OBJECTIVE To observe the short-term efficacy and safety of venetoclax combined with homoharringtonine and cytarabine in the treatment of acute myeloid leukemia （AML）. METHODS The data of 40 newly diagnosed AML patients admitted to our hospital from October 2022 to November 2023 were retrospectively collected and divided into observation group and control group according to treatment plan， with 20 cases in each group. The patients in the control group were given Daunorubicin hydrochloride for injection+Cytarabine for injection， and the patients in the observation group were given Venetoclax tablets+ Homoharringtonine injection+Cytarabine for injection. The patients in both groups were given relevant medicine， with 28 days as one cycle. The short-term efficacy， negative rate of minimal residual disease （MRD）， duration of granulocyte deficiency， duration of platelet （PLT） ＜20×109 L－1， transfusion volume of suspended red blood cells and platelet， and the occurrence of adverse drug reactions were evaluated in both groups after 1 cycle of induction chemotherapy. RESULTS The complete remission or complete remission with incomplete hematologic recovery （CR/CRi） rate in the observation group was significantly higher than control group （P＜0.05）， and the negative rate of MRD in the observation group was also significantly higher than control group （P＜0.05）. However， in low-， medium- and high-risk patients， there was no statistical significance in CR/CRi rates between the two groups （P＞0.05）. There were no significant differences in the duration of agranulocytosis， the duration of PLT ＜20×109 L－1， the amount of suspended red blood cell transfusion， the amount of platelet transfusion， the incidence of hematologic toxicity and the incidence of non-hematologic toxicity between 2 groups （P＞0.05）. CONCLUSIONS Venetoclax combined with homoharringtonine and cytarabine show good short-term efficacy and safety in the treatment of AML.

Objective To investigate the risk factors associated with the presence of multiple Lugol-voiding lesions(LVLs)in patients with early esophageal cancer and the correlation with alcohol dehy-drogenase 1B(ADH1B)and aldehyde dehydrogenase 2(ALDH2)polymorphisms.Methods Patients who underwent endoscopic submucosal dissection due to early esophageal cancer were divided into group with multiple LVLs and group without multiple LVLs based on their endoscopic features.Their clinical data and the genotype of ADH1B and ALDH2 were collect-ed and SPSS 27.0 was used to statistically analyze the above data.Results A total of 83 subjects were included in the study,23 had multiple LVLs,most of them were seen in males,alcohol drinkers,and smokers with smoking index≥1 000,and multivariate analysis showed that alcohol consumption was an independent risk factor for it(OR=6.215,P=0.008).The gene polymorphism of ADH1B and ALDH2 and their interactions did not have any sig-nificant correlation with multiple LVLs.However,among alcohol drinkers,there was a 12-fold increased risk of multiple LVLs in patients carrying the ALDH2 A allele and drinking≥50 g per day compared to those carrying the ALDH2 GG genotype and drinking<50 g per day(P=0.045).Conclusion Alcohol consumption is an inde-pendent risk factor of multiple LVLs of the esophageal mucosa in patients with early esophageal cancer,and heavy alcohol consumption in carriers of the ALDH2 A allele will significantly increase the risk of multiple LVLs,and such patients should be closely followed up with endoscopy.

Pyroptosis is a recently discovered programmed cell death mediated by cysteinyl aspartate specific proteinase （Caspase）， which may lead to the release of intracellular inflammatory substances to extracellular and induce inflammatory cascades.Autoimmune diseases （ADs） is a kind of disease in which the body's immune tolerance is impaired， and the body overproduces autoantibodies， causing damage to its tissues.The pathogenic factors of ADs are complex and the pathogenesis is still unclear. With the deepening of the research on pyroptosis， more and more results show that pyroptosis is involved in the pathogenesis of various ADs such as rheumatoid arthritis， ulcerative colitis， systemic lupus erythematosus， and psoriasis. Glucocorticoid drugs， anti-rheumatism drugs， and biological agents are mostly used in the clinical treatment of ADs， but the therapeutic effect of some drugs is limited， and there are some long-term adverse reactions. Chinese medicine in the treatment of ADs has been proven to be safe and effective in long-term clinical practice. It has the characteristics of multiple targets and few side effects and has certain advantages in controlling the course of the disease. More and more studies have found that a variety of Chinese medicine formulations， single Chinese medicine， and active ingredients of Chinese medicine treat ADs through the intervention of pyroptosis. Therefore， this paper reviewed the experimental studies on the effect of Chinese medicine on pyroptosis in ADs in recent years， hoping to provide references for clinical treatment and scientific research.

Objective : To investigate the effect of platelet particles on the extent of intestinal inflammation and in⁃ testinal mucosal permeability in mice with dextran sodium sulfate induced colitis. Methods : The experiment was divided into four groups : normal control group ( n = 10 , drinking sterile distilled water + intraperitoneal injection of 0. 9% sodium chloride solution) , PMPs group ( n = 10 , drinking sterile distilled water + intraperitoneal injection of PMPs) , DSS model group ( n = 10 , drinking DSS solution + intraperitoneal injection of 0. 9% sodium chloride solution) , and experimental group ( n = 15 , drinking DSS solution + intraperitoneal injection of PMPs) . Peripheral blood⁃derived PMPs suspension was collected from inflammatory bowel disease ( IBD) patients. A colitis model was constructed in mice by allowing them to freely drink a 5% DSS solution for 1 week , followed by continuous intraperitoneal injection of PMPs for 7 days. Disease activity index (DAI) scores was recorded daily and the severity of intestinal inflammation with histopathological scores (HI) was assessed by HE staining of colon samples at the end of the experiment. Myeloperoxidase (MPO) , neutrophil elastase (NE) , citrullinated histone H3 (citH3) , and free DNA levels were measured in colon homogenate , observe intestinal mucosal structure by transmission electron microscopy , and intestinal permeability was tested using fluorescein isothiocyanate⁃dextran (FITC⁃D) . Results: Compared with the normal control group , the colonic mucosa of mice in the PMPs group showed edema , severe destruction of epithelial structure , extensive aggregation of inflammatory cells , and increased overall HI score (P < 0. 01) ; the levels of inflammatory factors such as IL⁃1β and TNF⁃α in colonic tissue homogenates of mice in the PMPs group increased (P < 0. 05) , and the expression of NETs increased (P < 0. 05) ; the plasma FITC⁃D level of mice in the PMPs group significantly increased (P < 0. 05) , and the permeability of intestinal mucosa increased. Compared with the DSS group , the experimental group mice had higher plasma FITC⁃D levels ( P < 0. 05 ) and more electron microscopic colonic epithelial damage. Conclusion PMPs induces NETs formation in mice , promotes colonic inflammation in mice , increases intestinal mucosal permeability and aggravates intestinal inflammation in mice with DSS colitis.

Zn²⁺ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn²⁺ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn²⁺. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn²⁺ exporter. Loss of SLC-30A9 leads to mitochondrial Zn²⁺ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn²⁺ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn²⁺ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn²⁺ pool from which mitochondrial Zn²⁺ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn²⁺ levels for normal mitochondrial structure and functions.
Animals ; Caenorhabditis elegans/metabolism* ; Cation Transport Proteins/genetics* ; Homeostasis ; Mitochondria/metabolism* ; Zinc/metabolism*

Objective To investigate the changes and formation mechanism of plasma endothelial microparticles (EMPs) in patients with acute pancreatitis (AP). Methods Blood samples were collected from 60 patients with AP who were treated in The First Affiliated Hospital of Anhui Medical University from August 2020 to June 2021, and these patients were divided into mild acute pancreatitis (MAP) group with 23 patients, moderate-severe acute pancreatitis (MSAP) group with 23 patients, and severe acute pancreatitis (SAP) group with 14 patients; 20 individuals who underwent physical examination were enrolled as control group.Differential centrifugation was used to obtain platelet-poor plasma, flow cytometry was used to measure the level of CD31 + CD41 - EMPs, and ELISA was used to measure the levels of endothelin-1(ET-1), von Willebrand factor (vWF), nitric oxide (NO), and vascular cell adhesion molecule-1(VCAM-1).HUVECs were stimulated by the plasma of AP patients, and then flow cytometry and qRT-PCR were used to measure the changes in EMPs, reactive oxygen species (ROS), and mitochondrial membrane potential and the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1(ICAM-1), VCAM-1, NADPH oxidase, and P-selectin.A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups and within each group.The chi-square test was used for comparison of categorical data between groups, and the Pearson correlation test was used for correlation analysis. Results Compared with the control group, the MAP, MSAP, and SAP groups had a significant increase in the level of EMPs (all P < 0.05).Compared with the MAP and MSAP groups, the SAP group had a significant increase in the level of EMPs (both P < 0.05).In the patients with AP, the level of EMPs was negatively correlated with Acute Physiology and Chronic Health Evaluation Ⅱ score, Bedside Index for Severity in Acute Pancreatitis, Ranson score, CT score, and C-reactive protein ( r =0.686 2, 0.777 3, 0.713 8, 0.771 8, and 0.473 9, all P < 0.01).Compared with the control group, the MAP, MSAP, and SAP groups had significant increases in the levels of ET-1, vWF, and VCAM-1 and a significant reduction in the level of NO (all P < 0.05).Compared with the control group, the MSAP and SAP groups had the plasma that promoted the release of a large amount of EMPs (both P < 0.05).Compared with the control group, all the other groups, except the MAP group in terms of VCAM-1 and eNOS, had significant increases in the mRNA expression levels of eNOS, iNOS, ICAM-1, P-selectin, VCAM-1, and NADPH oxidase (all P < 0.05).Compared with the HC group, the MAP, MSAP, and SAP groups and the LPS group had a significant increase in the level of ROS and a significant reduction in mitochondrial membrane potential in HUVECs (all P < 0.05). Conclusion There is a significant increase in the plasma level of EMPs in AP patients, which is correlated with the severity of pancreatitis.Meanwhile, the plasma of AP patients can promote the formation of EMPs in HUVECs in vitro, which may be associated with cell oxidative injury.

Objective:To explore the relationship between rumination and depression and suicide attempts, and the mediating effect of rumination between depression and suicide attempts in adolescents with depressive disorder.Methods:Clinical interviews and questionnaires were conducted on 331 adolescents aged 11-18 with depressive disorders.Depressive symptoms were assessed with patient health questionnaire-9 (PHQ-9). Rumination was assessed with ruminative responses scale-10 (RRS-10), and Chinese version of the sociality module of MINI5.0 was used to assess suicide.SPSS 23.0 software was applied to descriptive statistics, Chi-square test, t-test, Spearman correlation analysis and hierarchical regression analysis, and the SPSS macro program PROCESS V 3.4 was used for Bootstrap mediating effect. Results:The incidence of suicide attempts in adolescents with depressive disorder was 53.78%, which was significantly higher in girls (59.48%) than that in boys (40.40%), and the difference was significant ( χ2=10.16, P<0.01). In contrast to the non-suicide attempt group, suicide attempt group had higher scores on PHQ-9((11.08±9.26) vs (14.43±7.49), t=-3.634, P<0.01), brooding ((10.76±3.89) vs (12.44±3.87), t=-3.926, P<0.01), reflection ((10.05±3.54) vs (11.20±3.33), t=-3.044, P<0.01) and rumination total score ((20.81±6.78) vs (23.64±6.42), t=-3.898, P<0.01). Regression analysis revealed that girl ( β=0.175, t=3.228, P=0.001), depressive symptoms ( β=0.168, t=3.082, P=0.002), rumination ( β=0.138, t=2.364, P=0.019) were risk factors for suicide attempts.Rumination played a complete mediating effect between depressive symptoms and suicide attempts (effect value=0.013, 95% CI=0.003-0.027). Depression symptoms significantly and positively predicted rumination ( P<0.01), and rumination significantly and positively predicted suicide attempts ( P<0.05). Conclusion:The incidence of suicide attempts was high in adolescents with depressive disorders.Depressive symptoms affect suicide attempts mainly through rumination.Clinicians should assess the rumination of adolescents with depressive disorders.In addition, clinicians should implement concurrent psychotherapy to adjust the cognitive response and reduce rumination, in order to improve the mental health and reduce suicide attempts.

Objective:To investigate the expression of Piezo1 in small intestinal mucosal epithelial cells of patients with Crohn′s disease (CD) and its clinical correlation with CD.Methods:From January 1st 2010 to November 30th 2020, the clinical data including age, gender, disease location and biological behavior, etc of 57 patients with CD (CD group) who underwent surgery at The First Affiliated Hospital of Anhui Medical University were retrospectively. And at same time the normal samll intestinal epithelial tissues of 10 healthy individuals who underwent colonoscopy were collected as the healthy control group. The expression of Piezo1 in small intestinal epithelial cells of CD patients with different disease sites, biological behavior and disease activity were detected by immunofluorescence staining and hematoxylin-eosin staining. The histological score system and intestinal fibrosis score were used to analyze the inflammation and fibrosis of the intestinal tissues of patients with CD. Semi-quantitative analysis of Piezo1 in small intestinal epithelial cells was analyzed by ImageJ software. And the correlation between Piezo1 expression and clinical characteristics and pathological features of small intestine was also analyzed. Independent sample t test and analysis of variance were used for statistical analysis. Results:In CD group, there were 37 males (64.9%) and 20 females (35.1%). The age was (39.1±14.2) years old, ranged from 18 to 71 years old, and the average duration of the disease was (26.5±24.1) months. There were 29 cases (50.9%)of ileal type, 26 cases (45.6%) of ileocolonin type and 2 cases (3.5%) of colonic type. There were 12 cases (21.1%) of non-penetrating non-stenotic type, 31 cases (54.4%) of stenotic type and 14 cases (24.6%) of penetrating type. There were 47 cases (82.5%) with moderate activity and 10 cases (17.5%) with severe activity. There were 17 cases (29.8%) of moderate intestinal inflammation, 40 cases (70.2%) of severe intestinal inflammation. The score of intestinal fibrosis in six cases (10.5%) was 1, 28 cases (49.1%) was 2, 18 cases (31.6%) was 3, five cases was 4. The relative expression level of Piezo1 in intestinal mucosal epithelial cells of CD group was higher than that of healthy control group (12.9±4.6 vs. 8.5±1.1), the relative expression of Piezo1 in intestinal mucosal epithelia cells of stenotic type and penetrating type CD patients were both higher than that of non-penetrating and non-stenotic CD patients (12.6±3.8 and 9.8±2.4 vs. 6.0±1.3), and the differences were all statistically significant ( t=3.00, -3.66 and -3.32, all P<0.01). The relative expression of Piezo1 in small intestinal epithelial cells of CD patients with severe intestinal inflammation was higher than that of CD patients with moderate intestinal inflammation (13.1±4.0 vs. 9.7±3.1), and the difference was statistically significant ( t=-2.65, P<0.05). The relative expression levels of Piezo1 in small intestinal epithelial cells of patients with intestinal fibrosis score of 4, 3, 2 and 1 were 17.6±5.2, 12.6±1.7, 9.1±2.1 and 5.8±1.1, respectively; the relative expression levels of Piezo1 in intestinal epithelial cells of patients scored 4 were higher than that of patients scored 3, 2 and 1, and that of patients scored 3 was higher than patients scored 2 and 1, and that of patients scored 2 was higher than that of patients scored 1, and the differences were all statistically significant ( t=-2.98, -5.10, -3.84, 4.60, 6.55 and 2.56, all P<0.05). The relative expression of Piezo1 in intestinal mucosal epithelial cells was related to the severity of intestinal inflammation and fibrosis. The more severe the intestinal inflammation and fibrosis, the higher the relative expression of Piezo1 in intestinal mucosal epithelial cells. Conclusions:The relative expression of Piezo1 in small intestinal epithelial cells is related to the biological behavior and the severity of intestinal inflammation and fibrosis of CD. It is speculated that the expression of Piezo1 in small intestinal epithelial cells may be clinically related to the process of intestinal wall fibrosis in CD to some extent, however whether it plays an important role in the process of intestinal wall fibrosis in CD and its specific mechanism need to be further studied.

Objective:To establish an analytical method for the simultaneous determination of five fat-soluble vitamins in serum using isotope dilution ultra high performance liquid chromatography-tandem mass spectrometry (ID-UPLC-MSMS).Methods:Fat-soluble vitamins were obtained from serum samples which collected from Shanghai Tenth People′s Hospital between April 2019 and August 2019 by the extraction method, and were detected by ID-UPLC-MSMS. The performance of the method was verified by referring to the relevant documents of the Clinical and Laboratory Standards Institute (CLSI).Results:The ID-UPLC-MSMS method for the rapid detection of various fat-soluble vitamins in serum was proposed and successfully verified. The linear range of the method: vitamin A: 25-2 500 μg/L, 25(OH)D 2: 2-200 μg/L, 25(OH)D 3: 2-200 μg/L, vitamin E: 0.25-50 mg/L, vitamin K1: 0.1-20 μg/L. The intra- and inter-assay precision standard deviations of the five analytes were within ± 15%, and the accuracy of the test results of the 25(OH)D 2 and 25(OH)D 3 standards was 96.44%-102.37%. Conclusion:The performance of ID-UPLC-MSMS method for the simultaneous determination of five fat-soluble vitamins is satisying, and the result is accurate and reliable, which suggested it can be used for the clinical sample.

Objective To investigate the effects of levothyroxine (Levo-thyroid hormone,L-TH4) in pregnancy subclinical hypothyroidism (SCHT), and study the relationship between L-TH4 with thyroid peroxidase (TPO) and glucose metabolism. The research could provide theoretical basis for the treatment of SCHT. Methods Sixty pregnant women were selected and signed the medical informed consent. The pregnancy were divided into three groups, 20 cases in each group.Normal control group: pregnancy underwent routine thyroid function normal; SCHT group: SCHT pregnancy patients who did not use drugs to treat SCHT; L-TH4 group: SCHT pregnancy patients given L-TH4 treatment. The blood was taken to test the contents of glucose level and HbA1c were observed; the activity of TSH and TPO were tested by ELISA method; HE staining method was used to observe the changing of placenta tissue. Results Compared with normal control group, the glucose and HbA1c were significantly increased in SCHT group (P<0.05). However, L-TH4 could decrease these index, compare with the SCHT group, and reduce the level of TSH and the activity of TPO, the difference was statistically significantly (P<0.05). Moreover, L-TH4 could improve the changing of placenta tissue. Conclusion L-TH4 could reduce blood glucose and HbA1c levels, also reduced the level of TSH and the activity of TPO in SCHT. L-TH4 could improve the changing of placenta tissue.