The Hippo-YAP/TAZ-TEAD axis promotes multipotency in bone marrow stromal cells.

The mechanisms by which bone marrow stromal cells (BMSCs) maintain multilineage potency in vitro remain elusive. To identify the transcriptional regulatory circuits that contribute to BMSC multipotency, we performed paired single-nucleus multiomics of the expansion of freshly isolated BMSCs and of BMSCs undergoing tri-lineage differentiation. By computationally reconstructing the regulatory programs associated with initial stages of differentiation and early expansion, we identified the TEAD family of transcription factors, which is inhibited by Hippo signaling, as highly active in the BMSC in vitro multipotent state. Pharmacological inhibition of TEAD enhanced BMSC osteogenic and adipogenic differentiation, whereas its activation maintained BMSCs in an undifferentiated state, supporting a model whereby isolation of BMSCs coincides with a TEAD-controlled transcriptional state linked to multipotency. Our study highlights the Hippo pathway as a pivotal regulator of BMSC multipotency, and our regulatory network inferences are a reservoir of testable hypotheses that link transcription factors and their regulons to specific aspects of BMSC behavior.

Global and regional estimates of tuberculosis burden attributed to high fasting plasma glucose from 1990 to 2019: emphasis on earlier glycemic control.

BACKGROUND: Previous studies have shown subjects suffering from diabetes or persistent hyperglycemia were more likely to develop tuberculosis (TB). However, the global burden of TB attributed to high fasting plasma glucose (HFPG) remains unclear. This study aimed to characterize the global, regional, and national TB burden attributed to HFPG from 1990 to 2019. METHODS: With Global Burden of Disease study 2019, the numbers and age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years (DALY) rates (ASDR) of TB attributed to HFPG at global, regional, and national levels from 1990 to 2019 were extracted. The locally weighted regression model was applied to estimate the TB burden for different socio-demographic index (SDI) regions. RESULTS: Globally, the ASMR and ASDR attributed to HFPG were 2.70 (95% UI, 1.64-3.94) and 79.70 (95% UI, 50.26-112.51) per 100,000 population in 1990, respectively. These rates decreased to 1.46 (95% UI, 0.91-2.08) and 45.53 (95% UI, 29.06-62.29) in 2019. The TB burden attributed to HFPG remained high in low SDI and Central Sub-Saharan Africa regions, while it declined with most significantly in high SDI and East Asia regions. Additionally, the ASMR and ASDR of TB attributed to HFPG were significantly higher in the male and the elderly population. CONCLUSIONS: The global TB burden attributable to HFPG decreased from 1990 to 2019, but remained high in low SDI regions among high-risk populations. Thus, urgent efforts are required to enhance the awareness of early glycemic control and TB treatment to alleviate the severe situation.

The electrodynamics of rod-like microparticles based on optically induced dielectrophoresis.

Due to its characteristics of noncontact, non-damage, high flux, and easy-to-achieve flexible manipulation, optically induced dielectrophoresis (ODEP) technology has been employed to manipulate microspherical biological particles, including separation, enrichment, capture, arrangement, and fusion. However, in nature, biomolecules are morphologically diverse, and some of them are rodlike. In order to illustrate the electrodynamics of rodlike particles under the action of ODEP, a transient multi-physical field coupling model of ODEP chip under the hypothesis of electrical double layer thin layer was established in this paper. The arbitrary Lagrangian-Eulerian method is used to track single-rod particle in the strong coupled flow field and electric field simultaneously. The influence of several key factors, including the applied alternating current (AC) electric voltage, the width of optical bright area, and the initial position of particle, on the trajectory of particle center was analyzed in positive dielectrophoresis (DEP) action and negative DEP action, respectively. Especially, the planar motion process of rodlike particles was discussed together. The research results reveal the electrodynamics behavior of rodlike particles based on the action of ODEP, which may provide theoretical support for the further design of rodlike biological cells manipulation chip based on AC ODEP technology in the future.

Application of Tivantinib for Hepatocellular Carcinoma: A Meta-Analysis Study.

Objectives: The efficacy of tivantinib may have some potential in treating MET-high hepatocellular carcinoma, and we aim to compare tivantinib with placebo for the treatment of MET-high hepatocellular carcinoma. Methods: Several databases including PubMed, Cochrane Library, Web of Science, EBSCO, and EMbase have been systematically searched through March 2022, and we included studies regarding the treatment of MET-high hepatocellular carcinoma by using tivantinib versus placebo. Results: We finally include three RCTs. In comparison with placebo for MET-high hepatocellular carcinoma, tivantinib reveals no significant influence on overall survival (P=0.21), progression-free survival (P=0.13), time to progression (P=0.38), or grade ≥3 anemia (P=0.50) but increases the incidence of grade ≥3 neutropenia (P=0.04). Conclusions: Tivantinib may provide no additional benefits for MET-high hepatocellular carcinoma.

Multiomics Integrated Analysis Identifies SLC24A2 as a Potential Link between Type 2 Diabetes and Cancer.

Background: So far, type 2 diabetes (T2D) is considered as an independent risk factor for various cancers, but the underlying mechanism remains unclear. Methods. SLC24A2 was first identified as a key gene strongly associated with fasting plasma glucose (FPG). Then, overlapped differentially expressed genes (DEGs) between T2D verse control and SLC24A2-high verse SLC24A2-low were extracted and imported into weighted correlation network analysis. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were used for functional enrichment analysis of DEGs. Least absolute shrinkage and selection operator was utilized to build a T2D prediction model. Timer and K-M plotters were employed to find the expression and prognosis of SLC24A2 in pan cancer. Results: Interestingly, both DEGs between T2D verse control and SLC24A2-high verse SLC24A2-low enriched in cancer-related pathways. Moreover, a total of 3719 overlapped DEGs were divided into 8 functional modules. Grey module negatively correlated with T2D and FPG and was markedly involved in ribosome biogenesis. Ten SLC24A2-related genes (RRP36, RPF1, GRWD1, FBL, EXOSC5, BCCIP, UTP14A, TWISTNB, TBL3, and SKIV2L) were identified as hub genes, based on which the LASSO model accurately predicts the occurrence of T2D (AUC = 0.841). In addition, SLC24A2 was only expressed in islet ß cells and showed abnormal expression in 17 kinds of cancers and significantly correlated with the prognosis of 10 kinds of cancers. Conclusion: Taken together, SLC24A2 may link T2D and cancer by influencing the ribosome function of islet ß cells and play different prognostic roles in different cancers.

Reconstruction of dynamic regulatory networks reveals signaling-induced topology changes associated with germ layer specification.

Elucidating regulatory relationships between transcription factors (TFs) and target genes is fundamental to understanding how cells control their identity and behavior. Unfortunately, existing computational gene regulatory network (GRN) reconstruction methods are imprecise, computationally burdensome, and fail to reveal dynamic regulatory topologies. Here, we present Epoch, a reconstruction tool that uses single-cell transcriptomics to accurately infer dynamic networks. We apply Epoch to identify the dynamic networks underpinning directed differentiation of mouse embryonic stem cells (ESCs) guided by multiple signaling pathways, and we demonstrate that modulating these pathways drives topological changes that bias cell fate potential. We also find that Peg3 rewires the pluripotency network to favor mesoderm specification. By integrating signaling pathways with GRNs, we trace how Wnt activation and PI3K suppression govern mesoderm and endoderm specification, respectively. Finally, we identify regulatory circuits of patterning and axis formation that distinguish in vitro and in vivo mesoderm specification.

Identification of immune-related genes and susceptible population of pulmonary tuberculosis by constructing TF-miRNA-mRNA regulatory network.

We aimed to explore the potential biomarkers and susceptible population for early diagnosis and treatment of tuberculosis (TB). Ten hub differentially expressed TB-related genes (DETRGs) from GSE83456 dataset were screened with the "limma" package and the GeneCards database. Unsupervised clustering was utilized to identify susceptible population among TB patients based on 10 hub DETRGs. TRANSFAC, MirTarbase, miRanda and TargetScan was used to predict microRNAs and transcription factors (TFs) and construct TF-miRNA-mRNA regulatory network. The results showed that a total of 266 DEGs were identified. Functional analysis mainly enriched in interferon pathway, cytokine and receptor interaction and host defense response to virus, while the four-module genes screened were closely related to interferon-γ signal transduction pathway as well. Based on 10 DETRGs, TB patients were divided into two clusters with significant differences in neutrophil function and 16 hub miRNAs and 10 hub TFs were predicted. Finally, NFATc1- (miR145) - STAT1 regulatory pathway was identified as the critical regulatory pathway, which mediates cytokine receptor binding, interleukin-1 receptor binding and TNF signaling pathway. Hence, we concluded that immunoheterogeneity exists among TB patients and NFATC1-(miR145)-STAT1 regulatory pathway might be associated with tuberculosis infection, which may be valuable targets for prevention and treatment of tuberculosis.

Enhancement of biotransformation of ginsenosides in white ginseng roots by aerobic co-cultivation of Bacillus subtilis and Trichoderma reesei.

In the present work, the biotransformation of ginsenosides in white ginseng roots was innovatively investigated using the aerobic fermentation by the co-cultivation of Bacillus subtilis and Trichoderma reesei. It is found that in the co-cultivation mode, the optimal nitrogen source was corn steep liquor, and the loading of ginseng powder and inoculation proportion of B. subtilis and T. reesei were 15 g/L and 1:4, respectively. The total ginsenoside yield and production of minor ginsenosides in the co-cultivation mode obviously enhanced in comparison to the monoculture mode. Meanwhile, the maximal total ginsenoside yield of 21.79% and high hydrolase activities were achieved using the staged inoculation at the inoculation proportion of 1:4 in the co-cultivation mode, the production of minor ginsenosides such as Rg3 and Rh1, Rh2 was significantly strengthened, and the pharmacological activities of the fermented solution obviously improved. The enhancement of ginsenoside transformation can be mainly attributed to hydrolysis of the produced hydrolases and metabolism of two probiotics. This result clearly reveals that using the staged inoculation in co-cultivation fermentation mode was favor of the ginsenoside biotransformation in ginseng due to non-synchronous cell growth and different metabolic pathways of both probiotics. This work can provide a novel method for enhancing ginsenoside transformation of ginseng.Key points• Co-cultivation fermentation significantly promoted ginsenoside biotransformation.• The staged inoculation in co-culture mode was an optimal operation method.• The pharmacological activity of the co-cultured solution was significantly enhanced.

Preparation of Naringenin Solution for In Vivo Application.

The preparation of a compound (phytochemical) solution is an overlooked but critical step prior to its application in studies such as drug screening. The complete solubilization of the compound is necessary for its safe use and relatively stable results. Here, a protocol for preparing naringenin solution and its intraperitoneal administration in a high-fat diet and streptozotocin (STZ)-induced diabetic model is demonstrated as an example. A small amount of naringenin (3.52-6.69 mg) was used to test its solubilization in solvents, including ethanol, dimethylsulfoxide (DMSO), and DMSO plus Tween 80 reconstituted in physiological saline (PS), respectively. Complete solubilization of the compound is determined by observing the color of the solution, the presence of precipitates after centrifugation (2000 x g for 30 s), or allowing the solution to stand for 2 h at room temperature (RT). After obtaining a stable compound/phytochemical solution, the final concentration/amount of the compound required for in vivo studies can be prepared in a solvent-only (no PS) stock solution, and then diluted/mixed with PS as desired. The antidiabetic osteoporotic effects of naringenin in mice (intraperitoneal administration at 2 mg/mL) were assessed by measuring blood glucose, bone mass (micro-CT), and bone resorption rate (TRAP staining and ELISA). Researchers looking for detailed organic/phytochemical solution preparations will benefit from this technique.

A LncRNA-miRNA-mRNA ceRNA regulatory network based tuberculosis prediction model.

The high incidence of tuberculosis (TB) has brought serious social burdens and it is urgent to explore the mechanism of TB development. This study was conducted to analyze the role of lncRNA-miRNA-mRNA regulatory network and its contained nodes involved in TB to identify crucial biomarkers for early diagnosis of TB. Long-noncoding RNAs (lncRNAs), messenger RNA (mRNAs) and microRNAs (miRNAs) expression profiles of TB patients and healthy individuals were downloaded from the GSE34608 dataset. Weighted gene co-expression network analysis (WGCNA) was performed to identified the key modules related to TB and the highly related mRNA-lncRNA pair in the module. Based on highly related mRNAs and lncRNAs in greenyellow module, lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network was constructed. The DE-mRNAs in the network were functionally enriched with Gene ontology (GO) and Gene set enrichment analysis (GSEA). Least absolute shrinkage and selection operator (LASSO) algorithm and receiver operating characteristic curve (ROC) were used to construct and evaluate the prediction model of TB. We identified 3267 DE-mRNAs, 484 DE-lncRNAs and 69 DE-miRNAs between the TB and healthy subjects, from which 8 DE-mRNAs, 14 DE-lncRNAs and 3 DE-miRNAs were used to construct the ceRNA network. The genes contained in the ceRNA network were mainly enriched in neutrophil mediated immune response, including neutrophil activation, degradation and signal transduction. ROC analysis revealed that has-miR-140-5p, has-miR-142-3p and the LASSO cox prediction model based on HMGA1 and CAPN1 have potential value for forecasting TB (AUC > 0.7). Hence, our study provides a new perspective from the lncRNA-miRNA-mRNA ceRNA regulatory network for TB diagnosis and treatment.

A Mouse Model of Lumbar Spine Instability.

Intervertebral disc degeneration (IDD) is a common pathological change leading to low back pain. Appropriate animal models are desired for understanding the pathological processes and evaluating new drugs. Here, we introduced a surgically induced lumbar spine instability (LSI) mouse model that develops IDD starting from 1 week post operation. In detail, the mouse under anesthesia was operated by low back skin incision, L3-L5 spinous processes exposure, detachment of paraspinous muscles, resection of processes and ligaments, and skin closure. L4-L5 IVDs were chosen for the observation. The LSI model develops lumbar IDD by porosity and hypertrophy in endplates at an early stage, decrease in intervertebral disc volume, shrinkage in nucleus pulposus at an intermediate stage, and bone loss in lumbar vertebrae (L5) at a later stage. The LSI mouse model has the advantages of strong operability, no requirement of special equipment, reproducibility, inexpensive, and relatively short period of IDD development. However, LSI operation is still a trauma that causes inflammation within the first week post operation. Thus, this animal model is suitable for study of lumbar IDD.

Evaluating the transcriptional fidelity of cancer models.

BACKGROUND: Cancer researchers use cell lines, patient-derived xenografts, engineered mice, and tumoroids as models to investigate tumor biology and to identify therapies. The generalizability and power of a model derive from the fidelity with which it represents the tumor type under investigation; however, the extent to which this is true is often unclear. The preponderance of models and the ability to readily generate new ones has created a demand for tools that can measure the extent and ways in which cancer models resemble or diverge from native tumors. METHODS: We developed a machine learning-based computational tool, CancerCellNet, that measures the similarity of cancer models to 22 naturally occurring tumor types and 36 subtypes, in a platform and species agnostic manner. We applied this tool to 657 cancer cell lines, 415 patient-derived xenografts, 26 distinct genetically engineered mouse models, and 131 tumoroids. We validated CancerCellNet by application to independent data, and we tested several predictions with immunofluorescence. RESULTS: We have documented the cancer models with the greatest transcriptional fidelity to natural tumors, we have identified cancers underserved by adequate models, and we have found models with annotations that do not match their classification. By comparing models across modalities, we report that, on average, genetically engineered mice and tumoroids have higher transcriptional fidelity than patient-derived xenografts and cell lines in four out of five tumor types. However, several patient-derived xenografts and tumoroids have classification scores that are on par with native tumors, highlighting both their potential as faithful model classes and their heterogeneity. CONCLUSIONS: CancerCellNet enables the rapid assessment of transcriptional fidelity of tumor models. We have made CancerCellNet available as a freely downloadable R package ( https://github.com/pcahan1/cancerCellNet ) and as a web application ( http://www.cahanlab.org/resources/cancerCellNet_web ) that can be applied to new cancer models that allows for direct comparison to the cancer models evaluated here.

Transcriptomic alterations underline aging of osteogenic bone marrow stromal cells.

BACKGROUND: Multipotent bone marrow stromal cells (BMSCs) are adult stem cells that form functional osteoblasts and play a critical role in bone remodeling. During aging, an increase in bone loss and reduction in structural integrity lead to osteoporosis and result in an increased risk of fracture. We examined age-dependent histological changes in murine vertebrae and uncovered that bone loss begins as early as the age of 1 mo. AIM: To identify the functional alterations and transcriptomic dynamics of BMSCs during early bone loss. METHODS: We collected BMSCs from mice at early to middle ages and compared their self-renewal and differentiation potential. Subsequently, we obtained the transcriptomic profiles of BMSCs at 1 mo, 3 mo, and 7 mo. RESULTS: The colony-forming and osteogenic commitment capacity showed a comparable finding that decreased at the age of 1 mo. The transcriptomic analysis showed the enrichment of osteoblastic regulation genes at 1 mo and loss of osteogenic features at 3 mo. The BMSCs at 7 mo showed enrichment of adipogenic and DNA repair features. Moreover, we demonstrated that the WNT and MAPK signaling pathways were upregulated at 1 mo, followed by increased pro-inflammatory and apoptotic features. CONCLUSION: Our study uncovered the cellular and molecular dynamics of bone aging in mice and demonstrated the contribution of BMSCs to the early stage of age-related bone loss.

Luteolin inhibits autophagy in allergic asthma by activating PI3K/Akt/mTOR signaling and inhibiting Beclin-1-PI3KC3 complex.

Allergic asthma is a common chronic inflammatory disease characterized by airway inflammation, mucus hypersecretion and airway remodeling. Autophagy is a highly conserved intracellular degradation pathway in eukaryotic cells. There is growing evidence suggesting that dysregulation of autophagy is involved in the pathological process of asthma. Luteolin is a typical flavonoid compound with anti-inflammatory, anti-allergic and immune-enhancing functions. Previous studies have shown that luteolin can attenuate airway inflammation and hypersensitivity in asthma. However, whether luteolin can play a role in treating asthma by regulating autophagy remains unclear. The aim of the present study was to evaluate the therapeutic effect of luteolin on ovalbumin (OVA)-induced asthmatic mice, observe its effect on the level of autophagy in lung tissues, and further elucidate its underlying mechanism. The results showed that OVA-induced mice developed airway hyperresponsiveness, mucus over-production and collagen deposition. The number of inflammatory cells, levels of interleukin (IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid (BALF) and OVA-specific IgE in serum were significantly increased. Furthermore, the infiltration of inflammatory cells was observed along with the activation of autophagy in lung tissues. Luteolin treatment significantly inhibited the OVA-induced inflammatory responses and the level of autophagy in lung tissues as well. Moreover, luteolin activated the PI3K/Akt/mTOR pathway and inhibited the Beclin-1-PI3KC3 protein complex in lung tissues of asthmatic mice. In conclusion, this study explored the regulatory mechanism of luteolin on autophagy in allergic asthma, providing biologic evidence for its clinical application.

Clinical significance of the serum IgM and IgG to SARS-CoV-2 in coronavirus disease-2019.

OBJECTIVE: To explore the clinical value of serum IgM and IgG to SARS-CoV-2 in COVID-19. METHODS: 105 COVID-19 patients were enrolled as the disease group. 197 non-COVID-19 patients served as the control group. Magnetic chemiluminescent immunoassay (MCLIA) was used to detect the IgM and IgG. RESULTS: The peak of positive rates of SARS-CoV-2 IgM was about 1 week earlier than that of IgG. It reached to peak within 15-21 days and then began a slowly decline. The positive rates of IgG were increased with the disease course and reached the peak between 22 and 39 days. The differences in sensitivity of the three detection modes (IgM, IgG, and IgM + IgG) were statistically significant. The largest group of test cases (illness onset 15-21 days) showed that the positive rate of IgG was higher than IgM. Also, the sensitivity of IgM combined with IgG was higher than IgM or IgG. IgM and IgG were monitored dynamically for 16 patients with COVID-19, the results showed that serological transformation of IgM was carried out simultaneously with IgG in seven patients, which was earlier than IgG in four patients and later than IgG in five patients. CONCLUSION: The detection of SARS-CoV-2 IgM and IgG is very important to determine the course of COVID-19. Nucleic acid detection combined with serum antibody of SARS-CoV-2 may be the best laboratory indicator for the diagnosis of SARS-CoV-2 infection and the phrase and predication for prognosis of COVID-19.

[Value of Serum Light Chain in Diagnosis and Evaluation of Efficacy for Multiple Myeloma].

OBJECTIVE: To explore the clinical application value of serum light chain (sLC) in the diagnosis and therapeutic efficacy evaluation for multiple myeloma. METHODS: 46 patients with newly diagnosed multiple myeloma were selected as MM group and 50 healthy persons as control group. Rate scattering immunoturbidimetry was used to detect serum light chain and immunoglobulin (Ig) in two groups, serum protein electrophoresis was used to detect M protein by agarose gel. Then, the sensitivity and specificity of the two methods in MM diagnosis were analyzed and compared, and the significance of sLC detection in MM diagnosis were discussed. In addition, 15 MM patients after received conventional therapy were tracked, sLC levels in five different therapentic times were recorded, and the effect of sLC in efficacy evaluation of MM was analyzed. RESULTS: There were 11 cases of IgA type, 15 cases of IgG type, 8 cases of light chain κ type, 8 cases of light chain λ type, 2 cases of IgD type, and 2 cases of non-secretion type. The sLC-κ, sLC-λ and their ratio (including light chain type and double clone type), IgA and IgG (except IgD type), as well as albumin, beta-globulin and gamma-globulin levels showed statistically significant differences (P＜0.05) compared with the control group. The sensitivity of serum protein electrophoresis, Ig quantification, sLC and its ratio in the diagnosis of multiple myeloma were 57%, 76% and 65%, and their specificity were 83%, 61% and 90%, respectively. After the second or third chemotherapy, the sLC-κ/λ ratio gradually approached the normal range as the disease reliefes, and the sLC-κ/λ ratio continued to be on or off the line at outliers or further away from the reference value as the disease progresses in MM patients with κ type or λ type. CONCLUSION: sLC detection shows positive significance in early diagnosis of multiple myeloma, SLC monitoring can be used for the efficacy evaluation for treatment of MM patients.

A single cell transcriptional atlas of early synovial joint development.

Synovial joint development begins with the formation of the interzone, a region of condensed mesenchymal cells at the site of the prospective joint. Recently, lineage-tracing strategies have revealed that Gdf5-lineage cells native to and from outside the interzone contribute to most, if not all, of the major joint components. However, there is limited knowledge of the specific transcriptional and signaling programs that regulate interzone formation and fate diversification of synovial joint constituents. To address this, we have performed single cell RNA-Seq analysis of 7329 synovial joint progenitor cells from the developing murine knee joint from E12.5 to E15.5. By using a combination of computational analytics, in situ hybridization and in vitro characterization of prospectively isolated populations, we have identified the transcriptional profiles of the major developmental paths for joint progenitors. Our freely available single cell transcriptional atlas will serve as a resource for the community to uncover transcriptional programs and cell interactions that regulate synovial joint development.

Do genetic polymorphisms of B-cell CLL/lymphoma 2 confer susceptibility to anti-tuberculous therapy-associated drug-induced liver injury?

OBJECTIVES: The aim of this study was to identify the relationship between B-cell CLL/lymphoma 2 (BCL2) polymorphisms and susceptibility to anti-tuberculous therapy-associated drug-induced liver injury (ATT-DILI). METHODS: A total of 746 tuberculosis (TB) patients were enrolled in this study. Twenty-one selected single nucleotide polymorphisms in BCL2 were analyzed by custom-by-design 2×48-Plex SNPscan kit. The allele and genotype frequencies between patients with and without ATT-DILI were compared using three different genetic models. RESULTS: A total of 727/746 participants were successfully genotyped, and 112 of them were diagnosed with ATT-DILI. The A allele of rs8085707, G allele of rs76986960, and A allele of rs949037 conferred an increased risk of ATT-DILI, with estimated odd ratios (ORs) of 2.181 (95% confidence interval (CI) 1.345-3.536, p=0.001), 1.983 (95% CI 1.060-3.709, p=0.029), and 1.390 (95% CI 1.032-1.873, p=0.03), respectively. Bonferroni correction indicated that the A allele of rs8085707 was a risk factor for ATT-DILI (Bonferroni correction: p=0.026). The additive model suggested that patients with the AA genotype of rs8085707 had a significantly higher risk of ATT-DILI compared with those with the GG genotype (Bonferroni correction: p=0.036). The influence of BCL2 polymorphisms on clinical characteristics (clinical symptoms, disease subtypes, and laboratory indicators) was also identified. CONCLUSIONS: This study is novel in suggesting an association between BCL2 polymorphisms and the risk of ATT-DILI.