Mutation characteristics of angioimmunoblastic T-cell lymphoma: an analysis of 75 cases / 中华病理学杂志

Objective: To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL). Methods: Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed. Results: 492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations (P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive (P<0.05). Conclusions: The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats

Abstract Objectives: This study aimed to explore the effects of bone marrow-derived Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) treating diabetic foot ulcers in rats. Methods: Models of T2DM rats were induced by a high-fat diet and intraperitoneal injection of STZ in SD rats. Models of Diabetic Foot Ulcers (DFUs) were made by operation on hind limbs in diabetic rats. Rats were divided into four groups (n = 6 for each group), i.e., Normal Control group (NC), Diabetes Control group (DM-C), MSC-CM group and Mesenchymal Stem Cells group (MSCs). MSC-CM group was treated with an injection of conditioned medium derived from preconditioned rats' bone marrow MSCs around ulcers. MSCs group were treated with an injection of rats' bone marrow MSCs. The other two groups were treated with an injection of PBS. After the treatment, wound closure, re-epithelialization (thickness of the stratum granulosums of the skin, by H&E staining), cell proliferation (Ki67, by IHC), angiogenesis (CD31, by IFC), autophagy (LC3B, by IFC and WB; autoly-sosome, by EM) and pyroptosis (IL-1β, NLRP3, Caspase-1, GSDMD and GSDMD-N, by WB) in ulcers were evaluated. Results: After the treatment wound area rate, IL-1β by ELISA, and IL-1β, Caspase-1, GSDMD and GSDMD-N by WB of MSC-CM group were less than those of DM group. The thickness of the stratum granulosums of the skin, proliferation index of Ki67, mean optic density of CD31 and LC3B by IFC, and LC3B by WB of MSC-CM group were more than those of DM group. The present analysis demonstrated that the injection of MSC-CM into rats with DFUs enhanced the wound-healing process by accelerating wound closure, promoting cell proliferation and angiogenesis, enhancing cell autophagy, and reducing cell pyroptosis in ulcers. Conclusions: Studies conducted indicate that MSC-CM administration could be a novel cell-free therapeutic approach to treat DFUs accelerating the wound healing process and avoiding the risk of living cells therapy.

Effects of eccentric training on balance in athletes / Efeitos do treinamento excêntrico sobre o equilíbrio dos atletas / Efectos del entrenamiento excéntrico en el equilibrio de los deportistas

ABSTRACT Introduction: Basketball is a sport of skillful competition. It demands characteristics from its athletes such as agility, balance, and a confrontational spirit. This requires a great improvement in strength, speed, endurance, and physical conditioning. Objective: Study the effects of eccentric muscle strength training in the lower limbs on balance ability in basketball players. Methods: Current scientific literature was used to design an experimental method with statistical data analysis. The research subjects were divided into 4 groups for a 6-week eccentric training intervention, and the effect of eccentric exercise on flexibility and balance in basketball players was investigated. Results: Compared to the pre-test and after the training intervention in the test group, there was a very significant difference (P<0.01); only the intervention group showed a significant difference (P<0.05). Conclusion: Eccentric training at the end of basketball training has a positive effect on improving flexibility and balance in basketball players. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O basquetebol é um esporte de competição habilidosa. Exige características dos seus atletas como agilidade, equilíbrio e espírito de confronto. Para isso, é necessário um grande aperfeiçoamento de força, velocidade, resistência e condicionamento físico. Objetivo: Estudar os efeitos do treinamento de força muscular excêntrico nos membros inferiores sobre a capacidade de equilíbrio nos jogadores de basquetebol. Métodos: Utilizou-se a literatura científica atual para elaborar um método experimental, com análise estatística de dados. Os sujeitos da pesquisa foram divididos em 4 grupos para intervenção de treinamento excêntrico de 6 semanas, foi investigado o efeito do exercício excêntrico sobre a flexibilidade e equilíbrio nos jogadores de basquete. Resultados: Em comparação com o pré-teste e após a intervenção de treinamento no grupo de teste, houve uma diferença muito significativa (P<0,01), somente o grupo de intervenção apresentou uma diferença significativa (P<0,05). Conclusão: O treinamento excêntrico ao final do treinamento de basquete tem um efeito positivo na melhoria da flexibilidade e equilíbrio nos jogadores de basquete. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El baloncesto es un deporte de competición de habilidad. Exige a sus atletas características como la agilidad, el equilibrio y el espíritu de confrontación. Para ello, es necesaria una gran mejora de la fuerza, la velocidad, la resistencia y el acondicionamiento físico. Objetivo: Estudiar los efectos del entrenamiento de la fuerza muscular excéntrica en los miembros inferiores sobre la capacidad de equilibrio en jugadores de baloncesto. Métodos: Se utilizó la literatura científica actual para diseñar un método experimental, con análisis de datos estadísticos. Los sujetos de la investigación se dividieron en 4 grupos para una intervención de entrenamiento excéntrico de 6 semanas, y se investigó el efecto del ejercicio excéntrico en la flexibilidad y el equilibrio de los jugadores de baloncesto. Resultados: En comparación con la pre-prueba y después de la intervención de entrenamiento en el grupo de prueba hubo una diferencia muy significativa (P<0,01), sólo el grupo de intervención mostró una diferencia significativa (P<0,05). Conclusión: El entrenamiento excéntrico al final del entrenamiento de baloncesto tiene un efecto positivo en la mejora de la flexibilidad y el equilibrio de los jugadores de baloncesto. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Treatment advice of small molecule antiviral drugs for elderly COVID-19 / 中国药理学通报

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Effect of cangfudaotan decoction on TLR4/NF-κB p65 signaling pathway in obese PCOS-IR rats / 中国药理学通报

Aim To explore the regulatory effect of Cangfudaotan Decoction on the ovarian Toll receptor 4 (TLR4)/nuclear transcription factor kBp65 (NF-κB p65) signaling pathway in obese PCOS-IR rats. Methods Forty-eight female rats were randomly divided into normal group (n = 8) and model group (n = 40). The obese PCOS-IR rats were established by letrozole (1 mg · kg

Effect of Sea Cucumber Enzymolysis Fermentation Liquid on immunosuppressed mice based on metabonomics / 中国药理学通报

Aim To prepare the sea cucumber enzy¬molysis fermentation liquid (SCEFL) by enzymatic hydrolysis of protease and fermentation of probiotics and to investigate the effect of SCEFL on the immunosup-pression induced by cyclophosphamide in mice and to explore its mechanism by metabomic method. Methods The immunosuppressive model was induced by in-traperitoneal injection of cyclophosphamide. C57BL/6J mice were randomly divided into normal group, model group, Levamisole group, SCEFL groups (at low, medium and high doses). The pathological changes of spleen were observed by HE staining. The proportion of CD4

Mechanism of isovitexin in alcoholic fatty liver based on metabolomics combined with molecular docking analysis / 中国药理学通报

Aim To explore the effects of isovitexin (IVT) on alcoholic fatty liver disease (AFLD) and its mechanism based on metabolomics and in vivo methods and combined molecular docking. Methods 8-week-old male C57BL/6J mice were randomly divided into control, model and IVT groups, with 6 mice in each group. The control group was fed with alcoholic liquid feed control feed, the model group and IVT group were fed with alcoholic liquid feed model feed, and the IVT group was fed daily gastric IVT (100 mg • kg

corilagin protects non-alcoholic fatty liver disease in mice induced by high fat and high sugar diet via regulating AMPK-autophagy signaling / 中国药理学通报

Aim To explore the effects of corilagin on non-alcoholic fatty liver disease induced by high-fat and high-sugar diet in mice via regulating AMPK-autophagy signaling. Methods Healthy 8-week-old male C57BL/6J mice were randomly divided into control group, model group and corilagin group. The mice of model group and corilagin group were fed with a high-fat and high-sugar diet for four weeks at the age of eight weeks. The corilagin group mice were also intraperitoneally injected with corilagin (20 mg • k g

Peptide P3 ameliorates foam cell formation in RAW264.7 cells and its molecular mechanisms / 中国药理学通报

Aim To examine the effect of peptide P3 on lipid accumulation in RAW264.7 cells and the underlying molecular mechanism. Methods MTT method was used to screen the concentration of peptide P3 and oxidized low density lipoprotein(ox-LDL),and RAW.264.7 cells were induced to form foam cells by ox-LDL with 80 mg·L

Effects of AR on proliferation and lipid synthesis of myocardial fibroblasts in high glucose environment / 中国药理学通报

Aim To explore the effect of androgen receptor AR on the proliferation and lipid synthesis of cardiac fibroblasts under high-glucose conditions and the possible molecular mechanism.Methods The hearts of neonatal rats were dissected for primary culture of cardiac fibroblasts. Then the growth status of CFs was observed under the inverted microscope, and the identification of CFs was performed by immunofluorescence staining using anti-vimentin. After cell adherence, the cells were divided into blank control group, high glucose model group, negative control group, and overexpressed AR group. The glucose concentration was 33.0 mmol·L-1 except that the blank control group was 5.5 mmol·L-1. After 24 hours of CFs culture, Western blot and RT-qPCR were used to detect the expression of AR, FASN, PCNA, cyclin D1, α-SMA, and collagen . Oil red O and CCK-8 were used to detect the changes in lipid synthesis and cell proliferation ability, respectively.Results Compared with the blank control group, the lipid synthesis and proliferation of CFs in the high glucose model group were enhanced. Western blot and RT-qPCR results showed that the expression of AR decreased, while the expression of fat lipid synthase(FASN), proliferation marker PCNA, cyclin D1 and fibrosis marker α-SMA and collagen increased. After AR overexpressed plasmid was transfected into the CFs treated by high glucose, AR overexpression markedly decreased the expression of FASN, PCNA, cyclin D1, α-SMA and collagen compared with the empty plasmid‐transfected group. Meanwhile, oil red O staining and CCK-8 results showed that the lipid synthesis and proliferation ability of the overexpressed AR group decreased compared with the empty vector group, respectively. Conclusions High glucose promotes the proliferation and lipid synthesis of cardiac fibroblasts. Besides, the mechanism may be related to the regulation of lipid synthesis regulated by AR.

Clinical analysis of 10 cases of multi-center tumor necrosis factor receptor-associated periodic syndrome / 中华儿科杂志

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.

Diagnosis status and genetic characteristics analysis of Fanconi anemia in China / 中华儿科杂志

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.

Wedelolactone alleviates hyperoxia-induced acute lung injury by regulating ferroptosis / 中华危重病急救医学

OBJECTIVE@#To study whether wedelolactone can reduce hyperoxia-induced acute lung injury (HALI) by regulating ferroptosis, and provide a basic theoretical basis for the drug treatment of HALI.@*METHODS@#A total of 24 C57BL/6J mice were randomly divided into normal oxygen control group, HALI model group and wedelolactone pretreatment group, with 8 mice in each group. Mice in wedelolactone pretreatment group were treated with wedelolactone 50 mg/kg intraperitoneally for 6 hours, while the other two groups were not given with wedelolactone. After that, the HALI model was established by maintaining the content of carbon dioxide < 0.5% and oxygen > 90% in the molding chamber for 48 hours, and the normal oxygen control group was placed in indoor air. After modeling, the mice were sacrificed and lung tissues were collected. The lung histopathological changes were observed under light microscope and pathological scores were performed to calculate the ratio of lung wet/dry mass (W/D). The levels of tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-1β), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in lung tissues of mice in each group were determined. The protein expression of glutathione peroxidase 4 (GPX4) in lung tissue was detected by Western blotting.@*RESULTS@#Under light microscope, the alveolar structure of HALI model group was destroyed, and a large number of neutrophils infiltrated the alveolar and interstitial lung, and the interstitial lung was thickened. The pathological score of lung injury (score: 0.75±0.02 vs. 0.11±0.01) and the ratio of lung W/D (6.23±0.34 vs. 3.68±0.23) were significantly higher than those in the normal oxygen control group (both P < 0.05). Wedelolactone pretreated mice had clear alveolar cavity and lower neutrophil infiltration and interstitial thickness than HALI group. Pathological scores (score: 0.43±0.02 vs. 0.75±0.02) and W/D ratio (4.56±0.12 vs. 6.23±0.34) were significantly lower than HALI group (both P < 0.05). Compared with the normal oxygen control group, the levels of SOD (kU/g: 26.41±4.25 vs. 78.64±3.95) and GSH (mol/g: 4.51±0.33 vs. 12.53±1.25) in HALI group were significantly decreased, while the levels of MDA (mmol/g: 54.23±4.58 vs. 9.65±1.96), TNF-α (μg/L: 96.32±3.67 vs. 11.65±2.03), IL-6 (ng/L: 163.35±5.89 vs. 20.56±3.63) and IL-1β (μg/L: 72.34±4.64 vs. 15.64±2.47) were significantly increased, and the protein expression of GPX4 (GPX4/β-actin: 0.44±0.02 vs. 1.00±0.09) was significantly decreased (all P < 0.05). Compared with the HALI group, the levels of SOD (kU/g: 53.28±3.69 vs. 26.41±4.25) and GSH (mol/g: 6.73±0.97 vs. 12.53±1.25) were significantly higher in the wedelolactone pretreatment group, and the levels of MDA (mmol/g: 25.36±1.98 vs. 54.23±4.58), TNF-α (μg/L: 40.25±4.13 vs. 96.32±3.67), IL-6 (ng/L: 78.32±4.65 vs. 163.35±5.89), and IL-1β (μg/L: 30.65±3.65 vs. 72.34±4.64) were significantly lower (all P < 0.05), and protein expression of GPX4 was significantly higher (GPX4/β-actin: 0.68±0.04 vs. 0.44±0.02, P < 0.05).@*CONCLUSIONS@#Wedelolactone attenuates HALI injury by regulating ferroptosis.

Cancer statistics in China, 2016 / 中华肿瘤杂志

Objective: Data for 2016 from cancer registries were used to estimate cancer incidence and mortality in China in 2016. Methods: According to the quality control process of the National Central Cancer Registry, the data from 683 cancer registries submitted by each province were evaluated, and the data of 487 cancer registries were qualified and included in the final analysis. Age-specific incidence and mortality rates were calculated by area (urban/rural), sex, age and cancer site, combined with national population data to estimate cancer incidence and mortality in China in 2016. Chinese population census in 2000 and Segi's population were used for age-standardized incidence and mortality rates. Results: Total population covered by 487 cancer registries was 381 565 422 (192 628 370 in urban and 188 937 052 in rural areas). The percentages of morphologically verified (MV%) and death certificate-only cases (DCO%) accounted for 68.31% and 1.40%, respectively, and the mortality to incidence ratio was 0.61. It was estimated about 4 064 000 new cases occurred in China in 2016, with the crude incidence rate being 293.91/100 000 (the rates of males and females were 315.52/100 000 and 271.23/100 000), age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 190.76/100 000 and 186.46/100 000, with the cumulative incidence rate (0-74 years old) being 21.42%. The crude incidence and ASIRC were 314.74/100 000 and 196.38/100 000 in urban areas, whereas in rural areas, they were 265.90/100 000 and 182.21/100 000, respectively. It was estimated about 2 413 500 cancer deaths occurred in China in 2016, the crude mortality rate was 174.55/100 000 (216.16/100 000 in males and 130.88/100 000 in females), the age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 106.00/100 000 and 105.19/100 000, and the cumulative mortality rate (0-74 years old) was 11.85%. The crude mortality and ASMRC were 180.31/100 000 and 104.44/100 000 in urban areas, whereas in rural areas, they were 166.81/100 000 and 108.01/100 000, respectively. The most common cancer cases include lung, colorectal, stomach, liver and female breast cancers. The top five cancers accounted for about 57.27% of all cancer cases. The most common cancer deaths included lung, liver, stomach, colorectal and esophageal cancers. The top five cancers accounted for about 69.25% of all cancer deaths. Conclusions: The burden of cancer shows a continuous increasing trend in China. Regional and gender differences in cancer burden are obvious. The cancer patterns still show the coexistence of cancer patterns in developed countries and developing countries. The situation of cancer prevention and control is still serious in China.

Diagnostic Efficacy of 68Ga-Labeled Prostate-Specific Membrane Antigen and 18F-Labeled Sodium Fluoride PET/CT in Prostate Cancer With Bone Metastasis / 中国医学科学院学报

Objective To compare the efficiency of 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA-11) and 18F-labeled sodium fluoride (18F-NaF) PET/CT in the diagnosis of bone metastasis in the patients with prostate cancer.Methods The prostate cancer patients suspected of bone metastasis who underwent 68Ga-PSMA-11 PET/CT and 18F-NaF PET/CT from January 2018 to January 2021 were included in this study.The number of lesions,maximum standardized uptake value (SUVmax),and tumor-to-background (T/B) ratio were compared between the two methods.Results 18F-NaF PET/CT detected more metastases than 68Ga-PSMA-11 PET/CT (310 vs.264,P<0.001).The median SUVmax[23.2 (16.4,33.4) vs.4.1 (2.5,5.6)] and median T/B ratio[7.0 (4.9,9.9) vs.6.7 (3.7,9.6)] of 18F-NaF PET/CT were higher than those of 68Ga-PSMA-11 PET/CT (all P<0.001).With the number of lesions as the indicator,the sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of 18F-NaF PET/CT were 100.0%,92.0%,92.0%,98.7%,and 100.0% respectively,and those of 68Ga-PSMA-11 PET/CT were 85.2%,94.0%,79.2%,98.9%,and 50.5%,respectively.Conclusion 18F-NaF PET/CT is superior to 68Ga-PSMA-11 PET/CT in the detection of bone metastases of prostate cancer.

Theory and application of pulse diagnosis at Renying and Cunkou regions / 中国针灸

Renying and Cunkou pulse diagnostic method is one of the important parts of the pulse diagnosis in Huangdi Neijing (Inner Canon of Yellow Emperor) and has been controversial since its proposal. This article takes WANG Shu-he's diagnostic operation as the evidence, and is in reference of the statement, "Cun region (the region ahead of Guan region of Cunkou) determines the human life, that on the left hand refers to Renying, while on the right hand is Qikou". The pulse conditions on the left and right hands represent yin and yang. If Renying pulse on the left is greater, the diseases are in yang meridians, while if Cunkou pulse on the right is bustling, the diseases are in yin meridians. By comparing the pulse condition and strength, as well as the pulse beating (rapid and urgent) between Guan region and region ahead of Guan on the same side, the conditions of three yang and three yin meridians are detected. In treatment, based on the records of Renying and Cunkou pulse diagnosis in Huangdi Neijing, the principles are proposed for reinforcing and reducing methods on hand and foot meridians of yin and yang. Five-shu points and yuan-source points are taken as the main acupoints in acupuncture treatment. During treatment, the changes in pulse conditions should be emphasized specifically and those at Renying and Cunkou regions are the criteria for judging qi arrival and qi regulation.

Establishment and Evaluation of Intestinal Injury Model of Mouse Acute Graft Versus Host Disease Based on An Organoid Technology / 中国实验血液学杂志

OBJECTIVE@#To establish an intestinal organoid model that mimic acute graft versus host disease (aGVHD) caused intestinal injuries by using aGVHD murine model serum and organoid culture system, and explore the changes of aGVHD intestine in vitro by advantage of organoid technology.@*METHODS@#20-22 g female C57BL/6 mice and 20-22 g female BALB/c mice were used as donors and recipients for bone marrow transplantation, respectively. Within 4-6 h after receiving a lethal dose (8.0 Gy) of γ ray total body irradiation, a total of 0.25 ml of murine derived bone marrow cells (1×107/mice, n=20) and spleen nucleated cells (5×106/mice, n=20) was infused to establish a mouse model of aGVHD (n=20). The aGVHD mice were anesthetized at the 7th day after transplantation, and the veinal blood was harvested by removing the eyeballs, and the serum was collected by centrifugation. The small intestinal crypts of healthy C57BL/6 mice were harvested and cultivated in 3D culture system that maintaining the growth and proliferation of intestinal stem cells in vitro. In our experiment, 5%, 10%, 20% proportions of aGVHD serum were respectively added into the organoid culture system for 3 days. The formation of small intestinal organoids were observed under an inverted microscope and the morphological characteristics of intestinal organoids in each groups were analyzed. For further evaluation, the aGVHD intestinal organoids were harvested and their pathological changes were observed. Combined with HE staining, intestinal organ morphology evaluation was performed. Combined with Alcian Blue staining, the secretion function of aGVHD intestinal organoids was observed. The distribution and changes of Lgr5+ and Clu+ intestinal stem cells in intestinal organoids were analyzed under the conditions of 5%, 10% and 20% serum concentrations by immunohistochemical stainings.@*RESULTS@#The results of HE staining showed that the integrity of intestinal organoids in the 5% concentration serum group was better than that in the 10% and 20% groups. The 5% concentration serum group showed the highest number of organoids, the highest germination rate and the lowest pathological score among experimental groups, while the 20% group exhibited severe morphological destruction and almost no germination was observed, and the pathological score was the highest among all groups(t=3.668, 4.334,5.309,P<0.05). The results of Alican blue staining showed that the secretion function of intestinal organoids in serum culture of aGVHD in the 20% group was weaker than that of the 5% group and 10% of the organoids, and there was almost no goblet cells, and mucus was stainned in the 20% aGVHD serum group. The immunohistochemical results showed that the number of Lgr5+ cells of intestinal organoids in the 5% group was more than that of the intestinal organoids in the 10% aGVHD serum group and 20% aGVHD serum group. Almost no Clu+ cells were observed in the 5% group. The Lgr5+ cells in the 20% group were seriously injuried and can not be observed. The proportion of Clu+ cells in the 20% group significantly increased.@*CONCLUSION@#The concentration of aGVHD serum in the culture system can affect the number and secretion function of intestinal organoids as well as the number of intestinal stem cells in organoids. The higher the serum concentration, the greater the risk of organoid injury, which reveal the characteristics of the formation and functional change of aGVHD intestinal organoids, and provide a novel tool for the study of intestinal injury in aGVHD.

Analysis of the Prognostic Value and Risk Factors of Early Relapse for Newly Diagnosed Multiple Myeloma Patients in the Era of Novel Agents / 中国实验血液学杂志

OBJECTIVE@#To investigate the influece of early relapse in the era of novel drugs on the prognosis of the patients with newly diagnosed multiple myeloma（NDMM） and risk factors, and to provide the basis for the early identification of the high-risk patients and guiding the treatment.@*METHODS@#The clinical data of the patients with NDMM admitted to our hospital from November 2011 to May 2022 were retrospectively analyzed. According to whether the progression free survival（PFS） was more than 12 months, they were divided into early relapse group（≤12 months） and late relapse group（＞12 months）. The high-risk factors of the patients in two groups were analyzed, including age, anemia, renal insufficiency, hypercalcemia, increasing of lactate dehydrogenase（LDH） level, Extramedullary disease (EMD), International Staging System（ISS） stage, Revised International Staging System （R-ISS） stage, cytogenetic abnormalities(CA) detected by fluorescence in situ hybridization（FISH）, and treatment efficacy. The meaningful clinical indicators were screened, and multivariate analysis was used to explore the high-risk factors of early relapse.@*RESULTS@#170 patients with NDMM were collected, including 25 cases in early relapse group and 145 cases in late relapse group. The median OS time of the patients in early death group was 20 months, and 140 months in late relapse group by the end of follow-up, there was significant difference in OS of the patients between two groups（P<0.001）. Fifteen patients（56.0％）in early relapse group obtained ≥VGPR, and 113（77.9%） patients in late relapse group, the difference was statistically significant（P=0.011）. Survival outcomes remained poor among early relapse patients irrespective of depth of response to initial therapy. Multivariate analysis showed that the EMD and high-risk CA predicted early relapse.@*CONCLUSION@#The prognosis of patients with early relapse in NDMM is poor. EMD and high-risk CA is an independent prognostic factor of early relapse.

Nutritional status and its influencing factors in children with newly diagnosed inflammatory bowel disease / 中国当代儿科杂志

OBJECTIVES@#To investigate the nutritional status and its influencing factors in children with newly diagnosed inflammatory bowel disease (IBD).@*METHODS@#A retrospective analysis was conducted on the clinical data of children who were diagnosed with IBD for the first time in Hunan Children's Hospital from January 2015 to December 2021. Diagnostic delay was defined as the time from the symptom onset to IBD diagnosis being in the upper quartile (P76-P100) of all IBD children in the study. Multivariate logistic regression analysis was used to explore the risk factors for emaciation and growth retardation.@*RESULTS@#A total of 125 children with newly diagnosed IBD were included, with Crohn's disease being the main type (91.2%). The rates of emaciation and growth retardation were 42.4% (53 cases) and 7.2% (9 cases), respectively, and the rate of anemia was 77.6% (97 cases). Diagnostic delay was noted in 31 children (24.8%), with the time from the symptom onset to IBD diagnosis of 366 to 7 211 days. Multivariate logistic regression analysis showed that diagnostic delay was a risk factor for emaciation and growth retardation (OR=2.73 and OR=4.42, respectively; P<0.05) and that age was positively associated with emaciation (OR=1.30, P<0.05).@*CONCLUSIONS@#Children with newly diagnosed IBD have poor nutritional status, and the rates of anemia, emaciation, and growth retardation are high. Diagnostic delay is associated with malnutrition in children with IBD.

Effect of Bushen Chushi() decoction combined with platelet-rich plasma on regulating TGF-β1 and Smad-1 expression in serum of knee osteoarthritis patient / 中国骨伤

OBJECTIVE@#To investigate the effect of Bushen Chushi decoction combined with platelet-rich plasma(PRP) to treat knee osteoarthritis(KOA) in early and middle stage and its regulation on TGF-β1 and Smad-1 expression in serum.@*METHODS@#Total of 45 patients with KOA in early and middle stage from May 2020 to April 2022 were treated and divided into control group and observation group. In control group, there were 30 patients including 12 males and 18 females, aged from 43 to 69 years old with an average of(57.3±6.5) years old and disease duration ranged from 1.5 to 5.0 years with an average of(3.8±1.7) years, and there were 8 cases in gradeⅠ, 13 cases in gradeⅡ, and 9 cases in grade Ⅲ according to Kellgren-Lawrence Grade, PRP 5 ml was injected into knee joint on the first day of No1, 3 week together for 2 times. In the observation group, there were 15 cases including 7 males and 8 females, aged from 45 to 70 years old with an average of (56.7±6.2) years old and disease duration ranged from 1.8 to 5.7 years with an average of (4.0±1.8) years, there were 4 cases in gradeⅠ, 9 cases in gradeⅡand 4 cases in grade Ⅲ according to the Kellgren-Lawrence Grade, PRP 5 ml were injected into knee joints that the time and frequency were the same as those in the control group, and at the same time Bushen Chushi decoction orally were taken 1 dose per day with a total of 28 doses. All patients were treated for four weeks. Visual analogue scale(VAS) and Lequesne MG score before and after treatment were used to evaluate improvement of knee pain and joint function. The TGF-β1 and Smad-1 levels in serum were measured before and after treatment in two groups. The incidence of complications in two groups was observed.@*RESULTS@#All patients were followed up for 26 to 30 days with an average of (28.0±0.6) days. There was no significant difference in VAS and knee Lequesne MG scores between two groups before treatment(P>0.05). The scores of VAS and knee Lequesne MG on the first day after treatment in both groups were lower than those before treatment(P<0.05). The VAS and knee Lequesne MG scores in observation group were lower than those in control group(P<0.05) on the first day after treatment. The TGF-β1 level in serum after treatment were higher significantly than that before treatment in two groups(P<0.05). After treatment, TGF-β1 level in serum in observation group were lower than those in control group with statistically significant differences(P<0.05). The Smad-1 levels in serum after treatment in observation group were higher significantly than that in control group(P<0.05). The levels of Smad-1 were not statistically significant between before and after treatment(P>0.05). There was no significant difference in postopertaive complications between two groups (P>0.05).@*CONCLUSION@#The efficacy of Bushen Chushi decoction combined with PRP in treatment of early and middle KOA is better than that of PRP injection alone. The combined treatment could reduce TGF-β1 level and increase Smad-1 level in serum, which may be a mechanism to inhibit inflammation and alleviate cartilage degeneration to some extent.