[Cytopathological characterization of ascites for the diagnosis of serous ovarian carcinoma].

Objective: To investigate the cytomorphological and immunocytochemical features of tumor cells in the ascites of ovarian plasmacytoma (SOC). Methods: Specimens of serous cavity effusions were collected from 61 tumor patients admitted to the Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2015 to July 2021, including ascites from 32 SOC, 10 gastrointestinal adenocarcinomas, 5 pancreatic ductal adenocarcinomas, 6 lung adenocarcinomas, 4 benign mesothelial hyperplasia and 1 malignant mesothelioma patients, pleural effusions from 2 malignant mesothelioma patients and pericardial effusion from 1 malignant mesothelioma. Serous cavity effusion samples of all patients were collected, conventional smears were made through centrifugation, and cell paraffin blocks were made through centrifugation of remaining effusion samples. Conventional HE staining and immunocytochemical staining were applied to observe and summarize cytomorphological characteristics and immunocytochemical characteristics. The levels of serum tumor markers carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected. Results: Of the 32 SOC patients, 5 had low-grade serous ovarian carcinoma (LGSOC) and 27 had high-grade serous ovarian carcinoma (HGSOC). 29 (90.6%) SOC patients had elevated serum CA125, but the difference was not statistically significant between them and patients with non-ovarian primary lesions included in the study (P>0.05); The serum CEA was positive in 9 patients with gastrointestinal adenocarcinoma and 5 patients with lung adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.001); The serum CA19-9 was positive in 5 patients with gastrointestinal adenocarcinoma and 5 patients with pancreatic ductal adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.05). The serum CA125, CEA and CA19-9 were within the normal range in 4 patients with benign mesothelial hyperplasia. LGSOC tumor cells were less heterogeneous and aggregated into small clusters or papillary pattern, and psammoma bodies could be observed in some LGSOC cases. The background cells were fewer and lymphocytes were predominant; the papillary structure was more obvious after making cell wax blocks. HGSOC tumor cells were highly heterogeneous, with significantly enlarged nuclei and varying sizes, which could be more than 3-fold different, and nucleoli and nuclear schizophrenia could be observed in some cases; tumor cells were mostly clustered into nested clusters, papillae and prune shapes; there were more background cells, mainly histiocytes. Immunocytochemical staining showed that AE1/AE3, CK7, PAX-8, CA125, and WT1 were diffusely positively expressed in 32 SOC cases. P53 was focally positive in all 5 LGSOCs, diffusely positive in 23 HGSOCs, and negative in the other 4 HGSOCs. Most of adenocarcinomas of the gastrointestinal tract and lung had a history of surgery, and tumor cells of pancreatic ductal adenocarcinoma tend to form small cell nests. Immunocytochemistry can assist in the differential diagnosis of mesothelial-derived lesions with characteristic "open window" phenomenon. Conclusion: Combining the clinical manifestations of the patient, the morphological characteristics of the cells in the smear and cell block of the ascites can provide important clues for the diagnosis of SOC, and the immunocytochemical tests can further improve the accuracy of the diagnosis.

[The impact of diabetic retinopathy on vision-related quality of life].

Objective: To assess the effect of diabetic retinopathy (DR) on vision-related quality of life (VRQoL) in patients with type 2 diabetes. Methods: In this cross-sectional study, patients with type 2 diabetes residing in 15 residency communities in Fushun, Liaoning province were enrolled from July 2012 to May 2013. We measured the VRQoL by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). Patients were grouped according to their age, gender, presence of visual impairment, and affected eyes. NEI-VFQ-25 scores were compared between/among groups using the Wilcoxon rank-sum test or Kruskal-Wallis H test. The severity of DR in the eyes was graded into no DR, mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR). Severity scores from both eyes were then summarized to create a single per-person grade ranging from 1 (no DR in either eye) to 7 (bilateral PDR). Generalized linear models were used to assess the linear relationship between NEI-VFQ-25 scores and DR severity. Locally weighted scatterplot smoothing plots were generated to evaluate the possible nonlinear associations between concatenated severity of DR and VRQoL. Results: A total of 1 537 patients were recruited, including 836 (54.4%) with no DR, 479 (31.2%) with mild NPDR, 90 (5.9%) with moderate NPDR, 72 (4.7%) with severe NPDR and 60 (3.9%) with PDR. Compared with patients with unilateral DR, bilaterally involved subjects were statistically significantly compromised in general vision [70.2 (66.5, 72.5) vs. 68.9 (63.9, 71.6), Z=90.222, P=0.038], near activities [90.5 (85.8, 94.0) vs. 88.8 (84.5, 92.5), Z=114.942, P=0.005], dependency [91.1 (85.6, 96.5) vs. 89.3 (83.8, 94.5), Z=91.934, P=0.033], mental health [80.0 (73.4, 84.9) vs. 77.5 (70.8, 82.0), Z=118.388, P=0.003], role difficulties [76.8 (70.1, 82.4) vs. 74.5 (67.6, 80.6), Z =90.791, P=0.036] and NEI-VFQ-25 composite [88.3 (84.2, 91.0) vs. 86.9 (82.8, 90.1), Z=96.207, P=0.024]. Scores on general vision (χ2=85.665), near activities (χ2=78.462), distance activities (χ2=145.489), social function (χ2=53.629), dependency (χ2=86.710), mental health (χ2=68.281), role difficulties (χ2=45.357), color vision (χ2=68.176), peripheral vision (χ2=116.179) and NEI-VFQ-25 composite (χ2=133.291) decreased gradually as DR severity increased (all P<0.001). On role difficulties, locally weighted scatterplot smoothing plots showed significant"turning points"from bilateral mild NPDR to mild NPDR/>mild NPDR (slope m=-4.7) and from moderate NPDR/≥moderate NPDR to severe NPDR/≥severe NPDR (slope m=-12.6). Conclusion: Both greater severity and bilaterality of DR were associated with lower vision-specific VRQoL, particularly role difficulties and mental health.

Discrepancies between actual weight, weight perception and weight loss intention amongst persons with NAFLD.

BACKGROUND: Currently, weight loss remains the main management strategy for NAFLD, but the weight loss intention and methods remain poorly characterized. METHODS: We analysed data about the perception of weight status, intention and methods to lose weight amongst 3,822 persons with NAFLD (United States Fatty Liver Index ≥ 30) from the National Health and Nutrition Examination Survey, 2001-2014. RESULTS: Only 53.9% of people with NAFLD intended to lose weight, 91.8% with perception of overweight and 8.2% with normal weight perception. Persons with perception of overweight or overweight/obese status were four times more likely to try to lose weight (adjusted odds ratios 3.9 and 4.2, respectively, both P < 0.0001). Younger age, women, higher educational level, Hispanic and blacks (versus whites) were significant independent factors associated with weight loss intention. Notably, ≤10% attended weight loss programme. Metabolic equivalent of task hours per week was significantly higher in whites who exercised to lose weight (vs. no exercise, P = 0.003) but not in other racial/ethnic groups. Interestingly, calorie intake was similar between those who dieted versus not (2056 vs. 1970 kcal/day, P = 0.11). About 30% reported ≥ 10-lb weight loss, with 50% higher odds of success for men but there was no difference by race/ethnicity. CONCLUSION: Overweight or obese perception was a key driver in weight loss activities but was inconsistent with actual weight status and varied by race/ethnicity and other sociodemographic factors. Weight loss programme is under-utilized and should take in account of weight perception training and culturally appropriate approach.

[Treatment and prognosis of retroperitoneal liposarcoma with multiple primary tumor].

Objective: To investigate the multiple origin of retroperitoneal liposarcoma and its postoperative prognosis. Methods: A total of 49 retroperitoneal liposarcoma patients underwent total (ipsilateral) retroperitoneal lipectomy in our center from May 2017 to December 2019 were recruited. Clinical data and the follow-up information were reviewed and the origin and prognosis were analyzed. Results: A total of 15 patients were pathologically diagnosed as multiple primary cancer (MPC), the incidence rate of retroperitoneal liposarcoma with MPC was 30.6% (15/49), while other 34 cases was non-MPC. The postoperative recurrence rates of patients with high differentiation and de-differentiation retroperitoneal liposarcoma were 31.8% and 44.4%, without significant difference (P>0.05). The postoperative recurrence rates of MPC and non-MPC were 40.0% and 38.2%, without significant difference (P>0.05). Five cases died within the follow-up. Conclusion: Retroperitoneal liposarcoma might origin form MPC, and total (ipsilateral) retroperitoneal lipectomy is recommended to reduce the recurrence rate.

[Epstein-Barr virus infection-related post-transplant lymphoproliferative disorders in transplanted lung: a clinicopathological analysis].

Objective: To investigate the clinicpathological characteristics of post-transplant lymphoproliferative disorders (PTLD) in transplanted lung, and to improve its diagnosis and treatment. Methods: The clinicopathological characteristics of PTLD in three transplanted lungs were evaluated at Wuxi People's Hospital Affiliated to Nanjing Medical University from 2014 to 2019. HE, immunohistochemical staining and in situ hybridization were performed. The relevant literature of PTLD was reviewed. Results: All three patients had chronic obstructive pulmonary disease (COPD) before lung transplantation. After receiving both lung transplants, they were all treated with anti-rejection drugs tacrolimus or mycophenolate mofetil, and combined with antiviral and/or rituximab. The time from transplantation to diagnosis of PTLD was four years, seven months, and five months, respectively. Two patients died one month and five months after initial diagnosis, and one patient was alive with no disease after one year. Histologically, all cases were monomorphic B-cell PTLD (diffuse large B-cell lymphoma, unspecified), and the tumor cells were positive for Epstein-Barr virus by in situ hybridization; one of the late-onset patients had herpes simplex virus infection. Conclusions: PTLD in the post-transplant lung tissue shows unique morphology and clinical characteristics, and is closely related to Epstein-Barr virus infection. Patients who receive lung transplantation due to COPD are more susceptible to develop PTLD, while late-onset ones occur more commonly in the hilum of lungs, and the prognosis is relatively poor.

Prevalence, characteristics and mortality outcomes of obese, nonobese and lean NAFLD in the United States, 1999-2016.

BACKGROUND: Updated prevalence and outcome data for nonobese NAFLD for the multi-ethnic US population is limited. OBJECTIVES: We aimed to investigate the prevalence, clinical characteristics and mortality of obese and nonobese individuals with NAFLD in the United Sates. METHODS: A retrospective study was conducted using the 1999-2016 NHANES databases. We determined hazard ratio stratified by obesity status in NAFLD individuals using Cox regression and log-rank test. RESULTS: Overall NAFLD prevalence was 32.3%: 22.7% were obese and 9.6% were nonobese, with increasing trend over time for obese NAFLD, but not nonobese NAFLD. Amongst those with NAFLD, 29.7% (95% CI: 27.8%-31.7%) were nonobese, of which 13.6% had lean NAFLD. Nonobese NAFLD was more common in older (40.9% if ≥ 65 vs. 24.2% if < 65 years), male (34.0% vs. 24.2%) and foreign-born Asian people (39.8% vs. 11.4%) and uncommon in black (11.5% vs 30-35% in other ethnicities, P < 0.001). Metabolic comorbidities were common in nonobese NAFLD individuals who also had more advanced fibrosis. Nonobese NAFLD individuals had higher 15-year cumulative all-cause mortality (51.7%) than obese NAFLD (27.2%) and non-NAFLD (20.7%) (P < 0.001). However, DM and fibrosis, but neither obese nor nonobese NAFLD compared to non-NAFLD was independently associated with higher mortality. CONCLUSION: Nonobese NAFLD makes up about one-third of the NAFLD in the United States (even higher in older, male and foreign-born individuals) and carries higher mortality than obese NAFLD. Screening for NAFLD should be considered in high-risk groups even in the absence of obesity.

Adjuvant chemotherapy for patients with gastric neuroendocrine carcinomas or mixed adenoneuroendocrine carcinomas.

BACKGROUND: The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G-NECs) or mixed adenoneuroendocrine carcinomas (G-MANECs). METHODS: The study included patients with G-NECs or G-MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan-Meier method. RESULTS: In total, 804 patients with resectable G-NECs or G-MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no-chemotherapy group. Among patients with G-NECs, survival in the fluorouracil (5-FU)-based chemotherapy group and the non-5-FU-based chemotherapy group was similar to that in the no-chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G-NECs. Among patients with G-MANECs, OS in the non-5-FU-based chemotherapy group was worse than that in the no-chemotherapy group. Patients with G-MANECs did not have better OS when platinum-based chemotherapy was used. CONCLUSION: There was no survival benefit in patients who received adjuvant chemotherapy for G-NECs or G-MANECs.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G-NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G-MANECs). MÉTODOS: Se incluyeron pacientes con G-NECs y G-MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan-Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento. RESULTADOS: En total, se incluyeron en el estudio 804 pacientes con G-NECs y G-MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G-NECs, la supervivencia en los grupos con quimioterapia basada en 5-FU (fluorouracilo) y de quimioterapia sin 5-FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G-NECs. En pacientes con G-MANECs, la OS del grupo con quimioterapia sin 5-FU fue peor que la del grupo sin quimioterapia. Los pacientes con G-MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos. CONCLUSIÓN: La administración de quimioterapia adyuvante en pacientes con G-NECs y G-MANECs no mejoró la supervivencia.

[Analysis of the missed diagnosis of invasive carcinoma under the microscope in HSIL diagnosed by colposcopy-guided biopsy and related influencing factors].

Objective: To observe the missed diagnosis of invasive carcinoma under the microscope (ICUM) in high grade squamous intraepithelial neoplasia (HSIL) , and analyze associated factors influencing missed ICUM. Methods: A retrospective study was performed on patients diagnosed with HSIL by colposcopy-guided biopsy and treated with loop electrosurgical excision procedure (LEEP) at the First Affiliated Hospital of Nanjing Medical University, from December 2014 to December 2016. They were non-pregnant, ≤50 years old and the cervical volume without obvious enlargement and exogenous surface without and ulcerative lesions. A total of 283 cases with early cervical cytology results, never received cervical traumatic treatment or cervical biopsy in another hospital before, and their colposcopic images were clear enough to reevaluate. The ultimate pathological diagnosis was based on the higher-level pathological diagnosis between the results of cervical biopsy and LEEP to evaluate ICUM missed in HSIL and the risk factors. Results: (1) Among the 283 cases with HSIL diagnosed by colposcopy-directed biopsy, 44 cases (15.5%, 44/283) were missed diagnosis of ICUM, which consisted of 29 cases Ⅰ a1, 4 cases Ⅰ a2 and 11 cases Ⅰ b1 in the ultimate pathology. (2) Analysis of associated factors for missed ICUM: univariate analysis showed that, as the age increased, the risk of missed ICUM also increased (the rates of missed diagnosis for <30, 30-39, 40-50 years were 7.7%, 11.5%, 22.0%, respectively; χ(2)=6.254, P=0.012 by trend test) . The more the number of high-grade features, the higher risks (the rates of missed diagnosis for 1, 2, 3, 4 high-grade features were 10.2%, 17.6%, 23.8%, 30.8%, respectively; χ(2)=7.686, P=0.006 by trend test) . The locations of HSIL were only endocervical, only ectocervical and mixed, the risk increased by this sequence (2.8%, 5.1%, 28.7%; χ(2)=26.193, P<0.01 by trend test) . The rate of missed diagnosis for not completely visible squamocolumnar junction (SCJ) was higher than that of the completely visible one (22.3% vs 2.1%; χ(2)=19.680, P<0.01) . The rate of missed diagnosis was higher for existing atypical vessels than those without (60.7% vs 10.6%; χ(2)=48.279, P<0.01) . The rate of missed diagnosis for visible lesion size ≥40 mm(2) was higher than that of <40 mm(2) (27.3% vs 4.2%; χ(2)=28.921, P<0.01) . The rate of missed diagnosis for the proportion of visible lesion size in ectocervical size ≥0.75 was higher than that of <0.75 (83.3% vs 14.1%; P<0.01) . The rate of missed diagnosis for the maximum linear length of visible lesion ≥10 mm was higher than that of <10 mm (46.9% vs 9.0%; χ(2)=44.473, P<0.01) . But the different severity of cervical cytology before colposcopy was not associated with missed ICUM (P>0.05) . Multivariable analysis found that visibility of SCJ, atypical vessels, visible lesion size and maximum linear length of visible lesion were associated with missed diagnosis of ICUM (all P<0.05) . Conclusions: The diagnostic value of HSIL by colposcopy is limited. Meanwhile, for the patients who are ≤50 years old with HSIL diagnosed by cervical biopsy, invisibility of SCJ, atypical vessels, visible lesion size and maximum linear length of visible lesion evaluated by colposcopy are the independent risk factors of missed ICUM. Thereby, it is necessary to take active intervention for HSIL with these risk factors.

[Expression and prognostic values of PD-1, PD-L1 and IDO-1 in sinonasal malignant mucosal melanoma].

Objective: To investigate the correlation between the expression of programmed death-1(PD-1), PD ligand-1(PD-L1), indoleamine 2, 3-dioxygenase 1(IDO-1) and clinical parameters in sinonasal malignant mucosal melanoma (SNM). Methods: Samples from 86 SNM patients who did not receive immune-targeted therapy and radio-chemotherapy were analyzed for PD-1, PD-L1, and IDO-1 expression by immunohistochemistry. Results: High clinical/pathologic staging, brain metastases and advanced age were independent risk factors of poor prognosis. The overall survival rate of SNM without pigment was lower than that with pigment. PD-1, PD-L1 and IDO-1 expression was not correlated with tumor pigmentation, but correlated with different primary site.PD-1, PD-L1 and IDO-1 were expressed in 47.6% (41/86), 53.5% (46/86) and 58.1% (50/86)of SNM samples respectively. PD-1 was associated with brain metastasis. Negative expression of PD-1(P=0.031) and IDO-1(P=0.017 9) correlated with worse disease-free survival. No significant association was found between PD-L1 and prognosis. For stages Ⅲ, ⅣA and ⅣB patients, PD-1 expression was associated with better outcome (P=0.025), but PD-L1 negative and IDO-1 positive patients hadworse outcome (P>0.05). PD-1 positive and IDO-1 negative stage ⅣC patients had poorer overall survival. Conclusions: In SNM patients, clinical/pathologic staging, brain metastases, age and pigmentation were prognostic indicator. IDO-1 and PD-1 can also be used as reference to evaluate prognosis. Anti-IDO-1 targeted therapy may be suitable for middle to late stage patients, while advanced stage patients might benefit from anti-PD-1 targeted therapy. PD-1/PD-L1 and IDO-1 may be considered as joint targeted therapy.The predictive value of PD-L1 requires further study.

Prenatal diagnosis of trisomy 21, 18 and 13 by quantitative pyrosequencing of segmental duplications.

Chromosomal aberration mostly occurs in chromosomes 21, 18 and 13, with an incidence approximately 1 out of 160 live births in humans, therefore making prenatal diagnosis necessary in clinics. Current methods have drawbacks such as time consuming, high cost, complicated operations and low sensitivity. In this paper, a novel method for rapid and accurate prenatal diagnosis of aneuploidy is proposed based on pyrosequencing, which quantitatively detects the peak height ratio (PHR) of different bases of segmental duplication. A direct polymerase chain reaction (PCR) approach was undertaken, where a small volume of amniotic fluid was used as the starting material without DNA extraction. Single-stranded DNA was prepared from PCR products and subsequently analyzed using pyrosequencing. The PHR between target and reference chromosome of 2.2 for euploid and 3:2 for a trisomy fetus were used as reference. The reference intervals and z scores were calculated for discrimination of aneuploidy. A total of 132 samples were collected, within trisomy 21 (n = 11), trisomy 18 (n = 3), trisomy 13 (n = 2), and unaffected controls (n = 116). A set of six segmental duplications were chosen for analysis. This method had consistent results with karyotyping analysis, a correct diagnosis with 100% sensitivity and 99.9% specificity.

Mechanism of age-related changes of bone marrow mesenchymal stem cells in senile osteoporosis.

This study was carried out to explore the age-related changes of bone marrow mesenchymal stem cells (BMMSCs) in mice as well as the influence of autophagy on the age-related changes of BMMSCs. BMMSCs aging-associated protein acetylation P53, P21 and P16 expressions in young and senile mice, protein expression of telomerase reverse transcriptase (TERT) as well as reactive oxygen species (ROS) level were detected and compared; the expression of BMMSCs autophagy associated gene, autophagy related protein molecule and LC3 molecule were detected; the influence of differently concentrated rapamycin and 3-MA on BMMSCs autophagy level was observed to select effective concentrations; the influence of rapamycin and 3-MA on BMMSCs cell cycle-related gene expression, apoptosis related gene expression and ROS level were discussed. Results revealed that the senile BMMSCs group had higher acetylation P53, P21 and P16 expression and fluorescence intensity than the young group, but its TERT expression, Beclin1 and LC3 gene expression and fluorescence intensity were lower than the young group. Both rapamycin and 3-MA inhibited CyclinD1 (CCND1) and CyclinD2 (CCND2) expression. Rapamycin promoted the expression of apoptosis-related genes Caspase3 and Caspase8 in the senile group, while 3-MA inhibited them in both the young and senile groups. It can therefore be concluded that senile BMMSCs have multiple age-related changes, performing as decrease of osteogenic capability and multiplication capacity, increase of acetylation P53, P21 and P16 protein expression, apoptosis and ROS level as well as decrease of telomerase activity. Furthermore, the autophagy level in senile BMMSCs reduced compared with young cells; autophagy activation can decrease ROS level and autophagy suppression improves ROS level; and autophagy regulation affects cell cycle and apoptosis.

[An analysis of risk factors and prognosis of Epstein-Barr virus infection after allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To analyze the incidence of Epstein-Barr virus (EBV) infection in patients after allogeneic hematopoietic stem cell transplantation (HSCT), and investigate its risk factors and prognosis. METHODS: A total of 402 patients receiving HSCT were retrospectively studied from November 2011 to November 2014 in the 307th Hospital of Chinese People's Liberation Army.The cumulative incidence (CI) of EBV infection and survival rate were analyzed by Kaplan-Meier method, while risk factors were assessed by logistic regression model. RESULTS: The one-year CI of EBV viremia and post-transplant lymphoproliferative disease (PTLD) were 42.0% and 1.5%, respectively.Using antithymocyte globulin (ATG) (P<0.001, OR=9.92) and acute graft-versus-host disease (GVHD) grade Ⅲ to Ⅳ (P<0.01, OR=2.42) were related risk factors of EBV viremia.There was a higher CI of EBV viremia in patients with 2 risk factors compared with those without (87.5% vs 24.6%, P<0.001). Patients with EBV viremia had significant shorter three-year overall survival than patients without (58.5% vs 75.4%, P<0.001). CONCLUSIONS: The incidence of EBV infection in patients undergoing HSCT is high, which poses a threat on prognosis.Risk factors of EBV viremia include administration of ATG and severe acute GVHD.

[The effect of Notch1 on myocardial ischemia reperfusion injury].

OBJECTIVE: To investigate the protective effects of Notch1 on myocardial ischemia reperfusion injury and explore underlying molecular mechanism. METHODS: H9c2 cells were exposed to hypoxia/reoxygenation (H/R), ischemic preconditioning (IPC) and ischemic postconditioning (IPost) treatment following infection with lentiviral vector-Notch1 intracellular domain (Lv-N1ICD) or Lv-N1ICD-shRNA, and divided into control group, H/R group, H/R+ N1ICD group, IPC group, IPC+ N1ICD-shRNA group, IPost group, IPost+ N1ICD-shRNA group, respectively. Apoptosis was detected by Annexin V/propidium iodide (PI), and reactive oxygen species (ROS) was detected by 2', 7'dichlorofluorescin-diacetate (DCFH-DA). The expression of p-glycogen synthase kinase-3ß (p-GSK-3ß)/GSK-3ß were detected by Western blot analysis. RESULTS: The apoptosis rate of cardiomyocytes in control group, H/R group, H/R+ N1ICD group, IPC group, IPC+ N1ICD-shRNA group, IPost group, IPost+ N1ICD-shRNA group was (5.34±1.70)%, (47.03±4.10)%, (33.89±12.25)%, (35.85±3.17)%, (51.12±8.22)%, (37.35±3.82)%, (47.90±3.08)%, respectively, showing significant differences in all group (F=18.47, P<0.05). ROS in control group, H/R group, H/R+ N1ICD group, IPC group, IPC+ N1ICD-shRNA group, IPost group, IPost+ N1ICD-shRNA group was 624.66±79.52, 1 221.87±63.66, 913.12±115.82, 935.85±201.62, 1 204.03±113.82, 967.15±106.11, 1 296.59±222.38, respectively, showing significant differences in all group (F=8.77, P<0.05). The ratio of p-GSK-3ß to GSK-3ß in control group, H/R group, H/R+ N1ICD group, IPC group, IPC+ N1ICD-shRNA group, IPost group, IPost+ N1ICD-shRNA group was 0.58±0.12, 0.62±0.20, 1.24±0.09, 1.16±0.12, 0.72±0.15, 1.16±0.12, 0.75±0.12, respectively, showing significant differences in all group (F=11.21, P<0.05). CONCLUSION: As an endogenous cardioprotective factor, Notch1 reduces myocardial ischemia reperfusion injury by promoting GSK-3ß phosphorylation, inhibiting cardiomyocyte apoptosis and reducing ROS formation.

Study of the significance of iron deficiency indexes and erythrocyte parameters in anemic pregnant women and their newborns.

This study aimed to analyze the iron deficiency index and erythrocyte parameters in anemic pregnant women and their newborns, and explore their implications for anemia during pregnancy. Pregnant women (70) in the third trimester with hemoglobin (Hb) <100 g/L who registered and delivered from June 2012-2013 were randomly selected as the observation group, 70 pregnant women at similar gestational ages with Hb >110 g/L were selected as the control group, and 70 newborns delivered by women in each group were included in corresponding offspring observation and control groups, respectively. Periodic physical examinations were conducted on the infants, and blood samples were drawn from the women and infants at birth, 42 days, 4 months, and 6 months old for detection of Hb and soluble transferrin receptor (sTfR) levels. Pregnant women and their 6-month-old infants in the observation group had significantly different Hb and sTfR levels compared to controls (P < 0.01). There were no significant differences in Hb and sTfR levels of infants at birth, 42 days, and 4 months old (P > 0.05). The detection rate of iron deficiency anemia (IDA) was significant, at 61.43% among 6-month-old infants in the observation group and 22.86% among controls (P < 0.01). There were no significant differences in the detection rate of IDA among infants at birth, 42 days, and 4 months old between observation and control groups (P > 0.05). Therefore, anemia during pregnancy is a major contributing factor of IDA and subclinical iron deficiency among 6-month-old infants.

Systematic review of uterus-preserving treatment modalities for abnormally invasive placenta.

This is a systematic review for evaluating failure rates (secondary hysterectomy or maternal mortality) and success rates (subsequent menstruation or pregnancy) following radiological or conservative surgical interventions for abnormally invasive placenta (AIP). Twelve cohort studies and 8 case series or case reports were included. The cumulative outcomes showed success rates of 159/177 (89.8) for arterial embolisation, a secondary hysterectomy in 20/177 (11.3%), a subsequent menstruation in 74/85 (87.1%) and a subsequent pregnancy in 3/10 (30%). Artery occlusion balloon presented a success rate of 33/42 (78.6%), and a secondary hysterectomy presented that of 8/42 (19%). Uterus-preserving surgery showed a success rate of 48/76 (63.2), a secondary hysterectomy in 23/76 (30%), maternal mortality in 2/54 (3.7%), a subsequent menstruation in 20/37 (81.1%) and a subsequent pregnancy in 21/27 (77.8%). This review indicates that different uterine-sparing radiological and surgical techniques may be effective in managing AIP in select patients.

[A simulation study of the reliability and accuracy of Cox-TEL method for estimating hazard ratio and difference in proportions for long-term survival data containing cured patients].

OBJECTIVE: To explore the applicable conditions of the Cox-TEL (Cox PH-Taylor expansion adjustment for long-term survival data) method for analysis of survival data that contain cured patients. METHODS: The simulated survival data method based on Weibull distribution was used to simulate and generate the survival data with different cure rates, censored rates, and cure rate differences. The Cox-TEL method was used for analysis of the generated simulation data, and its performance was evaluated by calculating its type Ⅰ error and power. RESULTS: Almost all the type Ⅰ error of the hazard ratios (HRs) obtained by the Cox-TEL method under different conditions were slightly greater than 0.05, and this method showed a good test power for estimating the HRs for data with a large sample size and a large difference in proportions (DPs). For the data of cured patients, the type Ⅰ error of the DPs obtained by the Cox-TEL method was well around 0.05, and its test power was robust in most of the scenarios. CONCLUSION: The Cox-TEL method is effective for analyzing data of uncured patients and obtaining reliable HRs for most of the survival data with a sample size, a low censored rates, and a large difference in cure rates. The method is capable of accurately estimating the DPs regardless of the sample size, censored rates, or the cure rates.

[Comparison of 7 methods for sample size determination based on confidence interval estimation for a single proportion].

OBJECTIVE: To compare different methods for calculating sample size based on confidence interval estimation for a single proportion with different event incidences and precisions. METHODS: We compared 7 methods, namely Wald, AgrestiCoull add z2, Agresti-Coull add 4, Wilson Score, Clopper-Pearson, Mid-p, and Jefferys, for confidence interval estimation for a single proportion. The sample size was calculated using the search method with different parameter settings (proportion of specified events and half width of the confidence interval [ω=0.05, 0.1]). With Monte Carlo simulation, the estimated sample size was used to simulate and compare the width of the confidence interval, the coverage of the confidence interval and the ratio of the noncoverage probability. RESULTS: For a high accuracy requirement (ω =0.05), the Mid-p method and Clopper Pearson method performed better when the incidence of events was low (P < 0.15). In other settings, the performance of the 7 methods did not differ significantly except for a poor symmetry of the Wald method. In the setting of ω=0.1 with a very low p (0.01-0.05), failure of iteration occurred with nearly all the methods except for the Clopper-Pearson method. CONCLUSION: Different sample size determination methods based on confidence interval estimation should be selected for single proportions with different parameter settings.

[Genetic characteristics and survival analysis of 27 cases of juvenile myelomonocytic leukemia].

Objective: To investigate the genetic and genomic profiling of juvenile myelomonocytic leukemia (JMML) and factors affecting its survival rate. Methods: Clinical characteristics, cytogenetics, molecular biology results and survival status of children with 27 JMML cases admitted to the Hematology Department of Children's Hospital, Capital Institute of Pediatrics from December 2012 to December 2021 were analyzed retrospectively, and the outcomes of the children were followed up. Kaplan-Meier method was used for survival analysis. Univariate analysis was used for analyzing factors affecting the overall survival (OS) rates of patients who received hematopoietic stem cell transplantation (HSCT). Log-Rank test was used for comparison of survival curves. Results: Among 27 JMML cases, there were 11 males and 16 females. The age of disease onset was 28 (11,52) months. There are 20 cases of normal karyotype, 4 cases of monosomy 7, 1 case of trisomy 8,1 case of 11q23 rearrangement and 1 case of complex karyotype. A total of 39 somatic mutations were detected.Those involved in RAS signal pathway were the highest (64%(25/39)), among which PTPN11 mutation was the most frequent (44% (11/25)). A total of 17 cases (63%) received HSCT, 8 cases (30%) did not receive HSCT, and 2 cases (7%) lost follow-up. For children receiving transplantation, the follow-up time after transplantation was 47 (11,57) months. The 1-year OS rate of high-risk transplantation group (17 cases) and high-risk non transplantation group (6 cases) was (88±8)% and (50±20)% respectively, with a statistically significant difference (χ2=5.01, P=0.025). The 5-year OS rate of the high-risk transplantation group was (75±11)%. The survival time of those who relapsed or progressed to acute myeloid leukemia after transplantation was significantly shorter than that of those who did not relapse (χ2=6.80, P=0.009). The OS rate of patients with or without PTPN11 mutation was (81±12) % and (67±19)% respectively (χ2=0.85, P=0.356). Conclusions: The main pathogenesis involved in JMML is gene mutation related to RAS signaling pathway, and the most common driver gene of mutation is PTPN11. Allogeneic HSCT can significantly improve the survival rate of high-risk JMML patients. The recurrence or progression after transplantation was related to poor prognosis.