Experimental study of transplantation of human umbilical cord mesenchymal stem cells in the treatment of alkali-burned cornea / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the efficacy of transplantation of human umbilical cord mesenchymal stem cells(hUCMSCs)in the treatment of corneal alkali burn in rabbits, and study the infiltration of polymorphonuclear neutrophils(PMNs)and the changes of vascular endothelial growth factor(VEGF)expression.METHODS: Corneal alkali burn models were established in right eyes of 75 healthy Japanese white rabbits, which were divided into three groups(group A, B and C), with 25 rabbits in each group. Group A was treated with amniotic membrane combined with hUCMSCs on the day after corneal alkali burn. Group B was treated with amniotic membrane only. Group C did not give any treatment after corneal alkali burn. At 3, 7, 14, 21 and 28d after corneal alkali burn, the corneal recovery was observed by slit lamp and photographed, the growth of corneal neovascularization(CNV)was scored, and corneal tissue was separated to make pathological sections. PMNs infiltration was observed by hematoxylin-eosin(HE)staining, and the expression of VEGF was determined by immunohistochemical staining.RESULTS: The growth of CNV in group A was much slower than that in group B at 14d after alkali burn. The CNV growth score around lesions of group A was significantly lower than that of group B(P<0.05). The quantity of PMNs increased on the 3d with the stromal layer of cornea infiltrated, relatively decreased on the 7d, shown a peak on the 14d, and then decreased gradually. Early infiltration after alkali burn was in the corneal stroma of the lesion area, and the extent of infiltration was equal to the ulcer area at later stage. The cell densities of corneal PMNs in group A and group B were significantly lower than those in group C at all time points after alkali burns(P<0.05), and those in group A were significantly lower than group B at 14 and 21d(P<0.05). The expression levels of corneal VEGF in all groups after alkali burn reached peak at 7～14d and decreased significantly at 28d, and the expression levels of VEGF in group A and group B at all time points after alkali burn were significantly lower than those in group C(P<0.05), and group A was significantly lower than that in group B at 7, 14 and 21d(P<0.05).CONCLUSION: The transplantation of hUCMSCs after alkali burn cornea can reduce the formation of CNV and inhibit corneal revascularization after alkali burn. The corneal pathological lesions and vascularization are closely related to PMNs and VEGF.

Anatomical classification of and laparoscopic surgery for left-sided colorectal cancer with persistent descending mesocolon / 中华胃肠外科杂志

Objective: To investigate anatomical morphology and classification of persistent descending mesocolon (PDM) in patients with left-sided colorectal cancer, as well as the safety of laparoscopic radical surgery for these patients. Methods: This is a descriptive study of case series. Relevant clinical data of 995 patients with left colon and rectal cancer who had undergone radical surgery in Fujian Medical University Union Hospital from July 2021 to September 2022 were extracted from the colorectal surgery database of our institution and retrospectively analyzed. Twenty-four (2.4%) were identified as PDM and their imaging data and intra-operative videos were reviewed. We determined the distribution and morphology of the descending colon and mesocolon, and evaluated the feasibility and complications of laparoscopic surgery. We classified PDM according to its anatomical characteristics as follows: Type 0: PDM combined with malrotation of the midgut or persistent ascending mesocolon; Type 1: unfixed mesocolon at the junction between transverse and descending colon; Type 2: PDM with descending colon shifted medially (Type 2A) or to the right side (Type 2B) of the abdominal aorta at the level of the origin of the inferior mesentery artery (IMA); and Type 3: the mesocolon of the descending-sigmoid junction unfixed and the descending colon shifted medially and caudally to the origin of IMA. Results: The diagnosis of PDM was determined based on preoperative imaging findings in 9 of the 24 patients (37.5%) with left-sided colorectal cancer, while the remaining diagnoses were made during intraoperative assessment. Among 24 patients, 22 were male and 2 were female. The mean age was (63±9) years. We classified PDM as follows: Type 0 accounted for 4.2% (1/24); Type 1 for 8.3% (2/24); Types 2A and 2B for 37.5% (9/24) and 25.0% (6/24), respectively; and Type 3 accounted for 25.0% (6/24). All patients with PDM had adhesions of the mesocolon that required adhesiolysis. Additionally, 20 (83.3%) of them had adhesions between the mesentery of the ileum and colon. Twelve patients (50.0%) required mobilization of the splenic flexure. The inferior mesenteric artery branches had a common trunk in 14 patients (58.3%). Twenty-four patients underwent D3 surgery without conversion to laparotomy; the origin of the IMA being preserved in 22 (91.7%) of them. Proximal colon ischemia occurred intraoperatively in two patients (8.3%) who had undergone high ligation at the origin of the IMA. One of these patients had a juxta-anal low rectal cancer and underwent intersphincteric abdominoperineal resection because of poor preoperative anal function. Laparoscopic subtotal colectomy was considered necessary for the other patient. The duration of surgery was (260±100) minutes and the median estimated blood loss was 50 (20-200) mL. The median number of No. 253 lymph nodes harvested was 3 (0-20), and one patient (4.2%) had No.253 nodal metastases. The median postoperative hospital stay was 8 (4-23) days, and the incidence of complications 16.7% (4/24). There were no instances of postoperative colon ischemia or necrosis observed. One patient (4.2%) with stage IIA rectal cancer developed Grade B (Clavien-Dindo III) anastomotic leak and underwent elective ileostomy. The other complications were Grade I-II. Conclusions: PDM is frequently associated with mesenteric adhesions. Our proposed classification can assist surgeons in identifying the descending colon and mesocolon during adhesion lysis in laparoscopic surgery. It is crucial to protect the colorectal blood supply at the resection margin to minimize the need for unplanned extended colectomy, the Hartmann procedure, or permanent stomas.

Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the clinical efficacy and safety of decitabine combined with modified CAG regimen (D-CAG regimen) in patients aged ≥70 years with newly diagnosed acute myeloid leukemia (AML).@*METHODS@#The clinical data of 59 AML patients (≥70 years old) who were newly diagnosed and treated in the Hematology Department of the First Affiliated Hospital of Nanjing Medical University from November 2010 to June 2021 were retrospectively analyzed.@*RESULTS@#Among the 59 AML patients, 28 were males and 31 were females, with a median age of 74 (70-86) years. The complete remission (CR) rate was 69.4% (34/49), and the median duration of CR was 10.7 (0.6-125.4) months after 2 courses of D-CAG treatment. According to the British Medical Research Council (MRC) classification, there was only one patient in the favorable-risk group, and the CR rate was 71.8% (28/39) in the intermediate-risk group, and 55.6% (5/9) in the adverse-risk group, respectively. There was no statistical difference in the CR rate between the intermediate-risk and adverse-risk group. Referring to ELN 2017 genetic risk classification, CR rate was 88.2% (15/17) in the favorable-risk group, 45.5% (5/11) in the intermediate-risk group, and 66.7% (14/21) in the adverse-risk group. There was no significant difference in CR rate between the favorable-risk and adverse-risk categories, but both were significantly higher than that in the intermediate-risk group (P <0.05). Next-generation sequencing (NGS) analysis showed that 11 gene mutations with a frequency of more than 10%, including TET2 mutation (35.6%), ASXL1 mutation (30.5%), NPM1 mutation (28.8%), FLT3-ITD mutation (27.1%), DNMT3A mutation (22.0%), IDH1 mutation (15.3%), CEBPA single mutation (13.6%), TP53 mutation (13.6%), IDH2 mutation (11.9%), RUNX1 mutation (11.9%), and NRAS mutation (10.2%). There were no statistical differences in mutation frequency of these 11 genes between CR group and non-CR group. Compared with normal karyotypes, patients with complex karyotypes were more likely to develop TP53 mutations (P <0.001), while FLT3-ITD and DNMT3A mutations were more likely to occur in patients with normal karyotypes (P =0.04, P =0.047). The median follow-up, overall survival (OS), and event-free survival (EFS) of all the patients was 11.7 (1.5-128.2) months, 12.3 (1.5-128.2) months, and 8.5 (1.5-128.2) months, respectively. The median OS and EFS of CR patients were 19.8 and 13.3 months, respectively, which were significantly longer than 6.4 and 5.7 months in patients experiencing treatment failure (P < 0.001, P =0.009). In regard to genes with mutation frequency >10%, there were no statistical differences in CR rate, median OS, and median EFS between mutated and wild-type patients by Chi-square test and survival analysis. Univariate analysis showed that age, hemoglobin, lactate dehydrogenase, cytogenetics and CR were factors affecting prognosis, while multivariate analysis showed that only CR failure was an independent adverse prognostic factor for OS. The major adverse reactions to D-CAG regimen were grade 3-4 myelosuppression, pulmonary infection, and fever (infection focus was not identified).@*CONCLUSION@#D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.

Exploration of construction mode of real-world data system / 中华流行病学杂志

Real-world data study evidence, as an important part of evaluating the safety and effectiveness of drugs and devices, has attracted increasing attention from regulatory agencies and scholars both at home and abroad, and has become an essential source of evidence to support the development and review of drugs and devices. This paper systematically discusses the process and mode of real-world data system construction based on the preliminary practical study of real-world data according to the guidelines/technical specifications issued by regulatory agencies and academic research results. This study result provides not only reference for the generation of clinical evaluation evidence to meet the regulatory requirements for innovative drugs and devices, but also reference for researchers, sponsors and regulators to carry out real-world data studies successfully.

Traditional Chinese medicines and their active ingredients sensitize cancer cells to TRAIL-induced apoptosis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The rapidly developing resistance of cancers to chemotherapy agents and the severe cytotoxicity of such agents to normal cells are major stumbling blocks in current cancer treatments. Most current chemotherapy agents have significant cytotoxicity, which leads to devastating adverse effects and results in a substandard quality of life, including increased daily morbidity and premature mortality. The death receptor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can sidestep p53-dependent pathways to induce tumor cell apoptosis without damaging most normal cells. However, various cancer cells can develop resistance to TRAIL-induced apoptosis via different pathways. Therefore, it is critical to find an efficient TRAIL sensitizer to reverse the resistance of tumor cells to TRAIL, and to reinforce TRAIL's ability to induce tumor cell apoptosis. In recent years, traditional Chinese medicines and their active ingredients have shown great potential to trigger apoptotic cell death in TRAIL-resistant cancer cell lines. This review aims to collate information about Chinese medicines that can effectively reverse the resistance of tumor cells to TRAIL and enhance TRAIL's ability to induce apoptosis. We explore the therapeutic potential of TRAIL and provide new ideas for the development of TRAIL therapy and the generation of new anti-cancer drugs for human cancer treatment. This study involved an extensive review of studies obtained from literature searches of electronic databases such as Google Scholar and PubMed. "TRAIL sensitize" and "Chinese medicine" were the search keywords. We then isolated newly published studies on the mechanisms of TRAIL-induced apoptosis. The name of each plant was validated using certified databases such as The Plant List. This study indicates that TRAIL can be combined with different Chinese medicine components through intrinsic or extrinsic pathways to promote cancer cell apoptosis. It also demonstrates that the active ingredients of traditional Chinese medicines enhance the sensitivity of cancer cells to TRAIL-mediated apoptosis. This provides useful information regarding traditional Chinese medicine treatment, the development of TRAIL-based therapies, and the treatment of cancer.

A Retrospective Analysis of TKI Discontinuation in Patients with CML / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics of the patients with chronic myeloid leukemia (CML) discontinued tyrosine kinase inhibitors (TKI) therapy and the outcome of the patients.@*METHODS@#35 cases of CML patients experienced initiative discontinuation of TKI therapy in our hospital from June 1st 2015 to December 31th 2019 were retrospectively analyzed. The TFR of the patients and the factors affecting it were analyzed.@*RESULTS@#The median duration of TKI administration was 72 (range 35-173) months in the 35 patients. Among these patients, 8 had experienced TKI dose reduction or suspension. All the enrolled patients have achieved at least MMR. The median time for these patients achieving MMR was 15 (range 3-75) months after administration of TKI, and for MMR maintenance before TKI suspension was 55 (range 13-164) months. After TKI withdrawal the median follow up time was 20.3 (range 3-57.9) months, 22 out of 35 patients kept TFR, among them, 2 （5.71%） patients restarted TKI after 12 month suspension, and maintained MMR during suspension. 13 （37.1%）patients lost MMR, among them, 9 patients restarted TKI treatment, and 5 of them achieved MR4.0 after the median duration of 3(2-5) month. No patients were found to have disease progression. The estimated TFR rate was 57.8% and 51.8% at 12 and 24 months after discontinuation, respectively. Other clinical characteristic related to relapse were also analyzed, including the cumulative TKI administration duration, cumulative MMR duration, time to achieve MMR, median age at diagnosis, risk stratification by Sokal score, TKI dose reduction and discontinuation history, and second-generation TKI administration before stopping TKI, however, no statistical difference was found.@*CONCLUSION@#TKI discontinuation is practical for CML patients in our center.

The impact of obstructive sleep apnea hypopnea syndrome on the perioperative and long-term outcome in patients with Stanford type A aortic dissection / 中华耳鼻咽喉头颈外科杂志

Objective: To confirm the impact of obstructive sleep apnea hypopnea syndrome (OSAHS) on perioperative and long-term outcome in patients with Stanford type A aortic dissection. Methods: From June 2010 to July 2017, the clinical data of 91 patients with Stanford type A aortic dissection were analyzed. Among them, 51 patients with OSAHS were included in the study group and 40 patients without OSAHS were included in the control group. After 36 months follow-up, all-cause death was regarded as the end event. The clinical baseline data, perioperative period and 36 months survival rate of the two groups were compared. Kanplan-Meier method was used to describe the 36 month survival curve of the two groups. Cox proportional risk model was used to evaluate the risk ratio (HR) and 95%CI of 36 month survival rate. Results: The mortality rate during hospitalization was 5.9% (3 cases) in the study group and 5.0% (2 cases) in the control group, and the difference was not statistically significant (χ~2=0.03, P>0.05). The actual follow-up was (36.2±1.5) months, 88 cases were followed up and 3 cases were lost. The all cause mortality rate of 36 months was 27.5% (14/51)in the study group and 10.0%(4/40) in the control group, the difference was statistically significant (χ~2=4.30, P<0.05).By Cox proportional risk model analysis, 36 months after operation, the study group was compared with the control group after adjusting for age, male, bicuspid of aortic valve, chronic obstructive pulmonary disease, anemia, preoperative pericardial tamponade, postoperative organ dysfunction, preoperative LVEF, emergency operation, Sun's operation, coronary artery bypass grafting, hypertension, cardiac arrhythmia, and advanced avulsion of distal aortic dissection The survival rate was lower, the difference was statistically significant (P<0.05).In addition to OSAHS, coronary artery bypass grafting and preoperative pericardial tamponade were also risk factors for the increase of 36 month mortality rate (HR=11.28,95%CI: 1.98-46.25, P=0.009; HR=9.08, 95%CI: 2.22-41.3, P=0.032). Conclusions: There was no significant difference in mortality during hospitalization in patients with Stanford A aortic dissection combined with OSAHS. The survival rate of 36 months after operation was lower than that of the control group.

Distribution of Natural Killer Cell in Patients with Newly Diagnosed Myelodysplastic Syndromes and Its Correlation with Prognosis / 中国实验血液学杂志

OBJECTIVE@#To investigate the distribution of peripheral blood lymphocytes and natural killer (NK) cells, and its influence on the prognosis of patients with myelodysplastic syndromes (MDS).@*METHODS@#The lymphocytes proportion, absolute lymphocyte counts (ALC), NK cell proportion and absolute NK cell counts (ANKC) as well as the related data of 95 MDS patients diagnosed between 2013 and 2017 analyzed retrospectively. The correlation of ALC and ANKC with prognosis was also analyzed.@*RESULTS@#As compared with low ALC patients, MDS patients with ALC≥0.885×10/L had a higher overall response rate (66.7% vs 35.8%) (P＜0.01). The ALC of effective patients after treatment significatitly increased in compaison of ALC at diagnosis. Multivariate analysis indicated that patients with ALC≥0.885×10/L had long overall survival (OS) time in comparison with patients with low level (16.4 vs 12.4 months) (P＜0.05). The OS time of patients with ANKC≥0.110×10/L was shorter in comparison with patients with low level (10.9 vs 16.3 months) (P＜0.01). Otherwise, blast, cytogenetic risks and treatment response were also independent risk factors of MDS (P＜0.05). Revised International Prognostic Scoring System (IPSS-R) combined with ANKC could improve predictive accuracy of IPSS-R alone (AUC 0.718 vs 0.674) (P＜0.05).@*CONCLUSION@#Lymphocytes and NK cells are important for the prognosis evaluation of MDS patients.

Clinical analysis of 100 adult patients with pure red cell aplasia / 中国实用内科杂志

OBJECTIVE: To evaluate clinical characteristics and treatment response of 100 patients with pure red cell aplasia(PRCA).METHODS: We retrospectively analyzed the clinical data of 100 adult patients with acquired PRCA from October2009 to July 2019, and compared the difference in efficacy between idiopathic and secondary patients.RESULTS: 100 patients were evaluated, including 60 idiopathic patients and 40 secondary patients.The most common reasons for secondary PRCA were large granular lymphocytic leukemia(LGLL)(28 cases,70.0%)and thymoma(6 cases, 15.0%). The remission induced regimens included corticosteroids(CS), cyclosporine A(CsA), or other agents, and the response rate were 66.7%,71.4% and 50%, respectively(P=0.336). Secondary PRCA was less effective than idiopathic PRCA(52.5%,78.3%,P=0.007). PRCA related to large granular lymphocytic leukemia was also less effective compared to idiopathic PRCA(46.4%,79.3%,P=0.003). When treated by CsA, idiopathic PRCA was more effective than secondary PRCA and LGLL related PRCA(P=0.001, P=0.000). Logistic regression analysis showed that lower response rate was related to secondary PRCA and LGLL related PRCA.CONCLUSION: The response rate were similar by different induced regimens. Idiopathic PRCA could acquired better response to CsA than secondary, LGLL related PRCA was less effective to treatment.

Eltrombopag for the treatment of refractory acquired pure red cell aplasia / 中国实用内科杂志

OBJECTIVE: To investigate the efficacy of eltrombopag in the treatment of refractory acquired pure red cell aplasia(PRCA). METHODS: Three patients with refractory acquired PRCA treated in the First Affiliated Hospital of Nanjing Medical University/Jiangsu Province Hospital from March 2018 to May 2019 were treated with eltrombopag(75 mg/d). The clinical data were collected for evaluating efficacy and tolerance. RESULTS: The erythrocyte count(P=0.039), hemoglobin concentration(P=0.018) and reticulocyte percentage(P=0.046) in 3 patients were significantly higher than those before treatment. The platelet count was higher than that before treatment(P=0.024). The leukocyte count and absolute neutrophil count increased in 2 patients, and decreased in 1 patient, but still remained in the normal range(P=0.924; P =0.565). Total bilirubin(TBIL) and direct bilirubin(DBIL) increased in 1 case; alanine aminotransferase(ALT), aspartate aminotransferase(AST) and serum creatinine(Scr) increased in 1 case; palpitation occurred in 1 case. All the side effects were alleviated after symptomatic treatment. CONCLUSION: Eltrombopag has certain efficacy and good tolerance in the treatment of refractory acquired PRCA, which is worthy of further exploration.

Spectrum of thalassemia mutations in fetuses of Han and Li ethinicities in Hainan province, China

To analyze the frequency and spectrum of thalassemia mutations in amniotic fluid samples collected from Han and Li people in Hainan province of China. Methods: We carried out a retrospective analysis on prenatal diagnosis of amniotic fluid samples collected from pregnant women who may have next generation with high risks of medium or severe thalassemia between 2005 and 2016. Diverse fetal thalassemia genotypes and mutated alleles in Han and Li people were analyzed and cmpared. Results: We examined 536 amniotic fluid samples from Han people and 588 from Li people, among which 406 Han and 500 Li samples were found to carry at least one thalassemia gene mutation, with a detection rate of 75.75% and 85.03%, respectively. Among all - and β-thalassemia mutant alleles detected, the most frequently found mutations in Han and Li samples were SEA-type of -thalassemia and 41/42 (-CTTT) of β-thalassemia, respectively. A total of 75 severe thalassemia cases were identified in Han samples and 53 in Li samples. In most of these severe cases, parents chose to terminate pregnancy after being informed of thalassemia-related risks. Conclusions: The thalassemia mutations shows ethnic and area specificity, and that prenatal diagnosis for high-risk thalassemia carrier pregnant women is an efficient approach to prevent and control the occurrence of severe thalassemia in the high-prevalence areas.

Analysis of the characteristics and clinical diagnosis and treatment of avulsion fracture of the lateral edge of tibial plateau / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the characteristics and clinical treatment of avulsion fracture of the lateral edge of tibial plateau(segond fracture) in knee joint injuries.</p><p><b>METHODS</b>From January 2011 and December 2015, 29 patients with Segond fracture were treated with minimally invasive arthroscopy technology in intra-articular injuries combined with double anchor nail fixation in avulsion fracture of the lateral edge of tibial plateau, including 17 males and 12 females with an average age of 41 years old ranging from 27 to 62 years old. Among them, there were 20 cases of anterior cruciate ligament rupture (ACL rupture) involving the anterior cruciate ligament tibial eminence avulsion fracture included, 3 cases of posterior cruciate ligament rupture (PCL rupture), 1 case of ACL rupture combined with PCL rupture, 3 cases of medial collateral ligament tear, and 2 cases combined fractures of tibial plateau (1 case of the medial platform fractures and 1 cases of lateral fracture). All the patients were confirmed by X-rays, CT and MRI. The procedures were performed at 5 to 14 days after the injury(means 7 days). Lysholm scores were used to assess the knee function before and after the operation.</p><p><b>RESULTS</b>The operation time was 40 to 125 minutes (means 85 minutes), the intraoperative blood loss was 10 to 30 ml (means 15 ml). All paients were followed up for 12 to 18 months(means 14 months). The Lysholm scores were significantly improved from preoperative 52.0±4.2 to 91.9±1.4(=-49.24,<0.05). The results of drawer test, Lachman test and lateral stress test were negative in all 29 cases, all the fractures of 29 patients were bony union.</p><p><b>CONCLUSIONS</b>The avulsion fracture of the lateral tibial plateau suggests that there are knee joint static and stable structures(joint ligament, joint capsule, meniscus, et al) and even intra articular fractures. Therefore, besides conventional imaging examinations, arthroscopic exploration was also necessary to avoid misdiagnose and provide comprehensive assessments and treatment. This can create favorable conditions for the knee joint function restore maximum.</p>

Association between Thioridazine Use and Cancer Risk in Adult Patients with Schizophrenia-A Population-Based Study

OBJECTIVE: Several cell line studies have demonstrated thioridazine’s anticancer, multidrug resistance-reversing and apoptosis-inducing properties in various tumors. We conducted this nationwide population-based study to investigate the association between thioridazine use and cancer risk among adult patients with schizophrenia. METHODS: Based on the Psychiatric Inpatient Medical Claim of the National Health Insurance Research Database of Taiwan, a total of 185,689 insured psychiatric patients during 2000 to 2005 were identified. After excluding patients with prior history of schizophrenia, only 42,273 newly diagnosed patients were included. Among them, 1,631 patients ever receiving thioridazine for more than 30 days within 6 months were selected and paired with 6,256 randomly selected non-thioridazine controls. These patients were traced till 2012/12/31 to see if they have any malignancy. RESULTS: The incidence rates of hypertension and cerebrovascular disease were higher among cases than among matched controls. The incidence of hyperlipidemia, coronary artery disease and chronic pulmonary disease did not differ between the two groups. By using Cox proportional hazard model for cancer incidence, the crude hazard ratio was significantly higher in age, hypertension, hyperlipidemia, cerebrovascular disease, coronary artery disease and chronic pulmornary disease. However, after adjusting for other covariates, only age and hypertension remained significant. Thioridazine use in adult patients with schizophrenia had no significant association with cancer. CONCLUSION: Despite our finding that thioridazine use had no prevention in cancer in adult patients with schizophrenia. Based on the biological activity, thioridazine is a potential anticancer drug and further investigation in human with cancer is warranted.

Mean Corpuscular Volume Can Be A Predictor for Therapeutic Response of Patients with Chronic Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>The past studies found that the treatment of chronic myeloid leukemia (CML) with imatinib can induce the macrocytic anemia, moreover the incidence of anemia increases along with enhancement of imatinib concentration. This study was aimed to evaluate the potential relation of erythrocyte mean corpuscular volume (MCV) increase after the treatment with tyrosine kinase inhibitors (TKI) with the therapeutic response in patients with CML-chronic phase (CML-CP).</p><p><b>METHODS</b>The clinical and hematologic data including MCV, molecular and cytogenetic response of 119 patients with CML-CP were collected after treatment with TKIs, and the relation of MCV changes after treatment with the clinical characteristics and therapeutic efficacy for patients with CML-CP was analyzed.</p><p><b>RESULTS</b>The MCV in patients treated with TKIs for 12 months significantly increased as compared with that at initial diagnosis (P<0.05). The proportion of patients with increased MCV in group of complete cytogenetic response (CCyR) was significantly higher than that in group of non-CCyR (P<0.05). As compared with decreased MCV group, the patients in increased MCV group much more easily achieved CCyR after treatment for 6, 12 months (P<0.05, P<0.05) respectively, furthermore, much more easily maintained MMR (P<0.05).</p><p><b>CONCLUSION</b>The MCV as a parameter which is easily acquired may be a new marker for prodecting the therapeutic response of patients treated with TKIs.</p>

Efficacy of cognitive behavioral therapy in children and adolescents with insomnia: a systematic review and meta-analysis

Insomnia is highly prevalent in children and adolescents. However, the efficacy of cognitive behavioral therapy for insomnia (CBT-i) in children and adolescents remains controversial. Therefore, this systematic review and meta-analysis aimed to assess the efficacy of CBT-i in children and adolescents. We conducted a search of PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO to select primary studies evaluating CBT-i in children and adolescents that were primarily diagnosed through standardized diagnostic criteria. The primary outcomes of the meta-analysis included sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency (SE%). Six randomized controlled trials and four open-label trials met all inclusion criteria. A total of 464 participants (ranging from 5-19 years of age) were included. Based on the results from sleep logs, a significant pooled effect size was observed for SOL and SE%. However, no significant pooled effect size was found for WASO or TST. Results from actigraphy were consistent with the sleep logs. A significant pooled effect size was observed for SOL and SE%, and no significant pooled effect size was found for WASO or TST. CBT-i might be effective in the treatment of children and adolescents with insomnia.

Analysis of prognosis of acute myeloid leukemia patients based on genetic mutations / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To correlate the clinical features of patients with acute myeloid leukemia (AML) with mutations of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 genes as well as chromosomal aberrations.</p><p><b>METHODS</b>Somatic mutations of aforementioned genes in 412 newly diagnosed AML patients were detected with PCR and direct sequencing. All patients were also subjected to R-banding chromosomal analysis. The results were correlated with the clinical features and prognosis of the patients.</p><p><b>RESULTS</b>The mutation rates of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 were 9.0% (26/289), 19.1% (50/262), 18.9% (34/180), 3.4% (7/208), 6.6% (9/137) and 6.9% (4/58), respectively. Patients with poor prognosis based on genetic mutations had lower blood platelet count than those with intermediate and good prognosis (P=0.001 and P=0.001, respectively). None of the three groups attained median overall survival (OS) (P> 0.05). The complete remission (CR) was similar among the three groups (P> 0.05). For patients with different prognosis based on cytogenetic findings, white blood cell count in those with intermediate prognosis was higher than those with good and poor prognosis (P< 0.001 and P=0.004, respectively), while the blood platelet count of the intermediate group was higher than that of the group with good prognosis (P=0.018). No significant difference was found among the three groups in terms of hemoglobin level (P> 0.05). The group with poor prognosis has attained shorter OS compared with those with good and intermediate prognosis (P< 0.001 and P=0.003, respectively). However, the CR rate of the group with good prognosis was higher than that of the intermediate group (P=0.001). For the group with intermediate prognosis, presence of genetic mutations did not correlate with the clinic characteristics such as white blood cell count, blood platelet count, hemoglobin level, OS and CR rate (P> 0.05 for all comparisons).</p><p><b>CONCLUSION</b>Genetic mutations combined with cytogenetic analysis can facilitate the prognosis and personalized treatment for patients with AML.</p>

Expression of Wntless in gastric carcinoma and its clinical significance / 基础医学与临床

Objective To explore the expression of Wnt secret protein Wntless in gastric carcinoma and normal mu-cosa,and to analyze the clinical significance of Wntless expression. Methods To detecte the expression of Wntless protein in gastric adenocarcinoma and normal gastric mucosa by immunohistochemistry. Results In 104 specimens of gastric cancer,the expression of Wntless in gastric adenocarcinoma was: 7.7% (8/104) cases were 0 or 1+, 36.5% (38/104) cases were 2+,and 55.8% (58/104) cases were 3+. While in normal mucosa,the expression of Wntless was:71.2% (74/104) cases were 0 or 1+, 19.2% (20/104) cases were 2+, and 9.6% (10/104) cases were 3+.The expression of Wntless in gastric adenocarcinoma was significantly higher than that in normal gas-tric mucosa (P<0.001). The expression of Wntless protein was positively correlated with tumor differentiation(P<0.05),and was positively correlated with lymph node metastasis (P<0.05).Conclusions Wntless is highly ex-pressed in gastric carcinomas and may have role in the oncogenesis. Wntless may be used as a new marker for pro-gression and metastasis of gastric carcinoma.

Distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015: results from a multicenter, retrospective study / 中华血液学杂志

Objective@#To describe the distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015 to provide reference for empirical anti-infection treatment.@*Methods@#Pathogens were from hematology department of 26 tertiary hospitals in Jiangsu Province from 2014 to 2015. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or agar dilution method. Collection of drug susceptibility results and corresponding patient data were analyzed.@*Results@#The separated pathogens amounted to 4 306. Gram-negative bacteria accounted for 64.26%, while the proportions of gram-positive bacteria and funguses were 26.99% and 8.75% respectively. Common gram-negative bacteria were Escherichia coli (20.48%) , Klebsiella pneumonia (15.40%) , Pseudomonas aeruginosa (8.50%) , Acinetobacter baumannii (5.04%) and Stenotropho-monas maltophilia (3.41%) respectively. CRE amounted to 123 (6.68%) . Common gram-positive bacteria were Staphylococcus aureus (4.92%) , Staphylococcus hominis (4.88%) and Staphylococcus epidermidis (4.71%) respectively. Candida albicans were the main fungus which accounted for 5.43%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were 3.5%-6.1% and 5.0%-6.3% respectively. The rates of Pseudomonas aeruginosa resistant to tobramycin and amikacin were 3.2% and 3.3% respectively. The resistant rates of Acinetobacter baumannii towards tobramycin and cefoperazone/sulbactam were both 19.2%. The rates of Stenotrophomonas maltophilia resistant to minocycline and sulfamethoxazole were 3.5% and 9.3% respectively. The rates of Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis resistant wards vancomycin were 0, 6.4% and 1.4% respectively; also, the rates of them resistant to linezolid were 1.2%, 0 and 1.6% respectively; in addition, the rates of them resistant to teicoplanin were 2.8%, 14.3% and 8.0% respectively. Furthermore, MRSA accounted for 39.15% (83/212) .@*Conclusions@#Pathogens were mainly gram-negative bacteria. CRE accounted for 6.68%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were lower compared with other antibacterial agents. The rates of gram-positive bacteria resistant to vancomycin, linezolid and teicoplanin were still low. MRSA accounted for 39.15%.

Accurate Detemination of Isotopic Abundance of Intracellular Metabolites of Saccharopolysporaerythraea Based on Ultra Performance Liquid Chromatography-Triple Quadrupole Mass Spectrometry / 分析化学

A method for measuring 13C isotopic abundance of intracellular metabolites of Saccharopolysporaerythraea by ultra-high performance liquid chromatography (UPLC)-triple quadrupole mass spectrometry was established.First, the chromatographic conditions of UPLC were optimized, and then the MS conditions such as unique tube lens voltage, collision energy, and ion pair were optimized.On the bases of length of the parent and daughter ions carbon chains and whether the daughter ions contain 13C atoms, the one-to-one method, one-to-many method and SIM method were established for measuring 13C isotopic abundance.Then these methods were used to measure naturally labeled intracellular metabolite standards and 13C labeled samples, and according to the gap between the experimental value and the theoretical value, the best method was established for each metabolite of different characteristics.The results showed that one-to-one method was most effective for measuring the metabolites of daughter ions not containing 13C atoms represented by sugar phosphates, one-to-many method was the best for measuring the metabolites of both parent and daughter ions containing 13C short carbon chains represented by carboxylic acids, SIM method could play a role in measuring the metabolites of both parent and daughter ions containing 13C long carbon chains represented by coenzyme A.This method had a good measurement precision and could be applied to the measurement of Saccharopolysporaerythraea intracellular metabolites, which contributed to the consequent study of metabolic mechanism and the efficient expression of erythromycin.

Efficacy observation of standard-dose IA regimen in treatment of ≥ 55 years old newly diagnosed patients with acute myeloid leukemia / 白血病·淋巴瘤

Objective To explore the clinical efficacy and toxicity of standard-dose IA regimen as induction chemotherapy in treating initially diagnosed acute myeloid leukemia (AML) patients ≥55 years old. Methods A total of 32 patients were enrolled in this study. The remission, survival time and adverse effects after IA regimen were retrospectively analyzed. Results The complete remission (CR) rate, partial remission (PR) rate and overall response (OR) rate were 71.9%(23/32), 9.4%(3/32), 81.3%(26/32) after IA regimen. In favorable, intermediate and poor prognosis groups (grouped by cytogenetic or molecular factors), 6, 14 and 3 cases achieved CR (χ2= 5.571, P= 0.067), 1, 2 and 0 cases achieved PR, while OR rates were 100.0 %(7/7), 84.2 % (16/19), 50.0 % (3/6) (χ2= 2.114, P= 0.359). The median overall survival (OS) time of three groups were 28.07 months (6.57-46.33 months), 16.93 months (0.40-87.57 months) and 3.03 months (2.00-6.00 months) (Z=9.630, P=0.008) and the 2-year OS rates were 83.33%, 46.80%and 0, respectively (χ2=12.206, P< 0.001). Myelosuppression and infections due to neutropenia were the main adverse effects and severe non-hemotologic toxicities were not observed. Conclusion The standard-dose IA regimen can increase CR/OR rate and prolong the median OS time of patients with favorable and intermediate prognosis and it can be used as the first induction chemotherapy regimen for elderly AML patients of ≥55 years old.