Diagnosis and treatment of passenger lymphocyte syndrome following secondary ABO-incompatible allogeneic hematopoietic stem cell transplantation / 中国输血杂志

【Objective】 To investigate the clinical characteristics and diagnosis and treatment of passenger lymphocyte syndrome (PLS) in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). 【Methods】 A total of 489 patients who underwent allo-HSCT in Suzhou Hongci Hematology Hospital were retrospectively enrolled. The clinical process, diagnosis and treatment measures and prognosis of four patients complicated with PLS after transplantation were analyzed. 【Results】 Among the 489 patients, 4 were diagnosed with PLS. The blood types of donor/recipient ABO were all secondary incompatible (The blood type of donors were O and the recipients were A or B). The overall incidence of PLS in allo-HSCT was 0.82%(4/489)and 2.2%(4/179)in transplants with donor/recipient secondary incompatible ABO-blood types. PLS occured in 6-13 days after donor stem cell infusion. Clinical manifestations were dizziness and fatigue, low back pain, jaundice, deepening urine, rapid decrease in hemoglobin on laboratory tests, elevated indirect bilirubin and lactate dehydrogenase, positive urobilinogen, positive direct anti-human globulin test (DAT), and anti-A or anti-B antibodies against recipient red blood cells were detected in plasma. After the treatment of O-type washed red blood cells, methylprednisolone, gamma globulin, rituximab and other treatments, the hemolysis was improved. All patients achieved engraftment of neutrophil and platelet. Red blood cell transfusion was halted in 3 weeks. 【Conclusion】 PLS is a rare complication of allo-HSCT, which mainly occurs in allo-HSCT patients with secondary incompatibility of ABO blood group of donor/recipient. The clinical prognosis is good after properly treatment.

Analysis and suggestions on conflict of interest in the transformation of scientific and technological achievements in medical institutions / 中华医院管理杂志

In recent years, the issue of conflicts of interest in the transformation of scientific and technological achievements in medical institutions in China has become prominent, mainly manifested as personal and institutional conflicts of interest, with the characteristics of complexity and sustainability. At present, there were some problems in the conflict management of scientific and technological achievements transformation of medical institutions, such as insufficient support of relevant laws, regulations and policies, insufficient supervision of medical institutions, and the lack of industry management atmosphere. The author suggestted that government departments should strengthen the formulation of relevant policies and regulations, medical institutions should establish an interest conflict management system and an independent management department, and industry associations should give full play to their role in assisting, so as to provide reference for promoting medical institutions to effectively manage interest conflicts in the transformation of scientific and technological achievements.

Tislelizumab bridging to umbilical cord blood transplantation therapy for relapsed/refractory acute myeloid leukemia: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To explore the efficacy of tislelizumab combined with umbilical cord blood transplantation (UCBT) in relapsed/refractory acute myeloid leukemia (R/R AML) patients.Methods:The diagnosis and treatment of 1 patient with R/R AML who received tislelizumab bridging to UCBT after the failure of re-induction treatment in the First Affiliated Hospital of Soochow University in November 2021 was retrospectively analyzed.Results:The 59-year-old male patient with R/R AML achieved a complete remission after initial induction chemotherapy regimen of decitabine and venetoclax, and then additional consolidation therapy regimens of decitabine and middle-dose cytarabine, middle-dose cytarabine and idarubicin were performed. The patient relapsed 16 months later and failed to achieve a second remission after re-induction therapy regimens of cladribine, azacitidine, venetoclax combined with chemotherapy, and homoharringtonine, cytarabine combined with granulocyte colony-stimulating factor. Tislelizumab significantly reduced tumor burden and the patient achieved the complete remission after bridging to UCBT. After transplantation, the patient was given maintenance treatment with azacitidine and he had sustained remission without severe transplant-related complications during 9-month follow-up.Conclusions:The use of tislelizumab bridging UCBT can be a potential therapeutic strategy for R/R AML patients.

Antibacterial effect of low-temperature plasma on Enterococcus faecalis in dentinal tubules in vitro / 北京大学学报(医学版)

OBJECTIVE@#To construct a model of Enterococcus faecalis (E. faecalis) infection in dentinal tubules by gradient centrifugation and to evaluate the antibacterial effect of low-temperature plasma on E. faecalis in dentinal tubules.@*METHODS@#Standard dentin blocks of 4 mm×4 mm×2 mm size were prepared from single root canal isolated teeth without caries, placed in the E. faecalis bacterial solution, centrifuged in gradient and incubated for 24 h to establish the model of dentinal tubule infection with E. faecalis. The twenty dentin blocks of were divided into five groups, low-temperature plasma jet treatment for 0, 5 and 10 min, calcium hydroxide paste sealing for 7 d and 2% chlorhexidine gel sealing for 7 d. Scanning electron microscopy and confocal laser scanning microscope were used to assess the infection in the dentinal tubules and the antibacterial effect of low-temperature plasma.@*RESULTS@#The results of scanning electron microscopy and confocal laser scanning microscopy showed that after 24 h of incubation by gradient centrifugation, E. faecalis could fully enter the dentinal tubules to a depth of more than 600μm indicating that this method was time-saving and efficient and could successfully construct a model of E. faecalis infection in dentinal tubules. Low-temperature plasma could enter the dentinal tubules and play a role, the structure of E. faecalis was still intact after 5 min of low-temperature plasma treatment, with no obvious damage, and after 10 min of low-temperature plasma treatment, the surface morphology of E. faecalis was crumpled and deformed, the cell wall was seriously collapsed, and the normal physiological morphology was damaged indicating that the majority of E. faecalis was killed in the dentinal tubules. The antibacterial effect of low-temperature plasma treatment for 10 min exceeded that of the calcium hydroxide paste sealing for 7 d and the 2% chlorhexidine gel sealing for 7 d. These two chemicals had difficulty entering deep into the dentinal tubules, and therefore only had a few of antibacterial effect on the bacterial biofilm on the root canal wall, and there was also no significant damage to the E. faecalis bacterial structure.@*CONCLUSION@#Gradient centrifugation could establish the model of E. faecalis dentin infection successfully. Low-temperature plasma treatment for 10 min could kill E. faecalis in dentinal tubules effectively, which is superior to the calcium hydroxide paste sealing for 7 d and the 2% chlorhexidine gel sealing for 7 d.

Overview of surface-enhanced Raman spectroscopy in combination with other detection techniques / 药学实践杂志

As an increasingly mature analytical technique, surface-enhanced Raman spectroscopy has the ability to identify, detect, and even quantitatively measure many single substances in nature. However, in the actual sample analysis, the tested samples were often a mixed system of various substances, and it was impossible to accurately characterize the components of the mixed system only by relying on SERS technology. Therefore, SERS combined with other techniques to accurately determine the measured substances has become an inevitable trend. Through the combination, the deficiency of SERS in detection and characterization was improved, and the purpose of efficient, sensitive and accurate determination of substances to be measured was achieved.

Study on the relationship among the extracurricular time management ability, self-efficacy and learning effect of medical undergraduates / 中华医学教育探索杂志

Objective:To understand the current situation of management ability and self-efficacy of medical undergraduates in Suzhou and their influence on the learning effect.Methods:General data questionnaire, present situation of college students' spare time management ability questionnaire and Chinese general self-efficacy scale were used to collect data from September 2018 to April 2019 in 5 colleges and 5 grades of medicine in a comprehensive university in Suzhou using cluster sampling method. A total of 450 full-time undergraduates completed the questionnaire. SPSS 22.0 was used for t-test, one-way ANOVA and Chi-square test. Multiple Logistics regression analysis was used to analyze the influence of extracurricular time management ability and self-efficacy on academic performance. Results:A total of 450 questionnaires were distributed, and 421 were recovered, with the effective recovery rate of 93.6%. The extracurricular time of full-time medical undergraduates was relatively low, and the management ability of extracurricular time was different in different grades, whether to be a student leader, professional interests, economic status and other aspects. Students of different grades had different levels of self-efficacy. Multivariate Logistics regression analysis was carried out with the dependent variables, with the model fitted χ2=220.488, P=0.002 and the determination coefficient = 0.660. The management ability and self-efficacy in spare time were independent influencing factors of academic performance. Conclusion:Schools should take specific measures to improve the learning effect and educational quality of medical students.

Loss of O-GlcNAcylation on MeCP2 at Threonine 203 Leads to Neurodevelopmental Disorders / 神经科学通报·英文版

Mutations of the X-linked methyl-CpG-binding protein 2 (MECP2) gene in humans are responsible for most cases of Rett syndrome (RTT), an X-linked progressive neurological disorder. While genome-wide screens in clinical trials have revealed several putative RTT-associated mutations in MECP2, their causal relevance regarding the functional regulation of MeCP2 at the etiologic sites at the protein level requires more evidence. In this study, we demonstrated that MeCP2 was dynamically modified by O-linked-β-N-acetylglucosamine (O-GlcNAc) at threonine 203 (T203), an etiologic site in RTT patients. Disruption of the O-GlcNAcylation of MeCP2 specifically at T203 impaired dendrite development and spine maturation in cultured hippocampal neurons, and disrupted neuronal migration, dendritic spine morphogenesis, and caused dysfunction of synaptic transmission in the developing and juvenile mouse cerebral cortex. Mechanistically, genetic disruption of O-GlcNAcylation at T203 on MeCP2 decreased the neuronal activity-induced induction of Bdnf transcription. Our study highlights the critical role of MeCP2 T203 O-GlcNAcylation in neural development and synaptic transmission potentially via brain-derived neurotrophic factor.

Research on prediction of daily admissions of respiratory diseases with comorbid diabetes in Beijing based on long short-term memory recurrent neural network / 浙江大学学报·医学版

To compare the performance of generalized additive model (GAM) and long short-term memory recurrent neural network (LSTM-RNN) on the prediction of daily admissions of respiratory diseases with comorbid diabetes. Daily data on air pollutants, meteorological factors and hospital admissions for respiratory diseases from Jan 1st, 2014 to Dec 31st, 2019 in Beijing were collected. LSTM-RNN was used to predict the daily admissions of respiratory diseases with comorbid diabetes, and the results were compared with those of GAM. The evaluation indexes were calculated by five-fold cross validation. Compared with the GAM, the prediction errors of LSTM-RNN were significantly lower [root mean squared error (RMSE): 21.21±3.30 vs. 46.13±7.60, <0.01; mean absolute error (MAE): 14.64±1.99 vs. 36.08±6.20, <0.01], and the value was significantly higher (0.79±0.06 vs. 0.57±0.12, <0.01). In gender stratification, RMSE, MAE and values of LSTM-RNN were better than those of GAM in predicting female admission (all <0.05), but there were no significant difference in predicting male admission between two models (all >0.05). In seasonal stratification, RMSE and MAE of LSTM-RNN were lower than those of GAM in predicting warm season admission (all <0.05), but there was no significant difference in value (>0.05). There were no significant difference in RMSE, MAE and between the two models in predicting cold season admission (all >0.05). In the stratification of functional areas, the RMSE, MAE and values of LSTM-RNN were better than those of GAM in predicting core area admission (all <0.05). has lower prediction errors and better fitting than the GAM, which can provide scientific basis for precise allocation of medical resources in polluted weather in advance.

Preparation and evaluation of quality management samples for noninvasive prenatal screening / 中华医学遗传学杂志

OBJECTIVE@#To prepare a quality control sample for non-invasive prenatal screening (NIPS) and evaluate its quality and stability.@*METHODS@#According to the biological characteristics of cell-free fetal DNA derived from the plasma of pregnant women, the simulated samples were prepared by mixing genomic DNA fragments derived from individuals with trisomy 21, trisomy 18 and trisomy 13 and background plasma. The samples were then compared with commercially made quality control products tested on various NIPS platforms and stored at -80℃, -20℃, 4℃, 24℃ and 37℃ for various periods of time.@*RESULTS@#The simulated samples have attained the expected results and could be detected on various platforms and stored at -80℃and -20℃ for at least 30 days.@*CONCLUSION@#A simulated sample was successfully prepared and possessed good stability. It can be used as the quality control sample for NIPS.

Safety and efficacy of left atrial appendage closure combined with patent foramen ovale closure for atrial fibrillation patients with patent foramen ovale / 中华心血管病杂志

Objective: To analyze the safety and efficacy of combined left atrial appendage (LAA) and patent foramen ovale (PFO) closure in adult atrial fibrillation (AF) patients complicating with PFO. Methods: This study is a retrospective and cross-sectional study. Seven patients with AF complicated with PFO diagnosed by transesophageal echocardiography (TEE) in Zhoupu Hospital Affiliated to Shanghai University of Medicine & Health Sciences from June 2017 to October 2020 were selected. Basic data such as age, gender and medical history were collected. The atrial septal defect or PFO occluder and LAA occluder were selected according to the size of PFO, the ostia width and depth of LAA. Four patients underwent left atrial appendage closure(LAAC) and PFO closure at the same time. PFO closure was performed during a one-stop procedure of cryoablation combined with LAAC in 2 patients. One patient underwent PFO closure at 10 weeks after one-stop procedure because of recurrent transient ischemic attack (TIA). All patients continued to take oral anticoagulants. TEE was repeated 8-12 weeks after intervention. In case of device related thrombus(DRT), TEE shall be rechecked 6 months after adjusting anticoagulant and antiplatelet drug treatment. Patients were follow-up at 1, 3, 6, 12, 24 months by telephone call, and the occurrence of cardio-cerebrovascular events was recorded. Results: Among the 7 patients with AF, 2 were male, aged (68.0±9.4) years, and 3 had a history of recurrent cerebral infarction and TIA. Average PFO diameter was (3.5±0.8)mm. Three patients were implanted with Watchman LAA occluder (30, 30, 33 mm) and atrial septal defect occluder (8, 9, 16 mm). 2 patients were implanted with LAmbre LAA occluder (34/38, 18/32 mm) and PFO occluder (PF1825, PF2525). 2 patients were implanted with LACbes LAA occluder (24, 28 mm) and PFO occluder (PF2525, PF1825) respectively. The patients were followed up for 12 (11, 24) months after operation. TEE reexamination showed that the position of LAA occluder and atrial septal defect occluder or PFO occluder was normal in all patients. DRT was detected in 1 patient, and anticoagulant therapy was adjusted in this patient. 6 months later, TEE showed that DRT disappeared. No cardiovascular and cerebrovascular events occurred in all patients with AF during follow-up. Conclusions: In AF patients complicated with PFO, LAAC combined with PFO closure may have good safety and effectiveness.

Efficacy of Watchman occlusion of the left atrial appendage in patients ≥85 years with atrial fibrillation / 中华老年医学杂志

Objective:To analyze the safety and efficacy of left atrial appendage closure(LAAC)with Watchman in patients ≥85 years with atrial fibrillation(AF).Methods:515 elderly patients with atrial fibrillation, including 73 patients aged 85 years or older(85~91), who had undergone Watchman LAAC at Zhoupu Hospital affiliated to Shanghai Health Medical College from August 2016 to December 2020, were retrospectively analyzed.Of those ≥85 years, 44(60.3%)with transesophageal echocardiography records were assigned to the elderly group.Fifty-three patients aged 60 to 65 were selected as the control group.Differences in baseline data, intraoperative conditions, antithrombotic treatment plans and 1-year follow-up prognosis were compared between the two groups.Results:Compared with the control group, there was no difference in AF types, history of ischemic stroke/transient ischaemic attack(all P>0.05), but there were higher incidences of coronary heart disease and renal insufficiency, more severe heart failure, higher CHA 2DS 2-VASC(6.0±1.5 vs.3.6±1.5), HAS-BLED(3.2±1.2 vs.2.3±1.3)scores( t values were 7.682 and 3.871, respectively, P<0.05), and a lower one-stop surgery rate(6 cases or 13.6% vs. 27 cases or 50.9%, χ2=10.517, P<0.05)in the advanced age group.There was no difference in the diameter of the Watchman device, rate of device replacement, compression percentage and residual flow between the two groups during the perioperative period.The incidences of device-related thrombosis were 4.5%(2/44)and 3.8%(2/53)for the advanced age group and the control group, respectively, but the difference was not statistically significant( P>0.05). During the 12-month follow-up, there were no cases of ischemic stroke or intracerebral hemorrhage.Three died of heart failure and 1 died of cancer. Conclusions:LAAC with Watchman is safe and effective for patients over 85 years with AF, but the decision on the procedure should be based on careful assessment of patients' cardiac and renal function and general health.

A new γ-valerolactone derivative from the roots of Ardisia crispa / 药学学报

Four compounds were isolated from the 70% EtOH extract of Ardisia crispa by using various chromatographic techniques, including silica gel, ODS and semi-preparative HPLC. The structures of 1-4 were elucidated based on physicochemical properties and spectroscopic data. These compounds were defined as crispalactone A (1), (+)-pinoresinol (2), 3,5-dimethoxy-4- hydroxyphenol-1-O-β-D-glucopyranoside (3) and (+)-schizandriside (4). Compound 1 is a new γ-valerolactone derivative, and compounds 2-4 are firstly isolated from Ardisia crispa.

Effect of Insoles on Patients with Adolescent Idiopathic Scoliosis / 中国康复理论与实践

Objective:To observe the effect of braces combined with insoles on scoliosis and walking performance in patients with adolescent idiopathic scoliosis (AIS). Methods:From September, 2019 to September, 2020, 42 subjects with AIS were selected and randomly divided into brace group (n = 21) and brace combined with insole group (n = 21). Both groups received two-month routine rehabilitation, including braces for 22 to 23 hours a day and gymnastics for 30 minutes a day. The brace combined with insole group additionally wore insoles, at least eight hours a day for two months. Meanwhile, 32 even-aged adolescents were recruited as healthy controls. Firstly, gait and plantar pressure of 42 patients and 32 healthy adolescents were compared to find out abnormal indicators. Secondly, the scoliosis and above abnormal indicators were compared between the brace group and the brace combined with insole group Results:The center of pressure excursion index (CPEI) was higher in AIS group than in the healthy group (F = 3.120, P < 0.05), and there was no significant difference in walking speed, gait cycle and phase between two groups (P>0.05). An obvious imbalanced pressure was observed between the medial and lateral heel of the single foot and the bilateral foot in AIS patients (P < 0.05). After treatment, the Cobb's angle decreased in AIS patients (t > 7.552, P < 0.001), however, no difference was found between the brace group and the brace combined with insole group (t = 0.459, P > 0.05); the CPEI decreased (t = 2.209, P < 0.05), and the pressure in medial and lateral heel as well as the left and right foot tended to be balanced (t > 2.306, P < 0.05) in the brace combined with insole group, and were better than that of the brace group (|t| > 2.319, P < 0.05). Conclusion:Plantar pressure distribution shows obvious local and global asymmetric changes in AIS patients. The efficacy of insoles on the scoliosis is limited, but the insole can effectively improve the abnormal biomechanics and balance the force.

Advances in direct-acting antiviral therapy for liver transplant recipients with HCV-related hepatocellular carcinoma / 临床肝胆病杂志

The launch of direct-acting antiviral agents is a milestone in the treatment of hepatitis C, but further studies are needed to explore its specific timing and effectiveness in liver transplantation for HCV-related hepatocellular carcinoma (HCC). This article summarizes related guidelines, consensus statements, and recommendations in China and globally and the advantages of different treatment timing strategies. Furthermore, a retrospective analysis of related studies is performed to investigate the controversial topic of the impact of direct-acting antiviral agents on the recurrence rate of HCV-related HCC after liver transplantation, and it is pointed that direct-acting antiviral agents can reduce the risk of HCC recurrence in liver transplant recipients with HCV-related HCC. The selection of treatment timing should consider various factors such as liver function, waiting time for donors, and utilization of HCV-positive organs.

Advances in direct-acting antiviral therapy for liver transplant recipients with HCV-related hepatocellular carcinoma / 临床肝胆病杂志

The launch of direct-acting antiviral agents is a milestone in the treatment of hepatitis C, but further studies are needed to explore its specific timing and effectiveness in liver transplantation for HCV-related hepatocellular carcinoma (HCC). This article summarizes related guidelines, consensus statements, and recommendations in China and globally and the advantages of different treatment timing strategies. Furthermore, a retrospective analysis of related studies is performed to investigate the controversial topic of the impact of direct-acting antiviral agents on the recurrence rate of HCV-related HCC after liver transplantation, and it is pointed that direct-acting antiviral agents can reduce the risk of HCC recurrence in liver transplant recipients with HCV-related HCC. The selection of treatment timing should consider various factors such as liver function, waiting time for donors, and utilization of HCV-positive organs.

Haploidentical hematopoietic stem cell transplantationversus HLA-matched stem cell transplantation for refractory or relapsed aggressive non-Hodgkin lymphoma / 中华器官移植杂志

Objective:To examine the efficacy of haploidentical stem-cell transplantation (haplo-SCT) for patients with refractory relapsed (R/R) non-Hodgkin lymphoma (NHL) by comparing with those contemporaneously undergoing HLA-matched SCT in myeloablative conditioning settings.Methods:Between January 2006 and December 2018, a total of 151 patients undergoing haplo-SCT ( n=81) or HLA-matched SCT ( n=70, sibling or unrelated) were enrolled. Median age of alloSCT was 30(5-59) years. And 150 patients received myeloablative conditioning (MAC) consisting of total body irradiation (12 Gy) plus cyclophosphamide or busulfan plus cyclophosphamide. Only one case had reduced intensity conditioning (RIC) with R-FBA (fludarabine, busulfan & cytarabina). It was followed by an infusion of granulocyte-colony stimulating factor-primed bone marrow (G-BM) and/or peripheral blood stem cells without in vitro T cell depletion. In haplo-SCT and HLA-matched unrelated donor for SCT, GVHD prophylaxis consisted of antithymocyte globulin, cyclosporine A, mycophenolate mofetil and a short course of methotrexate. Clinical efficacy, hematopoietic reconstitution and transplant-related complications were retrospectively analyzed. Results:Among them, 146(96%) patients engrafted with a median time to neutrophil and platelet recovery of 12 and 15 days respectively. During a median follow-up period of 19 months, 66 of them survived (43.7%) and 67 (44.4%) died (39 disease recurrence, 27 transplantation-related mortality). Between haplo-SCT and HLA-matched SCT groups, progression-free survival (PFS) rate was 49.4% and 50.5% ( P=0.577); overall survival (OS) rate 56.7% and 57.4% respectively ( P=0.963). The cumulative incidences of relapse (CIR) were 36.6% and 37.7% ( P=0.836) and those of cumulative incidences of non-relapse mortality (NRM) 22.0% and 24.7% ( P=0.530). And the cumulative incidences of chronic GVHD were 42.3% and 39.6% ( P=0.46) respectively. Conclusions:No inter-group difference exists in each major HSCT endpoint. Multivariate analysis reveals that occurrence of grade Ⅲ-Ⅳ aGVHD has a significantly worse prognosis. And primary chemorefractoriness is a strongest relapsing factor.

Exploration and practice of the training mode of nursing professionals in higher vocational colleges under the 1+X certificate system / 中国实用护理杂志

Objective:To explore a new training mode for nursing professionals suitable for the 1+X certificate system, and realize the training goal of "one specialty and multi-ability" compound technical nursing talents.Methods:To take the "1+ X" certificate standard as the basis for the construction of nursing specialty, to reconstruct the talent training program of integration of graduation certificate and certificate. To take the content of "1+X" certificate as the basis for the construction of professional courses, construct the core curriculum system of integration of curriculum and certificate. To build a "new double-qualified" teaching staff and constructing of new double-qualified teachers and accelerate the development of quality resources.Results:The talent training mode of integration of graduation certificate and certificate under the 1+X certificate system was constructed. The curriculum structure has been optimized. The teachers′ability of teaching, training and examination was improved.Conclusions:The new mode of training nursing professionals under the 1+X certificate system meets 1 degree education and X vocational training of nursing students and achieve a "1" and "X" seamless convergence. It provides innovative ideas for the promotion and implementation of 1+X certificate system pilot work in the field of nursing education nationwide.

Analyses of progression pattern of acquired resistance to osimertinib and the effect of salvage therapy in advanced lung cancer / 肿瘤研究与临床

Objective:To investigate the progression pattern of acquired resistance to osimertinib and the treatment method as well as the therapeutic effect of salvage therapy in advanced lung cancer patients with epidermal growth factor receptor (EGFR) sensitive mutation or T790M mutation after the treatment of tyrosine-kinase inhibitor (TKI).Methods:The data of 145 patients with advanced lung cancer treated with osimertinib in Jiangsu Cancer Hospital between April 2017 (the approval time of osimertinib in China) and May 2019 were collected. At the last follow-up (December 2019), a total of 87 (60.0%) patients had acquired resistance to osimertinib, 61 (70.1%) of whom received salvage treatment; for patients with dramatic progression after resistance, chemotherapy was mainly given in the salvage therapy; for patients with gradual or local progression after resistance, the continuing targeted drug therapy and the local therapy were given. Imaging evaluation and Kaplan-Meier method were used to analyze the progression pattern of acquired resistance to osimertinib and the survival status, and to compare the salvage treatment results among subgroups.Results:The median follow-up time of 61 patients receiving salvage therapy was 11 months (4-32 months), among which 58 (95.1%) patients again had resistance to osimertinib, and 24 (39.3%) patients died of lung cancer. The median progression-free survival (PFS) time and overall survival (OS) time for the whole cohort was 2.5 months (95% CI 2.1-3.0 months) and 19.0 months (95% CI 13.7-26.3 months), respectively. The 1-year and 2-year OS rate was 72.1% and 41.7%, respectively. Among 61 patients receiving salvage therapy, 8 (13.1%) , 30 (49.2%) and 23 (37.7%) cases had dramatic progression, gradual progression and local progression, respectively; when given timely and proper salvage treatment, there were no statistically differences in PFS and OS of the patients in the above three subgroups (all P>0.05). There were no statistically differences in PFS and OS between patients receiving local therapy (24 cases) and patients not receiving local therapy (37 cases) after the progression occurred (all P>0.05). Among 58 patients with resistance to osimertinib again after the salvage therapy, 6 patients with gradual or local progression had more than 6-mouth PFS after the salvage therapy. Conclusions:Dramatic, gradual and local progression are the main patterns in patients with acquired resistance to osimertinib. The therapeutic efficacy of salvage therapy still shows some disappointing results.

Effect analysis of rituximab-containing chemotherapy regimen in treatment of mantle cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the effect and prognostic factors of rituximab-containing chemotherapy regimen in treatment of patients with mantle cell lymphoma (MCL).Methods:The clinical data of 56 patients aged ≤65 years in the First Affiliated Hospital of Soochow University from June 2007 to November 2018 were retrospectively analyzed. Rituximab-containing chemotherapy regimen was used, and the effects of clinical features, treatment regimen and biological indexes on overall survival (OS) and progression-free survival (PFS) were observed.Results:The median age of 56 patients was 57 years old, including 43 males and 13 females. Among these cases, 24 patients received R-CHOP chemotherapy regimen; 29 patients received cytarabine-containing chemotherapy regimen, including R-hyper CVAD/R-MA regimen used in 15 patients and R-CHOP alternating with R-DAHP regimen used in 14 patients; and 3 patients received other treatment regimens. Among 56 patients, 19 patients received autologous hematopoietic stem cell transplantation (ASCT) consolidation therapy. The median OS time was 74 months, 2-year OS rate was 83.8%, 3-year OS rate was 70.9%, 2-year PFS rate was 72.0% and 3-year PFS rate was 49.7%. International prognostic index (IPI) high-risk and receiving ASCT or not during the treatment were independent influencing factors of OS and PFS in MCL patients. The overall response rate (ORR) in cytarabine-containing regimen group was higher compared with that in R-CHOP regimen group (93.1% vs. 83.3%), and there was no statistically significant difference ( χ2=0.465, P=0.495). In addition, there were no significant differences between two groups in both OS ( χ2=0.291, P=0.590) and PFS ( χ2=0.912, P=0.339). ASCT consolidation prolonged the median OS time (72 months vs.124 months, χ2=3.973, P=0.040) and the median PFS time (34 months vs. 90 months, χ2=3.984, P=0.046) in MCL patients achieving remission after induction therapy. Among patients in simplified MCL IPI (sMIPI) score middle-high risk group, compared with those not receiving ASCT, patients receiving ASCT therapy could obtain better OS and PFS (OS: χ2=5.037, P=0.025; PFS: χ2=6.787, P=0.009); among patients of sMIPI score low risk, there were no statistically significant differences in OS and PFS between the group receiving ASCT and not (all P > 0.05). Conclusions:Cytarabine-containing chemotherapy regimen has no predicatively satisfactory value in improving the prognosis and survival for MCL patients. For MCL patients who have achieved remission after reduction therapy and those in sMIPI score middle-high risk group, ASCT consolidation therapy can improve the prognosis and can be taken as the first-line consolidation treatment in young patients.

Clinical Effect of Tyrosine Kinase Inhibitors in the Treatment of P230 Chronic Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the curative efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of e19a2 transcript (P230) CML chronic phase (CML-CP) patients.@*METHODS@#The clinical data of 11 P230 CML-CP patients were collected from July 2008 to December 2019. Blood routine examination, bone marrow cytology, chromosome, and BCR-ABL qualitative and quantitative tests were performed at initial diagnosis. After TKIs treatment, BCR-ABL (P230)/ABL in peripheral blood was regularly detected to evaluate molecular response by real-time quantitative PCR.@*RESULTS@#There were 11 patients (7 males and 4 females) in chronic phase from 6 domestic hospitals enrolled, their median age was 46 years old (range from 19 to 56 years old). Among 4 patients treated with imatinib (400 mg, qd) firstly, 3 cases switched to nilotinib (400 mg, bid) and 1 case switched to dasatinib (100 mg, qd) due to failure to achieve best molecular response at the landmark time or mutation of ABL kinase. Then major molecular response (MMR) was obtained within 1 year. In addition, 5 patients were treated with nilotinib (300 mg, bid) and 2 patients with dasatinib (100 mg, qd) as first-line treatment, all of them got MMR within 6 months.@*CONCLUSION@#For intolerance or resistance to imatinib, second-generation TKIs can enable P230 CML patients to achieve deeper molecular response, and MMR in a short time.