[Analysis of changes in intrinsic neural timescales in male smoking addicts based on whole brain resting-state functional magnetic resonance imaging].

Objective: To investigate the abnormal changes of intrinsic neural time scale (INT) in male smoking addicts based on whole brain resting state functional magnetic resonance imaging (rs-fMRI). Methods: A case-control study. The clinical data and whole brain rs-fMRI data of 139 male subjects, aged (34.1±8.8) years, recruited through the online platform from January 2019 to December 2021 were retrospectively analyzed. According to the existence of smoking addiction, they were divided into smoking addiction group (n=83) and healthy control group (n=56).INT was calculated to reflect the brain neural activity dynamics. Single sample t test was used to obtain the whole brain spatial distribution maps of INT in smoking addiction group and the control group. Then two-sample t test was conducted to explore the difference of INT between the smoking addition group and the healthy control group, with age and years of education as covariates. Finally, Spearman correlation analysis was used to explore the relationship between INT and nicotine dependence scale score and smoking index. Results: Subjects with smoking addiction and healthy control group showed a similar pattern of hierarchical neural timescales, namely shorter INT in sensorimotor areas and longer INT in parietal lobe, posterior cingulate cortex. In addition, in the smoking addiction group, the left medial occipital gyrus (peak t=-3.18), left suproccipital gyrus (peak t=-3.66), bilateral pericalar cleft cortex (left: peak t=-3.02, right: peak t=-3.22), bilateral lingual gyrus (left: peak t=-3.10, right: t peak=-3.04), left cuneus (peak t=-2.97), default network associated brain region [left anterior cuneus(peak t=-3.23), left angular gyrus (peak t=-3.07), and left posterior cingulate cortex (peak t=-3.54) were significantly lower than those of healthy controls (gaussian random field correction, voxel level all P<0.005, mass level all P<0.05). However, there was no significant correlation between INT and nicotine dependence scale score and smoking index (both P>0.05 after Bonferroni correction). Conclusion: Compared with healthy controls, smoking addicts showed abnormal changes in the dynamics of neural activity in the visual cortex and the default network.

[Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study].

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.

[Comparation of outcomes of iliac crest bone graft and accessory navicular bone graft in the Cotton osteotomy for pediatric and adolescent flexible flatfoot].

Objective: To compare the outcomes between iliac crest and accessory navicular as different bone grafts in the Cotton osteotomy in the treatment of pediatric flexible flatfoot deformity. Methods: A retrospective cohort study. The clinical data of pediatric flexible flatfoot patients with symptomatic accessory navicular received operations from July 2018 to March 2022 in Beijing Tongren Hospital were retrospectively analyzed. All the patients were treated with Cotton osteotomy. According to the different sources of bone grafting in Cotton osteotomy, the patients were divided into iliac crest group and accessory navicular group. There were 12 patients (19 feet) in iliac crest group, including 9 males and 3 females with a median age M(Q1, Q3) of 11(11, 12) years and were followed-up for 36(6, 48) months. There were 9 patients (16 feet) in accessory navicular group, including 6 males and 3 females, with a median age M(Q1, Q3) of 11(11, 11) years and were followed-up for 12(6, 17) months. Radiographic evaluations were reviewed and compared between the two groups before surgical treatment and at final follow-up, included talo-1st metatarsal angle (T1MT), talonavicular coverage angle (TNCA), talocalcaneal angle (TCA) in weight bearing anteroposterior view, and Meary angle, calcaneal Pitch angle, Kite angle, cuneiform articular angle (CAA) in weight bearing lateral view, and hindfoot alignment angle (HAA) in calcaneal long axial view. Functional scores included American Orthopedic Foot and Ankle Society (AOFAS), visual analog scale (VAS), and Maryland scores were recorded and compared before and after the operation. The complications were also recorded. Results: Total of 21 patients were successfully followed in this study. The radiographic measurements in the two groups, such as T1MT, TNCA, Meary angle, Pitch angle, Kite angle, CAA, HAA, were all significantly improved at the last follow-up when compared with those before the surgery (all P<0.05); and the AOFAS, VAS, Maryland scores in both groups were all improved after the surgery (all P<0.05). There was a significant difference in CAA alteration (∆CAA) after the operation between the two groups, the ∆CAA in iliac crest group and the accessory navicular group was 6.0°±2.6° and 4.3°±1.3°, respectively (P=0.017). There was no significant differences in the improvement of other radiographic measurements between the two groups (all P>0.05). All the patients had a successful bone union. Two patients had donor site pain in the iliac crest group and were treated conservatively. Conclusion: Compared with iliac crest bone graft, accessory navicular bone graft could achieve comparable outcomes in radiographic measurements and functional scores in the treatment of pediatric flexible flatfoot with accessory navicular pain.

[Correlation between first tarsometatarsal joint sagittal mobility and hallux valgus combined with transfer metatarsalgia].

Objective: To investigate the correlation between the first tarsometatarsal joint (TMT1) sagittal mobility and hallux valgus (HV) combined with transfer metatarsalgia (TM). Methods: The weight-bearing CT (WBCT) imaging data of 111 HV patients (167 feet) who were treated at the Foot and Ankle Surgery Center, Beijing Tongren Hospital Affiliated to Capital Medical University from January 2018 to January 2020 were retrospectively analyzed. The patients underwent PedCAT WBCT scans of both feet, and the hallux valgus angle (HVA), intermetatarsal angle (IMA), plantar distance (PD), medial cuneiform-first metatarsal angle (CMA) and metatarsal protrusion distance (MPD) were measured using CubeVue software. PD and CMA were signs of TMT1 instability. Visual analogue scale (VAS) and foot and ankle ability measures (FAAM) scores were obtained. The patients were divided into TM group and non-TM group according to the presence of metatarsalgia. The TM group and the non-TM group were compared in terms of HVA, IMA, PD, CMA, MPD, VAS and FAAM. Correlations between PD, CMA and HVA, IMA, VAS, FAAM were analyzed using Spearman correlation. Results: Total of 111 cases were included in this study, there were 35 males and 76 females with a mean age of (57.7±14.1) years. The average values of HVA (37.9°±8.6°), IMA (17.9°±2.6°), CMA (2.1°±0.3°) and PD [(1.8±0.4) mm] in TM group were all significantly higher than those in the non-TM group [HVA (32.5°±9.1°), IMA (15.1°±3.4°), CMA (1.7°±0.3°) and PD (1.6±0.2) mm] (All P<0.001). There was no significant difference in MPD between the two groups (P=0.580). The TM group demonstrated a higher VAS score when compared with the non-TM group (P<0.001). The FAAM score of the TM group (54.1±11.8) was significantly lower than that in the non-TM group (66.2±11.4) (P<0.001). The results of Spearman correlation analysis showed that there was no correlation between PD and HVA, IMA and VAS score. There was a negative correlation between PD, CMA and FAAM score, and the difference was statistically significant (rs=-0.637, -0.254, both P<0.001); CMA was positively correlated with HVA, IMA, and VAS score (rs=0.603, 0.971, 0.269, all P<0.001). Conclusions: WBCT is helpful for the diagnosis of TMT1 sagittal instability. The severity of TMT1 sagittal instability is positively correlated with hallux valgus and TM. The TMT1 instability may play an important role in the pathogenesis of hallux valgus.

[Retrospective analysis and a cross-sectional questionnaire survey of lung cancer concomitant with interstitial lung disease].

Objective: To describe the clinical characteristics and prognosis of lung cancer concomitant with interstitial lung disease (LC-ILD), and to understand the current status of knowledge of LC-ILD by physicians in the departments related to the treatment of the disease. Methods: We conducted a retrospective analysis of in-hospitalized pathology identified lung cancer (LC) patients who were admitted to our hospital between January 2014 and December 2018. After reviewing their chest CT imagings and pathological reports, 70 patients who were concomitant with interstitial lung disease (ILD) were enrolled in our study. On the other hand, a cross-sectional survey using an online questionnaire was conducted in LC-ILD management doctors who came from 29 provincial hospitals. The perceptions of demographic features, LC characteristics and management, ILD characteristics and management, and the prognosis of LC-ILD were investigated. Results: Among the 70 enrolled LC-ILD cases, there were 52 males, and the mean age was (64.3±7.63) years (ranged from 49 years to 84 years). There were 51 patients who were older than 59 years. The most common pathological pattern of LC was adenocarcinoma. Most of them were diagnosed with LC and ILD simultaneously, and they were usually treated with chemotherapy while unresectable. There were 11 patients (15.7%) with positive EGFR or ALK mutation. Forty-five patients (64.3%) died during the follow-up, and 33 were died from LC progression. There were no significant differences between the surgical group and non-surgical group on age, pathological patterns, EGFR or ALK mutation. However, LC-ILD patients in the surgical group were diagnosed with earlier TNM classification and with better prognosis. A total of 1 014 doctors answered the questionnaire completely. In the feedback, patients aged 60 years and older (785 doctors/77.4%), and male patients (720 doctors/71%) were the predominant LC-ILD patients. Adenocarcinoma (390 doctors/38.5%), adenocarcinoma or squamous-cell cancer (SCC) (182 doctors/17.9%), and SCC (151 doctors/14.9%) were considered as the common pathological patterns of LC-ILD patients. In most doctors' feedback, the EGFR or ALK mutation was not common for LC-ILD: low (646 doctors/63.7%) or hardly (306 doctors/30.5%) positive mutation. The diagnosis of ILD was earlier than LC (506 doctors/49.9%) or there was no identified precedence of LC and ILD diagnosis (208 doctors/20.5%). Most of the doctors (693 doctors/68.3%) agreed that the vital factor for surgery or not was the severity of ILD for LC-ILD patients. There were great divergences on the treatment protocol both for the advanced LC and ILD. The patients with LC-ILD were died mostly from LC progression and ILD exacerbation (542 doctors/53.5%), followed by ILD exacerbation (237 doctors/23.4%) or LC progression (226 doctors/22.3%). Conclusions: The elderly male patients were predisposed to LC-ILD, and adenocarcinoma was the common pathological pattern. The LC-ILD patients with non-advanced LC who were performed with surgery had better prognosis. However, it is recommended to consider whether to perform surgery in combination with the severity of the ILD.

[Analysis of effective connectivity in default mode network in male long-term smokers based on dynamic causal modeling].

Objective: To investigate the alterations in effective connection of default mode network (DMN) in long-term male smokers and its correlation with clinical characteristics of smoking. Methods: A total of 131 subjects through WeChat platform and underwent resting-state functional magnetic resonance (rs-fMRI) examinations were recruited, including 76 long-term smokers [long-term smoking group, male, aged 20 to 55 (32.1±6.3) years] and 55 non-smokers [healthy controls, male, aged 20 to 55(32.3±7.4) years] from January 2014 to December 2018. Long-term smokers were defined as those who smoked at least 10 cigarettes per day for more than 2 years, and met the Diagnostic and Statistical Manual of Mental Disorders-Four Edition (DSM-Ⅳ) criteria for substance dependence. Four major nodes of DMN, including left inferior parietal lobule (LIPL), right inferior parietal lobule (RIPL), posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC) were chosen as for the region of interest. The effective connectivity (EC) alterations of DMN between smoking group and healthy controls were compared using dynamic causal modeling (DCM). The correlation between EC with significant difference among the two groups and Nicotine Dependence Scale (FTND) score, pack-year score and smoking duration were evaluated. Results: Compared to the healthy controls, the EC of LIPL to PCC and PCC to mPFC were decreased in the smoking group (EC = -0.091, -0.174, respectively, Bayesian-PP>0.95), and the EC of RIPL to PCC was increased (EC = 0.136, Bayesian-PP>0.95). Besides, EC of LIPL to PCC showed negative correlation with pack-year scores(r=-0.282,P=0.017). No significant linear correlations were observed between EC with significant group difference and FTND score or smoking duration (r=-0.103、-0.089,all P>0.05). Conclusion: Long-term smokers showed multiple abnormalities in IPL-PCC-mPFC circuits, and associated with the pack-year scores.

[Analysis of liver cancer screening results and influencing factors of urban residents in Zhejiang Province from 2013 to 2018].

Objective: To analyze the results of liver cancer screening for urban residents in Zhejiang Province from 2013 to 2018 and explore the influencing factors of the detection rate. Methods: From September 2013 to August 2019, six urban communities in Hangzhou (Jianggan District and Gongshu District), Ningbo (Haishu District, Yinzhou District and Jiangbei District), and Quzhou (Kecheng District) were selected as study sites. All permanent residents aged 40-74 (with local household registration and living in the local area for more than 3 years) were selected as the research subjects by using cluster sampling method. Patients with confirmed cancers and other serious medical and surgical diseases were excluded. A total of 166 293 research subjects were included. Basic demographic characteristics and risk factors of subjects were obtained through questionnaire surveys. The cancer risk assessment system was used to evaluate the liver cancer risk of subjects. Clinical screening participation and screening results for subjects at high risk of liver cancer were obtained from participating hospitals. The high-risk rate of liver cancer, clinical screening rate, detection rate of positive lesions, and detection rate of suspected liver cancer were analyzed. Poisson regression was used to analyze the influencing factors of detection rate. Results: The age of 166 293 subjects was (56.01±8.40) years, of which 41.36% (68 777) were males. A total of 23 765 high-risk subjects for liver cancer were screened (the high-risk rate was 14.29%). Among them, a total of 12 375 subjects participated in clinical screening for liver cancer, with a screening rate of 52.07% (12 375/23 765). A total of 297 cases of positive lesions were detected and the detection rate was 2.40% (297/12 375). A total of 8 cases of suspected liver cancer were detected, with a detection rate of 0.06% (8/12 375). The results of multivariate Poisson regression model analysis showed that compared with men, people who never smoked, never ate pickled food, had low oil content, and had no history of hepatobiliary disease, female, people who were smoking or had smoked, sometimes ate pickled food, ate higher oil content, and had a history of hepatobiliary disease had a higher detection rate of positive lesions. The incidence rate ratio (IRR) (95%CI) values were 1.98 (1.45-2.70), 2.23 (1.61-3.09)/2.08 (1.31-3.28), 1.82 (1.22-2.70), 1.44 (1.08-1.91), and 1.45 (1.05-2.00), respectively. Compared with those aged from 40 to 49 years old and without HBsAg test, the IRR (95%CI) of suspected liver cancer in people aged 70 to 74 years old and HBsAg positive were 16.30 (1.32-200.74) and 6.43 (1.24-33.22), respectively. Conclusion: The urban cancer early diagnosis and early treatment project in Zhejiang Province has good compliance in clinical screening of liver cancer. Abdominal ultrasound examination and serum alpha-fetoprotein detection are helpful to detect liver cancer and its precancerous lesions in the high-risk population of liver cancer.

[Results and cost-effectiveness of colorectal cancer screening program among urban residents in Zhejiang province, 2013-2018].

Objective: To analyze the results and cost-effectiveness of colorectal cancer (CRC) screening program among Zhejiang urban residents so as to provide evidence for further optimization of CRC screening strategies. Methods: Based on the Cancer Screening Program in Urban China which was conducted in Zhejiang province from 2013-2018, data related to the rates on compliance and detection through the CRC screening program among the 40-74 year-old residents were analyzed. Chi-square tests were used to compare the differences among groups, and multivariate logistic regression models were applied to explore the potential risk factors. Cost-effectiveness ratio (CER) was calculated by using the cost per lesion detected as the indicator. Results: Among all the 166 285 participants who completed the risk assessment questionnaire, 21 975 (13.2%) were recognized as under the high risk of CRC and 4 389 (20.0%) of them received the colonoscopy. The detection rates of CRC, advanced adenoma, and non-advance adenoma were 0.3% (11 cases), 2.7% (119 cases), and 5.2% (229 cases), respectively. Results from the multivariate logistic regression analyses showed that factors as age, gender, education level, smoking, drinking alcohol, previous fecal occult blood test (FOBT), polyp history, and family history of CRC were significantly associated with the compliance rate of colonoscopy while age, smoking and polyp history were significantly associated with the detection rate of advanced neoplasms (CRC and advanced adenoma). The costs were ï¿¥22 355.74 Yuan for every CER advanced neoplasm detection and ï¿¥264 204.18 Yuan per CRC detection, respectively. The CER decreased along with ageing. Sensitivity analysis showed that CERs were expected to decrease when the compliance rate of colonoscopy was increasing. Conclusions: The current screening program seems effective in detecting the precancerous colorectal lesions, but the relatively low compliance rate of colonoscopy restricting both the diagnostic yields and economic benefits. It is necessary to improve the awareness and acceptance of colonoscopy among the high-risk CRC population.

[Expression of CD7 and its correlation with prognosis in patients with NK/T-cell lymphoma].

Objective: To analysis the expression of CD7 in NK/T-cell lymphoma as well as study the correlations between CD7 and clinical survival and prognosis. Methods: The clinical and pathological indicators of 112 NKTCL patients who were admitted to or consulted at the First Affiliated Hospital of Zhengzhou University between May 2008 and December 2019 were analyzed retrospectively. The CD7 expression in the tumor tissues was detected using immunohistochemistry staining, and the influence of CD7 expression on the survival and prognosis in the patients was analyzed. Results: The CD7 expression rate was 84.82% in 112 NKTCL patients, and its expression was not influenced by sex, age, and the primary site. An analysis of the complete clinical data of 72 patients showed that the CD7 expression was significantly correlated with the PINK score, tumor metastasis, and peripheral blood EBV-DNA level. However, the Ann Arbor stage, bone marrow involvement, B symptoms, IPI/aaIPI score, Ki-67, EBER, TIA-1, Granzyme B, LDH, and ß(2)-MG were not associated with the CD7 expression. The 1-year, 3-year, and 5-year overall survival (OS) rates of the 72 patients were 81.2%, 61.8%, and 58.8%, respectively, and the progression-free survival (PFS) rates were 53.5%, 29.4%, and 24.0%, respectively. The median overall survival (median-OS, mOS) was 81 mon, and the median progression-free survival (median-PFS, mPFS) was 14 mon. The 3-year OS rates in the CD7-positive group and the CD7-negative group were 58.1% and 83.9%, respectively, (P>0.05) . The 3-year PFS rates were 21.7% and 51.9%, respectively (P<0.05) . The univariate analysis showed that age, primary tumor site, Ann Arbor stage, IPI/aaIPI score, PINK score, LDH, ß(2)-microglobulin, EBV-DNA, Ki-67, and CD7 influenced patient prognosis. The multivariate analysis showed that Ann Arbor stage and CD7 were independent prognostic factors for PFS, while PINK score and Ki-67 were independent prognostic factors for OS. Conclusions: The expression rate of CD7 in NKTCL was high and was closely related to poor patient prognosis. The patients with high levels of EBV-DNA, metastatic disease, or high PINK score were more likely to express CD7.

Clinical features and survival impact of EBV-positive diffuse large B-Cell lymphoma with different age cutoffs.

OBJECTIVE: In 2016 WHO classification, EBV +DLBCL of the elderly was replaced by EBV+ DLBCL NOS. This is due to the fact that many young patients of EBV+ DLBCL were found in recent years. PATIENTS AND METHODS: In this study, we retrospectively analyzed clinical features and survival outcomes of EBV positive DLBCL patients in different age groups. All the patients treated at a single center. RESULTS: When we use different ages (40, 50 and 60 years old) as cutoffs, the prevalence of EBV positive DLBCL was 12.0%, 12.3% and 13.0% in younger patients and 19.0%, 15.4% and 13.8% in elder patients respectively. Whatever the age cutoff was, EBV positive associated with unfavorable clinical prognosis in elder groups. When we use 40 and 50 years old as age cutoffs, poor impacts of EBV positive on overall survival and progression-free survival were observed only in elder patients, but not in younger patients. It should be noted that when we use 60 years old as age cutoff, the results were the opposite. CONCLUSIONS: EBV+ DLBCL patients with age of 40 to 60 years old showed poorer prognostic features than EBV- DLBCL patients; however, patients in other age groups did not show evident differences in prognosis between EBV+ DLBCL patients and EBV- DLBCL patients. This finding was not reported before.

[Hepatic metastases after cervical cancer surgery: clinical analysis of 13 cases].

Objective: To investigate the clinical characteristics of patients with hepatic metastasis after cervical cancer operation, and analyze the risk factors and prognostic factors of hepatic metastasis. Methods: A total of 1 312 patients with stage Ⅰa2-Ⅱb2 cervical cancer received radical surgery from January 2013 to January 2016 in the First Affiliated Hospital of Zhengzhou University were collected, of which 13 cases (0.99%, 13/1 312) had hepatic metastasis after operation. A retrospective analysis was conducted on clinical features of patients with hepatic metastasis after cervical cancer operation. T-test, chi-square test, rank sum test and logistic regression were used to analyze the risk factors of hepatic metastasis after surgery of cervical cancer operation. Kaplan-Meier method was used for survival analysis. Log-rank test was used for screening of prognostic factors in patients with postoperative hepatic metastasis. Results: (1) Clinical features: there were 3 cases of simple hepatic metastasis without obvious clinical symptoms, 2 patients with perihepatic lymph node metastasis showed only low back pain, 8 patients with multiple extrahepatic metastases, and their clinical symptoms were related to the site of metastasis. Five cases out of 9 (5/9) with liver metastasis had abnormal tumor marker results. The abnormal kinds of tumor markers were mainly carcinoembryonic antigen (CEA), CA(125), CA(199), and CA(72-4). The interval time of hepatic metastasis after operation was 2-22 months. (2) Analysis of risk factors for hepatic metastasis: univariate analysis showed that lymph node metastasis, histological type, infiltration depth, and lymph-vascular space invasionwere associated with hepatic metastasis after cervical cancer surgery (P<0.05).Multivariate analysis showed that lymph node metastasis and small cell carcinoma were independent risk factors for postoperative hepatic metastasis (P<0.05). (3) Prognostic factors in patients with hepatic metastasis:among 13 patients with postoperative hepatic metastases from cervical cancer, 9 died during the follow-up period and 4 survived. The median total survival time after hepatic metastases was 7 months (range 3-32 months). Univariate analysis showed that multiple extrahepatic metastases and treatment after hepatic metastasis had significant effects on the prognosis of patients with hepatic metastasis after cervical cancer operation (P<0.05). Conclusions: The interval of hepatic metastasis after surgery for cervical cancer operation is within 2 years. Patients with lymph node metastasis and small cell carcinoma are more prone to postoperative hepatic metastasis. The prognosis of patients with extrahepatic multiple metastases is poor, and individualized treatment should be carried out after comprehensive analysis for patients with hepatic metastasis after cervical cancer operation.

[Outcomes of 33 patients with anaplastic large cell lymphoma treated after hematopoietic stem cell transplantation].

Objective: To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) . Methods: The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis. Results: The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK(+) and 9 ones (27.3%) ALK(-). Of them, 25 patients (19 ALK(+) and 6 ALK(-)) underwent auto-HSCT and 8 cases (5 ALK(+) and 3ALK(-)) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively. Conclusion: ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.

[Clinical analyses of 24 patients with primary pulmonary NK/T-cell lymphoma].

Objective: To explore the clinical characteristics, the best treatment and prognostic factors of primary pulmonary NK/T-cell lymphoma. Methods: A total of 24 cases with primary pulmonary NK/T-cell lymphoma from April 2011 to May 2019 were analyzed retrospectively. Survival analysis was performed using the Kaplan-Meier method and groups were compared using the log-rank test. Multivariate analysis using Cox proportional hazard regression model was conducted to confirm independent prognostic factors for overall survival (OS) and progression-free survival (PFS) . Results: ①The cohort of 24 patients included 16 male and 8 female with a median age of 49 years (range, 4-76 years) old. ②Most patients initially presented with a fever (66.7%) , cough and dyspnea. Chest imaging manifestations were primarily unilateral (45.8%) or bilateral (54.2%) pulmonary consolidation, nodules or mass. ③20 patients received chemotherapy, radiotherapy or hematopoietic stem cell transplantation, the rest 4 cases palliative treatment. Median OS was 9.5 months (range, 0.1-26.0 months) . The estimated 1-year OS rate was 45.8%. Overall response rate of patients treated with asparaginase-based regimen was 88.2%. ④In univariate survival analysis, age≤60 was prognostic for longer OS and PFS, compared with age>60 (P=0.002 and 0.004, respectively) ; ECOG≤2 was prognostic for longer OS and PFS, compared with ECOG>2 (P=0.042 and 0.004, respectively) . In multivariate survival analysis, age>60 and ECOG>2 were significantly correlated with inferior OS and PFS (OS: P=0.024 and 0.024, respectively; PFS: P=0.035 and 0.024, respectively) . Conclusions: Primary pulmonary NK/T-cell lymphoma was a rare disease with poor prognosis. Asparaginase-based regimens appeared to be effective. Age and ECOG served as independent prognostic factors for primary pulmonary NK/T-cell lymphoma patients.

[Evaluation of clinical outcomes of allogeneic hematopoietic stem cell transplantation for relapsed/refractory peripheral T-cell lymphoma with chemoresistance].

Objective: To evaluate the clinical outcomes in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) who had undergone allogeneic hematological stem cell transplantation (allo-HSCT). Methods: From June 2007 to June 2017, the clinical data of PTCL patients who underwent HSCT from eight hospitals were assessed retrospectively. Results: There were 23 patients diagnosed as relapsed or refractory PTCL with chemoresistance who underwent allo-HSCT. Among these patients, 18 were identified as progressive disease (PD) status and 5 patients as stable disease (SD) status before allo-HSCT. Seventeen patients received allo-HSCT from matched sibling donor (MSD),2 patients from matched unrelated donor and 4 patients from related haplo-identical donor (HD). After a median follow-up of 29 months, 21 patients survived longer than 28 days after allo-HSCT. Hematopoietic reconstitution was achieved in 20 of the 21 patients. The median time of myeloid and platelet engraftment were+13 (9-22) d and+16(10-38) d, respectively. The 100-d treatment-related mortality rate was 13.1%. Acute GVHD occurred in 11(47.8%) patients at a median time of 22(6-82) d after transplantation. Grade Ⅱ~Ⅳ aGVHD occurred in 6 patients. Chronic GVHD occurred in 10 patients at a median of 7.9 (3.5-27) months. After a median follow-up of 29 months, 13 patients died after HSCT. Four of them died of complications associated with allo-HSCT, and other 9 patients died of the primary lymphoma. The 3-years cumulative overall survival (OS) and progress-free survival (PFS) were 43.03% (95%CI: 29.79-69.16) and 39.13% (95%CI: 23.50-65.14), respectively. No significant difference was found in the 3-year PFS between patients with PD status and SD status before allo-HSCT (P=0.133). Conclusion: Allo-HSCT can be a promising treatment for relapsed or refractory PTCL with chemoresistance.

Effect of IL-1ß on apoptosis of synovial cells in rheumatoid arthritis rats via the NF-κB pathway.

OBJECTIVE: The aim of this study was to investigate the role of interleukin-1ß (IL-1ß) in the apoptosis of synovial cells in rheumatoid arthritis (RA) rats, and to explore the underlying mechanism. MATERIALS AND METHODS: The apoptosis of the synovial cells in RA rats in the IL-1ß group and the control group was analyzed by scoring under an electron microscope. The expressions of cleaved-poly (ADP-ribose) polymerase (PARP), PARP and anti-apoptosis gene products in synovial cells of IL-1ß treated RA rats were explored as well. Meanwhile, the expressions of B-cell lymphoma 2 (Bcl-2), Bcl-xL, and Active-Caspase3 in the synovial cells of RA rats with IL-1ß treatment were evaluated by the Western blotting. To further clarify the relationship between IL-1ß and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in the synovial cells of RA rats, the expressions of NF-κB regulated the gene products of matrix metalloproteinase-3 (MMP-3), MMP-9, cyclooxygenase-2 (Cox-2), and vascular endothelial growth factor (VEGF) in synovial cells of RA rats after that we investigated the treatment with IL-1ß (was investigated). In addition, the expression of NF-κB in the synovial cells of RA rats treated with IL-1ß was determined. RESULTS: The results showed that, compared with the control group, IL-1ß treatment significantly increased the number of apoptotic cells. This meant that IL-1ß treatment could promote the apoptosis of the synovial cells (p<0.05). IL-1ß treatment significantly promoted the expression level of cleaved-PARP (p<0.05). However, it remarkably reduced the expressions of Bcl-2 and Bcl-xL (p<0.05). Meanwhile, the level of the active-Caspase3 in the synovial cells of RA rats treated with IL-1ß was significantly enhanced (p<0.01). In comparison with the control group, the IL-1ß group exhibited significantly elevated expressions of NF-κB-regulated gene products in the synovial cells of RA rats (p<0.01). Besides, the positive markers of the activated NF-κB were detected in the synovial cells of RA rats in the IL-1ß group and the control group. The results demonstrated that they were mainly located in the nucleus of the IL-1ß group. CONCLUSIONS: IL-1ß can promote the apoptosis of the synovial cells in RA rats via the NF-κB pathway.

[14-3-3ζ protein mediates gemcitabine resistance in NK/T-cell lymphoma].

Objective: To explore the molecular mechanisms of 14-3-3ζ in gemcitabine resistance in extranodal NK/T-cell lymphoma, nasal type (ENKTL) . Methods: The effects of cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and transwell assay. YTS cells were exposed to gradually increased concentrations of gemcitabine to establish gemcitabine-resistant YTS cells (YTS-gem) in vitro. 14-3-3ζ specific siRNA lentiviral vector was transfected into YTS and YTS-gem cells to downregulate 14-3-3ζ expression, and stable transfected cell clones were screened. The protein expression was determined by Western blot. Results: ①14-3-3ζ expression was significantly up-regulated in gemcitabine resistant YTS-gem cells, comparing with that of YTS cells (P<0.05) . ②The results of CCK-8 and transwell assay showed that downregulation of 14-3-3ζ significantly reduced the cell proliferation and invasion abilities (P<0.05) . ③Downregulation of 14-3-3ζ could restore gemcitabine sensitivity in gemcitabine resistant YTS-gem cells (P<0.05) . ④Western blotting results showed that knockdown of 14-3-3ζ significantly upregulated pro-apoptotic Bax, and downregulated anti-apoptotic Bcl-2, Caspase-3, cleaved caspase-3, Cyclin D1 in gemcitabine-resistant YTS-gem cells (P<0.05) . There was no significant difference in p53 ang P-gp expression levels. Conclusions: 14-3-3ζ was upregulated in gemcitabine resistant YTS cells. Overexpression of 14-3-3ζ promoted cell proliferation and enhanced cell migration. 14-3-3ζ contributed to gemcitabine resistance to ENKTL through anti-apoptosis.

[PD-L1 expression is related with prognosis of small cell lung cancer].

Objective: To explore the correlation between programmed death ligand 1 (PD-L1) expression and clinicopathological features and prognosis of small cell lung cancer (SCLC). Methods: The clinicopathological data of 64 patients with small cell lung cancer from January 2013 to December 2016 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed in this study. The correlation between PD-L1 expression and the clinicopathological features and prognosis of SCLC was analyzed. Results: Immunohistochemical staining revealed that PD-L1 expression was observed in 60.9% (39/64) of patients with small cell lung cancer. PD-L1 expression was significantly related to stages (P<0.001). Univariate analysis showed that the median overall survival of PD-L1 negative group was longer than PD-L1 positive group (16 months vs 14 months, P<0.001). Median progression-free survival of PD-L1 negative group was longer than PD-L1 positive group(15 months vs 9 months, P<0.000 1). In multivariate analysis, PD-L1 positive was significantly correlated with inferior progression-free survival (P=0.006). Conclusions: PD-L1 expression rate was high in small cell lung cancer. PD-L1 expression was an independent predictor for poor prognosis of patients with small cell lung cancer.

The aberrant activation of Wnt pathway caused by ß-catenin mutation and its prognostic significance in NK/T-cell lymphoma.

The aberrant activation of the Wnt/ß-catenin signal has an important role in the progression of cancers. Herein, we investigated ß-catenin mutation and the activation of the Wnt pathway in association with the clinical-pathological characteristics, chemo-resistance and prognosis of NK/T-cell lymphoma (NKTCL). Real-time quantitative PCR, immunocytochemistry and immunohistochemistry SP methods detected the levels of ß-catenin, c-myc and cyclin D1 in human NKTCL cell lines (SNK-6 and YTS) and NKTCL tissues. Mutation analysis was detected in exon 3 of ß-catenin gene; and we analyzed cell viability after histone deacetylase inhibitor (HDACi) treatment. As a result, 19 (38%) of NK/T-cell lymphoma displayed nuclear ß-catenin and 16 (32%) contained mutations in exon 3; while no mutations were detected in lymphomas negative for ß-catenin nuclear staining (p<0.05). Most mutations affecting ß-catenin were adjacent to regulatory phosphorylation sites. ß-catenin, c-myc and cyclin D1 were significantly elevated in SNK-6 and YTS cell lines compared to normal NK/T cells (p<0.05). Furthermore, the high expression of ß-catenin, c-myc and cyclin D1 significantly correlated with the III/IV Ann Arbor stage. Additionally, the expression of ß-catenin in the SNK-6 cell line decreased significantly after treatment with HDACi, and Kaplan-Meier survival analysis revealed that the elevated expression of ß-catenin correlated with poor prognosis in NKTCL patients (23.66±2.77 months vs 31.65±1.78 months, p=0.023). In conclusion: mutations in exon 3 of ß-catenin and the activated Wnt pathway are common in NK/T-cell lymphoma that has nuclear ß-catenin, and it is closely correlated with the Ann Arbor stage and prognosis in NKTCL patients.

[Clinical outcomes of hematopoietic stem cell transplantation for angioimmunoblastic T-cell lymphoma].

Objective: To evaluate clinical outcomes of autologous (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for angioimmunoblastic T-cell lymphoma (AITL) . Methods: From June 2007 to June 2017, clinical data of AITL patients who underwent HSCT in eight hospitals were assessed retrospectively. Results: Of 19 patients, 13 male and 6 female with a median age of 50 (32-60) years old, 12 auto-HSCT and 7 allo-HSCT recipients were enrolled in this study, all donors were HLA-identical siblings. Two of allo-HSCT recipients were relapsed auto-HSCT ones. There were 5 patients (5/12) in complete response (CR) status and 7 (7/12) in partial remission (PR) status before transplantation in auto-HSCT group, and 2 (2/7) in PR status and 3 (3/7) in progression disease (PD) status before transplantation in allo-HSCT group. The median follow-up for the surviving patients was 46.5 months (range, 1-100 months) for the whole series, two patients lost in auto-HSCT group. Three patients developed acute graft-versus-host disease (aGVHD) and 5 chronic graft-versus-host disease (cGVHD) after allo-HSCT. Three patients died of primary disease and 1bleeding in auto-HSCT group. One patient died of primary disease and 2 transplantation-related mortality in allo-HSCT group. The 3-year cumulative overall survival (OS) were 56% (95%CI 32%-100%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.979) . The 3-year cumulative progression-free survival (PFS) were 34% (95%CI 14%-85%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.451) . Conclusion: Both auto-HSCT and allo-HSCT were optimal choices for AITL. In clinical practice, which HSCT was better for AITL patients should be based on comprehensive factors including sensitivity to chemotherapy, risk stratification and disease status at transplantation.