activation mapping, pacing was guided by three-dimensional mapping (Carto) system, localization of the right phrenic nerve was defined by pacing map, the superior vena cava-right atrial muscle sleeves was determined according to the change of potential during SVC isolation, segmental RFCA was performed for SVC isolation, the three-dimensional distribution of functional sinus node, right phrenic nerve and superior vena cava(SVC)-right atrial muscle sleeves was determined by three-dimensional electrophysiological technique. Immediate SVC isolation was achieved in all patients. Patients were evaluated immediately after RFCA and patients were followed at 3, 6, 9, and 12 months after RFCA. Holter monitoring was performed every 3 months, the chest radiograph and the SVC ultrasonic examination were performed every 6 months after RFCA. Postoperative complications were assessed. Results: The mean age of the 136 patients with AF was (51.6±14.2) years, 86 (63.2%) were male, 98 cases (72.1%) were paroxysmal AF and 38 cases (27.9%) were persistent AF. Right atrium activation mapping revealed that 17 (12.5%) functional sinus node were located in the SVC, 78 (57.4%) were located at the SVC-right atrium junctions, 41 (30.1%) were located below the junction level. From the head to foot view, 83 (61.0%) functional sinus node were located at the anterior lateral segment of the SVC-right atrium three-dimensional reconstruction model, 34 (25.0%) located at the posterior lateral segment, 15 (11.0%) located at the anterior wall, 4 (2.9%) located at posterior wall or anterior septum. A total of 294 SVC muscle sleeves were detected among all patients, 94 (32.0%) SVC muscle sleeves were located at the anterior septum of the SVC-right atrium three-dimensional reconstruction model, 76 (25.9%) were located at the posterior septum, 21(7.1%) were located at the posterior free wall, 11 (3.7%) were located at the posterior lateral, 27 (9.2%) were located at anterior lateral wall and 65 (22.1%) were located at the anterior free wall. Right phrenic nerve positioned relatively fix, 133 (97.8%) were located at the lateral segment of the SVC-right atrium three-dimensional reconstruction model, 3 (2.2%) were located at the anterior free wall. Sinus rhythm and SVC isolation were successfully restored immediately after RFCA, no significant SVC stenosis, right phrenic nerve palsy and functional sinus node injury occurred immediately post procedure. All patients were followed up for (11.2±3.6) months and none had postoperative complication. Conclusions: Three-dimensional electrophysiological can determine the spatial location of functional sinus node, right phrenic nerve and SVC-right atrial sleeves. On this basis, segmental RFCA is a safe and effective method to achieve complete isolation of SVC.

Metformin plus megestrol acetate compared with megestrol acetate alone as fertility-sparing treatment in patients with atypical endometrial hyperplasia and well-differentiated endometrial cancer: a randomised controlled trial.

OBJECTIVE: To assess the efficacy of metformin in megestrol acetate (MA)-based fertility-sparing treatment for patients with atypical endometrial hyperplasia (AEH) and endometrioid endometrial cancer (EEC). DESIGN: A randomised, single-centre, open-label, controlled trial conducted between October 2013 and December 2017. SETTING: Shanghai OBGYN Hospital of Fudan University, China. POPULATION: A total of 150 patients (18-45 years old) with primary AEH or well-differentiated EEC were randomised into an MA group (n = 74) and an MA plus metformin group (n = 76). METHODS: Patients with AEH or EEC were firstly stratified, then randomised to receive MA (160 mg orally, daily) or MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day). MAIN OUTCOMES AND MEASURES: The primary efficacy parameter was the cumulate complete response (CR) rate within 16 weeks of treatment (16w-CR rate); the secondary efficacy parameters were 30w-CR rate and adverse events. RESULTS: The 16w-CR rate was higher in the metformin plus MA group than in the MA-only group (34.3 versus 20.7%, odds ratio [OR] 2.0, 95% confidence interval [CI] 0.89-4.51, P = 0.09) but the difference was more significant in 102 AEH patients (39.6 versus 20.4%, OR 2.56, 95% CI 1.06-6.21, P = 0.04). This effect of metformin was also significant in non-obese (51.4 versus 24.3%, OR 3.28, 95% CI 1.22-8.84, P = 0.02) and insulin-sensitive (54.8 versus 28.6%, OR 3.04, 95% CI 1.03-8.97, P = 0.04) subgroups of AEH women. No significant result was found in secondary endpoints. CONCLUSION: As a fertility-sparing treatment, metformin plus MA was associated with a higher early CR rate compared with MA alone in AEH patients. TWEETABLE ABSTRACT: For AEH patients, metformin plus MA might be a better fertility-sparing treatment to achieve a higher early CR rate compared with MA alone.