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30 April 2024, Volume 19 Issue 02 Previous Issue   
Original article
Clinical efficacy of venetoclax combined with azacytidine in treatment of newly treated elderly patients with acute myeloid leukemia who were intolerant to intensive chemotherapy
ZHAO Huijin, JIN Zhen, ZHANG Yunxiang, WU Min, ZHENG Yu, WU Wen, SHEN Yang, CHEN Qiusheng, LI Junmin, CHEN Yu
2024, 19 (02):  89-94.  DOI: 10.16138/j.1673-6087.2024.02.01
Abstract ( 42 )   HTML ( 1 )   PDF (996KB) ( 12 )  

Objective To investigate the clinical characteristics of 35 elderly patients with acute myeloid leukemia (AML) who were newly treated and intolerant to intensive chemotherapy and evaluate treatment efficacy and safety of venetoclax combined with azacytidine (VEN+AZA). Methods Between February 2021 and March 2022, 35 AML elderly patients who were intolerant to intensive therapy were enrolled in the study. They received VEN+AZA induction therapy. The disease characteristics, VEN+AZA induced remission and treatment safety were retrospectively analyzed and reported. Results The median age of enrolled patients was 68 year old, and there were 9 cases diagnosed with secondary AML. All patients completed bone marrow cytogenetic and molecular biology evaluation and were stratified by European LeukemiaNet (ELN) genetic risk classification. Thirty-five patients were classified as low risk group (10 of 35 cases), intermediate risk group (12 of 35 cases) and high risk group (13 of 35 cases). Common genetic mutations included DNA methyltransferase 3A (DNMT3A) (n=11), isocitrate dehydrogenase (IDH) 1/2 (n=11), ten-eleven translocation 2 (TET2) (n=9), NPM1 (n=8) and Fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) (n=6). The overall complete remission (CR) rate of treatment was 65.7% (n=23), and the CR rate of patients with mutation of NPM1, FLT3-ITD, IDH1/2 were 87.5%, 66.7% and 72.7%, respectively. The total negative rate of minimal residual disease (MRD) among CR patients was 73.9%, the median follow-up time was 10.1 months and median event-free survival (EFS) was 11.3 months. Among remission patients, MRD-negative patients had longer EFS and overall survival than MRD-positive patients(P<0.05). The early mortality rate was 5.7%. The most common adverse reaction during treatment was hematological toxicity (treatment-induced grade 3-4 neutropenia 31.4%, grade 3-4 thrombocytopenia 25.7%, febrile neutropenia 48.6%) and pulmonary infection (17.1%). Conclusions Our results showed that VEN+AZA has a higher overall response rate in newly treatment elderly AML who were intolerant to intensive chemotherapy, which was similar with the clinical trial results. NPM1 mutation might indicate higher CR rate. The EFS and OS of MRD-negative patients were longer than those of MRD-positive patients, and the risk of death was reduced. In summary, VEN+AZA regime was currently one of the most promising strategies for newly treated elderly AML who couldn’t tolerate intensive chemotherapy.

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Study on correlation between thyroid hormone levels and cardiac function in type 2 diabetes mellitus patients
CHEN Junxiu, SHI Qun, QIN Li, WU Yiming
2024, 19 (02):  95-101.  DOI: 10.16138/j.1673-6087.2024.02.02
Abstract ( 22 )   HTML ( 5 )   PDF (920KB) ( 15 )  

Objective To determine the relationship between thyroid hormones levels and cardiac function and structure in type 2 diabetes mellitus (T2DM) patients with normal thyroid function. Methods Totally 526 cases of T2DM patients with normal thyroid function were enrolled, and their information including gender, age, course of disease, blood pressure, blood lipids, liver and kidney functions, and thyroid function were collected; Color diagnostic ultrasound equipment was used to analyze the structure and function of the heart. Results Compared with the male group, the indexes including total cholesterol(TC), high density lipoproteincholesterol (HDL-C), low density lipoproteincholesterol(LDL-C), left ventricular ejection fraction(LVEF), and thyroid stimulating hormone(TSH) were significantly higher in the female group, while the indexes including height, weight, hemoglobin(Hb), blood urea nitrogen(BUN), creatinine(Cr), uric acid(UA), left atrial diameter (LAD), interventricular septum thickness(IVST), left ventricular end diastolic diameter (LVEDD), left ventricular posteriorwall thickness(LVPWT), left ventricular end systolic diameter(LVESD), aortic root diameter(AORD), free triiodothyronine(FT3), and free thyroxine(FT4) were significantly lower in the female group (all P<0.05). Correlation analysis showed that FT3 was positively correlated with LVPWT, LVESD and AORD in the general population (all P<0.05 ). In the male group, TSH was positively correlated with LVESD; in female group, FT3 was positively correlated with LAD and LVESD, and FT4 was negatively correlated with LVEF(P<0.05). Multiple linear regression analysis showed that for female patients, FT3 was an independent fact of LVESD, as the other independents factors, which were age, duration of diabetes, body mass index (BMI), glycosylated hemoglobin, diastolic blood pressure and systolic blood pressure. Conclusions For T2DM patients with normal thyroid function, as the increase of circulating thyroid hormones, LVPWT and LVESD increase. Multiple regression analysis showed that FT3 was independently and positively correlated with cardiac structure in female patients. These results indicate that thyroid hormone levels in patients with T2DM might have an impact on the heart changes even if they are within the normal range.

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Analysis of related factors of sarcopenia in type 2 diabetic nephropathy patients on maintenance hemodialysis
WU Mengmeng, YANG Fuyan, LIU Yuchen, LU Xuke, GAO Jingge, YE Ziling
2024, 19 (02):  102-106.  DOI: 10.16138/j.1673-6087.2024.02.03
Abstract ( 18 )   HTML ( 1 )   PDF (821KB) ( 8 )  

Objective To analyze related factors of sarcopenia in type 2 diabetic nephropathy patients on maintenance hemodialysis (MHD), in order to reduce the incidence of sarcopenia. Methods The clinical data of 237 patients with MHD complicated with sarcopenia were collected from the Blood Purification Center of the Affiliated People’s Hospital of Xinxiang Medical College from September 2021 to April 2023 retrospectively and analyzed. The patients were divided into type 2 diabetic nephropathy group (100 cases) and non-diabetic nephropathy group (137 cases), and the clinical data and the result of bioelectrical impedance analysis (BIA) were compared between the two groups. Multivariate Logistic regression model was used to analyze the related factors affecting sarcopenia in MHD patients with diabetic nephropathy. Results There were significant differences in gender, fasting blood glucose, serum creatinine, albumin, prealbumin, 25-hydroxyvitamin D, body mass index (BMI), fat mass (FM), arm circumference (AC), visceral fat area (VFA) and 50 kHz phase angle between the two groups(all P<0.05). Multivariate Logistic regression analysis showed that gender, fasting blood glucose, albumin and BMI were independent influencing factors of sarcopenia in MHD diabetic nephropathy patients (odds ratio =0.372, 1.350, 0.925, 1.451, all P<0.05). Conclusions Male, hypoalbuminemia, hyperglycemia and high BMI patients with MHD are more likely to have sarcopenia among diabetic nephropathy patients with MHD.

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Study on correlation between serum apelin-12 level and coronary artery calcification
ZHAO Anqi, YANG Ling, ZHA Qing, YANG Ke, LIU Yan
2024, 19 (02):  107-114.  DOI: 10.16138/j.1673-6087.2024.02.04
Abstract ( 14 )   HTML ( 1 )   PDF (1081KB) ( 4 )  

Objective To investigate the correlation between serum vasoactive polypeptide-12 (apelin-12) and coronary artery calcification (CAC). Methods Totally 197 cases of patients, who were treated with coronary artery CT angiography (CTA) in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2015 to December 2018 were selected. According to Agatson score, the patients were divided into two groups, which were CAC scores≤100(n=72)and CAC scores>100 (n=125). The relevant clinical indexes of patients were collected, and the serum apelin-12 level was detected by enzyme-linked immunosorbent assay to explore its relationship with CAC and its related cardiovascular events. Results The baseline characteristics in two groups showed that serum apelin-12 level in CAC scores >100 group was lower than that in CAC scores ≤100 group [79.50 (68.35,97.49) ng/L vs 91.94 (80.13,110.19) ng/L], which showed significant difference(P=0.02). Binary Logistic regression analysis showed that apelin-12 levels were associated with the occurrence of CAC in the unadjusted model (P=0.013). After adjusting for the indicators with baselines difference, apelin-12 levels were still associated with the occurrence of CAC. Kaplan-Meier survival analysis found that compared to higher apelin-12 levels, lower apelin-12 levels were associated with an increased risk of cardiovascular events(Log rank test, P=0.019). In subgroups with CAC scores >100, apelin-12 levels were associated with an increased risk of outcome events (Log rank test, P=0.035). Cox regression analysis was used to determine the predictive effect of apelin-12 levels in different subgroups and found that the predictive effect of apelin-12 levels on outcome events was found to be stronger in patients aged > 65 years, with renal insufficiency and diabetes mellitus. Conclusions Serum apelin-12 is correlated with CAC and related cardiovascular events, suggesting that apelin-12 may be a biomarker for predicting CAC and its prognosis.

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Pinocembrin alleviates BEAS-2B cell damage induced by chronic intermittent hypoxia through inhibiting autophagy
HE Yanjie, HE Meijuan, WANG Yun, ZHU Chunxue, HUANG Hanpeng
2024, 19 (02):  115-120.  DOI: 10.16138/j.1673-6087.2024.02.05
Abstract ( 29 )   HTML ( 1 )   PDF (1410KB) ( 6 )  

Objective To investigate the effect of pinocembrin (PIN) on BEAS-2B human bronchial epithelial cell injury induced by chronic intermittent hypoxia (CIH) and its possible regulatory mechanism. Methods The optimal CIH intervention duration and PIN treatment concentration were determined by cell counting kit 8 (CCK8) in BEAS-2B cells. BEAS-2B cells were divided into control group (CON group), CIH group and CIH+PIN group. The proliferation activity of BEAS-2B cells in different treatment groups was detected by CCK8. Western blotting (WB) was used to detect the protein expression levels of hypoxia-inducible factor 1α (HIF-1α), apoptosis related gene [cleaved caspase 3, B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax)] and autophagy related genes [light chain 3(LC3)-Ⅱ, beclin-1, P62]. After adding the autophagy inhibitor 3-methyladenine (3-MA), the cells were divided into five groups: CON group, CIH group, CIH+3-MA group, CIH+PIN group, and CIH+3-MA+PIN group, and the expression levels of HIF-1α, apoptosis and autophagy related genes in each group were detected. Results CCK8 showed that the proliferation activity of BEAS-2B cells significantly decreased between 24-48 h with the prolongation of hypoxia time. PIN could up-regulate the proliferative activity of BEAS-2B cells under CIH. The results of WB showed that compared with CON group, the protein expressions of HIF-1α, Bax, LC3-Ⅱ and beclin-1 were increased in CIH group (P<0.05). The expression of P62 and anti-apoptosis gene Bcl-2 protein was significantly down-regulated (P<0.05). After adding 3-MA, the protein expression level of HIF-1α was reduced, autophagy and apoptosis were inhibited. The same trend was observed after adding PIN. Conclusions PIN can reduce CIH-induced BEAS-2B cell damage and exert a protective effect. The mechanism may be related to down-regulating autophagy level and inhibiting cell apoptosis.

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Investigation and analysis of clinical blood transfusion situations
ZHANG Yi, XIE Dongfu, LIU Dongsheng, ZHENG Yi, YANG Jianhao, SUN Jie
2024, 19 (02):  121-125.  DOI: 10.16138/j.1673-6087.2024.02.06
Abstract ( 21 )   HTML ( 1 )   PDF (890KB) ( 5 )  

Objective To provide evidence-based medical basis for evaluation of blood transfusion in patients with different diseases and achieve precise blood transfusion through the investigation and analysis of blood transfusion situation in several hospitals. Methods The data of blood transfusion patient in two general tertiary hospitals and three general secondary hospitals in Shanghai using the largest amount of blood from July to December 2021 was collected, and the information including age, blood type, department, disease, blood transfusion volume and blood transfusion components of patients were analyzed. Results The total red blood cell infusion was 37 813 U [median is 2(2, 4) U]in tertiary hospitals and 45 577 U [median is 4(2, 8) U] in secondary hospitals, and the difference was statistically significant (P<0.05). The total plasma infusion was 33 689 U [median was 2(0, 4) U] in tertiary hospitals and 26 822 U [median was 0(0, 4)U] in secondary hospitals., and there was significant difference between the two groups (P<0.05). The total platelet transfusion volume was 3 586 U [median was 0(0, 0) U] in the tertiary hospitals and 23 414 U [median was 0(0, 5) U] in the secondary hospitals, and the results showed statistically different (P<0.05). The per capita infusion volume of suspended red blood cells and platelets was the highest in patients with hematology diseases(respectively 6(2,11) U and 5(1, 9) U), while the per capita plasma infusion volume was the highest in patients with neurological diseases [4(0, 32) U]. Conclusions There is large variation in the transfusion volumes of different types of blood components in different departments in hospitals of different size. Each hospital should make blood transfusion evaluation plan based on evidence-based medicine according to its own conditions and the patient disease, so as to achieve precise blood transfusion and ensure scientific and rational use of blood in clinic.

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Research report
Occurrence and risk factors of hypoglycemia in type 2 diabetes mellitus patients treated with continuous subcutaneous insulin infusion during perioperative period
BAI Yuanyuan, HUO Lili, LI Wei, LAN Ling, DENG Wei
2024, 19 (02):  126-129.  DOI: 10.16138/j.1673-6087.2024.02.07
Abstract ( 17 )   HTML ( 1 )   PDF (829KB) ( 7 )  

Objective To investigate the occurrence and risk factors of type 2 diabetes mellitus (T2DM) patient treated with continuous subcutaneous insulin infusion (CSII) hypoglycemia during perioperative period. Methods A total of 96 patients with fractures and T2DM who received CSII therapy during perioperative period in Beijing Jishuitan Hospital were selected as research subjects. Clinical data including medical history, glycosylated hemoglobin (HbA1c), liver and kidney function, occurrence of hypoglycemia and postoperative complications were collected. Logistic regression analysis was used to analyze the risk factors of hypoglycemia. Results The average time reaching the blood glucose target was (2.8±1.3) d in the perioperative patients with T2DM received intensive CSII treatment, and the overall incidence of hypoglycemia was 15.6%. There were 15 patients in the hypoglycemia group and 81 patients in the non-hypoglycemia group. Compared with the non-hypoglycemia group, the hypoglycemia group was older [(71.1±11.1) years vs (56.0±10.6) years, P=0.000] and had longer course of disease [14.0 (8.8-17.8) years vs 5 (2.8-12.0) years, P=0.017], lower estimated glomerular filtration rate (eGFR) [(78.7±27.5) mL/(min·1.73 m2) vs (106.8±15.0) mL/(min·1.73 m2), P=0.005], and higher incidence of postoperative infection (25% vs 3%, P=0.024). Logistic regression analysis showed that older age (OR=1.172, 95%CI: 1.027-1.091, P=0.012), longer course of disease (OR=1.193, 95%CI: 1.001-1.420, P=0.049) and lower eGFR (OR=0.950, 95%CI: 0.903-0.998, P=0.049) were independent risk factors for hypoglycemia in perioperative T2DM patients treated with CSII. Conclusions The perioperative T2DM patients can quickly achieve the blood glucose target through CSII therapy. Older age, long course of diabetes and low eGFR level are risk factors for hypoglycemia.

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Review
Role of gut microbiota in mediating metabolic and cardiovascular abnormalities in patients with obstructive sleep apnea and related mechanisms
ZHU Xiaowen, WANG Hongchao, WU Wenjun
2024, 19 (02):  130-135.  DOI: 10.16138/j.1673-6087.2024.02.08
Abstract ( 25 )   HTML ( 3 )   PDF (850KB) ( 12 )  

Obstructive sleep apnea (OSA) is a common sleep disorder characterized by intermittent hypoxia and sleep fragmentation, which is closely associated with the development of hypertension, atherosclerosis, insulin resistance and other metabolic diseases. A lot of studies have found that OSA can cause the disturbance of gut microbiota and affect human health. This paper reviews the possible mechanisms of gut microbiota disturbance and related metabolic and cardiovascular changes caused by OSA in clinical trials and animal models, and the new complementary therapies derived from them. The aim of the paper is to use gut microbiota as an entry point to re-understand the relationship between OSA and metabolic and cardiovascular abnormalities, and provides new ideas for early intervention of OSA and related complications.

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Advances in study of PCSK9 inhibitors in treatment of non-alcoholic fatty liver disease
SHEN Yun, XU Yijiao, WEI Xiao, ZHANG Ruixiang, LIU Chao
2024, 19 (02):  136-139.  DOI: 10.16138/j.1673-6087.2024.02.09
Abstract ( 33 )   HTML ( 4 )   PDF (842KB) ( 15 )  

Non-alcoholic fatty liver disease (NAFLD) is the chronic liver disease with the highest incidence rate, and its main cause is due to disorders of lipid metabolism and damage to the liver caused by ectopic fat deposition. Proprotein convertase bacillus subtilis/ kexin type 9 (PCSK9), as a lipid-regulating protease in vivo, plays a key role in abnormal lipid metabolism. Dyslipidemia levels can be significantly improved by inhibiting PCSK9 binding to receptors circulating in vivo. Therefore, PCSK9 inhibitors may improve the condition of NAFLD patients and achieve therapeutic effects.

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Progress in treatment of activated phosphoinositide 3-kinase δ syndrome
WU Tao, LIU Wenhui
2024, 19 (02):  140-143.  DOI: 10.16138/j.1673-6087.2024.02.10
Abstract ( 23 )   HTML ( 1 )   PDF (904KB) ( 13 )  

Phosphoinositide 3-kinase δ (PI3Kδ) activated phosphoinositide 3-kinase δ syndrome (APDS) was first reported in 2013. APDS is an autosomal dominant primary immunodeficiency disease (PID) caused by mutations in the PIK3CD gene or PIK3R1 gene. The clinical manifestations of APDS are recurrent respiratory tract infection, non-neoplastic lymphoid hyperplasia, autoimmune diseases and lymphoma. In this paper, the treatment of APDS is introduced in detail. In addition to conventional treatment for immunodeficiency, treatment such as antimicrobial prophylaxis, immunoglobulin replacement therapy and hematopoietic stem cell transplantation were reviewed, and more specific mammalian target of rapamycin (mTOR) inhibitors and PI3Kδ inhibitors were also discussed.

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New dietary concepts for patients with gout and hyperuricemia
WU Julei, MAO Lihua, YU Tingting, LIN Cong, MIAO Yu, ZHU Xiaoxia, CAO Ling
2024, 19 (02):  144-148.  DOI: 10.16138/j.1673-6087.2024.02.11
Abstract ( 30 )   HTML ( 8 )   PDF (832KB) ( 13 )  

The prevalence of gout and hyperuricemia is increasing year by year, leading to a rise in the disease burden. Reasonable dietary interventions for patients or high-risk groups are beneficial in reducing the incidence of these diseases and improving the quality of chronic disease self-management for patients. The research progress on dietary patterns for patients with gout and hyperuricemia was analyzed in this article, which recommended adherence to generally recognized healthy eating patterns for the long-term dietary management, rather than simply distinguishing between “good” or “bad” foods or excessively following a low-purine diet. The aim of the study is to provide better guidance for the self-management of gout and hyperuricemia patients.

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Conference summary
Proceedings of Ninth International Conference of Parkingson’s Disease & Movement Disorders and Tele-Medicine Seminar of Chinese Stroke Association
WANG Bin, WANG Shuhong, WANG Xiaoping
2024, 19 (02):  149-151.  DOI: 10.16138/j.1673-6087.2024.02.12
Abstract ( 12 )   HTML ( 0 )   PDF (794KB) ( 9 )  

This proceeding paper introduced the Ninth International Conference of Parkingson’s Disease (PD) & Movement Disorders and Tele-Medicine Seminar of Chinese Stroke Association in Shanghai on June 8-10th, 2023. The conference was supported by the Core Faculty Team of World Congress on Controversies in Neurology, and hosted by the First People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and Jiading Branch. Prof Xiaoping Wang, Amos D Korczyn, and Gang Zhao served as the chairman of the conference. Ten well-known experts and professors from Pakistan, Israel, United States, Greece, Sweden gave conference lectures through Zoom meeting and conducted extensive discussions and lively debate on rare cases such as Parkinson’s disease, cerebrovascular disease, epilepsy, migraine, and hepatolenticular degeneration, which was similar to the World Congress on Controversies in Neurology. A number of professional bilingual translators were invited to conduct English Chinese simultaneous translation. The conference attracted more than 30 000 international viewers and listeners and achieved good communication effects.

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