Objective To observe the efficacy and safety of VA regimen(venetoclax + azacitidine)in the treatment of patients with newly diagnosed unfit acute myeloid leukemia(AML).Methods From April 2021 to February 2023,55 unfit AML patients who were treated with VA regimen in the First Affiliated Hospital of Anhui Medical University were retrospectively analysed.The therapeutic efficacy and safety of VA regimen were evaluated.Results The median treatment courses of AML patients was 3(1-10),and complete response(CR)/CR with incomplete blood count recovery(CRi)rate was 78.2%and minimal residual(MRD)negative conversion rate was 61.8%after the first treatment course.CR/CRi rate and MRD negative conversion rate increased gradually with the increase of treatment course.Patients with IDH1/IDH2,NPM1,ASXL1 mutations and without TP53 mutations responded well to the VA regimen.The median follow-up time was 9.1(1.2-24.0)months.39 patients survived and 16 patients died.The median overall survival(OS)was 17.4 months.Patients with CR/CRi had significantly longer OS duration than patients with partial response or non-response(P<0.001).Almost all patients had different degrees of anemia,thrombocytopenia,leukopenia.In terms of non-hematological adverse events,infection was the most common.Conclusion The VA regimen achieved a higher treatment response rate in newly diagnosed unfit AML patients,and partial response patients could quickly obtain negative MRD.IDH1/IDH2,ASXL1,NPM1,TP53 mutations may be the predictors of patient outcomes.

Purpose To investigate the expression of C1GALT1 in gastric cancer and its effect on the biological be-havior of BGC-823 in gastric cancer cells.Methods The ex-pression of C1GALT1 mRNA and protein in gastric cancer tis-sues and normal gastric mucosa,gastric cancer cells and normal gastric mucosal cells was analyzed by bioinformatics,qRT-PCR and Western blot;the transient transfection of siRNA into BGC-823 cells was designed with C1GALT1 cDNA sequence as the target.Transwell assay was used to detect the effect of C1GALT1-siRNA on the migration and invasion ability of BGC-823 cells in gastric cancer.Western blot method detected the expression of epithelial-mesenchymal transition(EMT)-related proteins in BGC-823 after transfection of C1GALT1-siRNA.Re-sults C1GALT1 was highly expressed in gastric cancer tissues and cell lines BGC-823,SGC-7901 and MGC-803,and the ex-pression levels were positively correlated with gastric cancer pathological stages Ⅰ and Ⅱ(P＜0.05).After interfering with C1GALT1 in BGC-823 cells,the ability of migration and inva-sion decreased(P＜0.05),epithelial cell markers E-cadherin and Claudin-1 protein expression increased,while mesenchymal cell markers vimentin and Slug protein expression decreased(P＜0.05).Conclusion C1GALT1 is highly expressed in gastric cancer tissues and cells,silencing of C1GALT1 can inhibit mi-gration and invasion ability of gastric cancer,the mechanism may be related to EMT.

Objective:To identify tooth number abnormalities on pediatric panoramic radiographs based on deep learning.Methods:Eight hundred panoramic radiographs of children aged 4 to 11 years meeting the inclusion and exclusion criteria were selected and randomly assigned by writing programs in Python (version 3.9) to the training set (480 images), verification set (160 images) and internal test set (160 images), taken in Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology between November 2012 to August 2020. And all panoramic radiographs of children aged 4 to 11 years taken in the First Outpatient Department of Peking University School and Hospital of Stomatology from June 2022 to December 2022 were collected as the external test set (907 images). All of the 1 707 images were obtained by operators to determine the outline and to label the tooth position of each deciduous tooth, permanent tooth, permanent tooth germ and additional tooth. The deep learning model with ResNet-50 as the backbone network was trained on the training set, validated on the verification set, tested on the internal test set and external test set. The images of test sets were divided into two categories according to whether there was abnormality of tooth number, to calculate sensitivity, specificity, positive predictive value and negative predictive value, and then divided into four types of extra teeth and missing permanent teeth both existed, extra teeth existed only, missing permanent teeth existed only, and normal teeth number, to calculate Kappa values. Results:The sensitivity, specificity, positive predictive value and negative predictive value were 98.0%, 98.3%, 99.0% and 96.7% in the internal test set, and 97.1%, 98.4%, 91.9% and 99.5% in the external test set respectively, according to whether there was abnormality of tooth number. While images were divided into four types, the Kappa value obtained in the internal test set was 0.886, and that in the external test set was 0.912. Conclusions:In this study, a deep learning-based model for identifying abnormal tooth number of children was developed, which could identify the position of additional teeth and output the position of missing permanent teeth on the basis of identifying normal deciduous and permanent teeth and permanent tooth germs on panoramic radiographs, so as to assist in diagnosing tooth number abnormalities.

Up-frameshift 1 (UPF1), as the most critical factor in nonsense-mediated messenger RNA (mRNA) decay (NMD), regulates tumor-associated molecular pathways in many cancers. However, the role of UPF1 in lung adenocarcinoma (LUAD) amino acid metabolism remains largely unknown. In this study, we found that UPF1 was significantly correlated with a portion of amino acid metabolic pathways in LUAD by integrating bioinformatics and metabolomics. We further confirmed that UPF1 knockdown inhibited activating transcription factor 4 (ATF4) and Ser51 phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), the core proteins in amino acid metabolism reprogramming. In addition, UPF1 promotes cell proliferation by increasing the amino-acid levels of LUAD cells, which depends on the function of ATF4. Clinically, UPF1 mRNA expression is abnormal in LUAD tissues, and higher expression of UPF1 and ATF4 was significantly correlated with poor overall survival (OS) in LUAD patients. Our findings reveal that UPF1 is a potential regulator of tumor-associated amino acid metabolism and may be a therapeutic target for LUAD.
Activating Transcription Factor 4/genetics* ; Adenocarcinoma of Lung ; Amino Acids ; Cell Proliferation ; Eukaryotic Initiation Factor-2 ; Humans ; Lung Neoplasms ; RNA Helicases/metabolism* ; RNA, Messenger/metabolism* ; Trans-Activators/metabolism*

AIM: To evaluate the clinical efficacy and safety of oral proteasome inhibitor ixazomib in the treatment of multiple myeloma. METHODS: Eighty patients with multiple myeloma treated with ixazomib-containing therapy in the department of hematology, the First Affiliated Hospital of Anhui Medical University from January 2019 to December 2020 were retrospectively analyzed, including 38 patients with relapsed/refractory multiple myeloma (RRMM)and 42 patients who switched treatment due to adverse events (AEs) after initial induction therapy with bortezomib. Treatment was a two-drug or three-drug regimen containing ixazomib, and the clinical efficacy and safety of ixazomib were evaluated. RESULTS: The overall response rate (ORR) of relapsed/refractory patients was 50%, ≥ VGPR 21.05%; the ORR of patients who switched treatment was 83.33%, compared with the ORR before switching (78.57%), the response rate was further improved, of which 45.24%(19/42) patients had deepened response; the main hematological AEs included granulocyte and platelet count reduction and anemia, non-hematological AEs were mainly diarrhea and fatigue. CONCLUSION: Ixazomib shows good clinical efficacy and safety in patients with RRMM and bortezomib-intolerant MM.

Objective:To analyze of the transmission characteristics of a cluster of COVID-19 cases in Chongqing and evaluate the infectivity of COVID-19 in the incubation period.Methods:A retrospective survey was conducted by using unified questionnaire through field and telephone interviews among 129 close contacts of COVID-19 cases. The relationship of transmission was indicated by transmission chain, and the infectivity was analyzed by the contact history.Results:This cluster of COVID-19 cases occurred after a classmate party involving members in three families and work fellows in a factory ( R0=3.8). The infection rate during the incubation period was 17.57%. On average, it was infectious three days before onset. There was significant difference in infection rate among different contact modes ( χ2=15.10, P<0.01), There was significant difference in infection rate among single exposureswith different time length ( χ2=25.08, P<0.01). Conclusions:COVID-19 is highly infectious in the incubation period. The more confined the space is, the higher the risk is,and the longer the single exposure is, the higher the risk of transmission is. Indirect contact transmission still exists

Reactive oxygen species(ROS)and immune response play critical roles in the progression of liver dis-eases.DJ-1,also known as Parkinson disease 7(Park7),is extensively expressed in cells and tissues,where it governs numerous biological functions including chaperone activity,protease function,tran-scriptional and mitochondrial regulation,and ROS modulation.Moreover,we have established that DJ-1 plays a critical role in initiating an inflammatory response by modulating ROS generation.Therefore,DJ-1 may play an important role in the progression of liver diseases by modulating ROS and the immune response.Recently,we have shown that DJ-1 deficiency negatively regulates proliferation of hepatic progenitor cells(HPCs)by impairing the formation of HPC-associated fibrosis and inflammatory niches.Deficiency of DJ-1 ameliorates liver fibrosis by inhibiting hepatic ROS production and inflammation;moreover,in a classic diethylnitrosamine(DEN)-mediated hepatocellular carcinoma(HCC)mouse model,deletion of DJ-1 ameliorates tumorigenesis and HCC cell proliferation by regulating hepatic inflammation and reducing the activity of the interleukin 6/signal transducer and activator of transcription 3(IL-6/STAT3)signaling pathway.Taken together,these data suggest a critical function for,and therapeutic value of,DJ-1 in treatment of liver diseases.The aim of this review is to summarize these functions and the underlying molecular mechanisms of DJ-1 in liver diseases,and to highlight the potential therapeutic value and future research direction of DJ-1 in liver diseases.

Objective:To investigate the serum level of IL-34 in patients with acute phase Henoch-Schoenlein purpura ( HSP) and its potential significance .Methods:38 HSP patients were recruited ,together with 21 healthy volunteers as control .The serum level of IL-34,IL-6 and TNF-αwere determined using enzyme-linked immunosorbent assay (ELISA) or chemiluminescence.The correlation analysis was performed to explore the correlation of IL-34 with clinical parameters and the serum level of IL-6,TNF-α.Results:The se-rum levels of IL-34,IL-6 and TNF-αin HSP patients were significantly higher as compared to the control group (P<0.001).The serum level of IL-34 was positively correlated with that of high sensitive C-reactive protein ( hs-CRP) and IL-6 ( r=0.453 ,P=0.004 and r=0.469,P=0.003,respectively).Conclusion:IL-34 might be involved in the pathogenesis of HSP ,and the potential mechanisms of ac-tion is associated with the aberrant expression of pro-inflammatory factors in HSP ,which promote the development of inflammation in the vascular system.

Objective To study the effects of modified Danggui Beimu Kushen Pills on the expressions of TLR2, TLR4, TLR6, TRAF6 and MyD88 in tumor tissues on MFC gastric cancer bearing mice; To discuss relevant mechanism of action. Methods MFC gastric cancer bearing mice were employed to perform anti-tumor experiment in vivo in this study. A total of eligible 48 mice were randomly divided into model group, DDP positive control group, modified Danggui Beimu Kushen Pills high-dose and low-dose groups, modified Danggui Beimu Kushen Pills high-dose and low-dose combined with DDP groups. The treatment was conducted once a day, and lasted for 14 continuous days. After the last administration of gavage orally treatment, all mice were anaesthetized and killed by cervical dislocation method to obtain tumor tissue completely for further HE staining measure and detection of TLR2, TLR4, TLR6, TRAF6 and MyD88 in tumor tissue with the method of RT-qPCR and immunohistochemistry. Meanwhile, the tumor growth was observed and the general conditions of mice were recorded. Results The model group was rich in tumor cells; the sizes of cells were different; the volume was large; the nucleus was deeply stained and the heterotypic shape was obvious, and the small focal necrosis was seen. The number of tumor cells in each administration group was reduced; the arrangement was loose; the cell volume was significantly reduced, and the nuclear pyknosis was reduced. Cell necrosis significantly increased; the number of interstitial blood vessels decreased; collagen fibers increased, especially in modified Danggui Beimu Kushen Pills high-dose and low-dose combined with DDP groups. Compared with the model group, the expressions of TLR2, TLR4, TLR6, TRAF6 and MyD88 mRNA and protein decreased in each administration group. TLR2, TLR4, TLR6, TRAF6 and MyD88 were lighter and weakly positive expressed in modified Danggui Beimu Kushen Pillshigh-dose and low-dose combined with DDP groups, the protein changes were more obvious Compared with DDP positive control group, modified Danggui Beimu Kushen Pills high-dose and low-dose groups. Conclusion Modified Danggui Beimu Kushen Pills can down-regulate TLR2, TLR4, TLR6, TRAF6 and MyD88 expression of tumor tissue in MFC gastric cancer bearing mice at both mRNA and protein levels to play anti-tumor pharmacology action.