Low-dose ATG combined with low-dose PTCY in preventing GVHD after haploidentical transplantation:a retrospective analysis of 90 cases / 陆军军医大学学报

Objective To retrospectively analyze the efficacy and safety of low-dose antithymocyte globulin(ATG)combined with low-dose post transplantation cyclophosphamide(PTCY)in prevention of graft versus host disease(GVHD)after haploidentical transplantation.Methods Clinical data of 90 patients receiving haplotype matched transplantation in No.920 Hospital of PLA Joint Logistic Support Force from January 2022 to February 2023 were collected,and they were divided into study group(n=47)and control group(n=43)according to different GVHD prevention programs.The patients of the study group were given low-dose ATG combined with low-dose PTCY,and those of the control group received standard dose of PTCY.The implantation status,occurrence of GVHD,survival status and other indicators were analyzed between the 2 groups.Results ① Both groups of patients were successfully implanted,the median duration for neutrophil implantation(11 vs 17 d,P＜0.05)and platelet implantation(12 vs 20 d,P＜0.05)was significantly shorter in the study group than the control group.The incidence of grade Ⅱ～Ⅳ aGVHD(12.8％vs 34.9％,P＜0.05)and grade Ⅲ～Ⅳ aGVHD(6.4％ vs 20.9％,P＜0.05)was significantly lower in the study group than the control group,so was the non-recurrent mortality rate(6.4％vs 20.9％,P＜0.05)and the incidence of hemorrhagic cystitis(12.8％ vs 34.9％,P＜0.05).② By the end of the study,there were no significant differences in the incidence of mild and moderate and severe cGVHD,recurrence rate,reactivation rates of EBV and CMV,overall survival rate or progression-free survival rate between the 2 groups.Conclusion For haploidentical transplantation,low-dose ATG combined with low-dose PTCY has the advantages of lower incidence of GVHD,non-recurrent mortality,incidence of hemorrhagic cystitis and faster implantation.

Control effect of Dasatinib on the treatment of acute myeloid leukemia and adverse events of CD123 targeting CAR-T:a case report and literature review / 陆军军医大学学报

Objective To preliminarily explore the efficacy of chimeric antigen receptor T cells(CAR-T)targeting CD 123 in the treatment of acute myeloid leukemia(AML)and the role of dasatinib in the treatment of CD123 targeting CAR-T induced side effects.Methods Clinical data of 1 patient with relapsed AML admitted to No.920 Hospital of PLA Joint Logistic Support Force in September,2019 were collected.The patient relapsed after previous multi-line chemotherapy and was treated with CD123 targeting CAR-T therapy.The routine blood changes of the patient after treatment were observed.Dasatinib was used when agranulocytosis occurred,40 mg orally 3 times per day,and was stopped when agranulocytosis was relieved.Changes in blood cells,CAR-T amplification,and disease control were observed.The patient was followed up for over 1 year.Results Flow cytometry for bone marrow showed that minimal residual disease negative result was observed in 30 d after infusion.The patient remained disease-free for over 1 year.After CD 123 CAR-T cells infusion,significant expansion of CAR-T cells was observed,accompanied by granulocyte deficiency and cytokine release syndrome(CRS).After using dasatinib,inhibition of CAR-T cell expansion was observed,accompanied by blood cell recovery,and CRS symptoms were alleviated.After stop of dasatinib,CAR-T cells expanded again and blood cells decreased again.Conclusion CAR-T cells targeting CD 123 have certain efficacy in the treatment for relapsed AML.Dashatinib has a blocking effect on the amplification and function of CAR-T,which can alleviate bone marrow suppression caused by CD 123 targeting CAR-T and avoid severe CRS.

Study on Control Strategies on NOX Emissions to Meet Real Driving Emissions.

The aim of this study was to fulfill the NOx emissions standards for a light-duty diesel vehicle under real driving emissions (RDE) testing conditions by implementing various control strategies. In this study, RDE tests were performed by adjusting the air mass quantity and postinjection quantity in order to analyze engine-out and tail-pipe nitrogen oxides (NOx) emissions for different phases of RDE. The results showed that reducing in air mass quantity enabled the engine to operate in higher exhaust gas recirculation (EGR) rate regions, resulting in a 32.5% reduction in engine-out NOx emissions and an 80.4% decrease in tail-pipe NOx emissions. Increasing the postinjection quantity primarily enhanced the NOx conversion efficiency for the urban phase by 7.5%, leading to a 22.6% reduction in tail-pipe NOx emissions. By employing both strategies, vehicles can comfortably meet the CN6b emission regulations by a substantial margin.

Durable remission related to CAR-T persistence in R/R B-ALL and long-term persistence potential of prime CAR-T.

CD19-targeted chimeric antigen receptor T lymphocytes (CAR-T) has demonstrated a high proportion of complete remission in the treatment of relapsed refractory acute B cell lymphoblastic leukemia (r/r B-ALL). It is of great clinical significance to explore which factors will impact long-term disease-free survival of patients with r/r B-ALL after CAR-T therapy without bridging bone marrow transplantation. Our study found that, in patients with r/r B-ALL without bridging transplantation, the patients' age; infusion dosage; whether they had undergone allo-stem cell transplantation before CAR-T therapy, using CD-19-targeted or CD19/CD22-dual-targeted CAR-T; whether there is fusion gene; tumor burden before therapy; and comorbidity had no significant relationship with their long-term disease-free survival. We found only that CAR-T persistence was highly correlated with patients' long-term disease-free survival. So, we further profiled CAR-T cells using single-cell sequencing and found that there is a specific T cell subset that may be associated with the long-term persistence of CAR-T. Finally, according to the single-cell sequencing results, we established cell production process named PrimeCAR, which shared common signaling pathways with the T cell subset identified. In the preliminary clinical study, prime CAR-Ts yield good persistence in peripheral blood of patients with B-ALL and lymphoma, without observing grade 2 or higher cytokine release syndrome.

Connexin 43-modified bone marrow stromal cells reverse the imatinib resistance of K562 cells via Ca 2+ -dependent gap junction intercellular communication / 中华医学杂志(英文版)

BACKGROUND@#Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects minimal residual disease (MRD), but the mechanism remains unknown.@*METHODS@#Immunohistochemistry assays were employed to compare the expression of Cx43 and hypoxia-inducible factor 1α (HIF-1α) in bone marrow (BM) biopsies of CML patients and healthy donors. A coculture system of K562 cells and several Cx43-modified bone marrow stromal cells (BMSCs) was established under IM treatment. Proliferation, cell cycle, apoptosis, and other indicators of K562 cells in different groups were detected to investigate the function and possible mechanism of Cx43. We assessed the Ca 2+ -related pathway by Western blotting. Tumor-bearing models were also established to validate the causal role of Cx43 in reversing IM resistance.@*RESULTS@#Low levels of Cx43 in BMs were observed in CML patients, and Cx43 expression was negatively correlated with HIF-1α. We also observed that K562 cells cocultured with BMSCs transfected with adenovirus-short hairpin RNA of Cx43 (BMSCs-shCx43) had a lower apoptosis rate and that their cell cycle was blocked in G0/G1 phase, while the result was the opposite in the Cx43-overexpression setting. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca 2+ is the key factor mediating the downstream apoptotic pathway. In animal experiments, mice bearing K562, and BMSCs-Cx43 had the smallest tumor volume and spleen, which was consistent with the in vitro experiments.@*CONCLUSIONS@#Cx43 deficiency exists in CML patients, promoting the generation of MRD and inducing drug resistance. Enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy.

Pregnancy complicated with primary hyperparathyroidism: a report of 3 cases / 中华全科医师杂志

Clinical data of 3 pregnant women with primary hyperparathyroidism admitted in Jinan Maternal and Child Health Hospital from 2013 to 2021 were retrospectively reviewed. Hyperparathyroidism was diagnosed during pregnancy in all 3 cases. The clinical manifestations were non-specific, such as nausea, vomiting, anorexia, and fatigue. Patients also had gallbladder stones (1 case), gallbladder polyps (1 case), and renal parenchyma changes (2 cases). The hypercalcemia crisis occurred in all 3 cases, the blood Ca 2+ levels were 4.11 mmol/L, 2.92-3.82 mmol/L and 3.49-4.10 mmol/L, respectively; and preeclampsia developed in 2 cases. Sudden death occurred in case 1 who did not receive effective treatment during pregnancy; blood calcium was well controlled during pregnancy in case 2, and her neonate had hypocalcemia with good prognosis; case 3 underwent surgical treatment in early pregnancy, and then had missed abortion. Pathological examination revealed parathyroid tumors in all 3 cases.

Dual-task treadmill training improves the motor functioning of children with bilateral spastic cerebral palsy / 中华物理医学与康复杂志

Objective:To explore any effect of the single- and dual-task treadmill training on the functioning of children with bilateral spastic cerebral palsy.Methods:Fifty children with bilateral spastic cerebral palsy were randomly divided into a single-task treadmill training group (the control group, n=25) and a dual-task treadmill training group (the observation group, n=25). All of the children also received routine rehabilitation training, and the control and observation groups also conducted single- and dual-task treadmill training in addition to the routine rehabilitation training, respectively. Before and after 2 months of treatment, each child′s gross motor functioning was quantified using sections D (standing) and E (walking, running and jumping) of the Gross Motor Function Measurement-88 (GMFM-88) instrument. Balance was quantified using the Pediatric Balance Scale (PBS) and walking mobility was quantified using a 1 minute walking test (1MWT). Modified and dual task Timed Up and Go (mTUG) tests and dual-task effects (DTE) tests were also administered. Results:There were no significant differences in average test scores between the two groups before the treatment. After the treatment significant improvement was observed in both groups. There was no significant difference between the two groups in terms of average GMFM-88, PBS and 1MWT scores, but significantly greater improvement was observed in the average dual-task mTUG and DTE results of the observation group.Conclusion:Both single- and dual-task treadmill training are effective supplements to routine rehabilitation training for children with bilateral spastic cerebral palsy. Dual-task treadmill training is more effective than the single-task version.

Current situation and influencing factors of post-traumatic stress disorder among firefighters in Chongqing City / 中国职业医学

{L-End}Objective To analyze the current status of post-traumatic stress disorder (PTSD) among firefighters in Chongqing City and explore its influencing factors. {L-End}Methods A total of 1 021 firefighters in Chongqing City were selected as the study subjects using the convenient sampling method. The PTSD Checklist Civilian Version was used to assess their PTSD symptom and characteristics. The Trait Coping Style Questionnaire and the Social Support Rating Scale were used to investigate coping styles and the level of social support. {L-End}Results The positive detection rate of PTSD among the study subjects was 4.6%(47/1 021), with positive detection rates of re-experiencing, avoidance/numbing, and hyperarousal symptoms of 7.0%, 9.2%, and 16.5%, respectively. The positive detection rates of re-experiencing, avoidance/numbing, and hyperarousal symptoms in the PTSD firefighters were higher than those in non-PTSD firefighters (83.0% vs 3.3%, 93.6% vs 5.1%, 100.0% vs 12.1%, respectively; all P<0.01). The results of the multivariate logistic regression analysis showed that being injured in the past six months and adopting a negative coping style were risk factors for PTSD ［odds ratio (OR) and 95% confidence interval (CI) were 2.65 (1.07-6.56) and 1.26 (1.19-1.33), respectively; both P<0.05］, while adopting a positive coping style and having a higher level of social support were protective factors for PTSD ［OR and 95%CI were 0.90 (0.85-0.95) and 0.95 (0.91-0.99), respectively; both P<0.05］. {L-End}Conclusion The incidence of PTSD among the firefighters in Chongqing City is relatively high, with symptoms mainly characterized by hyperarousal. Being injured in the past six months, coping styles, and the level of social support are influencing factors for PTSD.

Magnetic bead-based adsorption strategy for exosome isolation.

Exosomes, one type of extracellular vesicle (EV) secreted by cells, participate in intercellular communication and other biological processes as carriers of lipids, functional proteins, mRNAs, miRNAs, lncRNAs, and DNA fragments. Their presence in biofluids makes them attractive candidates as innovative clinical diagnostic tools. However, the conventional isolation and analysis of high-purity exosomes in clinical application is challenging, with traditional methods facing a number of shortcomings, including low yield or purity, long periods of processing, high cost, and difficulties in standardization. In this study, we provide an overview of commonly used exosome isolation approaches with a focus on magnetic bead-based capture, an ideal methodology with high purity and integrality of exosomes. The current challenges on exosome isolation methods are also described to highlight areas for future research and development.

Analysis of clinical features and pathogenic variants in a Chinese pedigree affected with congenital glycosylation disease / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic basis for a Chinese pedigree diagnosed with congenital glycosylation disease (CGD).@*METHODS@#Clinical manifestations of two brothers were analyzed. Whole exome sequencing was carried out for the sib pair. Suspected variants were verified by Sanger sequencing.@*RESULTS@#Both the proband and her younger brother were found to carry compound heterozygous variants of the PMM2 gene, which included a known pathogenic mutation of c.395T>C (p.I132T) and a previously unreported c.448-1(delAG) in the 5' end of exon 6 of the gene.@*CONCLUSION@#The compound heterozygous variants of the PMM2 gene probably underlay the CGD in the sib pair.

Research progress on the relationship between the gut microbiota and geriatric diseases / 中华老年医学杂志

The human gut is populated by a complex community of microbiota that coexists with the host to maintain homeostasis.Macrogenomic and metabonomics analysis shows that the imbalance in gut microbiota composition and diversity, some bacterial components, metabolites and the signaling pathways mediated by them are involved in the occurrence and development of a variety of diseases, especially in the elderly.Intestinal microorganisms are one of the important factors affecting age-related diseases and can provide insights on treatment strategies for the elderly.This review focuses on the composition of the intestinal microbiota, interaction between the microbiota and the host, features of the gut microbiota in common geriatric diseases and pathogenic mechanisms.

Clinical Observation of Sacubitril Valsartan Sodium Tablets Combined with Bailing Capsules in the Treatment of Chronic Left Heart Failure with Renal Insufficiency / 中国药房

OBJECTIVE：To study the efficacy and safety of sacubitril valsartan sodium tablets combined with Bailing capsules in the treatment of chronic left heart failure with renal insufficiency ，and to provide reference for clinical drug use. METHODS ： Totally 96 patients with chronic left heart failure with renal insufficiency who sought medical care in our hospital from Nov. 2018 to Nov. 2019 were divided into group A ，B and C according to table of random numbers ，with 32 cases in each group. Group A received conventional heart failure treatment and and Bailing capsules （2 g each time ，3 times a day ）；group B received conventional heart failure treatment and Sacubitril valsartan sodium tablets （50 mg each time ，twice a day ）；group C was given with heart failure treatment and Sacubitril valsartan sodium tablets （50 mg each time ，twice a day ）and Bailing capsules （2 g each time，3 times a day ）. 3 groups received consecutive 6 months of treatment. Clinical response rates of 3 groups were compared. Left heart function indexes [left ventricular end systolic diameter （LVESD），left ventricular end-diastolic diameter （LVEDD），left ventricular ejection fraction （LVEF）] and serological indexes [interleukin 1（IL-1），IL-6，N terminal brain natriuretic peptide precursor，glomerular filtration rate （GFR）] were detected before and after treatment. The occurrence of ADR were observed and recorded. RESULTS ：During this study ，a total of 6 patients fell off ，and eventually 90 patients completed the study ，including 29 cases in group A ，30 cases in group B and 31 cases in group C. Before treatment ，there was no statistical significance in left heart function indexes or serological indexes among 3 groups（P＞ 0.05）. After 6 months of treatment ，clinical response rate of group C was significantly higher than those of group A and B 163.com （P＜0.05）. Compared with before treatment ， LVEDD， LVESD and serological indexes of 3 groups were decreased significantly after treatment （P＜0.05），while LVEF and GFR were increased significantly （P＜0.05）；the changes of above indexes （except for IL- 1 level in serum ） in group C were significantly better than group A and B ，the changes of above indexes in group B （except for GFR ）were significantly better than group A （P＜0.05）. No significant ADR were observed in 3 groups. CONCLUSIONS ：Sacubitril valsartan sodium tablets combined with Bailing capsules can significantly decrease the level of serum inflammation factors ，and improve cardiac and renal function in patients with chronic left heart failure with renal insufficiency ，with good safety.

Homogenization and optimization strategy for standard process of intensity-modulated radiotherapy for nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Radiotherapy is the most common treatment for nasopharyngeal carcinoma, and the radiotherapy technique is essential for the prognosis of nasopharyngeal carcinoma. Due to the complexity of the structure of the intensity-modulated device and the accuracy of the clinical requirements of radiotherapy, it is inevitable that higher requirements will be imposed on the process of intensity-modulated radiotherapy. Currently, gaps exist in the radiotherapy equipment and personnel qualification among radiotherapy units, and thus the homogenization in the radiotherapy remains to be strengthened in China. With the application of radiotherapy information management system, digital medicine and artificial intelligence technologies in the field of radiotherapy, the original process fails to meet the application needs of the new precise radiotherapy technology. Therefore, this process is designed based on the existing radiotherapy procedures for nasopharyngeal carcinoma in combination with the latest developments in the field of radiotherapy, aiming to establish a novel standard process recommendation, ensuring the standardization and homogenization of radiotherapy and achieve the individualized intensity-modulated radiotherapy for nasopharyngeal carcinoma patients.

Analysis of Clinical Efficacy of Recombinant Human Brain Natriuretic Peptide Combined with Levosimendan in the Treatment of Acute Decompensated Heart Failure Complicated with Renal Insufficiency / 中国药房

OBJECTIVE：To observe the clinical effect and safety of recombinant human brain natriuretic peptide （rhBNP） combined with levosimendan in the treatment of acute decompensated heart failure （ADHF）complicated with renal insufficiency. METHODS：A total of 156 patients with ADHF complicated with renal insufficiency admitted to the Dept. of Cardiology in the Affiliated Hospital of Southwest Medical University during Jan.-Dec. 2019 were randomly divided into rhBNP group ，levosimendan group and combination group ，with 52 patients in each group. All patients received rountine treatment. On this basis ，rhBNP group was given rhBNP for injection [after 1.5 μg/kg intravenous pulse injection，intravenous dripping for 24 h with 0.007 5 μg（/ kg· min）]；leosimendan group was given Leosimendan injection 12.5 mg [intravenous dripping for 1 h with 6-12 μg（/ kg·min），then intravenous dripping for 23 h with 0.1 μg（/ kg·min）]. Combination group received drug combination according to the administration method of single drug group. Three groups received treatment for consecutive 7 d. Cardiac function indexes [heart rate （HR），left ventricular ejection fraction （LVEF），left ventricular end-diastolic diameter （LVEDD）]，mean arterial pressure （MAP），pulmonary capillary pressure （PCWP），renal function indexes [estimated glomerular filtration rate （eGFR），serum creatinine （Scr）]，serum levels of cystatin C （Cys-c）and amino-terminal brain natriuretic peptide precursor （NT-proBNP）were observed in 3 groups before and after treatment. Clinical efficacy and the occurrence of ADR were recorded. RESULTS ：Three cases withdrew from the study in rhBNP group and 1 case in levosimendan group ；152 cases completed the study. Before treatment ，there was no statistical significance in cardiac function indexes ，MAP，PCMP，renal function indexes or serum levels of Cys-C and NT-proBNP among 3 groups（P＞0.05）. After treatment ，the HP ，MAP，PCWP and serum level of NT-proBNP in 3 group as well as serum level of Cys-C in combination group were decreased significantly （P＜0.05）；the LVEF in 3 group as well as the eGFR and Scr level in levosimendan group and combination group were significantly increased （P＜0.05），compared with before treatment ；above indexes of combination group were significantly better than those of rhBNP group and levosimendan group （P＜0.05）. Total effective rate of combination group was 94.23％ ，which was significantly higher than those of rhBNP group （77.55％）and levosimendan group （76.47％）（P＜0.05）. There was no significant difference in the incidence of ADR among 3 groups（P＞ 0.05）. CONCLUSIONS ：rhBNP combined with levosimendan in the treatment of ADHF complicated with renal insufficiency can significantly increase the clinical efficacy ，and improve cardiac and renal function but don ’t increase the incidence of ADR.

Effect of nectin-1 expression after being inhibited by lentivirus on epileptogenesis and mossy fiber sprouting / 中华神经医学杂志

Objective:To explore the effect of adhesion molecule nectin-1 expression on epileptic seizure and mossy fiber sprouting.Methods:(1) Adult male SD rats were randomly divided into control group ( n=6), empty vector group ( n=6) and lentivirus interfered group ( n=24), and rats in the lentivirus interfered group were further divided into 4 subgroups ( n=6) according to the time points of lentivirus injection (3, 7, 14 and 30 d after injection). The protein expression of nectin-1 in the hippocampus of rats was detected by Western blotting. (2) Another 12 male SD rats were randomly selected and divided into lentivirus epilepsy group ( n=6) and empty vector epilepsy group ( n=6). Lentivirus and empty lentivirus vector were injected into the hippocampus of the above two groups respectively, and then, pilocarpine epilepsy models were kindled; the behavior changes of these rats were recorded, and changes of mossy fiber sprouting in the hippocampus were observed by Timm staining. Results:(1) There were significant differences in hippocampal nectin-1 protein expressions in each group ( F=76.120, P=0.000); the nectin-1 expression in the 7, 14, and 30 d subgroups was significantly decreased as compared with that in the control group and empty vector group ( P<0.05). (2) The results of behavior changes showed that the times required for the lentivirus epilepsy group to be kindled successfully ([34.33±2.38] min) were significantly longer than those for the empty vector epilepsy group ([24.50±2.06] min, t=7.650, P=0.000). In terms of seizure level, the seizure level of rats in the lentivirus epilepsy group was significantly lower at each time point within one h modeling than that of rats in the empty vector epilepsy group ( P<0.05). After kindling, the time of spontaneous seizure appeared in the lentivirus epilepsy group was significantly longer than that in the empty vector epilepsy group, and the frequencies of spontaneous seizure in the lentivirus epilepsy group were significantly decreased as compared with those in the empty vector epilepsy group ( P<0.05). Timm staining scores in the lentivirus epilepsy group (3.500±0.224) were significantly lower than those in the empty vector epilepsy group (4.667±0.211, t=9.289, P=0.000). Conclusion:Inhibition of nectin-1 expression in hippocampal area of epileptic rats can delay the occurrence of epilepsy and reduce the frequencies of spontaneous seizures of epileptic rats, whose mechanism may be related to the reduction of nectin-1 in the formation of mossy fiber sprouting in abnormal neural circuits of hippocampal area.

Inhibiting effects of flue gas desulfurization gypsum on soil phosphorus loss in Chongming Dongtan, southeastern China.

To explore the possibility of using flue gas desulfurization gypsum (FGDG) for inhibiting phosphorus (P) loss due to agricultural runoff, a 3-year study was performed in the farmlands of Chongming Dongtan between 2012 and 2015. Five different quantities of FGDG were used to treat the soil, and the effects of different treatments on the characteristics of soil P and crop growth were investigated. The results showed that 2 years after application of FGDG, the soil density at a depth of 0-10 cm decreased by 4.35-7.97%, the porosity increased by 1.77-11.0%, and the topsoil permeability increased by 0.87-3.81 times. Although the use of FGDG did not change the total P concentration in the soil, it decreased the concentration of sodium bicarbonate extractable P in the soil. Compared to the control, the average extractable P concentration at depths of 0-10 cm, 10-20 cm, and 20-30 cm decreased by 22.0-46.1%, 26.9-40.5%, and 22.8-34.8%, respectively. The inorganic P in the soil increased as the amount of FGDG increased, and the increase was mainly as Ca-P in the forms Ca2-P and Ca10-P. The decrease in bicarbonate extractable P and increase in inorganic P in the soil did not affect the growth of the crops, and the biomass and output of the crops increased compared to the control. Therefore, FGDG can enhance soil P immobilization, thus reducing soluble P runoff from farm fields, and improving water quality in receiving lakes and rivers while maintaining P nutrition to the crops.

Preliminary study of sequential multi-modality adjuvant chemotherapy and radiation for advanced endometrial cancer / 中华妇产科杂志

Objective To evaluate the clinical outcomes and feasibility of multi-modality adjuvant chemotherapy and radiation, which was conducted as postoperative chemotherapy, radiation, and consolidation chemotherapy (CRC) mode for the treatment of advanced endometrial cancer. Methods A retrospective analysis of 124 patients with International Federation of Gynecology and Obstetrics (FIGO) stages Ⅲ and Ⅳ endometrial cancer from Jan. 2004 to Oct. 2012 was conducted in Peking University People′s Hospital and Beijing Obstetrics and Gynecology Hospital. Inclusion criteria were comprehensive staging procedure including hysterectomy, bilateral salpingo-oophorectomy, and (or) selective pelvic aortic lymphadenectomy, and treatment with adjuvant chemotherapy and (or) radiation. The average age of these patients was (55.9 ± 8.4) years old (range from 23 to 79 years old). According to different postoperative adjuvant treatment modes, the patients were divided into CRC group, chemotherapy-radiotherapy (CR) group and single chemotherapy (C) group. The survival and side effects of the three groups were compared. Results (1) One hundred and twenty-four patients with advanced stage endometrial cancer were identified and received postoperative adjuvant therapies.Sixty-one (49.2％, 61/124) cases of them received postoperative CRC fashion, 19 (15.3％, 19/124) received postoperative CR and 44 (35.5％, 44/124) cases received C. The age, stage, grade and type of surgery of the three groups were not significantly different (all P>0.05);while, the pathology, chemotherapy cycles and chemotherapy regimens differed significantly (all P<0.05). (2) The progression-free survivals (PFS) of the patients with CRC, CR, and C group were (121±7), (68± 15), and (100±11) months, respectively. The 3-year PFS rates were 87.9％, 43.7％, and 61.4％, respectively. The 5-year PFS rates were 82.2％, 36.4％, and 61.4％, respectively. The above indicators were significantly higher in the CRC group than in the CR group (all P<0.01), and there was no difference between the CRC group and the C group (P=0.037). The overall survival (OS) of patients with CRC, CR, and C group were (128 ± 6), (80 ± 12), and (99 ± 10) months, respectively. The 3-year OS rates were 87.8％, 72.4％, and 67.1％, the 5-year OS rate were 84.2％, 54.3％, and 64.1％, respectively. The above indicators were significantly higher in the CRC group than those in the CR group and C group (all P<0.01). (3) There was no difference in the frequency of adverse effects either chemotherapy, such as severe bone suppression or radiotherapy;hepatotoxicity,blood transfusion, dose modifications;or cycle delays between the CRC, CR and C group (all P>0.05). (4) In the univariate analysis shown that, stage, the fashion of postoperative adjuvant therapy and type of surgery were risk factors for tumor progression in patients with advanced endometrial cancer (P<0.05). After adjusted for FIGO stage and type of surgery, the tumor progression hazard ratio (HR) was 3.931 (95％CI:1.734-8.914, P=0.001) for the CR group and 2.188 (95％CI:1.010-4.741, P=0.047) for the C group, compared to the CRC group. Conclusion Sequential CRC delivered in a"sandwich"fashion for the treatment in advanced endometrial cancer could significantly improve the 3-year and 5-year OS rates and have a similar adverse effect profile compared with other sequencing modalities.

The clinical observation of serum specific biomarkers in patients with chronic graft-versus-host disease / 中华血液学杂志

Objective@#Chronic graft-versus-host disease (cGVHD) is a major long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . It is important to study the changes of serum biomarkers expression in patients for early diagnosis and treatment.@*Methods@#The expression levels of five serum protein markers (IL-1b, IL-16, CXCL9, CCL19, CCL17) in patients with or without cGVHD after allo-HSCT were detected by liquid suspension microarray.@*Results@#Compared with the control group without cGVHD, the expression levels of CXCL9 and CCL17 in serum of patients with cGVHD were significantly increased (P<0.05) . CCL17 was correlated with the severity of cGVHD (P<0.001) . CXCL9 was significantly increased in the serum of patients with skin lesion (P<0.01) , and CCL17 was significantly expressed in cGVHD patients with liver as the target organ (P<0.01) .@*Conclusion@#The combination of CXCL9 and CCL17 can be used as serum biomarkers of cGVHD, which has certain reference value in assisting the diagnosis and evaluation of cGVHD severity.

Targeted elimination of mutant mitochondrial DNA in MELAS-iPSCs by mitoTALENs

Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A>G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A>G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Furthermore, we successfully achieved reduction in the human m.3243A>G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.

Comparative study of endoscopic ultrasonography and CT in the diagnosis of patients with pancreatic and periampullary tumors / 中国基层医药

Objective To evaluate the clinical value of endoscopic ultrasonography and CT in the diagnosis of patients with pancreatic and periampullary tumors.Methods From February 2010 to January 2016,89 patients with suspected pancreatic and periampullary tumors in Yinzhou Hospital Affiliated to Medical College of Ningbo University were selected in this study.Endoscopic ultrasonography and CT were performed in 89 patients.Endoscopic ultrasonography and CT examination results were compared with surgical and pathological results ,and the sensitivity, specificity and accuracy of the two methods were recorded and compared.Results By pathological examination , 69 cases were diagnosed as pancreatic and periampullary tumors.The sensitivity of endoscopic ultrasonography was 95.65%(66/69),the specificity was 95.00%(19/20),and the accuracy was 95.51%(85/89).The sensitivity of CT diagnosis was 85.51%(59/69),and the specificity was 90.00%(18/20),and the accuracy was 86.52%(77/89).The sensitivity and accuracy of endoscopic ultrasonography were significantly higher than those of CT ,and the differences were statistically significant (χ2＝4.161,4.395,P ＝0.041,0.036).And there was no statistically significant difference in the specificity of endoscopic ultrasonography and CT (χ2＝0.360,P＝0.548).Conclusion Endoscopic ultrasonography and CT examination have high specificity in the diagnosis of patients with pancreatic and periampullary tumors,however,the sensitivity and accuracy of endoscopic ultrasonography are higher than CT ,the clinical appropriate diagnostic methods can be chosen according to the actual condition of the patients .