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.

Objective:To investigate serum vitamin A and vitamin D status in children aged 2-<7 years in 20 cities in China.Methods:A cross-sectional study was conducted. A total of 2 924 healthy children aged 2-<7 years were recruited from September 2018 to September 2019 from 20 cities in China, categorized by age groups of 2-<3 years, 3-<5 years, and 5-<7 years. The demographic and economic characteristics and health-related information of the enrolled children were investigated. Body weight and height were measured by professional staff members. The serum vitamin A and vitamin D levels were detected by high-performance liquid chromatography-tandem mass spectrometry. Chi-square test and Logistic regression were applied to analyze the association between vitamin A and vitamin D deficiency and insufficiency as well as their underlying impact factors.Results:The age of the 2 924 enrolled children was 4.33 (3.42, 5.17) years. There were 1 726 males (59.03%) and 1 198 females (40.97%). The prevalences of vitamin A and vitamin D deficiency in enrolled children were 2.19% (64/2 924) and 3.52% (103/2 924), respectively, and the insufficiency rates were 29.27% (856/2 924) and 22.20% (649/2 924), respectively. Children with both vitamin A and vitamin D deficiencies or insufficiencies were found in 10.50% (307/2 924) of cases. Both vitamin A ( χ2=7.91 and 8.06, both P=0.005) and vitamin D ( χ2=71.35 and 115.10, both P<0.001) insufficiency rates were higher in children aged 3-<5 and 5-<7 years than those in children aged 2-<3 years. Vitamin A and vitamin D supplementation in the last 3 months was a protective factor for vitamin A and D deficiency and insufficiency, respectively ( OR=0.68 and 0.22, 95% CI 0.49-0.95 and 0.13-0.40, both P<0.05). The rates of vitamin A and D insufficiency was higher in children with annual household incomes <60 000 RMB than in those with annual household incomes ≥60 000 RMB ( χ2=34.11 and 10.43, both P<0.01). Northwest and Southwest had the highest rates of vitamin A and vitamin D insufficiency in children aged 2-<7 yeas, respectively ( χ2=93.22 and 202.54, both P<0.001). Conclusions:Among 20 cities in China, children aged 2-<7 years experience high rates of vitamin A and vitamin D insufficiency, which are affected by age, family economic level, vitamin A and vitamin D supplementation, and regional economic level. The current results suggest that high level of attention should be paid to vitamin A and vitamin D nutritional status of preschool children.

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: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.

Objective: To establish a method for isolation and culture of primary endothelial cells from non-human primate coronary arteries, and to provide a cell model for the study of human coronary endothelial cells. Methods: The coronary arteries of macaca mulattas were separated aseptically. The primary endothelial cells were separatedviatissue adhesion after collagenase digestion. CD31 positive cells were detected and sorted by flow cytometry to determine the purity of endothelial cells. After stimulation with prostaglandin E2(PGE2), the cellular viability and proliferation ability of primary coronary endothelial cells from macaca mulattas were evaluated by high-content cell imaging and CCK-8 assay, and the migration ability and tube function of primary coronary endothelial cells from macaca mulattas were measured by Transwell method and Matrigel glue method, respectively. Results: The confluence percentage of primary coronary artery cells of macaca mulattas was about 80% after 10-14 daysin vitroculture, and the cellular morphology was irregular polygons and paver shape. The purity of endothelial cells was about 31.7% by flow cytometry. After sorting, the purity of endothelial cells was confirmed by flow cytometry, which was more than 95%. PGE2could significantly up-regulate the proliferation, migration and tube formation abilities of primary coronary endothelial cells of macaca mulattas. Conclusion This study successfully established the isolation and culture method of primary coronary endothelial cells from macaca mulattas, and proved that it could be used as anin vitrocell model to simulate human coronary endothelial cells through functional studies.

Objective: To compare the efficiency of different methods for extracting rhesus monkey lung fibroblasts and their effects on functions, so as to provide a method for obtaining primary lung fibroblasts that are closer to human fibroblasts. Methods: Two extraction methods for rhesus monkey lung fibroblasts were used, direct tissue block adhesion method and collagenase combined digestion with tissue block adhesion method. The cell morphology was observed with the inverted microscope, the purity of isolated rhesus monkey lung fibroblasts was identified by immunofluorescence, cell viability was detected by CCK-8, the expression of α-SMA was detected by flow cytometry and the effect of long-term in vitro culture on cell apoptosis was detected by apoptosis kit. Western blot was used to detect the expression of α-SMA protein. Results: The combined digestion with collagenase and tissue block adhesion method could see small and bright cells crawling out in 24 hours, and cells could be seen crawling out in a large area after 48 hours. The cells were in a long spindle shape, after 4 days to 5 days, a single layer of cells could be formed. Identified by immunofluorescence, all cells expressed α-SMA. Tissue adhesion method showed small and bright cells crawling out after 72 hours. After 4 days to 5 days, the cells crawled out in a small area and showed a long spindle shape. After a week, the cells crawled out in a large area and formed a single layer of cells and the cells are all expressed α-SMA by immunofluorescence. The experimental results showed that the cell viability of the cells crawled out by the collagenase digestion method was significantly higher than that of the tissue adhesion method. After TGF-β1 stimulates the cells, the cells extracted by collagenase digestion method proliferated faster and expressed α-SMA more obviously. Conclusion Both methods can isolate rhesus monkey lung fibroblasts in vitro, but the collagenase digestion method extracts cells in a shorter time and in better condition. The expression of related proteins is more stable after stimulation by stimulants, which is an effective method to obtain rhesus monkey lung fibroblasts, and it is also an effective method to obtain primary lung fibroblasts that are closer to human.

Abstract: To observe the histomorphological features of the hypothalamic-pituitary-adrenal axis in macaques to provide a reference for simulating the physiological functions and pathological responses of the human hypothalamic-pituitary-adrenal axis. Methods: After euthanasia of macaques, hypothalamus, pituitary and adrenal tissues were removed intact, fixed by PFA, and paraffin sections and frozen sections were prepared; the basic structure and cellular distribution were observed by HE staining; the secreted hormones and receptors were detected by immunohistochemistry; the effects of staining in frozen and paraffin sections were compared, and the cellular composition of some hypothalamus tissues was identified. Results: The hypothalamic region was hollow and funnel-shaped, the pituitary gland resembles a pea, and the right and left adrenal glands were located between the liver and kidneys; HE staining showed that the hypothalamic region was mainly composed of neurons and microglia, the pituitary gland was divided into neuro-pituitary and adeno-pituitary, and the adrenal gland was composed of cortex and medulla; immunohistochemical results showed that the hypothalamus secretes CRH and expresses GR, the pituitary gland secretes ACTH and expresses CRHR1 and GR, and the adrenal gland expresses ACTHR; immunofluorescence of frozen sections better showed that the hypothalamus contains neurons and microglia. Conclusion In this study, sections of hypothalamus, pituitary and adrenal gland tissues from macaques were successfully produced, and the relevant anatomical and morphological features were observed and examined, which provided a reference method for simulating the physiological and pathological responses of the human hypothalamic-pituitary-adrenal axis.

Objective:To study the clinical, histopathological, and genetic features of large B-cell lymphoma (LBCL) with IRF4 rearrangement.Methods:Six patients presenting at our center between December 2017 and October 2021 were evaluated by pathological examination, fluorescence in situ hybridization, and next-generation sequencing. The relevant literature was reviewed.Results:①The study sample included three males and three females with a median age of 33 years. Three tumors were in the tonsils, two in the lymphoid nodes, and one in the dorsal lump. All patients were treated using the RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, prednisone) regimen. All of them were alive at the time of follow-up in November 2021. ②Microscopic examination showed an entirely follicular pattern in one case and an entirely diffused pattern in 5 cases. The tumor cells were medium to large, and most of the lesions were dilatative with brisk mitotic activity ( n=five cases) and no starry sky pattern ( n=6 cases) . ③Four cases exhibited a GCB phenotype, and the other two exhibited a non-GCB phenotype. All of the cases were positive for CD20, PAX-5, MUM, and BCL6, and negative for CD5. Moreover, CD10, BCL2, and c-MYC were positive in 4, 3, and 2 cases, respectively.④IRF4 gene rearrangement was identified in all cases, BCL6 gene rearrangement was detected in 5 cases, and 2 cases were positive. BCL2 and MYC gene rearrangement were performed in 5 cases, all negative. ⑤Three paraffin tissue samples were used for next-generation sequencing, and lymphoma-related gene mutations such as IRF4, TP53, IGLL5, and MYD88 were detected in 3 cases. Conclusions:LBCL with IRF4 rearrangement is a rare entity with unique clinical, pathological, and genetic characteristics. This entity’s pathogenesis, treatment options, and long-term prognosis still need to be explored further.

Adaptation, Psychological ; Adolescent ; COVID-19 ; Child ; China ; Cross-Sectional Studies ; Female ; Humans ; Male ; SARS-CoV-2