Objective:To generate a chronic lymphocytic leukemia (CLL) mouse model with intact immune competence and short latency by adoptively transferring (AT) splenocytes from immunoglobulin heavy-chain enhancer-driven T-cell leukemia/lymphoma 1 (Eμ-TCL1) transgenic donors into wild-type (WT) recipients.Methods:Specific pathogen-free C57BL/6J WT mice and H11-Eμ-VH-TCL1-β-globin-PolyA knock-in mice were utilized. The H11-Eμ-VH-TCL1-β-globin-PolyA knock-in mice were generated using CRISPR/Cas9 technology, and their genotypes were confirmed by PCR. Experimental animals were randomly divided into an adoptive transfer (AT) group and a WT control group ( n=10 per group). Mice in the AT group received an intraperitoneal injection of splenocytes from H11-Eμ-VH-TCL1-β-globin-PolyA knock-in mice. The weight and general condition of the mice were monitored. Mice were euthanized by cervical dislocation at 9 weeks post-transplantation. The CLL model was validated using key indicators, including pathological manifestations, changes in peripheral blood leukocyte counts, and immunophenotype. Results:AT group mice exhibited significantly increased spleen weight [ (0.92±0.16) g vs (0.06±0.01) g in WT group, P<0.05] and liver weight [ (2.11±0.56) g vs (1.42±0.13) g in WT group, P=0.006], indicative of marked splenomegaly and hepatomegaly. The peripheral blood leukocyte count was significantly higher in the AT group [ (124.33±8.74) ×10 9/L] compared to the WT group [ (5.55±1.67) ×10 9/L] ( P=0.002). Similarly, the percentage of peripheral blood B lymphocytes was markedly increased in the AT group versus the WT group [ (69.13±6.88) % vs (39.78±5.94) %, P<0.05]. Histopathological examination revealed CLL manifestations in the spleen, lymph nodes, and bone marrow of AT group mice, with significant lymphocytic infiltration observed in the liver, lung, and kidney tissues. Flow cytometry analysis showed that the percentages of CD19 +CD5 + B lymphocytes among total lymphocytes in peripheral blood, bone marrow, and spleen of the AT group were (61.37±9.92) %, (28.61± 7.08) %, and (86.03±5.78) %, respectively. These were significantly higher (all P<0.05) than in the WT group [ (4.51±1.32) %, (5.58±1.46) %, and (14.33±3.20) %]. Furthermore, these CLL-like cells in the AT group were positive for CD43 and CD200, but showed lower expression of CD20, CD22, and CD79b compared to WT B cells. Conclusion:Adoptive transfer of splenocytes from Eμ-TCL1 transgenic mice successfully established a CLL mouse model with a relatively short latency period. This model represents a valuable preclinical tool for investigating CLL and related pathologies.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the differences of type 2 innate lymphocytes (ILC2) and interlukin 9 (IL-9) between chronic lymphocytic leukemia (CLL) patients and healthy controls, and to understand the effects of ILC2 on the function of regulatory T cells (Tregs), CD8⁺ T cells and CLL cells through IL-9. Methods Flow cytometry was used to detect the levels of ILC2 and Tregs in the peripheral blood of 45 newly diagnosed CLL patients and 24 healthy controls, and the expressions of granzyme B and perforin in CD8⁺ T cells in the peripheral blood of 28 patients and 15 healthy controls; ELISA was used to detect the level of IL-9 in the serum. ILC2 of patients and healthy controls was sorted by immunomagnetic beads and cultured separately, and the level of IL-9 in the culture supernatant was measured by ELISA. ILC2 sorted from CLL patients and healthy control-derived peripheral blood mononuclear cells(PBMCs) were co-cultured with the B cell leukemia MEC-1 cells, one group was supplemented with IL-9 antibody and the other group was not. After 72 hours of culture, the ratio of Tregs, programmed death 1 (PD-1), T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), cytotoxic T lymphocyte antigen 4 (CTLA-4) on Tregs, granzyme B and perforin in CD8⁺ T cells were measured by flow cytometry, IL-9 level of the culture supernatant was measured by ELISA, the apoptosis of MEC-1 cells was measured by Annexin V-PI. Results Compared with the healthy control group, the levels of ILC2, Tregs and IL-9 in the CLL group increased significantly. The levels of granzyme B and perforin in CD8⁺ T cells were positively correlated in the peripheral blood of CLL patients. Compared with the healthy control group, IL-9 levels in the supernatant of sorted ILC2 from CLL patients increased. In the anti-IL9 antibody group, the level of PD-1 and TIGIT on Tregs decreased, and the level of granzyme B in CD8⁺ T cells increased significantly. The level of IL-9 in the anti-IL9 antibody group decreased statistically. And MEC-1 cells showed increased early apoptotic rate in the anti-IL9 antibody group statistically. Conclusion In CLL, ILC2 affects CD8⁺ T cells and Tregs through IL-9, which weakens the anti-tumor effect of CD8⁺ T cells, enhances the immunosuppressive effect of Tregs, and plays a role in the occurrence and development of CLL disease.
Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/immunology* ; CD8-Positive T-Lymphocytes/immunology* ; T-Lymphocytes, Regulatory/immunology* ; Middle Aged ; Male ; Female ; Interleukin-9/blood* ; Aged ; Granzymes/metabolism* ; Perforin/metabolism* ; Immunity, Innate ; Adult ; Lymphocytes/immunology*

OBJECTIVES: We propose a segmented backprojection tensor degradation feature encoding (SBP-MAC) model for motion artifact correction in dental cone beam computed tomography (CBCT) to improve the quality of the reconstructed images. METHODS: The proposed motion artifact correction model consists of a generator and a degradation encoder. The segmented limited-angle reconstructed sub-images are stacked into the tensors and used as the model input. A degradation encoder is used to extract spatially varying motion information in the tensor, and the generator's skip connection features are adaptively modulated to guide the model for correcting artifacts caused by different motion waveforms. The artifact consistency loss function was designed to simplify the learning task of the generator. RESULTS: The proposed model could effectively remove motion artifacts and improve the quality of the reconstructed images. For simulated data, the proposed model increased the peak signal-to-noise ratio by 8.28%, increased the structural similarity index measurement by 2.29%, and decreased the root mean square error by 23.84%. For real clinical data, the proposed model achieved the highest expert score of 4.4221 (against a 5-point scale), which was significantly higher than those of all the other comparison methods. CONCLUSIONS The SBP-MAC model can effectively extract spatially varying motion information in the tensors and achieve adaptive artifact correction from the tensor domain to the image domain to improve the quality of reconstructed dental CBCT images.
Cone-Beam Computed Tomography/methods* ; Artifacts ; Humans ; Motion ; Image Processing, Computer-Assisted/methods* ; Signal-To-Noise Ratio ; Algorithms

Objective To analyze the distribution of serum food specific immunoglobulin(Ig)E and IgG antibodies in patients with adverse food reactions in Qingdao area.Methods The specific IgE test results of 4 199 patients with suspected food allergy and the specific IgG test results of 741 patients with food intoler-ance were collected from the Affiliated Hospital of Qingdao University from 2012 to 2022.A total of 4 199 pa-tients with suspected food allergy(2 308 males and 1 891 females)were enrolled in this study.According to the age,the patients were divided into infancy(＜1 year old)205 cases,early childhood(1-＜3 years old)1009 cases,childhood(3-＜14 years old)1 946 cases,adolescence(14-＜18 years old)99 cases,youth(18-＜40 years old)554 cases,middle age(40-＜65 years old)329 cases and old age(≥65 years old)57 cases.A to-tal of 741 patients with food intolerance(469 males and 272 females)were enrolled in this study.According to the age,the patients were divided into 81 cases in infancy(＜1 year old),298 cases in early childhood(1-＜3 years old)and 362 cases in childhood(3-＜14 years old).Enzyme-linked immunosorbent assay was used to detect the positive rates of IgE and IgG antibodies in serum of patients,and the positive rates of IgE and IgG antibodies in patients with different gender and age were compared.Results Egg white and cow's milk were the most sensitive foods in infants and young children.The positive rate of specific IgE antibody decreased gradually with the increase of age,and increased slightly in old age.The positive rate of specific IgE antibody in shrimp and crab increased first and then decreased with age,and it was higher in young and middle age.The tolerance of infants and children to meat and crustaceans was relatively strong,and the positive rate of food specific IgG to fish was higher than that to meat(P＜0.05).The positive rate of tomato-specific IgG was the highest in infancy and gradually decreased with age(P＜0.05).Conclusion With the increase of age and the change of dietary structure,the positive rate of food specific IgG antibody may change significantly.Clinicians should accurately grasp the epidemiological characteristics of food adverse reactions in this area,and adjust and optimize the diet structure of patients to make correct diagnosis and treatment.

Opium is obtained by air-drying the milky latex extracted from the unripe capsules of the opium poppy(Papaver somniferum).This latex is rich in benzylisoquinoline alkaloids(BIA),with major active compounds in-cluding morphine,codeine,thebaine,papaverine,and noscapine.Compound licorice oral solution and compound licorice tablets are derivative drugs containing opium.Initially classified as over-the-counter(OTC)medications,both formulations were later reclassified as prescription drugs by the National Medical Products Administration(NMPA),restricting their purchase without proper authorization.Although the national pharmacopeia standards specify the morphine content in the opium raw materials used for compound licorice oral solution and tablets,they lack mandatory requirements for the detection and quantification of the other four major alkaloids.Given the unique nature of opium raw materials and the stringent regulatory requirements for such drugs,it is imperative to enhance and refine simultaneous detection and control methods for all alkaloid components in these products.Furthermore,the establishment of scientific and reasonable detection and control standards for preservatives in compound licorice formulations is crucial to improving overall product quality management and ensuring drug safety and efficacy.This study analyzes and discusses the quality standards,detection methods,and research progress for opium and com-pound licorice preparations,aiming to explore the potential for technological innovation and ensure the safe use of these medications.

Objective:To investigate effect of rapamycin on proliferation of human chronic lymphoblastic leukemia tumor cell MEC-1 in vitro.Methods:Human γδT cells were cultured and expanded in vitro.Human γδT cells percentage was detected by flow cytometry on the 10th day.γδT cells were treated with different concentrations of rapamycin(0,50,100 and 200 nmol/L).After 48 h of intervention,IL-17,IL-12,IFN-γ and TNF-α contents secreted by γδT cells were determined by ELISA,and AKT/mTOR protein expression was detected by Western blot.Supernatant of γδT was collected and co-cultured with MEC-1 indirectly.Co-cultured experi-mental was divided into DMSO group,rapamycin group,γδT group,rapamycin treated γδT group and control group.Survival rate of MEC-1 cells in each group was determined by CCK-8 after 48 h of culture.Results:IL-12,IFN-γ and TNF-α levels secreted by γδT cells were the highest when rapamycin was 100 nmol/L,which was significantly higher than other groups(P<0.05).When rapamycin was 50 nmol/L,IL-17 secretion level of γδT cells was the highest,and IL-17 level secreted by γδT cells gradually decreased with increase of rapamycin concentration.Survival rates of MEC-1 cells in supernatant of DMSO group,rapamycin group,rapamycin treated γδT cell group and γδT cell group were(93.48±2.52)%,(71.44±4.31)%,(83.93±1.54)%and(57.97±2.47)%,whose differences were statistically significant compared with control group(P<0.05).Compared with control group,mTOR protein level of γδT cells was decreased in all rapamycin treated groups.Protein expressions of upstream AKT,pAKT and downstream specific transcription factor 4EBP-1 were decreased with increase of rapamycin concentration(P<0.05).Conclusion:There is a dose-effect relationship between rapamycin concentration and IL-17,IL-12,IFN-γ,TNF-α secretions by γδT cells.Rapamycin and γδT cells can inhibit pro-liferation of MEC-1 cells,and 100 nmol/L rapamycin can enhance inhibitory effect of γδT cells on proliferation of MEC-1 cells.Rapa-mycin can weaken AKT pathway on γδT cells,and rapamycin combined with γδT cells plays a positive role in anti-tumor application of leukemia.

Opium is obtained by air-drying the milky latex extracted from the unripe capsules of the opium poppy(Papaver somniferum).This latex is rich in benzylisoquinoline alkaloids(BIA),with major active compounds in-cluding morphine,codeine,thebaine,papaverine,and noscapine.Compound licorice oral solution and compound licorice tablets are derivative drugs containing opium.Initially classified as over-the-counter(OTC)medications,both formulations were later reclassified as prescription drugs by the National Medical Products Administration(NMPA),restricting their purchase without proper authorization.Although the national pharmacopeia standards specify the morphine content in the opium raw materials used for compound licorice oral solution and tablets,they lack mandatory requirements for the detection and quantification of the other four major alkaloids.Given the unique nature of opium raw materials and the stringent regulatory requirements for such drugs,it is imperative to enhance and refine simultaneous detection and control methods for all alkaloid components in these products.Furthermore,the establishment of scientific and reasonable detection and control standards for preservatives in compound licorice formulations is crucial to improving overall product quality management and ensuring drug safety and efficacy.This study analyzes and discusses the quality standards,detection methods,and research progress for opium and com-pound licorice preparations,aiming to explore the potential for technological innovation and ensure the safe use of these medications.

Objective:To investigate effect of rapamycin on proliferation of human chronic lymphoblastic leukemia tumor cell MEC-1 in vitro.Methods:Human γδT cells were cultured and expanded in vitro.Human γδT cells percentage was detected by flow cytometry on the 10th day.γδT cells were treated with different concentrations of rapamycin(0,50,100 and 200 nmol/L).After 48 h of intervention,IL-17,IL-12,IFN-γ and TNF-α contents secreted by γδT cells were determined by ELISA,and AKT/mTOR protein expression was detected by Western blot.Supernatant of γδT was collected and co-cultured with MEC-1 indirectly.Co-cultured experi-mental was divided into DMSO group,rapamycin group,γδT group,rapamycin treated γδT group and control group.Survival rate of MEC-1 cells in each group was determined by CCK-8 after 48 h of culture.Results:IL-12,IFN-γ and TNF-α levels secreted by γδT cells were the highest when rapamycin was 100 nmol/L,which was significantly higher than other groups(P<0.05).When rapamycin was 50 nmol/L,IL-17 secretion level of γδT cells was the highest,and IL-17 level secreted by γδT cells gradually decreased with increase of rapamycin concentration.Survival rates of MEC-1 cells in supernatant of DMSO group,rapamycin group,rapamycin treated γδT cell group and γδT cell group were(93.48±2.52)%,(71.44±4.31)%,(83.93±1.54)%and(57.97±2.47)%,whose differences were statistically significant compared with control group(P<0.05).Compared with control group,mTOR protein level of γδT cells was decreased in all rapamycin treated groups.Protein expressions of upstream AKT,pAKT and downstream specific transcription factor 4EBP-1 were decreased with increase of rapamycin concentration(P<0.05).Conclusion:There is a dose-effect relationship between rapamycin concentration and IL-17,IL-12,IFN-γ,TNF-α secretions by γδT cells.Rapamycin and γδT cells can inhibit pro-liferation of MEC-1 cells,and 100 nmol/L rapamycin can enhance inhibitory effect of γδT cells on proliferation of MEC-1 cells.Rapa-mycin can weaken AKT pathway on γδT cells,and rapamycin combined with γδT cells plays a positive role in anti-tumor application of leukemia.

Objective:To generate a chronic lymphocytic leukemia (CLL) mouse model with intact immune competence and short latency by adoptively transferring (AT) splenocytes from immunoglobulin heavy-chain enhancer-driven T-cell leukemia/lymphoma 1 (Eμ-TCL1) transgenic donors into wild-type (WT) recipients.Methods:Specific pathogen-free C57BL/6J WT mice and H11-Eμ-VH-TCL1-β-globin-PolyA knock-in mice were utilized. The H11-Eμ-VH-TCL1-β-globin-PolyA knock-in mice were generated using CRISPR/Cas9 technology, and their genotypes were confirmed by PCR. Experimental animals were randomly divided into an adoptive transfer (AT) group and a WT control group ( n=10 per group). Mice in the AT group received an intraperitoneal injection of splenocytes from H11-Eμ-VH-TCL1-β-globin-PolyA knock-in mice. The weight and general condition of the mice were monitored. Mice were euthanized by cervical dislocation at 9 weeks post-transplantation. The CLL model was validated using key indicators, including pathological manifestations, changes in peripheral blood leukocyte counts, and immunophenotype. Results:AT group mice exhibited significantly increased spleen weight [ (0.92±0.16) g vs (0.06±0.01) g in WT group, P<0.05] and liver weight [ (2.11±0.56) g vs (1.42±0.13) g in WT group, P=0.006], indicative of marked splenomegaly and hepatomegaly. The peripheral blood leukocyte count was significantly higher in the AT group [ (124.33±8.74) ×10 9/L] compared to the WT group [ (5.55±1.67) ×10 9/L] ( P=0.002). Similarly, the percentage of peripheral blood B lymphocytes was markedly increased in the AT group versus the WT group [ (69.13±6.88) % vs (39.78±5.94) %, P<0.05]. Histopathological examination revealed CLL manifestations in the spleen, lymph nodes, and bone marrow of AT group mice, with significant lymphocytic infiltration observed in the liver, lung, and kidney tissues. Flow cytometry analysis showed that the percentages of CD19 +CD5 + B lymphocytes among total lymphocytes in peripheral blood, bone marrow, and spleen of the AT group were (61.37±9.92) %, (28.61± 7.08) %, and (86.03±5.78) %, respectively. These were significantly higher (all P<0.05) than in the WT group [ (4.51±1.32) %, (5.58±1.46) %, and (14.33±3.20) %]. Furthermore, these CLL-like cells in the AT group were positive for CD43 and CD200, but showed lower expression of CD20, CD22, and CD79b compared to WT B cells. Conclusion:Adoptive transfer of splenocytes from Eμ-TCL1 transgenic mice successfully established a CLL mouse model with a relatively short latency period. This model represents a valuable preclinical tool for investigating CLL and related pathologies.