Objective:To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenstr?m macroglobulinemia (WM) .Methods:Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety.Results:A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion:Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

Purpose/Significance To construct a Chinese medical knowledge Q&A corpus dataset as a standardized evaluation bench-mark for large language models(LLMs)in the medical domain,so as to improve the accuracy and efficiency of LLMs in handling Chinese medical questions.Method/Process Chinese medical paper knowledge,medical terminology explanations and supplementary questions are acquired from the Chinese medical licensing examination,and open-source Chinese medical Q&A datasets are encompassed in the developed Q&A datasets.Result/Conclusion The Chinese medical knowledge Q&A corpus datasets enrich the sources of existing datasets and promote the objective and comprehensive quantitative evaluation of large models in the medical field.In the near future,additional data such as electronic medical records and those from online health communities will be used to strengthen the support of artificial intelli-gence for the Healthy China strategy.

Inorganic polyphosphate(polyP)is wide spread in biology and exhibits striking procoagulant ef-fects in vivo.Long-chain polyphosphate(such as those present in infectious microorganisms)is a potent,natural patho-physiologic activator of the contact pathway of blood clotting and promotes thrombosis and inflammation,which suggest that antagonizing polyP function in vivo may be an attractive approach for identifying novel antithrombotic agents,perhaps with reduced bleeding side effects compared with conventional anticoagulant drugs.Short-chain polyphosphate(secreted from activated human platelets)remarkably accelerates factor V activation,absolutely abrogates the anticoagulant function of tissue factor pathway inhibitor,increase fibrin clot structure,and accelerates factor XI activation by thrombin.So polyP may be used as hemostatic agent.In this paper,the procoagulant role of polyP and the mechanism underlying polyP modu-lates blood clotting and the strategy of screening polyP inhibitors are described in detail.

Humans ; Alzheimer Disease ; Cross-Sectional Studies ; Creatine Kinase ; Brain/metabolism*

Objective:To investigate the clinical and pathological features, treatment, and prognosis of gray zone lymphoma (GZL) .Methods:From July 2, 2013, to February 10, 2021, the clinical and pathological features, treatment, and outcomes of five patients with GZL at the Blood Diseases Hospital, Chinese Academy of Medical Sciences were studied retrospectively.Results:There were one male and 4 females, with a median age of 28 (16-51) years at diagnosis. Four patients had mediastinal (thymic) involvement, two of which had superior vena cava obstruction syndrome, and 3 patients had extra-nodal involvement. There was one case with a limited Ann Arbor stage and 4 cases with a progressive stage. Three patients had cHL-like pathomorphology with scattered Hodgkin-like cells, strongly positive for CD20, positive for CD30, and CD15 was negative; the other two patients had both cHL and DLBCL morphology, with some areas resembling Hodgkin cells and some areas resembling immunoblasts, strongly positive for CD30, and CD15 but negative CD20. Two patients were treated with cHL-like regimens for induction and achieved only partial remission; after salvage therapy with enhanced DLBCL-like regimens, all achieved complete remission (CR) . Three patients were treated with enhanced DLBCL-like immunochemotherapy regimens for induction, and two patients were effective, one of whom achieved CR. Four patients who did not achieve CR were given second or third-line salvage therapy, and all of them recovered. One patient lost parity, one died of disease progression at 35.9 months after diagnosis, and the remaining three maintained sustained remission.Conclusions:GZL is uncommon, usually affects younger patients, is mediastinal and is diagnosed using path morphology and immunophenotype. Patients with newly diagnosed GZL appear to be more sensitive to DLBCL-like immunochemotherapy regimens; relapsed or refractory patients were tended with non-cross-resistant combination chemotherapy or with new drugs.

Objective:This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) .Methods:A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model.Results:The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions:PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Objective:To understand the research ability, cognition, and training needs of clinical medical staff in a grade A tertiary hospital in Xinjiang and to analyze the influencing factors.Methods:A convenience sampling method was applied to survey the clinical medical staff of our hospital with a questionnaire including general information, a self-assessment scale of research ability, and a survey of research cognition and training needs. A total of 618 questionnaires were collected with 609 valid returned responses, resulting in an effective return rate of 98.54%. Univariate and multiple linear regression analysis were applied to analyze the influencing factors of the total score of clinical medical staff's research ability.Results:The total score of research ability of 609 clinical medical personnel was 60.73±13.59. The results of multiple linear regression showed that participation in scientific research conferences, enthusiasm for scientific research activities, and the need for scientific research training all had positive effects on the self-assessment of scientific research ability, which together explained 52% of the total variance (adjusted R2=0.520, P<0.001). The top three " very important" options for medical staff research training were data analysis, research design, and research topic selection. Conclusions:Medical staff research skills need to be improved and there is a strong need for research training. Managers should refine scientific research management initiatives and provide hierarchical and targeted scientific research training to improve the overall medical staff's scientific research literacy and research ability, thereby promoting the progress of medical care in hospitals.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Background:At present,domestic guidelines and consensus recommend the use of nutritional risk screening 2002(NRS 2002)and patient-generated subjective global assessment(PG-SGA)for nutritional risk screening and assessment of patients with gastrointestinal cancer during the perioperative period.However,PG-SGA has higher professional requirements,complex content and time-consuming.In the current busy situation of medical staff,NRS 2002 is more used for screening alone.Aims:To explore the consistency of NRS 2002 and PG-SGA in the assessment of nutritional status and clinical outcomes in patients with gastrointestinal malignancies,and to explore the accuracy of screening using NRS 2002 alone,so as to provide guidance for the establishment of clinical nutritional screening and assessment standards.Methods:A retrospective analysis was conducted on 157 patients with gastrointestinal malignancies who underwent radical operation in the Department of Gastrointestinal Surgery of Xiangya Hospital,Central South University from January 2020 to October 2022.Nutritional screening and evaluation were performed by NRS 2002 and PG-SGA scales and demographic data and nutrition-related laboratory indicators were collected to observe short-term postoperative clinical outcomes.Results:Patients with nutritional risk or malnutrition had lower body mass index(BMI),lymphocytes and prealbumin(P<0.05).The correlation and consistency of NRS 2002 and PG-SGA scales were good(r=0.728,κ=0.46)and the areas under the curve(AUC)for predicting postoperative complications were 0.691 and 0.702,respectively.In addition,nutritional risk and postoperative complications were significantly increased in patients with malnutrition(P<0.05).Conclusions:Therefore,gastrointestinal surgeons can only use NRS2002 to perform nutritional screening of patients and make corresponding nutritional treatment according to the screening results in the case of busy clinical work.