Objective:To investigate the effects of elesclomol-Cu(ES-Cu)on the proliferation and cuproptosis of human acute myeloid leukemia(AML)cells.Methods:The effects of ES-Cu on the proliferation of AML cells and the AML cells pre-treated with ammonium tetrathiomolybdate(TTM)were examined by CCK-8 assay.The Calcein/PI kit was used to detected the changes in activity and cytotoxicity of AML cells induced by ES-Cu.Flow cytometry and Cytation3 fully automated cell imaging multifunctional detection system were used to analyze DCFH-DA fluorescence intensity,so as to determine the level of reactive oxygen species(ROS).The GSH and GSSG detection kits were used to measure the intracellular GSH content.Western blot was used to detected the expression of cuproptosis-related proteins ATP7B,FDX1,DLAT and DPYD.Results:ES-Cu inhibited the proliferation of Kasumi-1 and HL-60 cells in a concentration-dependent manner(rKasumi-1=-0.99,rHL-60=-0.98).As the concentration of ES-Cu increased,the level of intracellular ROS also increased(P＜0.01-0.001).TTM could significantly reverse the inhibitory effect of ES-Cu on cell proliferation and its promoting effect on ROS.With the increase of ES-Cu concentration,the content of GSH was decreased(r=-0.98),and Western blot showed that the protein expressions of ATP7B,FDX1,DLAT and DPYD were significantly reduced(P＜0.05).Conclusion:ES-Cu can induce cuproptosis in AML cells,which provides a new idea for the treatment of AML.

Objective To propose a method for classifying small bowel capsule endoscopy images by combining the Swin Transformer network with an improved Adapt-RandAugment data augmentation approach,aiming to enhance the accuracy and efficiency of small bowel lesion classification and recognition.Methods An Adapt-RandAugment data augmentation approach was formulated based on the RandAugment data enhancement sub-strategy and the principles of no feature loss and no distortion when enhancing small bowel capsule endoscopy images.In the publicly available Kvasir-Capsule dataset of small bowel capsule endoscopic images,the Adapt-RandAugment data augmentation approach was trained based on the Swin Transformer network,and the convolutional neural networks ResNet152 and DenseNet161 were used as the benchmarks to validate the combined Swin Transformer network and Adapt-RandAugment data augmentation approach for small bowel capsule endoscopy image classification.Results The proposed algorithm gained advantages over ResNet152 and DenseNet161 networks in the indicators,which had the macro average precision(MAC-PRE),macro average recall(MAC-REC),macro average F1 score(MAC-Fi-S)being 0.383 2,0.314 8 and 0.290 5 respectively,the micro average precision(MIC-PRE),micro average recall(MIC-REC)and micro average F1 score(MIC-Fi-S)all being 0.755 3,and the Matthews correlation coe-fficient(MCC)being 0.452 3.Conclusion The proposed small bowel capsule endoscopy image classification method based on Swin Transformer network and Adapt-RandAugment data augmentation approach behaves well in classified recognition efficiency and accuracy.[Chinese Medical Equipment Journal,2024,45(6):9-16]

Objective To explore the clinical rational use evaluation method for high-value medical consumables in diagnosis related groups(DRG)using association rules in order to provide references for the supervision of clinical rational use of high-value medical consumables.Methods The cardiovascular department was taken as an example.Firstly,K-means algorithm was applied to cluster analysis of DRG cases in the department,and representative cases were selected as the research objects;secondly,Apriori algorithm was used to mine the frequent item sets of DRG patient groups,the high-value medical consumables in the department and the rules of association between DRG patient groups and medical consumables;finally,two indicators of the importance of regulation and rationality of the use of medical consumables were designed to evaluate the importance of regulation and rationality of the use of high-value medical consumables.Results There were two common DRG patient groups in the cardiovascular department,including FM39 percutaneous cardiac catheterization and FM19 percutaneous coronary stent implantation,and the frequently used medical consumables contained vascular sheath,contrast catheter,pressure monitoring kit,triple three-way stopcock and coronary guide wire in the two groups.The common combinations of medical consumables used in the FM39 DRG patient group comprised of vascular sheath,contrast catheter,pressure monitoring kit,triple three-way stopcock and coronary guide wire,which were close to that of the cardiovascular department;there were some additional consumables involved in the common combinations in the FM19 group such as occluder,coronary guide catheter,pressure pump,drug-eluting stent and coronary dilation balloon.The top three medical consumables in terms of regulatory importance were cutting balloon,coronary guide wire and drug-eluting stent;using the confidence level from January to September 2022 as a reference,from January to September 2023 the rationality of using high-value consumables in FM39 group went higher by 5.08％while that in FM19 group went lower by 9.23％.Conclusion The association rule-based evaluation method for the use of medical consumables in DRG patient groups can be used for assessing the importance of regulation and rationality of the use of high-value medical consumables,which provides references for the supervision of clinical rational use of high-value medical consumables.[Chinese Medical Equipment Journal,2024,45(11):67-71]

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Sustained and controlled release preparation is ideal for reducing the side effects of drugs, improving patient compliance and enhancing efficacy, among which oral sustained-release tablets are the most widely used. The in vitro release of the preparation is closely related to the in vivo absorption of the drug. However, current in vitro release experiments are labor-intensive and destructive, and the lack of big data also makes it difficult to establish good in vivo and in vitro correlations. Computer modeling, as a technical means that can transform objective principles into mathematical models, has great prospects in data prediction. This review explores the existing computer modeling methods that can be used to predict in vitro release profiles of oral sustained-release tablets, and further discusses auxiliary technologies that can improve the accuracy of the models, providing new ideas for drug development.

Isocitrate dehydrogenase 1 (IDH1) R132H is the most common mutated gene in grade II-III gliomas and oligodendrogliomas. Instead of activating telomerase (a reverse transcriptase which using RNA as a template to extend telomere length), the majority of IDH1^R132H mutant glioma maintain telomere length through an alternative mechanism that relies on homologous recombination (HR), which is known as alterative lengthening of telomere (ALT).The phenotype of ALT mechanism include: ALT associated promyelocytic leukemia protein (PML) bodies (APBs); extrachromosomal telomeric DNA repeats such as C- and T-loops; telomeric sister chromatid exchange (T-SCE), etc. The mechanism of ALT activation is not fully understood. Recent studies have shown that mutation IDH1 contributes to ALT phenotype in glioma cells in at least three key ways. Firstly, the IDH1^R132H mutation mediates RAP1 down-regulation leading to telomere dysfunction, thus ensuring persistent endogenous telomeric DNA damage, which is important for ALT activation. Spontaneous DNA damage at telomeres may provide a substrate for mutation break-induced replication (BIR)‑mediated ALT telomere lengthening, and it has been demonstrated that RAP1 inhibits telomeric repeat-containing RNA, transcribed from telomeric DNA repeat sequences (TERRA) transcription to down-regulate ALT telomere DNA replication stress and telomeric DNA damage, thereby inhibiting ALT telomere synthesis. Similarly, in ALT cells, knockdown of telomere-specific RNaseH1 nuclease triggers TERRA accumulation, which leads to increased replication pressure. Overexpression of RNaseH1, on the other hand, attenuates the recombination capacity of ALT telomeres, leading to telomere depletion, suggesting that RAP1 can regulate the level of replication pressure and thus ALT activity by controlling TERRA expression. Secondly, the IDH1^R132H also alters the preference of the telomere damage repair pathway by down-regulating XRCC1, which inhibits the alternative non-homologous end joining (A-NHEJ) pathway at telomeres and alters cellular preference for the HR pathway to promote ALT. Finally, the IDH1^R132H has a decreased affinity for isocitric acid and NADP+ and an increased affinity for α ketoglutarate (α‑KG) and NADPH, so that the mutant IDH1^R132H catalyzes the hydrogenation of α‑KG to produce 2-hydroxyglutarate (2-HG)in a NADPH-dependent manner. Because 2-HG is structurally similar to α‑KG, which maintains the trimethylation level of H3k9me3 by competitively inhibiting the activity of the α‑KG-dependent histone demethylase KDM4B, and recruits heterochromatin protein HP1α to heterochromatinize telomeres, and promote ALT phenotypes in cooperation with the inactivating of ATRX. In addition, it has been shown that APBs contain telomeric chromatin, which is essentially heterochromatin, and HP1α is directly involved in the formation of APBs. Based on these studies, this article reviews the mechanism of IDH1^R132H mediated telomere dysfunction and the preference of DNA repair pathway at telomeres in cooperate with ATRX loss to promote ALT, which may provide references for clinical targeted therapy of IDH1^R132H mutant glioma.

In order to promote the development of hair transplantation, particularly the establishment of standards, the Hair Transplantation Expert Group of Plastic and Aesthetic National Medical Quality Control Center invited experts in the field of hair transplantation across China and formed a draft of the Expert Consensus on Standard Terminology for Hair Transplantation based on the collation of relevant literature and monographs. By combining Delphi methodology and consensus meetings, the expert group conducted several rounds of consultations on issues such as follicular unit anatomy, harvesting, dissection, and implantation, ultimately presenting 54 terminologies. This consensus considers the original Chinese and English meanings as well as the professional characteristics of terms used in hair transplantation, highlights the unique features and advantages of hair transplantation, and preserves its essence while promoting innovation, with the hope of providing valuable reference for clinical researchers engaged in hair transplantation both domestically and internationally, and better facilitating the standardization and advancement of the field.

Objective To explore the influence of extracellular matrix protein ABI-interactor 3-binding protein(ABI3BP)on vesicular stomatitis virus(VSV)genome replication and innate immune signaling pathway. Methods The small interfering RNA(siRNA)was transfected to knock down ABI3BP gene in human skin fibroblast BJ-5ta cells.VSV-green fluorescent protein(VSV-GFP)-infected cell model was established.The morphological changes and F-actin stress fiber formation were detected on ABI3BP knockdown cells by phalloidin immunofluorescence staining.The mRNA level of virus replication was detected by RT-qPCR in BJ-5ta cells after VSV-GFP infection;western blotting was performed to detect the changes in interferon regulatory factor 3(IRF3)andTANK-binding kinase 1(TBK1)phosphorylation levels. Results The VSV-GFP-infected BJ-5ta cell model was successfully established.Efficient knockdown of ABI3BP in BJ-5ta cells was achieved.Phalloidin immunofluorescence staining revealed structural rearrangement of intracellular F-actin after ABI3BP gene knockdown.Compared with the control group,the gene copy number of VSV-GFP in ABI3BP knockdown cells increased by 2.2-3.5 times(P＜0.01)and 2.2-4.0 times(P＜0.01)respectively when infected with VSV of multiplicity of infection 0.1 and 1.The expression of viral protein significantly increased in ABI3BP knockdown cells after virus infection.The activation of type-Ⅰ interferon pathway,as determined by phosphorylated IRF3 and phosphorylated TBK1,was significantly decreased in ABI3BP knockdown cells after VSV-GFP infection. Conclusions Extracellular matrix protein ABI3BP plays an important role in maintaining the formation and rearrangement of actin structure.ABI3BP gene deletion promotes RNA virus replication,and ABI3BP is an important molecule that maintains the integrity of type Ⅰ interferon pathway.

Non-syndromic oral cleft (NSOC), a common birth defect, remains to be a critical public health problem in China. In the context of adjustment of childbearing policy for two times in China and the increase of pregnancy at older childbearing age, NSOC risk prediction will provide evidence for high-risk population identification and prenatal counseling. Genome-wide association study and second generation sequencing have identified multiple loci associated with NSOC, facilitating the development of genetic risk prediction of NSOC. Despite the marked progress, risk prediction models of NSOC still faces multiple challenges. This paper summarizes the recent progress in research of NSOC risk prediction models based on the results of extensive literature retrieval to provide some insights for the model development regarding research design, variable selection, model-build strategy and evaluation methods.
Humans ; Cleft Palate/genetics* ; Cleft Lip/genetics* ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Risk Factors ; Polymorphism, Single Nucleotide

Uveal melanoma(UM)is the most frequent and life-threatening ocular malignancy in adults.Aberrant histone methylation contributes to the abnormal transcriptome during oncogenesis.However,a comprehensive understanding of histone methylation patterns and their therapeutic potential in UM remains enigmatic.Herein,using a systematic epi-drug screening and a high-throughput transcriptome profiling of histone methylation modifiers,we observed that disruptor of telomeric silencing-1-like(DOT1L),a methyltransferase of histone H3 lysine 79(H3K79),was activated in UM,especially in the high-risk group.Concordantly,a systematic epi-drug library screening revealed that DOT1 L inhibitors exhibited salient tumor-selective inhibitory effects on UM cells,both in vitro and in vivo.Combining Cleavage Under Targets and Tagmentation(CUT&Tag),RNA sequencing(RNA-seq),and bioinformatics analysis,we identified that DOT1 L facilitated H3K79 methylation of nicotinate phosphoribosyltransferase(NAPRT)and epigenetically activated its expression.Importantly,NAPRT served as an oncogenic accel-erator by enhancing nicotinamide adenine dinucleotide(NAD+)synthesis.Therapeutically,DOT1L inhi-bition epigenetically silenced NAPRT expression through the diminishment of dimethylation of H3K79(H3K79me2)in the NAPRT promoter,thereby inhibiting the malignant behaviors of UM.Conclusively,our findings delineated an integrated picture of the histone methylation landscape in UM and unveiled a novel DOT1L/NAPRT oncogenic mechanism that bridges transcriptional addiction and metabolic reprogramming.