Effect of home-based cardiac rehabilitation for patients with heart failure: a systematic review and meta-analysis / Rehabilitación para pacientes con insuficiencia cardíaca: una revisión sistemática y metanálisis

SUMMARY: This study is to investigate the effect of home-based cardiac rehabilitation (HBCR) on quality of life, functional capacity, and readmission rates in patients with heart failure. Randomized controlled trials (RCTs) were screened from Cochrane Library, CINAHL, EMBASE, and MEDLINE. The intervention group received a standardized HBCR or a comprehensive rehabilitation strategy that included HBCR. The participants in the control group received CR at a medical center or usual care without CR intervention. The main outcome measurements included quality of life, exercise capacity, mortality and re-hospitalization. This meta-analysis included 20 RCTs, in which 16 studies compared HBCR with usual care, and 4 studies compared HBCR with center-based CR. In comparison with the usual care, HBCR improved the total quality of life score [MD=-5.85, 95 % CI (-9.76, - 1.94), P=0.003, I2=75 %]. Patients with HBCR and usual care were significantly different in VO2max [MD=1.05 mL/kg/min, 95 % CI (0.35, 1.75), P=0.003, I2=46 %]. However, VO2max of patients with HBCR was not significantly different from those with center-based CR [MD=0.08 mL/kg/min, 95 % CI (-1.29, 1.44), P=0.91, I2=0 %]. There was statistically significant difference in the 6-min Walk Distance between usual care and HBCR (for distance [MD=11.84, 95 % CI (7.41, 16.28), P<0.00001, I2=0 %]; and for feet [MD=98.93, 95 % CI (26.79, 171.08), P=0.007, I2=56 %]). However, there was no significant difference in 6-min Walk Distance between patients with HBCR and center-based CR [MD=12.45, 95 % CI (-9.81, 34.72), P=0.27, I2=0 %] , or in anxiety and depression between patients with usual care and HBCR (for anxiety, [MD=-0.25, 95 % CI (-0.56, 0.05), P=0.11, I2=0 %]; for depression, [MD=-0.18, 95 % CI (-0.51, 0.16), P=0.30, I2=0 %] . No significant difference was found in death number [RR=1.04, 95 % CI (0.55, 1.98), P=0.90, I2=0 %] or in the number of re-hospitalization [RR=0.88, 95 % CI (0.66, 1.18), P=0.40, I2=0 %] between usual care and HBCR. For patients with heart failure, compare with usual care and center-based CR, HBCR can improve the total quality of life. Compare with usual care, HBCR can improve VO2max and 6-min Walk Distance, but compare with center- based CR, there are no differences in mortality, re-hospitalization rate or incidence of anxiety and depression. Additionally, center- based CR and HBCR showed similar outcomes and medical costs.

El objetivo de este estudio fue investigar el efecto de la rehabilitación cardíaca domiciliaria (HBCR) sobre la calidad de vida, la capacidad funcional y las tasas de reingreso en pacientes con insuficiencia cardíaca. Se seleccionaron ensayos controlados aleatorios (ECA) de la Biblioteca Cochrane, CINAHL, EMBASE y MEDLINE. El grupo de intervención recibió un HBCR estandarizado o una estrategia de rehabilitación integral que incluía HBCR. Los participantes del grupo de control recibieron RC en un centro médico o atención habitual sin intervención de RC. Las principales medidas de resultado incluyeron la calidad de vida, la capacidad de ejercicio, la mortalidad y la rehospitalización. Este metanálisis incluyó 20 ECA, en los que 16 estudios compararon HBCR con la atención habitual y 4 estudios compararon que mejoró la puntuación total de calidad de vida [DM=-5,85, IC del 95 % (-9,76, -1,94), P=0,003, I2=75 %]. Los pacientes con HBCR y atención habitual fueron significativamente diferentes en el VO2máx [DM = 1,05 ml/kg/ min, IC del 95 % (0,35, 1,75), P = 0,003, I2 = 46 %]. Sin embargo, el VO2max de los pacientes con HBCR no fue significativamente diferente de aquellos con CR basada en el centro [DM = 0,08 ml/kg/min, IC del 95 % (-1,29, 1,44), P = 0,91, I2 = 0 %]. Hubo una diferencia estadísticamente significativa en la distancia de caminata de 6 minutos entre la atención habitual y HBCR (para la distancia [DM=11,84, IC del 95 % (7,41, 16,28), P<0,00001, I2=0 %]; y para los pies [DM= 98,93, IC 95 % (26,79, 171,08), P=0,007, I2=56 %]). Sin embargo, no hubo una diferencia significativa en la distancia de caminata de 6 minutos entre los pacientes con HBCR y CR basada en el cen- tro [DM = 12,45, IC del 95 % (-9,81, 34,72), P = 0,27, I2 = 0 %], o en la ansiedad y depresión entre pacientes con atención habitual y HBCR (para ansiedad, [DM=-0,25, IC del 95 % (-0,56, 0,05), P=0,11, I2=0 %]; para depresión, [DM=-0,18, 95 % IC (- 0,51, 0,16), P=0,30, I2=0 %] No se encontraron diferencias significativas en el número de muertes [RR=1,04, IC del 95 % (0,55, 1,98), P=0,90, I2=0 %] o en el número de reingresos [RR=0,88, IC 95 % (0,66, 1,18), P=0,40, I2=0 %] entre atención habitual y HBCR. Para los pacientes con insuficiencia cardíaca, en comparación con la atención habitual y la CR en un centro, la HBCR puede mejorar la calidad de vida total. En comparación con la atención habitual, la HBCR puede mejorar el VO2máx y la distancia recorrida en 6 minutos, pero en comparación con la CR basada en un centro, no hay diferencias en la mortalidad, la tasa de rehospitalización o la incidencia de ansiedad y depresión. Además, CR y HBCR basados en el centro mostraron resultados y costos médicos similares.

Curative effect of capreomycin in adjuvant treatment of multidrug-resistant pulmonary tuberculosis and its effect on quality of life and immune function / 中国热带医学

@#Abstract: Objective To investigate the efficacy of capreomycin adjuvant therapy for multidrug-resistant pulmonary tuberculosis (MDR-TB) and its effect on quality of life and immune function. Methods Eighty-eight elderly pulmonary tuberculosis patients admitted to Affiliated Hospital of Hebei University from October 2019 to October 2020 were selected and divided into two groups according to the random number table method. The control group (n=44) used 4-6Am-Mfx（Lfx）-Pto-Cfz-Z-Hhigh-dose-E/5 Mfx（Lfx）-Cfz-Z-E, the research group (n=44) used capreomycin on the basis of the control group. The 6-Minute Walk Test (6MWT) measured value/predicted value and quality of life [36-Item Short Form Health Survey Questionnaire (SF-36)] scores, safety evaluation results, chest CT cavity and lesion absorption rate and sputum culture turned negative were compared between the two groups, and the serum procalcitonin (PCT) expression levels and immune function were detected before and after treatment. Results The 6MWT measured value/predicted value of the research group and control group before the treatment were (0.48±0.11) and (0.64±0.13), which were significantly higher than corresponding (0.51±0.12) and (0.58±0.14) after treatment (t=6.23, 2.520, P<0.05), the measured/expected value of 6MWT increased in both groups after treatment. Compared with the same group before treatment, the SF-36 scores for each dimension increased in both groups after treatment (P<0.01). The expression levels of serum PCT in the research group and control group before the treatment were (0.37±0.09) ng/mL and (0.12±0.03) ng/mL versus (0.36±0.11) ng/mL and (0.21±0.06) ng/mL after treatment (t=17.480, 7.940, P<0.01). Compared with the same group before treatment, serum PCT expression levels decreased in both groups after treatment. Compared with the same group before treatment, CD3+, CD4+ and CD4+/CD8+ were elevated in both groups after treatment (P<0.05 or P<0.01); after treatment, CD3+, CD4+, and CD4+/CD8+ were significantly higher in research group compared to the control group (t=4.21, 8.02, 2.04, P<0.05). The absorption rate of chest CT cavity and lesions and negative rate of sputum culture in the research group were 88.64% (39/44) and 81.82% (36/44), which were significantly higher than corresponding 63.64% (28/44) and 61.36% (27/44) in the control group (P<0.05). Conclusions　Capreomycin can improve the quality of life of MDR-TB patients, extend the 6-minute walking distance, and regulate serum PCT expression levels and immune function, to promote the absorption of chest CT cavity and lesions, and sputum culture to turn negative, and the security is acceptable.

Comparison of serum levels of sclerostin, Dickkopf-related protein 1, and irisin in patients with type 1 and type 2 diabetes / 中华内分泌代谢杂志

Objective:Both type 1 diabetes and type 2 diabetes are associated with abnormal bone metabolism, but they have different pathogenic mechanisms. Sclerostin(SOST), Dickkopf-related protein 1(DKK-1), and irisin are newly discovered factors involved in the regulation of bone metabolism. This study aims to compare the differences in serum levels of SOST, DKK-1, and irisin between patients with type 1 diabetes and type 2 diabetes.Methods:This cross-sectional study included 101 patients with type 1 diabetes who visited the Endocrinology Department of Peking Union Medical College Hospital from 2017 to 2019, as well as 55 patients with type 2 diabetes and 59 individuals with normal glucose tolerance who were confirmed through an oral glucose tolerance test as part of the Beijing Changping Community Type 2 Diabetes Management Program from 2014 to 2015. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of SOST, DKK-1, and irisin.Results:There were more female participants than male participants, with an average age of 49 years. The group with type 1 diabetes had a longer duration of illness( P<0.001) and higher HbA 1C levels( P<0.001) compared to the group with type 2 diabetes, and there was no statistical difference in age between the two groups. Both the type 1 diabetes and type 2 diabetes groups had lower levels of serum procollagen type 1 N-terminal propeptide(P1NP) compared to the control group [(8 579±400)pg/mL, (7 268±552)pg/mL vs(10 051±618)pg/mL, P=0.039, P=0.001]; But the β isomer of C-terminal cross-linking telopeptide of type 1 collagen(β-CTX) showed no statistical difference compared to the control group. Patients with type 1 diabetes and type 2 diabetes had higher SOST than controls [(129.7±6.8)pg/mL, (104.8±6.8)pg/mL vs(85.9±5.3)pg/mL, P<0.001, P=0.030], the differences between the type 1 diabetes group and the control group lost statistical significance after adjusting for factors such as fasting blood glucose and lipid levels. There was no significant difference in SOST between type 1 diabetes and type 2 diabetes groups. There was no significant difference in DKK-1 among three groups, but DKK-1 in type 1 diabetes group was lower or tended to be lower than that in type 2 diabetes group. Serum irisin in patients with type 1 diabetes was higher than that in controls and patients with type 2 diabetes[(16.6±0.7)ng/mL vs (9.6±0.6)ng/mL, (9.8±0.6)ng/mL, both P<0.001], but there was no significant difference in irisin level between type 2 diabetes and controls. Conclusions:Patients with both type 1 and type 2 diabetes showed inhibition of the bone formation marker P1NP, while the bone resorption marker β-CTX did not significantly change. SOST levels were elevated or showed an increasing trend in both type 1 and type 2 diabetes patients, which may be related to the inhibition of bone formation. Additionally, type 1 diabetes patients had increased levels of irisin, which may be involved in abnormal bone turnover.

Serum Uric Acid Level and Its Influencing Factors in Patients with Diabetes Insipidus / 中国医学科学院学报

Objective To investigate the level of serum uric acid in patients with diabetes insipidus (DI),summarize the clinical characteristics of central diabetes insipidus (CDI) patients with hyperuricemia (HUA),and analyze the factors affecting the level of serum uric acid in the patients with CDI. Methods The clinical data of DI patients admitted to Peking Union Medical College Hospital from 2018 to 2021 were retrospectively analyzed.The patients were assigned into a child and adolescent group (≤ 18 years old) and an adult group (>18 years old) according to their ages.The demographic and biochemical data between two groups of patients with and without HUA were compared.Spearman correlation analysis and multiple linear regression analysis were performed to analyze the correlations between serum uric acid level and other factors. Results Among the 420 DI patients,411 patients had CDI (97.9%),including 189 patients with HUA (46.0%).Thirteen (6.9%) out of the 189 CDI patients with HUA presented the disappearance of thirst.The prevalence of HUA in children and adolescents was higher than that in adults (χ2=4.193,P=0.041).The level of serum uric acid in the CDI patients with HUA and disappearance of thirst was higher than those without disappearance of thirst (U=2.593,P=0.010).The multiple linear regression predicted serum creatinine (β=0.472,95%CI=2.451-4.381,P<0.001) and body mass index (β=0.387,95%CI=6.18-12.874,P<0.001) as the independent risk factors of serum uric acid level increment in children and adolescents,while serum creatinine (β=0.361,95%CI=1.016-1.785,P<0.001),body mass index (β=0.208,95%CI=2.321-6.702,P<0.001),triglyceride (β=0.268,95%CI=12.936-28.840,P<0.001),and total cholesterol (β=0.129,95%CI=2.708-22.250,P=0.013) were the independent risk factors in adults. Conclusions The patients with CDI were more likely to have HUA,and the prevalence of HUA in children and adolescents was higher than that in adults.Body mass index,serum creatinine,triglyceride,total cholesterol,and disappearance of thirst were the risk factors for the increased level of serum uric acid in CDI patients.

Clinical Characteristics of 5 Cases of Immune Checkpoint Inhibitor Induced Diabetes Mellitus / 罕见病研究

  Objective  By summarizing the clinical characteristics and follow-up outcomes of 5 patients with immune checkpoint inhibitor induced diabetes mellitus (ICI-DM) and reviewing the relevant literatures, the article aims at providing reference to clinicians in the diagnosis and treatment of the ICI-DM.  Methods  Clinical data of 5 patients with ICI-DM who were admitted to Peking Union Medical College Hospital from December 2018 to February 2023 and did retrospectively analyzed.  Results  Five patients with a mean age of (65±7)years received treatment by the programmed cell death 1 (PD-1) or its ligand inhibitor (PD-L1). The median time from the first immunotherapy to the discovery of elevated plasma glucose was 100 (43, 210)days, and the median cycle of immunotherapy was 7 (2.5, 10.5). The onset of the illness of all the 5 patients started with diabetic ketosis or ketoacidosis. At the onset, urine ketone bodies were positive, random plasma glucose was (36.36±15.89)mmol/L, glycosylated hemoglobin A1c (HbA1c)was (8.6%±0.66%), arterial blood pH was (7.28±0.16), and the median fasting C-peptide level was 0.09 (0.05, 0.32)μg/L. Five patients had an onset plasma glucose level of grade 3 or 4.Then, ICI treatment was discontinued in all patients and insulin therapy started. The daily dosage of insulin was (56±20)IU, supplemented with hypoglycemic drugs. After treatment, urine ketone body turned negative, pH value increased to normal range, and random plasma glucose decreased significantly (the median difference of random blood glucose before and after treatment was 21.30 mmol/L, P=0.043) showing that the treatment was effective. During the follow-up, all patients continued to use insulin. The PD-1 or PD-L1 inhibitors were restarted after hyperglycemia remission. The tumor condition was under control.  Conclusions  ICI-DM mainly occurs in patients who receive treatment with PD-1 or PD-L1 inhibitors usually with acute hyperglycemia whose laboratory tests indicate insulin secretion defects. Some patients had positive islet cell antibodies, glutamic acid decarboxylase antibodies and autoantibodies.Patients with positive autoantibodies needed early diagnosis and continuous insulin treatment. ICI treatment can be restarted after endocrinologists brought the blood glucose under control.

Study on the molecular mechanism of Cinnamomi Cortex-Rehmanniae Radix in preventing and treating osteoporosis based on multi-directional regulation of inflammatory factors, estrogen and bone homeostasis / 药学学报

In this study, the molecular mechanism of Cinnamomi Cortex-Rehmanniae Radix (CR) in the prevention and treatment of osteoporosis (OP) was investigated by integrating compatibility analysis of compound, bioinformatics and metabolomics. The rat OP models were established, and the Micro-CT indexes and pathological sections were comprehensively evaluated. The results showed that compared with the model group, the indexes such as bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were significantly increased after CR treatment (P < 0.05), and the bone trabeculae were arranged into mesh. The results of UHPLC-Q-TOF/MS mainly involved amino acid metabolism, lipid metabolism and estrogen metabolism pathways. Integrating bioinformatics and metabolomics analysis, it was finally found that: ① cinnamic acid and ethylcinnamate inhibit inflammatory factors such as TNF, IL-1β, and IL-13, thereby preventing and treating OP; ② multiple active ingredients of CR target ESR2, PPARG, and CYP19A1, GABRA1 and other targets, regulate cAMP synthesis, AMPK signaling pathway and lipid metabolism, thereby regulating estrogen levels to prevent and treat OP; ③ oleic acid, arachic acid, etc. act on AR, VDR and other targets, and regulate HIF-1 signaling pathway and AGE-RAGE signaling pathway, thereby regulating osteoblasts and osteoclasts, and affecting calcium and phosphorus absorption to maintain bone homeostasis. This study clarified the molecular mechanism of CR in preventing and treating OP from the perspective of multi-directional regulation of inflammatory factors, estrogen and bone homeostasis, and provided theoretical basis for the clinical application of CR and the development of compound. This experiment complied with the ethical standards of animal experiments and was approved by the Animal Ethics Committee of Shaanxi University of Chinese Medicine (No. SUCMDL20210309002).

Application of statins in nonalcoholic fatty liver diseases: Benefits and risks / 中华内分泌代谢杂志

Nonalcoholic fatty liver diseases (NAFLD) is a chronic epidemic disease characterized by liver steatosis which is driven by metabolic disorders. The prevalence of NAFLD increases annually and there are currently no available therapies. Statins can modulate lipid metabolism, and reduce systemic inflammation and liver fibrosis, which are thought to improve NAFLD and metabolic disorders. However, the mechanism has not yet been clarified, and benefits of statin therapy remain controversial. In this paper, we reviewed the mechanisms, benefits and risks of statin therapy for NAFLD.

Effect and Mechanism of Sulforaphane on G / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of sulforaphane (SFN) on G@*METHODS@#KG1a and KG1cells were treated by different concentrations of SFN for 48 h. Flow cytometry (FCM) was used to analyze the phase distribution of cell cycle. High-throughput sequencing was used to detect the effect of SFN on the expression of cell cycle related genes in KG1a cells. The mRNA expression of P53, P21, CDC2 and CyclinB1 were detected by qPCR. The protein expression of P53, CDC2, P-CDC2 and CyclinB1 were detected by Western blot.@*RESULTS@#Cells in the G@*CONCLUSION@#SFN induces leukemia cells to block in G

A three-year follow-up observation of a pedigree of maturity onset diabetes of the young caused by a novel mutation of glucokinase and literature review / 中华内科杂志

Objective:To explore the clinical characteristics and follow-up outcomes of a pedigree of maturity onset diabetes of the young (MODY) induced by a novel mutation of glucokinase (GCK).Methods:The clinical features and laboratory data of a pedigree diagnosed with GCK-MODY in Peking Union Medical College Hospital was analyzed. Genomic DNA was extracted, and Sanger sequencing was performed to detect the gene mutation of the family members. The proband and her father were followed up for 3 years. Wanfang and PubMed were used to search literatures on follow-up studies for treatment of GCK-MOYD.Results:Both the proband and her father were found to have a novel mutation on the GCK gene located in exo10 c.1348G.T (p. Ala450Thr). The proband was treated with diet and exercise control only. At the end of the follow-up, her fasting plasma glucose (FPG, 6.8 mmol/L), 2 h postprandial plasma glucose (2hPG, 7.4 mmol/L), and glycated hemoglobin (HbA1c, 6.3%) were all within the control targets. Additionally, the levels homeostasis model assessment of insulin resistance (HOMA-IR) tended to improved comparing to that at baseline (4.09 to 2.32), and glucose disposition index (DI) was improved compared with baseline (16.22 to 20.05). As to the proband′s father, the treatment with insulin plus acarbose was converted to sulfonylureas monotherapy. His FPG and 2hPG mostly were within the target range, and the levels of HbA1c were significantly reduced by 0.5%-0.7% when compared to that at baseline. The HOMA-IR or islet beta cell function was comparable to those at baseline.Conclusions:Screening patients whose clinical performance meets GCK-MODY and their family members with proper genetic testing is of great importance to reduce misdiagnosis of GCK-MODY, so as to obtain a better glucose control without unnecessary over-treatment and protect islet beta cell function.

The two-way regulation molecular network mechanism of Taohechengqi decoction in prevention and treatment of stroke based on vascular endothelial growth factor signaling pathway/tumor necrosis factor signaling pathway / 药学学报

Stroke has been harmful to human health for a long time, and there is no satisfactory treatment strategy because of its complex pathogenesis. Taohechengqi decoction has been effective in the treatment of stroke. In this study, the components were collected by TCMSP, TCMIP, BATMAN-TCM and TCMID databases, the targets were predicted and screened by PharmMapper and BATMAN-TCM databases, and the functional enrichment analysis of the targets was carried out by using R language package clusterProfiler. Finally, the key targets are verified by GEO database and molecular docking. The results showed that 51 active components of Taohechengqi decoction may regulate 15 key targets such as nitric oxide synthase, endothelial (NOS3), prostaglandin G/H synthase 2 (PTGS2), matrix metalloproteinase-9 (MMP9), affecting vascular endothelial growth factor signaling pathway and other pathways to play a role in the prevention of stroke, affecting tumor necrosis factor signaling pathway and other pathways to play a role in the treatment of stroke. GEO data analysis showed that androgen receptor (AR), caspase-8 (CASP8), intercellular adhesion molecule 1 (ICAM1), interleukin-1 beta (IL1B), mitogen-activated protein kinase 14 (MAPK14), MMP9, myeloperoxidase (MPO), peroxisome proliferator-activated receptor gamma (PPARG), PTGS2 and cellular tumor antigen p53 (TP53) were up-regulated genes, while serum albumin (ALB), estrogen receptor 1 (ESR1), NOS3, transcription factor p65 (RELA) and proto-oncogene tyrosine-protein kinase Src (SRC) were down-regulated genes. GEO analysis explained that Taohechengqi decoction may prevent stroke by down-regulating ESR1, NOS3, and treat stroke by up-regulating ICAM1, IL1B, MAPK14, MMP9, PPARG, PTGS2, TP53, and down-regulating RELA and SRC. The study found that in the process of prevention and treatment of stroke, Taohechengqi decoction played a two-way regulation role through multi-genes and multiple ways, which provided a new strategy for the treatment of stroke.

Efficacy and peripheral immunity analysis of allogeneic natural killer cells therapy in patients with hepatocellular carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the safety and efficacy of allogeneic natural killer (NK) cells in the treatment of primary hepatocellular carcinoma (HCC), and to elucidate the mechanism of NK cells therapy.@*METHODS@#Twenty-one patients with primary HCC treated with allogeneic NK cells at the Fifth Medical Center of the PLA General Hospital were followed up for 1 year. Peripheral blood mononuclear cells (PBMCs) were isolated from patient-related donors and cultured in vitro for 15 days and infused to the patients in two consecutive days. Clinical data and laboratory data were collected and analyzed, including survival, clinical features, imaging changes, hematology, immunology, and biochemical indicators to evaluate the safety and efficacy of allogeneic NK cell therapy. The changes of peripheral blood lymphocyte subsets after treatment were also analyzed to explore the possible anti-tumor mechanisms.@*RESULTS@#(1) Of the 21 patients with primary HCC, 11 patients were treated once, 5 patients were treated twice, and 5 patients were treated 3 times. After allogeneic NK cells infusion, 10 patients had fever, 1 patient had slight hepatalgia and 1 patient had slight headache, no other adverse events occurred including acute and chronic graft-versus-host disease (GVHD). They resolved spontaneously within 8 hours without other treatment. (2) The total disease control rate was 76.2% during one-year follow-up. Among them, the patients with Barcelona clinic liver cancer (BCLC) stage A had a disease control rate of 100%, stable disease (SD) in 10 cases; BCLC stage B patients had a disease control rate of 60%, partial response (PR) in 1 case, and SD 2 in cases; BCLC stage C patients had a disease control rate of 50%, complete response (CR) in 1 case, and 2 cases of PR. (3) The frequencies of NK cells and CD8+ T cells in peripheral blood were significantly lower than that before at 24 hours after treatment, and the frequencies of CD4+ T cells and CD4/CD8 were significantly higher than the baseline.@*CONCLUSION@#Allogeneic NK cells have good safety and efficacy in the treatment of primary HCC. The anti-tumor effect of the allogeneic NK cells may play an important role in the activation of the patient's natural immune system and delay disease progression, suggesting that allogeneic NK cells combined with sorafenib may be a very effective treatment for advanced HCC, and further large-sample multicenter randomized controlled clinical trials are needed to validate this result.

Effect of peritoneal dialysis on glycemic variability in patients with diabetes and its clinical implications / 中华临床营养杂志

Objective To compare glycemic profile between diabetic patients receiving peritoneal dialysis and diabetic patients with normal kidney function, and to investigate the impact of peritoneal dialysis on glycemic control through continuous glucose monitor system ( CGMS). Methods 19 diabetic patients with end-stage renal disease receiving regular peritoneal dialysis (DMPD group) and 8 patients with non-diabetic ne-phropathy receiving regular peritoneal dialysis ( PD group) were randomly selected and matched with 20 diabetic patients with normal kidney function (DM group) based on age, gender and 72 hours mean glucose. CGMS were applied on all patients for 72 hours. Glycemic variability parameters were compared among the three groups. Results Peritoneal transport function was positively correlated with mean glucose, glucose standard deviation and mean amplitude of glycemic excursion. Compared with PD group, multiple variation parameters, such as intraday glycemic standard deviation (P<0. 001), covariant efficiency (P=0. 009) and mean of daily difference (P=0. 043), were significantly lower in DMPD group. Though both DMPD and DM group exhibited profile as trough in wee hours and post-prandial hyperglycemia, DMPD had higher glycemic level in wee hours (P<0. 001). Conclusion Diabetic patients with end-stage renal disease receiving regular peritoneal dialysis have smaller glucose variability than diabetic patients with normal renal function.

Nonalcoholic Fatty Liver Disease and Weight Loss / 中国医学科学院学报

Nonalcoholic fatty liver disease(NAFLD)refers to hepatic steatosis without other known causes such as alcohol abuse or hepatic virus infection. NAFLD has become a chronic disease worldwide,and its prevalence is constantly growing. Hepatic insulin resistance caused by obesity results in the deposition of triglycerides in the liver,promoting the occurrence and development of NAFLD. Weight loss is the only safe and effective method for NAFLD. Lifestyle intervention plays a cornerstone role in treating NAFLD;however,most patients can not achieve and maintain the ideal body weight by lifestyle intervention alone. Glucagon-like peptide-1 receptor agonist and metabolic surgery are promising treatments for NAFLD.

Human insulin and its analog injection-induced localized lipoatrophy: 6 case reports and systemic review / 中华临床营养杂志

Objective To investigate clinical and pathological characteristics of insulin-induced localized lipoatrophy and treatment.Methods We retrospectively analyzed clinical manifestation, skin biopsy pathology, treatment regimen and follow-up of 6 diabetic patients with insulin-induced localized lipoatrophy in Peking Union Medical College Hospital from January, 2010 to March, 2016, with systemic review of related literatures.Results Among 6 cases with insulin-induced localized lipoatrophy, 5 patients were with insulin allergy.5 patients were with positive insulin-autoimmune antibody, which was similar to the ratio reported in the systematic review (18 out of 19).Insulin-induced lipoatrophy could be caused by various types of preparations of insulin and insulin analogs.Subcutaneous biopsy, performed on the atrophied area, revealed the decrease of the number and volume of adipocytes and tissue fibrosis, probably accompanied with lymphocytes, eosinophils or mast cells infiltration.Lipoatrophy could sometimes be relieved by changing injection sites, types of insulin preparations or drug-delivery way, sometimes by application of systemic/local glucocorticoid or local cromolyn sodium.Conclusions Insulin-induced localized lipoatrophy is a rare adverse reaction of insulin preparations.It might be related to immune response of local tissue and heterogeneous pathological manifestations.The lipoatrophy might be improved by changing injection sites, changing the type of insulin preparations or drug-delivery way, and with possibility to carry out targeted immunosuppressive therapy according to the biopsy pathology in the future.

The influence of icariin on apoptosis and cytoskeleton of osteoblasts in response to overload damage / 医用生物力学

Objective To study the effect of the icariin on apoptosis and cytoskeleton of osteoblasts in response to overload damage. Methods The four-point bending loading device was used to simulate the mechanical environment of overload damage and establish the cell overload damage model. According to whether the drugs were added before or after mechanical loading, the experiment was divided into blank control group, icariin group, damage group, damage prevention group and damage treatment group. Cell apoptosis was detected by flow cytometry. The specific fluorescent dyes were used to label the actin filament and the nucleus, and the changes of cytoskeleton were observed under laser scanning confocal microscope. Results Compared with control group, the apoptosis rate of damage group was the highest, and the icariin group was the lowest (P<0.05). Compared with damage group, the apoptosis rate of the damage prevention group was the lowest (P<0.05). The damage group showed cell shrinkage deformation, microfilaments disorganization, loosely arranged skeleton with vague outline, even broken skeleton. The morphological changes of cytoskeleton in damage prevention group were not significant, and there was no obvious change in cell nucleus. Conclusions Icariin can inhibit the apoptosis of osteoblasts after overload injury and maintain the stability of cytoskeleton to some extent.

DNA Methylation and Birth Weight: a Genome-wide Analysis / 生物医学与环境科学（英文）

The study illustrate the inner correlation between global DNA methylation variation and different birth weights. Infant birth weight was used to identify cases and controls. Cord blood and placentas were collected. We performed DNA methylation profiling of bisulphite-converted DNA. We have identified many differentially methylated CpG sites in experimental groups; these sites involved in hundreds of signalings. Among these, more than ten pathways were referred to the glucose and lipid metabolism. Methylation changes in the insulin-signaling pathway (ISP), adipocytokine signaling pathway (ASP) and MAPK signaling pathway are involved in the fetal programming of diabetes..

Association between the SNPs in microRNA bindingsites of ABCG5/8 and metabolism of glucose and lipid during pregnancy / 基础医学与临床

Objective To explore the relationship between SNPs in microRNA binding sites of ABCG5/8 and the glucolipid level during pregnancy.Methods 1 925 pregnant women were recruited at Peking Union Medical College hospital from 2006 to 2011.The clinical data were collected and the total genomic DNA was extracted from whole blood samples.ABCG5/8, which was reported to be related with the glucose and lipid metabolism closely, were selected as the candidate gene and the SNPs in its microRNA binding sites with minor allele frequency >5% in Han Chinese in Beijing were chosen.Then the genotyping was performed and analyzed.Results There was only one SNP matching the criteria, rs2278356, and it is significantly associated with LDL-C and TC level during pregnancy (LDL-C: b=0.104 mmol/L, 95% CI 0.023-0.185 mmol/L, P<0.05;TC: b=0.105 mmol/L, 95% CI 0.080-0.203 mmol/L, P<0.05).Conclusions The association of rs2278356 in 3′UTR of ABCG5/8 with LDL-C and TC level in pregnant Chinese Han women is found, which may provide an individualized treatment strategy for pregnant women with high cholesterol.

Effects of Arsenic Trioxide on K562 Cell Proliferation and Its Mechanisms / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of arsenic trioxide (AsO) on K562 cell proliferation by regulating cell cycle protein D1 and cyclin-dependent kinase inhibitor p27kip1.</p><p><b>METHODS</b>MTT was used to detect the effect of AsOon K562 cell proliferation, so as to screen out the appropriate drug concentration. Furthermore, the K562 cell apoptosis was observed by microscopy. The expression of CyclinD1 and p27kip1 in K562 cells treated with AsOwas analyzed by reverse transcription-polymerase chain reaction(RT-PCR), immunohistochemistry and Western blot.</p><p><b>RESULTS</b>AsOcould inhibit the proliferation of K562 cells in a dose- and time- dependent manner (r= 0.967). And the apoptosis cell number in AsOgroup was significantly higher than that in the control group(P<0.05). AsOcould markedly inhibit the expression of CyclinD1 in K562 cells(P<0.05), but the expression of P27kip1 was not significantly changed after AsOtreatment.</p><p><b>CONCLUSIONS</b>AsOcan induce K562 cell apoptosis and inhibit K562 cell proliferation by regulating the expression of CyclinD1.</p>

Retrospective analysis about effects of initiating insulin therapy on islet function patients with latent autoimmune diabetes in adults / 中华全科医师杂志

Objective To investigate the effects of initiating oral-medication and insulin-treatment to residual islet function in adult patients with latent autoimmune diabetes in adults (LADA).Methods Fifty nice inpatients and 11 outpatients of LADA were enrolled from the Peking Union Medical College Hospital from January 1981 to October 2014,including 34 cases with initiating insulin therapy and 36 cases with initiating oral medication.Patients were followed up at least twice and with a 6-month interval.The age,body mass index (BMI),diagnosis time,fasting C peptide (FCP),2-hour postprandial C peptide (2 hCP),glycosylated hemoglobin (HbA1c) were compared between two groups.Results The age of disease onset in insulin-treatment group was significantly lower than that in oral-medication group (t =2.049,P =0.045).The proportion of patients complicated with other autoimmune diseases in oralmedication group were higher than that in insulin-treatment group [24％ (8/34) vs.47％ (17/36),x2=4.275,P=0.039].The FCP and 2 hCP in insulin-treatment group were significantly higher than those in oral-medication group [FCP:0.25 (0.00-0.80) vs.0.00 (0.00-0.60) μg/L,Z =3.498,P =0.030,2 hCP:0.42(0.02-1.20) vs.0.14(0.02-0.19) μg/L,Z =3.235,P=0.001] on 6 month after treatment;however,there were no significant differences on 6-12 months,13-36 months or 37-60 months after treatment between two groups.No antibody negative conversion was detected in 10 inpatients,who were reexamined with glutamic acid decarboxylase antibody (GADA) more than twice.The detection rate of diabetes retinopathy was 4％ (1/26) in insulin-treatment group and 28％ (8/29) in oralmedication group (x2 =6.179,P =0.013).Conclusion Initiating insulin therapy at first diagnosis of LADA can protect the residual islet function,and may reduce the rate of diabetic retinopathy.

Associations of White Blood Cell Count,Alanine Aminotransferase,and Aspartate Aminotransferase in the First Trimester withGestational Diabetes Mellitus / 中国医学科学院学报

Objective To explore the associations of white blood cell (WBC) count,alanine aminotransferase (ALT),and aspartate aminotransferase(AST) in the first trimester of pregnancy with gestational diabetes mellitus (GDM). Methods Totally 725 GDM women and 935 women who remained euglycemic throughout pregnancy were enrolled in this study. Pre-pregnancy weight/height were recorded. WBC,ALT,and AST levels were detected between 8 and 12 weeks of pregnancy.At 24 to 28 weeks of pregnancy,the glucose and insulin levels were measured. The WBC,ALT,and AST levels were compared between two groups,and the associations of WBC,ALT,and AST levels with the blood glucose and insulin levels were retrospectively analyzed. Meanwhile,the potential associations of those factors with the occurrence of GDM were analzyed. Results WBC count [9.41(8.15,10.84)?10(9)/L vs. 9.04 (7.64,10.37)?10(9)/L,P=1.0?10(-5)] and ALT levels [18.00(12.00,30.00)U/L vs. 16.00 (11.00,26.00)U/L,P=0.004] in the first trimester of pregnancy were significantly increased in GDM subjects than in normal glucose tolerance(NGT)subjects;however,the AST level showed no significant difference between these two groups [41.00 (26.00,43.00)U/L vs. 41.00 (23.00,43.00)U/L,P=0.588]. Logistic regression analysis illustrated that elevated WBC count was an independent risk factor for GDM after adjustment for age,pre-pregnancy body mass index,blood pressure,and family history of diabetes(OR=1.119,P=0.001). The ROC curve revealed that threshold of WBC count was 7.965?10(9)/L(AUC=0.566,P=1?10(-5)),which had a sensitivity of 79.4% and a specificity of 31.3%. Multivariate linear regression analysis showed that homeostasis model assessment of insulin resistance was positively correlated with WBC count(B=0.051,P=0.022,R(2)=0.083);1-hour blood glucose after oral 50 grams of sugar (B=0.044,P=0.001,R(2)=0.044) and fasting plasma true insulin(B=0.214,P=0.032,R(2)=0.066) were positively correlated with WBC count;1-hour true insulin after 100 grams oral glucose to lerance test(OGTT) was positively correlated with AST (B=0.616,P=1.85?10(-5),R(2)=0.052);2-hour true insulin after 100 grams OGTT was positively correlated with ALT (B=0.148,P=0.027)and AST(B=0.936,P=3.71?10(-8),R(2)=0.077);and 3-hour true insulin after 100 grams oral glucose tolerance test(OGTT) was positively correlated with ALT (B=0.189,P=0.002) and AST (B=0.688,P=7.25?10(-6),R(2)=0.067).Conclusions The WBC count in the first trimester of pregnancy can increase the risk of GDM. Thus,WBC count may be a useful predictors of GDM.