Clinical study of DEP regimen as a salvage therapy for refractory macrophage activation syndrome / 中华风湿病学杂志

Objective:To investigate the efficacy of liposomal doxombicin combined with etoposide and high dose methylprednisolone (DEP) as a salvage therapy for refractory macrophage activation syndrome (MAS).Methods:Totally 38 patients with refractory MAS were enrolled in this study from January 2016 to January 2022 in Beijing Friendship Hospital, including clinical characteristics and laboratory test results before and after DEP treatment, were retrospectively collected. The efficacy was evaluated every 2 weeks according to the United States Midwest Cooperative HLH Group. Relevant samples were statistically analyzed using non-parametric tests.Results:Of 38 refractory MAS patients, 8 males and 30 females were included into this study.The median age was 30(15-69) years old. The underlying disease were adult onset Still's disease in 29 cases, Systemic lupus erythematosus in 6 cases, Rheumatoid arthritis in 1 case and Undifferentiated Connective-Tissue disease in 2. The overall response rate was 95% (36/38), including 9 patients (24%) achieved complete remission and 27 patients (71%) achieved partial remission after 2 weeks of treatment. The overall response rate was 97% (34/35), including 16 (46%) complete remission and 18 (51%) partial remission after 4 weeks of treatment(due to lack of data in some patients). The overall response rate was 97% (34/35), including 17 (49%) complete remission and 17 (49%) partial remission after 6 weeks of treatment. Patients who achieved partial remission or complete remission were actively treated for the underlying diseases after induction, and their conditions were in persistent remission.Conclusion:The DEP regimen may be an effective salvage therapy for the treatment of refractory MAS.

Recommendations for the diagnosis and treatment of rheumatic diseases-related hemophagocytic syndrome in China / 中华内科杂志

Hemophagocytic syndrome (HPS), which is currently named as hemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory syndrome characterized by persistent fever, hepatosplenomegaly, pancytopenia and hemophagocytosis found in bone marrow, liver, spleen and lymph nodes due to excessive activation of macrophages and cytotoxic T cells. Macrophage activation syndrome (MAS) is a specific form of HLH induced by autoinflammatory/autoimmune disorders which can be life-threatening and requires multiple disciplines. In order to improve clinicians′ understanding of MAS and standardize the clinical diagnosis and treatment practice of MAS, the rheumatology branch of Chinese Rheumatology Association organized domestic experts to formulate the diagnosis and treatment standard, in order to improve the diagnosis and treatment level of MAS and improve the prognosis of patients.

Clinical characteristics and treatment progress of microphthalmos-anophthalmos-coloboma / 国际眼科杂志(Guoji Yanke Zazhi)

Microphthalmos-anophthalmos-coloboma(MAC)is structurally and clinically correlated congenital ocular malformation. Although MAC is relatively rare, they still become an important cause of blindness in children. At present, the etiology of MAC is not clear; a variety of genetic or environmental factors may cause MAC. Because of its special anatomical structure, MAC has complex clinical manifestations and multiple complications. The complications including cataract, angle-closure glaucoma, uveal effusion, retinal detachment, orbital cyst, which are often accompanied with increased risks for surgery and poor prognosis. By summarizing the clinical features, the common types of ocular complications, and the progress of the treatment, this article will enhance clinicians' cognition of MAC and guide clinicians to formulate personalized and safe treatment plans for patients.

Effect of graded motor imagery combined with repetitive transcranial magnetic stimulation on upper limb function of stroke patients / 中国康复理论与实践

ObjectiveTo explore the effects of graded motor imagery (GMI) combined with repetitive transcranial magnetic stimulation (rTMS) on upper limb function and activities of daily living of stroke patients. MethodsFrom June, 2022 to February, 2023, 45 stroke patients from Xuzhou Rehabilitation Hospital and Xuzhou Central Hospital were recruited and divided into control group (n = 15), GMI group (n = 15) and combined group (n = 15) randomly. All the groups received conventional rehabilitation, in addition, GMI group received GMI and the combined group received GMI and rTMS, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Action Research Arm Test (ARAT), modified Barthel Index (MBI) and Hong Kong version of Functional Test for the Hemiplegic Upper Extremity (FTHUE-HK) before and after treatment. ResultsThe scores of FMA-UE, ARAT and MBI, and grades of FTHUE-HK improved in all the groups after treatment (|t| > 9.681, P < 0.001), and all these indexes were the best in the combined group (F > 13.241, P < 0.001). ConclusionGMI combined with rTMS can further improve the motor function of upper limbs and activities of daily living of stroke patients.

Research progress of palliative care for patients with lung transplantation / 中国实用护理杂志

This paper summarized the research progress of palliative care for lung transplantation patients, to summarize the necessity and influencing factors of palliative care for lung transplantation patients, and defined the research status of palliative care implementation mode for lung transplantation patients, with a view to providing ideas for further research of palliative care on lung transplantation patients in China.

Clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors / 中华内科杂志

Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8+T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.

The prospect and challenge of liquid biopsy in the diagnosis and treatment of chest malignancy / 中华预防医学杂志

In recent years, the incidence of chest malignant tumors in China has increased year by year, which has seriously threatened the health problems of people. Among them, early screening and intervention of patients with chest malignancies is the key to cancer prevention. Early detection, early diagnosis, and early treatment as the "three early prevention" of clinical practice are conducive to improve the survival rate of tumor patients. As a non-invasive and real-time reflection of tumor status, liquid biopsy has gradually received attention in clinical diagnosis and treatment. Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and exosomes as liquid biopsy "Three carriages" are not only widely used in the diagnosis, monitoring and prognostic evaluation of chest malignancies, but also face many unknown challenges. In this article, the application of liquid biopsy in chest malignancies in recent years is elaborated in detail, which provides a reference for the formulation of clinical tumor prevention and diagnosis and treatment strategies.

Advances in the research of HIV-1 envelope glycoprotein gp120 inhibitors / 药学学报

From the process of human immunodeficiency virus-1 (HIV-1) invading cells, the combination of gp120 and CD4 is the first step for HIV-1 to invade cells. Interfering with this process can prevent HIV from recognizing target cells and inhibit virus replication. Therefore, HIV-1 gp120 is an important part of the HIV-1 life cycle. Fostesavir, a phosphatate prodrug derived from the gp120 inhibitor BMS-626529 modified by the prodrug strategy, was approved for the treatment of adult patients with multidrug resistant HIV-1 infection by the US FDA and the European Medicines Agency in 2020 and 2021, respectively. In this review, we focus on the research progress of small molecule inhibitors targeting the interaction of gp120-CD4 from the perspective of medicinal chemistry, in order to provide reference for the subsequent research of gp120 inhibitors.

Effect of combination of pressure biofeedback therapy and Flexi-bar in sitting on chronic non-specific low back pain / 中国康复理论与实践

ObjectiveTo explore the immediate and short-term effects of pressure biofeedback therapy combined with Flexi-bar exercise in the sitting position on chronic non-specific low back pain (CNSLBP). MethodsFrom June to September, 2022, 27 CNSLBP students in Xuzhou Medical University and other universities around were randomly divided into pressure biofeedback unit (PBU) group (n = 9), Flexi-bar group (n = 9) and combined group (n = 9). On the basis of routine rehabilitation guidance, the PBU group accepted pressure biofeedback therapy, the Flexi-bar group accepted active vibration therapy, and the combined group accepted pressure biofeedback therapy and active vibration therapy, for three weeks. They were measured core stability with Stabilizer, lumbar joint repositioning error (LJRE) with iHandy, and bilateral transverse abdominis thickness and multifidus muscle cross-sectional area with ultrasonography; and assessed with Visual Analogue Scale for pain (VAS), Oswestry Disability Index (ODI) before and after treatment; and the core stability were measured immediately after the first treatment. ResultsThe indexes of core stability improved after the first treatment (|t| > 3.000, P < 0.05) in all groups, and improved the most in the combined group (F > 10.909, P < 0.001). All the indexes improved after three weeks of treatment (|t| > 2.604, P < 0.05), except for LJRE in PBU group; and they were the best in the combined group (|F| > 4.061, P < 0.05), except LJRE was not significantly different from the Flexi-bar group (P > 0.05). ConclusionPressure biofeedback therapy combined with Flexi-bar exercise in the sitting position can more effectively improve core stability and core muscles, proprioception, and pain for patients with CNSLBP.

CHD1 deletion stabilizes HIF1α to promote angiogenesis and glycolysis in prostate cancer / 亚洲男科学杂志(英文版)

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.

Overexpressed SIRT6 ameliorates doxorubicin-induced cardiotoxicity and potentiates the therapeutic efficacy through metabolic remodeling

Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without compromising antitumor efficacy. Herein, histone deacetylase SIRT6 expression was reduced in plasma of patients treated with anthracyclines-based chemotherapy regimens. Furthermore, overexpression of SIRT6 alleviated doxorubicin-induced cytotoxicity in cardiomyocytes, and potentiated cytotoxicity of doxorubicin in multiple cancer cell lines. Moreover, SIRT6 overexpression ameliorated doxorubicin-induced cardiotoxicity and potentiated antitumor efficacy of doxorubicin in mice, suggesting that SIRT6 overexpression could be an adjunctive therapeutic strategy during doxorubicin treatment. Mechanistically, doxorubicin-impaired mitochondria led to decreased mitochondrial respiration and ATP production. And SIRT6 enhanced mitochondrial biogenesis and mitophagy by deacetylating and inhibiting Sgk1. Thus, SIRT6 overexpression coordinated metabolic remodeling from glycolysis to mitochondrial respiration during doxorubicin treatment, which was more conducive to cardiomyocyte metabolism, thus protecting cardiomyocytes but not cancer cells against doxorubicin-induced energy deficiency. In addition, ellagic acid, a natural compound that activates SIRT6, alleviated doxorubicin-induced cardiotoxicity and enhanced doxorubicin-mediated tumor regression in tumor-bearing mice. These findings provide a preclinical rationale for preventing cardiotoxicity by activating SIRT6 in cancer patients undergoing chemotherapy, but also advancing the understanding of the crucial role of SIRT6 in mitochondrial homeostasis.

Investigation of sport-related habits in college students after covid-19 epidemic / Investigação sobre hábitos relacionados ao esporte em estudantes universitários após epidemia de covid-19 / Investigación de los hábitos relacionados con el deporte en estudiantes universitarios tras la epidemia de covid-19

ABSTRACT Introduction: China's covid-19 epidemic is under control. Universities and schools across the country have resumed physical education classes, but the mental health knowledge of college students in the aftermath of the covid-19 outbreak has not been investigated. Objective: To study college students' mental health and sports-related habits after the covid-19 outbreak. Methods: This study comprehensively used literature materials, expert interviews, mathematical statistics, and other methods to study the sports-related attitudes and health awareness of college students before and after the outbreak of the new epidemic, examining the health knowledge domain of college students. Results: In the survey dimensions related to students' sports knowledge, the highest mean score was for "emotional control" at 3.48, followed by "participation motivation" at 3.41 and "participation attitude" at 3.35. The scores of sports participation attitude, motivation, and sports emotion for males were equal and higher than in females, where the measures of emotional factors and motivation to participate reached significant levels. After the epidemic, the mean scores for students' participation attitude, sports emotion, and motivation to participate in sports exceeded the theoretical mean. Conclusion: After the health awareness and prevention work in the community and school network, university students' sports attitudes and awareness improved significantly compared to before the Covid-19 outbreak. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A epidemia de covid-19 em China encontra-se sob controle. Faculdades, escolas primárias e secundárias em todo o país retomaram as aulas de educação física, porém o conhecimento sobre a saúde mental dos estudantes universitários no estágio posterior do surto da Covid-19 não foi investigado. Objetivo: Estudar a saúde mental e os hábitos relacionados ao esporte nos universitários depois da epidemia da Covid-19. Métodos: Este estudo utilizou de forma abrangente materiais de literatura, entrevistas de especialistas, estatísticas matemáticas e outros métodos para estudar especificamente as atitudes relacionadas ao esporte e a conscientização na saúde dos estudantes universitários antes e depois do surto da nova epidemia, examinando o domínio do conhecimento em saúde dos estudantes universitários. Resultados: Nas dimensões da pesquisa relacionadas ao conhecimento esportivo dos alunos, a maior pontuação média foi de "controle emocional" como 3,48, seguida por "motivação de participação" como 3,41 e "atitude participativa" como 3,35. As pontuações de atitude de participação esportiva, motivação e emoção esportiva para os homens foram iguais e maior do que nas mulheres, onde as medidas de fator emocional e motivação para participar atingiram níveis significativos. Após a epidemia, as médias de atitude de participação dos alunos, emoção esportiva e motivação para participar do esporte superaram a média teórica. Conclusão: Após o trabalho de conscientização em saúde e prevenção, na rede comunitária e escolar, a atitude esportiva e a conscientização dos universitários foram significativamente aprimoradas em relação aos antecedentes ao surto de Covid-19. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La epidemia de covid-19 en China está bajo control. Los colegios y las escuelas primarias y secundarias de todo el país han reanudado las clases de educación física, pero no se ha investigado el conocimiento sobre la salud mental de los estudiantes universitarios en la última etapa del brote de covid-19. Objetivo: Estudiar la salud mental y los hábitos relacionados con el deporte en los estudiantes universitarios tras el brote de covid-19. Métodos: Este estudio utilizó de forma exhaustiva materiales bibliográficos, entrevistas a expertos, estadísticas matemáticas y otros métodos para estudiar específicamente las actitudes relacionadas con el deporte y el conocimiento de la salud de los estudiantes universitarios antes y después del estallido de la nueva epidemia, examinando el dominio del conocimiento de la salud de los estudiantes universitarios. Resultados: En las dimensiones de la encuesta relacionadas con los conocimientos deportivos de los estudiantes, la puntuación media más alta correspondió al "control emocional" con un 3,48, seguido de la "motivación para la participación" con un 3,41 y la "actitud para la participación" con un 3,35. Las puntuaciones de la actitud de participación deportiva, la motivación y la emoción deportiva de los varones fueron iguales y superiores a las de las mujeres, donde las medidas del factor emocional y la motivación para participar alcanzaron niveles significativos. Después de la epidemia, las puntuaciones medias de la actitud de participación, la emoción deportiva y la motivación para participar en el deporte de los alumnos superaron la media teórica. Conclusión: Tras el trabajo de concienciación y prevención sanitaria en la comunidad y la red escolar, la actitud y la conciencia deportiva de los estudiantes universitarios mejoraron significativamente en comparación con las anteriores al brote de Covid-19. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

The Relationship between MicroRNA Expression Profiling in Imatinib-Resistant Cell Line K562/G and Potential Mechanism through FOXO3/Bcl-6 Signaling Pathway / 中国实验血液学杂志

OBJECTIVE@#To investigate the drug resistant related FOXO3/Bcl-6 signaling pathway in K562/G cell line and its related microRNA(miRNA) mechanisms.@*METHODS@#The drug resistance potency of imatinib on K562/G was detected by MTT assay. The expression of FOXO3 and Bcl-6 proteins in K562 and K562/G cells was detected by Western blot. Real-time PCR (RT-PCR) was used to detect the expression of FOXO3 and Bcl-6 mRNA. The miRNA expression profiling in K562 and K562/G cells was analyzed by microarray technique, and the miRNA targeted to FOXO/Bcl-6 signaling pathway was identified.@*RESULTS@#The expression of FOXO3 and Bcl-6 protein was significantly increased in K562/G cells as compared with that in K562 cells (P<0.01), the expression level of Bcl-6 mRNA showed no increase in K562/G cells. However, FOXO3 mRNA was up-regulated in K562/G cells (P<0.05). MiRNA microarray results showed that 109 miRNAs were expressed differentially in K562 and K562/G cells. The expression of 81 miRNAs were up-regulated while 28 miRNAs were down-regulated. Through reverse prediction by bioinformatics, miR-6718-5p, miR-5195-5p, miR-4711-3p, miR-4763-5p, miR-4664-5p and miR-3176 were related to FOXO/Bcl-6 signaling pathway.@*CONCLUSION@#The FOXO3/Bcl-6 signaling pathway contributes to imatinib resistance in K562/G cell line, and the miRNA expression profiles showed significant differences between K562/G and K562 cells.

Isolation of High Purity Mouse Mesenchymal Stem Cells through Depleting Macrophages Using Liposomal Clodronate

BACKGROUND@#The use of mouse bone marrow mesenchymal stem cells (mBMSCs) represents a promising strategy for performing preclinical studies in the field of cell-based regenerative medicine; however, mBMSCs obtained via conventional isolation methods have two drawbacks, i.e., (i) they are heterogeneous due to frequent macrophage contamination, and (ii) they require long-term culturing for expansion. @*METHODS@#In the present study, we report a novel strategy to generate highly pure mBMSCs using liposomal clodronate.This approach is based on the properties of the two cell populations, i.e., BMSCs (to adhere to the plasticware in culture dishes) and macrophages (to phagocytose liposomes). @*RESULTS@#Liposomal clodronate added during the first passage of whole bone marrow culture was selectively engulfed by macrophages in the heterogeneous cell population, resulting in their effective elimination without affecting the MSCs.This method allowed the generation of numerous high-purity Sca-1 ＋ CD44 ＋ F4/80 - mBMSCs ([ 95%) with just one passaging. Comparative studies with mBMSCs obtained using conventional methods revealed that the mBMSCs obtained in the present study had remarkably improved experimental utilities, as demonstrated by in vitro multilineage differentiation and in vivo ectopic bone formation assays. @*CONCLUSION@#Our newly developed method, which enables the isolation of mBMSCs using simple and convenient protocol, will aid preclinical studies based on the use of MSCs.

Clinicopathological features of very well-differentiated adenocarcinoma of the stomach / 中华病理学杂志

Objective: To investigate the clinicopathological features of very well-differentiated adenocarcinoma (VWDA) of the stomach. Methods: The clinicopathological data of 12 cases of VWDA of the stomach were collected retrospectively at the People's Liberation Army Joint Logistics Support Force 989 Hospital (formerly 152 Hospital), Pingdingshan, China, from January 2013 to May 2021. The histological characteristics and immunophenotypes were observed and analyzed with review of current literature. Results: There were 8 males and 4 females with a median age of 63 years (range 47 to 80 years). The tumor involved in the upper part of the stomach in 6 cases, the middle part in 2 cases, and the lower part in 4 cases. The median diameter of the tumors was 17 mm (range 5-65 mm). The tumor cells were similar to absorbent cells, Paneth cells, foveolar epithelial cells, and goblet cells. The cells were arranged in a single layer, and the nuclei were slightly enlarged and located at the base. The nuclei were fusiform to slightly irregular, with loss of nuclear polarity. Early tubular VWDA was found in 9 cases, and the tumor glands were similar to intestinal metaplasia. In two cases the tumors infiltrated into the submucosa. The lesions in the mucosa and submucosa showed the glands with cystic expansion, bending, branching, spiky and abortive growth pattern. One case of early papillary tubular VWDA was confined to the mucosal layer and composed of foveolar-type epithelial cells. There were two cases of advanced papillary tubular VWDA, which consisted of foveolar-type epithelial, pyloric glands, or mucinous neck cells and were associated with intra-lymphatic cancer embolus and lymph node metastases. Background mucosal atrophy and intestinal metaplasia were observed in all cases. Immunohistochemical staining showed intestinal type VWDA in 1 case, mixed gastrointestinal type VWDA in 9 cases, and gastric type VWDA in 2 cases. The Ki-67 proliferation index of 8 cases limited to the mucosa was 40%-70%, 2 cases of infiltration into the submucosa and 2 cases of advanced carcinoma was 10%-25%. All the tumors showed a wild type of p53 protein expression pattern and negative HER2. Adenocarcinoma or high-grade dysplasia was diagnosed on preoperative biopsy in 5 cases, and chronic atrophic gastritis with intestinal metaplasia in 7 cases. The median follow-up time was 28 months (range 12-72 months). No recurrence was found in the 10 patients with early cancer. Of the two patients with advanced carcinoma, one patient had lung metastases and the other died. Conclusions: Gastric VWDA is a rare low-grade malignancy with structural features of highly differentiated adenocarcinoma and extremely low cytological atypia. The diagnostic value of structural abnormality is significantly greater than cytological atypia. The invasive growth of irregular glands in the deep mucosa and submucosa is reliable evidence for diagnosis. The diagnosis of intramucosal VWDA is challenging and very difficult in some biopsy specimens.

Relationship between preoperative inflammatory indexes and prognosis of patients with rectal cancer and establishment of prognostic nomogram prediction model / 中华肿瘤杂志

Objective: To compare the prognostic evaluation value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in rectal cancer patients. Nomogram survival prediction model based on inflammatory markers was constructed. Methods: The clinical and survival data of 585 patients with rectal cancer who underwent radical resection in the First Affiliated Hospital of Xi'an Jiao tong University from January 2013 to December 2016 were retrospectively analyzed. The optimal cut-off values of NLR, PLR, LMR, and SII were determined by the receiver operating characteristic (ROC) curve. The relationship between different NLR, PLR, LMR and SII levels and the clinic pathological characteristics of the rectal cancer patients were compared. Cox proportional risk model was used for univariate and multivariate regression analysis. Nomogram prediction models of overall survival (OS) and disease-free survival (DFS) of patients with rectal cancer were established by the R Language software. The internal validation and accuracy of the nomograms were determined by the calculation of concordance index (C-index). Calibration curve was used to evaluate nomograms' efficiency. Results: The optimal cut-off values of preoperative NLR, PLR, LMR and SII of OS for rectal cancer patients were 2.44, 134.88, 4.70 and 354.18, respectively. There was statistically significant difference in tumor differentiation degree between the low NLR group and the high NLR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative carcinoembryonic antigen (CEA) level between the low PLR group and the high PLR group (P<0.05). There was statistically significant difference in tumor differentiation degree between the low LMR group and the high LMR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative CEA level between the low SII group and the high SII group (P<0.05). The multivariate Cox regression analysis showed that the age (HR=2.221, 95%CI: 1.526-3.231), TNM stage (Ⅲ grade: HR=4.425, 95%CI: 1.848-10.596), grade of differentiation (HR=1.630, 95%CI: 1.074-2.474), SII level (HR=2.949, 95%CI: 1.799-4.835), and postoperative chemoradiotherapy (HR=2.123, 95%CI: 1.506-2.992) were independent risk factors for the OS of patients with rectal cancer. The age (HR=2.107, 95%CI: 1.535-2.893), TNM stage (Ⅲ grade, HR=2.850, 95%CI: 1.430-5.680), grade of differentiation (HR=1.681, 95%CI: 1.150-2.457), SII level (HR=2.309, 95%CI: 1.546-3.447), and postoperative chemoradiotherapy (HR=1.837, 95%CI: 1.369-2.464) were independent risk factors of the DFS of patients with rectal cancer. According to the OS and DFS nomograms predict models of rectal cancer patients established by multivariate COX regression analysis, the C-index were 0.786 and 0.746, respectively. The calibration curve of the nomograms showed high consistence of predict and actual curves. Conclusions: Preoperative NLR, PLR, LMR and SII levels are all correlated with the prognosis of rectal cancer patients, and the SII level is an independent prognostic risk factor for patients with rectal cancer. Preoperative SII level can complement with the age, TNM stage, differentiation degree and postoperative adjuvant chemoradiotherapy to accurately predict the prognosis of rectal cancer patients, which can provide reference and help for clinical decision.

miRNA-126 regulates the proliferation, apoptosis and migration of thyroid cancer cell SW579 by regulating the notch-1/Akt signaling pathway / 中华内分泌外科杂志

Objective:To investigate the effect of miRNA-126 on proliferation, apoptosis and migration of thyroid cancer SW579 cells, and further to explore its mechanism.Methods:Thyroid cancer SW579 cells were cultured in vitro, and the expression of miRNA-126 in normal thyroid Nthy-ori3-1 cells and SW579 cells was detected by qPCR. The cells were divided into blank control group (without any treatment) , experimental group (transfected with miRNA-126 expression plasmid) and negative control group (transfected with empty plasmid vector) . SW579 cells with overexpression of miRNA-126 were constructed by transfection of plasmids. CCK-8 test was used to detect cell proliferation; Transwell cell test was used to detect cell migration and invasion; Flow cytometry was employed to detect apoptosis and changes in reactive oxygen levels; Western blot was used to detect Notch-1/Akt pathway related protein expression.Results:The expression level of miRNA-126 in SW579 cells was 0.25±0.07, and the difference was statistically significant compared with that in Nthy-ori3-1 cells (P<0.001) . The cell survival rates of blank control group, experimental group and negative control group were (105.70 ± 7.61) , (98.60 ± 5.42) and (62.70 ± 3.82) ; The apoptosis rates were (9.14 ± 0.83) , (12.28 ± 1.34) and (36.39 ± 3.21) (all P < 0.05) ; The cell migration rates were (34.51 ± 2.45) , (33.29 ± 3.17) and (11.22 ± 1.23) (all P < 0.05) ; The levels of ROS were (1.02 ± 0.07) , (1.08 ± 0.11) and (6.54 ± 0.74) (all P < 0.05) .Conclusion:Overexpression of miR-NA-126 can inhibit Notch-1/Akt pathway by up-regulating intracellular reactive oxygen species, inhibit the proliferation and migration of SW579 cells, and induce apoptosis in SW579 cells, which provides a certain basis for the study of miRNA-126 in thyroid cancer.

Characteristic and prognosis of patients with non-EBV infection-associated hemophagocytic lymphohistiocytosis / 中华血液学杂志

Objective: To explore the clinical characteristics and outcomes of patients with non-Epstein-Barr virus (EBV) infection-associated hemophagocytic lymphohistiocytosis (IAHLH) . Methods: Clinical data of 48 patients diagnosed with non-EBV IAHLH in Beijing Friendship Hospital from January 2015 to March 2021 were collected, and the clinical characteristics, treatment, curative effect and prognosis of the patients were analyzed retrospectively. Results: This study included 48 patients, 28 males and 20 females, with a median (range) age of 34.5 (2-74) years. Pathogens that cause IAHLH were as follows: virus (16 cases, 33.3%) , bacteria (17 cases, 35.4%) , parasitic agents (13 cases, 27.1%) , and fungi (2 cases, 4.2%) . The median time from onset to diagnosis of hemophagocytic syndrome (HLH) was 40 (10-160) days. The median (range) time duration from prodrome to the definite diagnosis of IAHLH was 67 (23-270) days. The clinical characteristics were fever (48 cases, 100%) , splenomegaly (34 cases, 70.8%) , cytopenia (38 cases, 79.1%) , elevated ferritin (45 cases, 93.8%) , elevated fasting triglyceride levels (7 cases, 14.6%) , hypofibrinogenemia (17 cases, 35.4%) , decrease natural killer cell activity (26 in 44 cases, 59.1%) , and elevated sCD25 (35 cases, 74.5%) . Twenty-five patients (52.1%) had adenopathy. Once a certain pathogen was identified as the causative factor of hemophagocytic lymphohistiocytosis (HLH) , cytotoxic agents and glucocorticoids were withdrawn, and specific pathogen-directed treatment was initiated. After treatment, 36 cases (75.0%) achieved complete response, and 14 of 15 patients (93.3%) with parasitic and fungal HLH got a response; however, the response rate of patient with bacterial and viral HLH was only 66.7% (22 of 33 patients) . The estimated 5-year overall survival rate was 72.3% (95%CI 50.3%-69.8%) . The adverse prognostic factors were total bilirubin over the upper limit of normal (OR=20.0, 95%CI 1.1-378.3, P=0.046) and pathogenic infection not fully controlled (OR=19.9, 95%CI 2.9-134.5, P=0.002) . Conclusion: Non-EBV IAHLH has a good prognosis. When diagnosed, cytotoxic agents and glucocorticoids should be tapered off, and pathogen-targeted therapy should be critically administered to clear the triggering infection.

Ample dietary fat reduced the risk of primary vesical calculi by inducing macrophages to engulf budding crystals in mice

Although primary vesical calculi is an ancient disease, the mechanism of calculi formation remains unclear. In this study, we established a novel primary vesical calculi model with d,l-choline tartrate in mice. Compared with commonly used melamine and ethylene glycol models, our model was the only approach that induced vesical calculi without causing kidney injury. Previous studies suggest that proteins in the daily diet are the main contributors to the prevention of vesical calculi, yet the effect of fat is overlooked. To assay the relationship of dietary fat with the formation of primary vesical calculi, d,l-choline tartrate-treated mice were fed a high-fat, low-fat, or normal-fat diet. Genetic changes in the mouse bladder were detected with transcriptome analysis. A high-fat diet remarkably reduced the morbidity of primary vesical calculi. Higher fatty acid levels in serum and urine were observed in the high-fat diet group, and more intact epithelia in bladder were observed in the same group compared with the normal- and low-fat diet groups, suggesting the protective effect of fatty acids on bladder epithelia to maintain its normal histological structure. Transcriptome analysis revealed that the macrophage differentiation-related gene C-X-C motif chemokine ligand 14 (Cxcl14) was upregulated in the bladders of high-fat diet-fed mice compared with those of normal- or low-fat diet-fed mice, which was consistent with histological observations. The expression of CXCL14 significantly increased in the bladder in the high-fat diet group. CXCL14 enhanced the recruitment of macrophages to the crystal nucleus and induced the transformation of M2 macrophages, which led to phagocytosis of budding crystals and prevented accumulation of calculi. In human bladder epithelia (HCV-29) cells, high fatty acid supplementation significantly increased the expression of CXCL14. Dietary fat is essential for the maintenance of physiological functions of the bladder and for the prevention of primary vesical calculi, which provides new ideas for the reduction of morbidity of primary vesical calculi.

Analysis of demand utilization and satisfaction of residents in a district of Guangzhou City for community health services / 中华医学教育探索杂志

Objective:To understand the utilization situation of community health service institutions, the awareness of basic public health items and the degree of satisfaction of residents in Guangzhou City, so as to provide direction and reference for improving the quality of community health service in Guangzhou City.Methods:In December 2020, 1 050 residents in a district of Guangzhou City were selected by multi-stage random sampling method to fill out the questionnaire. Single factor analysis was used for Pearson chi-square test, and binary logistic regression analysis was used for multiple-factor analysis.Results:A total of 1 092 questionnaires were sent out and 1 050 were valid, with an effective rate of 96.2%. The average times of seeing a doctor or receiving other health services in community health service center in the past year were (4.60±4.10). The total awareness rate of basic public health services was 91.6%(962/1 050), and the total awareness rate of free public health services was 89.5% (940/1 050). The total scores of residents' satisfaction with community health service institutions were (4.61±0.75) points, among which the basic medical service scored the highest, and the institution facilities, system and basic information scored the lowest. Single factor analysis showed that 10 factors, such as type of medical insurance, preferred medical institution, walking time to community center and medical service time, were the influencing factors of residents' overall satisfaction. Multiple-factor analysis found that institutions and facilities, systems and basic conditions, basic medical services, medical expenses, the type of first-visited hospital were the four influencing factors of residents' overall satisfaction ( OR=21.294, 109.013, 18.203 and 20.989, respectively). Conclusion:The residents have a good utilization of community health services, and they have good awareness of public health service projects, but the residents' satisfaction with community health services still needs to be improved, especially in the aspects of facilities, equipment and service efficiency of medical staff.