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    Molecular study of benign and malignant thyroid nodules
    LI Haorong, HAN Rulai, YU Danyan, YE Lei
    Journal of Internal Medicine Concepts & Practice    2023, 18 (04): 266-269.   DOI: 10.16138/j.1673-6087.2023.04.011
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    Objective To establish a next-generation sequencing panel for the molecular diagnosis of thyroid nodules. Methods The panel, named ThyNod Panel, was designed to detect single nucleotide variant(SNV), indel, fusion, copy number variant (CNV) and RNA expression levels in 112 thyroid nodules associated genes, including benign and malignant molecular markers, thyroid differentiation or function genes and cell identity marker genes. Results The ThyNod Panel was successfully constructed and applied, and 856 benign or malignant thyroid nodules were completed sequencing. Totally 676 (79.0%) thyroid nodules were detected mutations. In 627 thyroid nodules with definite pathological diagnosis, 17.6% were benign nodules and 82.4% were malignant ones, in which malignant pathological types included classical papillary carcinoma, follicular variant papillary carcinoma, and medullary carcinoma. The most common mutant genes detected were BRAF (n=426), followed by RET (n=68), RET/PTC fusion (n=68), DICER1 (n=35), telomerase reverse transcriptase (TERT) (n=35), HRAS (n=24), NRAS (n=23), neurotrophin receptor kinase (NTRK3) fusion (n=19), and eukaryotic translation initiation factor 1A, X-chromosomal (EIF1AX) (n=11). The malignant percentage was counted for the detected mutations, and the malignant related variants such as BRAF V600E and RET fusion were higher than 90.0%, while the overall malignant percentage of RAS-like variants was only 18.9%. Conclusions ThyNod Panel can efficiently identify genetic characteristics in thyroid nodules and be applied in the molecular diagnosis of thyroid nodules.

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    Clinical and basic research on adrenal cortical carcinoma
    WU Luming, WANG Weiqing
    Journal of Internal Medicine Concepts & Practice    2023, 18 (04): 234-238.   DOI: 10.16138/j.1673-6087.2023.04.004
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    Clinical diagnosis and treatment progress of hypoglycemia caused by non-islet cell tumors
    ZHANG Jie, LU Jieli
    Journal of Internal Medicine Concepts & Practice    2023, 18 (04): 256-260.   DOI: 10.16138/j.1673-6087.2023.04.009
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    Diagnosis and treatment of primary hyperparathyroidism
    YANG Yuying, SUN Lihao, LIU Jianmin
    Journal of Internal Medicine Concepts & Practice    2023, 18 (04): 297-300.   DOI: 10.16138/j.1673-6087.2023.04.018
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    Relationship between serum uric acid and cognitive impairment
    LIN Weizhi, FU Yang, LUO Qi, CHEN Jie, MA Jianfang
    Journal of Internal Medicine Concepts & Practice    2023, 18 (04): 278-283.   DOI: 10.16138/j.1673-6087.2023.04.013
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    Objective To explore the relationship between serum uric acid and cognitive impairment. Methods This was a community-based prospective study. The baseline population(2011) was enrolled from a cohort(≥50 years old) of normal people in Wuliqiao and Malu community in Shanghai. The endpoint was the cognitive function assessment results of the last follow-up (2016). Cognitive assessment was performed using mini-mental status examination(MMSE). The uric acid level of the study population was divided into four quartiles from low to high score (Q1-Q4) in both male and female. Logistic regression was used to analyze the relationship between serum uric acid and cognitive impairment. Results A total of 312 people with an average age of (68.36±6.45) years old were enrolled, and there were 124 males (39.7%). During 5-year follow-up, the total people with cognitive impairments was 43, and the incidence rate was 13.8%. After adjusting age, gender and other related risk factors, multivariate Logistic regression analysis showed that people with higher uric acid level (Q3) had higher risk of cognitive impairment than those with low uric acid level (Q1), with an odds ratio(OR) of 2.53 [95% confidence interval (CI): 0.91-7.02]. After age stratification (50-70 years old; 70-90 years old), no positive results were found. However, stratified by gender, it was found that men with the highest uric acid level(Q4) had a higher risk of cognitive impairment than those with the lowest uric acid level (Q1)(OR=18.60,95%CI: 1.26-274.13), while no positive results were found in women. Conclusions Higher uric acid levels, especially in men, might increase the risk of cognitive impairment in people over 50 years.

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    New understanding of mechanism of Cushing’s disease
    ZHOU Weiwei, ZHENG Sichang, WANG Weiqing
    Journal of Internal Medicine Concepts & Practice    2023, 18 (04): 247-250.   DOI: 10.16138/j.1673-6087.2023.04.007
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    Research progress on molecular mechanism of primary aldosteronism
    JIANG Yiran, WANG Weiqing
    Journal of Internal Medicine Concepts & Practice    2023, 18 (04): 261-265.   DOI: 10.16138/j.1673-6087.2023.04.010
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    Research progress of cardiovascular damage in primary aldosteronism
    KE Yuya, GONG Yanchun
    Journal of Internal Medicine Concepts & Practice    2023, 18 (04): 301-304.   DOI: 10.16138/j.1673-6087.2023.04.019
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    Therapy progress for acromegaly
    ZHENG Sichang, ZHOU Weiwei, WANG Weiqing
    Journal of Internal Medicine Concepts & Practice    2023, 18 (04): 292-296.   DOI: 10.16138/j.1673-6087.2023.04.017
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    Ectopic adrenocorticotropic hormone syndrome
    ZHANG Cui, WANG Weiqing
    Journal of Internal Medicine Concepts & Practice    2023, 18 (04): 242-246.   DOI: 10.16138/j.1673-6087.2023.04.006
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    Clinical characteristics and prognosis of eosinophilic gastroenteritis in 71 cases
    BAI Yaya, TANG Biwen, HU Yueliang, ZUO Junli, YAO Weiyan
    Journal of Internal Medicine Concepts & Practice    2023, 18 (04): 270-277.   DOI: 10.16138/j.1673-6087.2023.04.012
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    Objectives To investigate the clinical features and prognosis of eosinophilic gastroenteritis (EGE). Methods Seventy-one cases diagnosed with EGE in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from October in 2003 to May in 2019 were recruited. The prognosis was followed up by telephone. The information including clinical manifestations, laboratory tests results, radiological features, endoscopic and pathological results, as well as prognosis were collected, and the statistical analysis was carried out using SPSS software. Results Seventy-one EGE patients [mean age (25.18±21.44)years, 64.8% males] were recruited in our study. 28/71(39.4%) cases had allergic history, in which 48.1% ones had food allergy. Abdominal pain (74.6%) was the most common symptom in the patients. The proportion of elevated peripheral blood eosinophils (EOS) direct count was significantly higher than that of EOS indirect count (P=0.043). 43/51 cases received gastroscopy biopsy and 45/53 cases received colonoscopy biopsy. As tissue EOS infiltration ≥20/HPF(high power field)was defined as pathologically positive, the positive rate of biopsy was significantly correlated with the number of biopsied sites (gastric: P=0.012, intestinal: P=0.014), but was not related to the total number of biopsy tissues(gastric: P=0.381, intestinal: P=0.553). 57/71 cases were followed-up successfully by telephone, in which 63.2% ones had recurrence. The patients with a higher rate of elevated peripheral EOS direct count and serum CRP (C-reactive protein), as well as a higher level of intestinal tissue EOS infiltration, showed significantly higher recurrence rate (P<0.05). The EGE patients using microflora regulator agents had significantly reduced recurrence rate [odds ratio (OR)=0.254, 95% confidence interval (CI): 0.068-0.946, P=0.041]. Conclusions EGE, as the disease commonly seen in young and middle-aged patients, is a chronic digestive disease related to food allergy, and its’ common clinical manifestation is abdominal pain. Testing peripheral EOS direct count could be more beneficial for the accurate assessment of peripheral EOS level. Multi-sites gastrointestinal endoscopy biopsy is helpful to increase the pathologically positive rate of EGE diagnosis. Increase of peripheral EOS count, serum CRP and intestinal EOS infiltration can be used to predict a higher risk of recurrence. Microflora regulator agents might help reduce the recurrence rate of EGE.

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    Efficacy and safety of daratumumab in treatment of relapsed/refractory multiple myeloma
    ZHOU Rui, WU Tao, XUE Feng, TIAN Hongjuan, LIU Wenhui, MAO Dongfeng
    Journal of Internal Medicine Concepts & Practice    2023, 18 (05): 348-351.   DOI: 10.16138/j.1673-6087.2023.05.008
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    Objective To explore the efficacy and safety of daratumumab(DARA) in the treatment of relapsed/refractory multiple myeloma (R/RMM). Methods We retrospectively analyzed 14 patients treated with DARA, who were diagnosed with R/RMM at our hospital during January 2020 to June 2022. The clinical efficacy, progress free survival (PFS), overall response rate (ORR) and safety after treatment were evaluated. Results Total of 14 patients included 8 males and 6 females, in which the median age was 56.5(33-72) years, and the median disease duration was 29.5(10-96) months. The diagnostic classifications were 2 cases of IgA-κ type, 1 case of IgA-λ type, 7 cases of IgG-κ type, 2 cases of IgG-λ type, 2 cases of unsecretory type, respectively. In 14 patients, 5 patients received 2-line therapy in the past, 6 patients received 3-line therapy, and 3 patients received 4-line therapy. All 14 patients completed the first course of DARA treatment and the treatment efficacy was able to be evaluated. Among them, 5 patients achieved hematological complete response (CR), 4 patients achieved very good partial response (VGPR), 2 patients achieved partial response (PR) and 3 patients achieved stable disease(SD). Among them, 13 patients survived, and 1 patient died of lung infection during non-treatment period. The median duration of the disease was 29.5(10-96) months, the median follow-up time was 6(2-14) months, the PFS time was 5(2-12) months, and the ORR was 78.6%. There were no grade Ⅳ adverse reactions during the treatment period. Among them, blood pressure in 1 patient increased and frequent ventricular premature beats occurred in 1 patient. These adverse reactions were both grade Ⅰ adverse reactions., and could be effectively controlled and improved after active treatment. Conclusions R/RMM treated with DARA on the basis of conventional treatment can improve ORR and depth of remission and prolong the PFS of patients, and shows high safety; but its long-term efficacy still needs to be further observed.
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    Importance of drug monitoring for compound sulfamethoxazole therapy in patients with Pneumocystis jiroveci pneumonia
    FANG Jie, CHEN Chao, ZHOU Min
    Journal of Internal Medicine Concepts & Practice    2024, 19 (01): 31-35.   DOI: 10.16138/j.1673-6087.2024.01.06
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    Pneumocystis jiroveci pneumonia (PJP) is one of the more common and serious opportunistic infections in patients with human immunodeficiency virus (HIV). With the use of immunosuppressants and chemotherapy drugs, most PJP cases reported in China are non-HIV immunosuppressed patients. Compound sulfamethoxazole (SMZco) is the first-line drug for the treatment of PJP, and there are wide individual differences in its pharmacokinetics. Through citing a PJP case treated with SMZco under drug monitoring, a systematic review was conducted from the aspects of SMZco pharmacokinetics, dose-related adverse reactions, and optimal therapeutic dose research. It aims to demonstrate the importance of drug monitoring for sulfamethoxazole therapy, which ensures the drug reaches effective therapeutic concentrations and the occurrence of its’ adverse reactions was reduced.

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    Research progress of hyaluronic acid and its related factors in pancreatic cancer
    GUO Xiaoqian, YAO Weiyan
    Journal of Internal Medicine Concepts & Practice    2023, 18 (04): 305-308.   DOI: 10.16138/j.1673-6087.2023.04.020
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    Comparison of efficacy and adverse effects of sevelamer with lanthanum carbonate on treatment of hyperphosphatemia in patients undergoing peritoneal dialysis
    BAO Lingling, HUANG Xiaomin, ZHANG Chunyan, ZHANG Qianying, WANG Zhaohui, XU Tian, REN Hong
    Journal of Internal Medicine Concepts & Practice    2023, 18 (06): 394-399.   DOI: 10.16138/j.1673-6087.2023.06.004
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    Objective To investigate the efficacy and adverse effects of different non-calcium-phosphate binders on the treatment of hyperphosphatemia in patients with end-stage kidney disease undergoing peritoneal dialysis. Methods A total of 124 patients with hyperphosphatemia undergoing peritoneal dialysis who were initially treated with non-calcium-phosphate binders agent were enrolled in the Department of Nephrology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from May in 2019 to March in 2021. Among them, 61 cases were treated with sevelamer and 63 cases were treated with lanthanum carbonate. Serum phosphorus, serum calcium, parathyroid hormone(PTH), 25-OH-VitD, alkaline phosphatase level and abdominal aortic calcification score (AACS) before and after treatment were compared in sevelamer or lanthanum carbonate treated groups, furthermore, the pill burden and cost were evaluated. Results The median follow-up time was 16.9 (9.0, 27.2) months until the end of October 2021. Serum phosphorus level was (1.70±0.31), (1.52±0.24) and (1.60±0.34) mmol/L at 1st, 3rd and 6th month after treatment, respectively, and significantly decreased than baseline [(2.08±0.31) mmol/L, P<0.05]. After 1 month and 3 months of treatment, the compliance rate in the lanthanum carbonate treated group was higher than that in the sevelamer treated group (27.0% vs 8.2%, P=0.006; 63.5% vs 39.3%, P=0.007); while after 6 months of treatment, there was no significant difference in PTH level and 25-OH-VitD level between sevelam treated group and lanthanum carbonate treated group[324.3 (178.1, 469.7) ng/L vs 304.4 (165.8, 413.3) ng/L, P=0.414; 15.01 (11.98, 22.75) nmol/L vs 20.02 (16.01, 27.19) nmol/L, P=0.376]. There were no significant differences in AACS and cardiac valve calcification score between the two groups before and after treatment. Gastrointestinal side effects such as nausea and vomiting were more common in lanthanum carbonate treated group (15.9% vs 1.6%, P=0.005). Conclusions Compared with sevelamer, lanthanum carbonate has a faster dephosphorization effect and higher initial serum phosphorus compliance rate, but the digestive tract tolerance is poor.

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    Evolution of understanding of primary bilateral macronodular adrenal hyperplasia
    ZHOU Weiwei, WANG Weiqing
    Journal of Internal Medicine Concepts & Practice    2023, 18 (04): 239-241.   DOI: 10.16138/j.1673-6087.2023.04.005
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    Research progress on diabetes patients combined with COVID-19 infection
    HUANG Xianna, CHEN Yunce, ZHOU Min, NI Lei
    Journal of Internal Medicine Concepts & Practice    2024, 19 (01): 77-81.   DOI: 10.16138/j.1673-6087.2024.01.14
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    Diabetic patients are not only susceptible population to COVID-19 infection,but also prone to develop immune imbalance, excessive inflammatory responses, multi-organ dysfunction, and other complications after infection, resulting in complicated condition and a significantly increased risk of critical illness. Therefore, it requires more attention of clinicians. The article reviews the relevant domestic and international literatures and summarizes the mechanisms of abnormal glucose metabolism induced by COVID-19 infection, clinical characteristics of diabetes patients infected with COVID-19, and the principles of blood glucose management, to improve the clinical understanding and treatment success rate of such patients.

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    Is severe pneumonia ARDS?
    HE Quanying
    Journal of Internal Medicine Concepts & Practice    2024, 19 (01): 19-24.   DOI: 10.16138/j.1673-6087.2024.01.04
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    The acute respiratory distress syndrome (ARDS) is an acute hypoxic respiratory insufficiency caused by severe infection, shock, trauma and burns. It is easily confused with severe pneumonia combined with hypoxemia and severe COVID-19 pneumonia. In this paper, the concept, pathogenesis, pathological changes, pathophysiology and definition of ARDS were discussed, and the similarities and differences between ARDS and severe pneumonia combined with hypoxemia or severe COVID-19 pneumonia were analyzed and conducted in-depth interpretation.

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    Metabolic risk factors for development of neuroendocrine tumors
    ZHANG Jie, BI Yufang
    Journal of Internal Medicine Concepts & Practice    2023, 18 (04): 251-255.   DOI: 10.16138/j.1673-6087.2023.04.008
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    M2-sEV inhibit endoplasmic reticulum stress to alleviate chronic intermittent hypoxic-induced H9C2 cardiomyocyte injury
    HE Meijuan, HE Yanjie, WANG Yun, ZHU Chunxue, HUANG Hanpeng
    Journal of Internal Medicine Concepts & Practice    2023, 18 (06): 416-423.   DOI: 10.16138/j.1673-6087.2023.06.008
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    Objective To investigate the effect and mechanism of M2 macrophages-derived small extracellular vesicle (M2-sEV) on injury of H9C2 cardiomyocytes induced by chronic intermittent hypoxia (CIH). Methods Interleukin-4(IL-4) was used to induce the polarization of RMa-bm macrophages to M2-type. The mRNA expression levels of M2-type markers CD206 and arginase-1(Arg-1) were detected by quantitative reverse transcription PCR (qRT-PCR). M2-sEV were extracted and identified. The signature proteins CD9, CD63 and CD81 of M2-sEV were detected by Western blotting(WB). H9C2 cells were randomly divided into control(CON) group, CIH group and CIH+M2-sEV group. CCK8 was used to detect cell viability, and qRT-PCR and WB were respectively used to detect mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α), IL-6、tumor necrosis factor-α(TNF-α)、transforming growth factor-β(TGF-β) and apoptotic factors(cleaved caspase-3、cleaved caspase-9、Bcl-2、Bax) as well as endoplasmic reticulum stress factors (IRE1α、XBP1、ATF6、GRP78). Results M2-type macrophages were polarized successfully and M2-sEV were extracted successfully. CCK8 showed that M2-sEV increased the proliferation activity of H9C2 cardiomyocytes under CIH. Compared with the CON group, the expression level of HIF-1α, inflammatory factors (IL-6,TNF-α,TGF-β), pro-apoptotic proteins(cleaved caspase-3, cleaved caspase-9, Bax) and endoplasmic reticulum stress factors (IRE1α, XBP1, ATF6, GRP78) were significantly increased in the CIH group(P<0.05) in both mRNA and protein level. The protein level of Bcl-2 in the CIH group was decreased, and the ratio of Bax/Bcl-2 was increased in the CIH group (P<0.05). However, after co-incubating with M2-sEV, the expressions of HIF-1α, inflammatory factors, pro-apoptotic proteins and endoplasmic reticulum stress factors in CIH group were significantly decreased (P<0.05), and the expression of Bcl-2 and the ratio of Bax/Bcl-2 were also decreased (P<0.05). Conclusions M2-sEV can alleviate the injury of H9C2 cell induced by CIH, which is related to the downregulation of endoplasmic reticulum stress, inhibition of inflammation and reduction of apoptosis.

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