Prognostic and clinical value of circPRKCI expression in diverse human cancers / 中华医学杂志(英文版)

BACKGROUND@#Highly expressed in various human cancers, circular RNA Protein Kinase C Iota (circPRKCI) has been reported to play an important role in cancer development and progression. Herein, we sought to reveal the prognostic and clinical value of circPRKCI expression in diverse human cancers.@*METHODS@#We searched the Pubmed, Web of Science, and the Cochrane Library databases from inception until May 16, 2021. The relationship between circPRKCI expression and cancer patients' survival, including overall survival (OS) and disease-free survival (DFS), was assessed by pooled hazard ratios (HR) with corresponding 95% confidence interval (CI). The correlation between circPRKCI expression and clinical outcomes was evaluated using odds ratios (OR) with corresponding 95% CI. The data were analyzed by STATA software (version 12.0) or Review Manager (RevMan 5.3).@*RESULTS@#A total of 15 studies with 1109 patients were incorporated into our meta-analysis. The results demonstrated that high circPRKCI expression was significantly related to poor OS (HR = 1.96, 95% CI: 1.61, 2.39, P <0.001) when compared with low circPRKCI expression in diverse human cancers. However, elevated circPRKCI expression was not associated with DFS (HR = 1.34, 95% CI: 0.93, 1.95, P = 0.121). Furthermore, the patient with a higher circPRKCI expression was prone to have a larger tumor size, advanced clinical stage, and lymph node metastasis, but it was not significantly correlated with age, gender, and distant metastasis.@*CONCLUSION@#Elevated circPRKCI expression was correlated with worse OS and unfavorable clinical features, suggesting a novel prognostic and predictive role of circPRKCI in diverse human cancers.

Genome-wide transcriptional analyses of Clarireedia jacksonii isolates associated with multi-drug resistance.

Emerging multidrug resistance (MDR) in Clarireedia spp. is a huge challenge to the management of dollar spot (DS) disease on turfgrass. Insight into the molecular basis of resistance mechanisms may help identify key molecular targets for developing novel effective chemicals. Previously, a MDR isolate (LT586) of C. jacksonii with significantly reduced sensitivities to propiconazole, boscalid, and iprodione, and a fungicide-sensitive isolate (LT15) of the same species were isolated from creeping bentgrass (Agrostis stolonifera L.). The present study aimed to further explore the molecular mechanisms of resistance by using genome-wide transcriptional analyses of the two isolates. A total of 619 and 475 differentially expressed genes (DEGs) were significantly down and upregulated in the MDR isolate LT586, compared with the sensitive isolate LT15 without fungicide treatment. Three hundreds and six and 153 DEGs showed significantly lower and higher expression in the MDR isolate LT586 than those in the sensitive isolate LT15, which were commonly induced by the three fungicides. Most of the 153 upregulated DEGs were xenobiotic detoxification-related genes and genes with transcriptional functions. Fifty and 17 upregulated DEGs were also commonly observed in HRI11 (a MDR isolate of the C. jacksonii) compared with the HRS10 (a fungicide-sensitive isolate of same species) from a previous study without and with the treatment of propiconazole, respectively. The reliability of RNA-seq data was further verified by qRT-PCR method using a few select potentially MDR-related genes. Results of this study indicated that there were multiple uncharacterized genes, possibly responsible for MDR phenotypes in Clarireedia spp., which may have important implications in understanding the molecular mechanisms underlying MDR resistance.

Current Development Status and Consideration for Rare Hemorrhagic Disease Drugs / 罕见病研究

Hemophilia is the only rare hereditary hemorrhagic disorder included in the First Rare Diseases catalogue. However, rare bleeding diseases identified in the clinic are far more common than hemophilia. Most other rare hemorrhagic disorders have less effective treatment than hemophilia. Hemophilia has a history of successful drug development in rare hemorrhagic diseases, and the cycle between clinical research and drug development has been gradually realized. Drug research and pharmaceutical companies can refer to the drug research and development process in the field of hemophilia, learn from the experience of hemophilia drug research and develop treatments. The industry can increase drug development by strengthening basic research, focusing on the value of natural history research, the application of quantitative pharmacological tools and improving the efficiency of drug development to meet the urgent unmet medical needs of patients with rare hemorrhagic diseases.

Appraisal Concerns for the Clinical Research and Development of Drugs for Rare Diseases / 罕见病研究

The incidence of each of the rare disease is very low. The complexity and diagnosis difficulty of the rare disease lead to the difficulties in the clinical research and development (R&D) of drugs for rare diseases. There is an urgent clinical need for the drug development of rare diseases in China. Encouraging R&D of new drugs, particularly the innovative drugs with China's own independent intellectural property is the basis for solving the predicament in drug shortage in China.. In order to further improve the efficiency of clinical R&D of drugs for rare diseases, the National Medical Products Administration (NMPA), Center for Drug Evaluation (CDE) issued Technical Guidance for Clinical Research and Development of Drugs for Rare Diseases. This is the first guidance for rare diseases in China that is drafted from the standpoint of the clinical technology research and development.The guidance is the scientifitc thinking and framework for the drug developing enterprises to research and develop drugs for rare disease efficiently and appropriately by following drug developing protocols and relating to the special features of rare disease.This paper presents the concepts and rationale in the guidance for the appraisal of rare disease drug research and development.

Considerations on Clinical Development and Regulatory of the Oversea License-in Anti-tumor Drugs / 中国肺癌杂志

With the boom of China's innovative pharmaceutical industry, licensing-in model has gradually become an important research and development model for innovative pharmaceutical companies. The in-licensed drugs at different stages need different research and development (R&D) strategy in China. The pharmaceutical companies take the responsibility to comprehensively collate the oversea clinical data and conduct a detailed analysis of clinical pharmacology, safety, efficacy and ethnic sensitivity. Clinical R&D strategy should be made based on the results of the above data and analysis. We encourage high-quality drugs which fill unmet clinical needs licensed in, and as early as possible, so as to conduct multi-regional clinical trials (MRCTs). The clinical R&D strategy in China is particularly important for the drug's approval. Guidelines published by the National Medical Products Administration (NMPA) and clinical associations should be followed. Communications about clinical R&D strategy with Center of Drug Evaluation (CDE) are encouraged.
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Consideration on the Research and Development of New Drugs for Rare Tumors / 中国肺癌杂志

In recent years, China's anti-tumor drugs has shown a continuous growth trend, and the activity of anti-tumor research and development in China accounts for a higher proportion in the world. However, further analysis of research and development hotspots show that the research and development of anti-tumor drugs is uneven among different tumor types. Due to the small number of the patients, it is difficult to conduct clinical trials, resulting in less drug development in the field of rare tumors. However, patients' treatment needs will also bring potential opportunities for pharmaceutical companies. The development of basic research and the discovery of new molecular tumor typing make "rare tumors" a dynamic concept. The scope of "rare tumors" may gradually expand with the precise development of treatment; or as the knowledge of tumors gradually develops from histocytology to the molecular level, It is possible that certain tumors with specific mutations can be combined into a group of non-rare "pan-tumors". Rare tumors are characterized by both rare diseases and tumors. Its drug research and development should not only meet the requirements of tumor drug research and development, but also adapt to the characteristics of rare diseases. Therefore, in the drug research and development, we can refer to the research and development principle of rare disease drugs, combine with the characteristics of tumor diseases, make full use of non-rare tumor clinical trials, make full use of scientific tools and exquisite trial design, and realize the promotion of the research and development of rare tumor drugs. This paper will summarize the thoughts in the review of new drugs in the field of rare tumors, in order to provide guidance for the industry.
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Considerations on pivotal clinical trial design of innovative new drugs for hematological malignancies / 白血病·淋巴瘤

The rapid changes in the research and development environment of new anti-tumor drugs in China have brought various challenges to drug innovation. How to explore the clinical advantages of new drugs in the early phase, and design scientific, reasonable and efficient pivotal clinical trials for drug registration accordingly, is one of the key challenges. This article takes innovative new drugs for hematological malignancies as an example, comprehensively elaborates the considerations on the timing for entering the pivotal clinical trial and the key elements of the trial design from the perspective of clinical reviewers.

KNTC1 knockdown suppresses cell proliferation of colon cancer.

Kinetochore-associated protein 1 (KNTC1) is a kind of kinetochore components that ensure the proper functioning of the spindle-assembly checkpoint. To date, the functional information of KNTC1 in colon cancer remains unknown. This study was aimed to investigate the role of KNTC1 in colon cancer. We found KNTC1 was significantly upregulated in the colon cancer compared to the normal tissues. ROC curve showed the area under the curve value of KNTC1 for the prediction of colon cancer was 0.93. Kaplan-Meier revealed highly expressed KNTC1 was associated with poor prognosis. KNTC1 was widely expressed in different colon cancer cell lines. Compared with the control lentiviral infected cells, KNTC1-shRNA cells exhibited significant reduction in cell growth rates and increase in the proportion of cells in the S phase, while decrease in the G1 and G2/M phase. Furthermore, knockdown of KNTC1 dramatically increased apoptosis in the colon cancer cells. Gene set enrichment analysis (GSEA) in gene ontology (GO) showed that KNTC1 is closely associated with cell mitosis-related components, such as nuclear chromatin, centrosome, and spindle. Moreover, upregulated KNTC1 is significantly enriched in the biological process of DNA repair, mRNA processing, microtubule cytoskeleton organization and the molecular function of helicase activity, protein heterodimerization activity and catalytic activity acting on DNA in molecular function. Our data reveal the important roles of KNTC1 in driving tumor progression in colon cancers.

Effect of recombinant human growth hormone on height and serum IGF-1 in children with idiopathic short stature / 中国基层医药

Objective:To study the effect of recombinant human growth hormone on height and serum insulin-like growth factor 1(IGF-1) in children with idiopathic short stature.Methods:Fifty children with idiopathic short stature admitted to Weihai Central Hospital from September 2015 to February 2017 were randomly divided into treatment group(25 cases) and control group(25 cases) according to the random digital table method.The control group received nutritional support treatment.The treatment group was treated with subcutaneous injection of recombinant human growth hormone on the basis of the control group.All the children were treated and observed for one year.The height, weight, growth rate, bone age, total thyroid hormone level, fasting blood glucose level, serum IGF-1 level and adverse reactions were compared before and after treatment.Results:After 1 year of treatment, the height, growth rate, and IGF-1 of the two groups were significantly higher than those before treatment ( t=4.427, 2.987, 7.459, 5.963, 31.389, 21.790, P<0.001, 0.004, <0.001, <0.001, <0.001, <0.001). which in the treatment group were significantly higher than those in the control group ( t=2.914, 2.480, 12.090, P=0.006, 0.017, <0.001). The body weight, bone age, total thyroid hormone levels, and fasting blood glucose levels in the two groups were not significantly different from those before treatment ( t=0.548, 1.931, 0.300, 1.367, 0.735, 0.759, 0.693, 0.920, P=0.586, 0.060, 0.765, 0.179, 0.466, 0.452, 0.492, 0.362), and there were no statistically significant differences between the two groups ( t=0.371, 0.141, 0.059, 0.318, P=0.713, 0.889, 0.953, 0.752). There was no statistically significant difference in adverse reactions between the two groups during treatment (χ 2=2.083, P=0.149). Conclusion:Recombinant human growth factor can effectively accelerate the growth rate of children with idiopathic short stature, increase the height of children, increase the level of serum IGF-1, and has no obvious side effects.

Effects of Krüppel-like factor 5 gene silencing on biological functions of rat intestinal epithelial cells IEC-6 after radiation / 中华放射医学与防护杂志

Objective:To investigate the effects of down-regulation of Krüppel-like factor 5 (KLF5) on biological functions of rat intestinal epithelial cells IEC-6 in response to ionizing radiation.Methods:Rat intestinal epithelial IEC-6 cells were irradiated with 0, 2, 4, 8, 12, 16 Gy of X-rays and 3 h later the expression of KLF5 in IEC-6 cells was detected by Western blot. IEC-6 cells were irradiated to 12 Gy and 0, 0.5, 1, 2, 3, 5, 7 and 24 h later the expression of KLF5 in IEC-6 cells was detected by Western blot. shRNA sequences targeting rat KLF5 gene were designed, synthesized and inserted into the lentiviral vector. The recombinant lentiviral vectors were packaged in human embryonic kidney 293T cells, and the lentivirus titers were determined. IEC-6 cells were infected with the recombinant lentivirus, and the transfection efficiency was observed under fluorescence microscope. Real-time PCR and Western blot were used to detect the expressions of KLF5 mRNA and protein in the transfected cells 72 h post transfection. The consequent experiments included four groups: negative control group, shKLF5 group, radiation group and radiation + shKLF5 group. The cell viability was observed in KLF5 silencing cells irradiated with 8 Gy by using CCK-8 assay. The cell cycle distribution and apoptosis were detected in KLF5 silencing cells irradiated with 8 Gy by flow cytometry. Immunofluorescence staining was applied to visualize the γ-H2AX foci in nucleus of KLF5 silencing cells irradiated with 2 Gy.Results:The expression of KLF5 increased with the different doses. The expression of KLF5 increased first, then decreased and peaked at 5 h post-irradiation with 12 Gy. KLF5 shRNA lentiviral vectors were successfully constructed. The mRNA and protein level of KLF5 were down-regulated in recombinant lentivirus transfected IEC-6 cells 72 h after transfection. Knockdown of KLF5 markedly induced G 2/M phase arrest ( t=11.56, P<0.05), proliferation inhibition, more apoptosis rate [radiation group: (7.42±0.49)%, radiation + shKLF5 group: (12.49±0.63)%, t=10.98, P<0.05], and more γ-H2AX foci in nucleus post-irradiation than negative control ( t=22.07, 23.89, 11.24, 59.97, 20.85, P<0.05). Conclusions:The KLF5 knockdown intestinal epithelial cell line was successfully established. The down-regulation of KLF5 expression could induce cell arrest at G 2/M, suppress the proliferation of irradiated cells and improve the cell apoptosis, enhance DNA double strand breaks and prolong DNA damage repair.

Clinical research and drug review of epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer / 中华肿瘤杂志

Lung cancer is the most frequently diagnosed cancer and the most common cause of cancer mortality in China. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers. The mutation rate of epidermal growth factor receptor (EGFR) gene is relatively high, accounts for 32%~38% of all NSCLC. During the last decade, the application of EGFR specific tyrosine kinase inhibitors (TKI) significantly improved prognosis of NSCLC patients with sensitive EGFR mutations. Thus, the research and development of third generation EGFR-TKI have entered the period of rapid development. The fourth generation EGFR-TKI which targeting EGFR C797S has even begun clinical development in China. This review will discuss the clinical research and drug review of EGFR-TKI from the perspective of drug review.

Considerations for anti-cancer drug application by single arm trials / 中华肿瘤杂志

Single arm trial (SAT) was widely used for new drug application (NDA) of novel anti-cancer drugs in recent years. The listing time was greatly shortened by SAT while comparing with randomized controlled trials (RCT). Thus, the companies intended to get NDA through SAT. To encourage innovation and accelerate the developments of anti-cancer agents, we summarize the background and key issues of SAT, discuss the conditions of accepting SAT for NDA, and systematically elaborate the design and principles of SAT in this review.

Effects of subcutaneous embedding of thumb-tack needle on tear film in patients with dry eye / 中国针灸

<p><b>OBJECTIVE</b>To observe the effects of subcutaneous embedding of thumb-tack needle combined with mytear and simple mytear on tear film in patients with dry eye.</p><p><b>METHODS</b>Eighty patients of dry eye (160 eyes) were randomly divided into an observation group and a control group, 40 cases in each group. The 0.1% sodium hyaluronate eye drop (alice) was applied in the control group, four times per day for two weeks. On the basis of the control group, the subcutaneous embedding of thumb-tack needle was used at ① Cuanzhu (BL 2), Sizhukong (SJ 23), Sibai (ST 2), ② Yintang (EX-HN 3), Yuyao (EX-HN 4), Taiyang (EX-HN 5). The two groups of acupoints were used alternately. The thumb-tack needle was placed for 2 to 3 days, once a week for two weeks. The subjective symptom score, Schirmer Ⅰ test (SⅠT), tear break-up time (BUT) and corneal fluorescein staining (CFS) were compared before treatment, after treatment and during 2-week follow-up visit in the two groups. The effects of the two groups were compared.</p><p><b>RESULTS</b>Compared before treatment, the subjective symptom score and CFS were reduced but SⅠT and BUT were increased after treatment and during follow-up visit in the two groups (all <0.05), which in the observation group were superior to those in the control group (all <0.05). The total effective rate was 90.0% (36/40) in the observation group, which was superior to 85.0% (34/40) in the control group (<0.05).</p><p><b>CONCLUSION</b>The subcutaneous embedding of thumb-tack needle could increase the amount of SIT, prolong BUT and repair pathological damage of cornea, which could relieve the symptoms of dry eye and improve visual quality.</p>

Analysis of Traditional Chinese Medicine Physique Types of Elderly Population from One University Community in Guangzhou / 广州中医药大学学报

Objective To provide epidemiological evidence for the application of traditional Chinese medicine (TCM) physique differentiation to the disease control and prevention, Chinese medicine health care, public education and so on in the elderly population. Methods TCM physique types of the elderly population aged over 65 years old from one University community in Tianhe district of Guangzhou city were analyzed by one-on-one questionnaire investigation with the Classification and Identification Scale for Senile Traditional Chinese Medicine Constitution, and the correlation of TCM physique types with gender, age group was also explored. Results (1) In the 65-year-old elderly population of 777 cases, 231(29.7％) were classified into phlegm-damp physique, 129(16.6％) into blood-stasis physique, and 71(9.1％) into harmony physique, which contributed to the major physique types. (2) Physique types varied in the gender. The male was dominated by phlegm-damp physique and damp-heat physique, and the female was dominated by yang-deficiency constitution, Qi-stagnation physique and interweaved physique. The differences of the constitution ratio of physique types in the gender were significant (P<0.01). (3) In various age groups, the leading 3 physique types were the same, and they were phlegm-damp physique, blood-stasis physique, and interweaved physique (P<0.01). With the increase of age years, the ratio of deficiency physique type showed an increasing trend while that of the non-deficiency physique type showed a decreasing trend. Conclusion The investigation revealed the distribution of TCM physique types of the elderly population from one University community in Guangzhou, which has important practical value for the intervention of the elderly population with Chinese medicine.

Study on Activities of Phase Ⅰ and Ⅱ Drug-metabolic Enzymes in Spleen of Rats with Spleen-Kidney Yang Deficiency Syndrome / 广州中医药大学学报

Objective To study the changes of activities of phase Ⅰ and Ⅱ drug-metabolic enzymes in the spleen of rats with spleen-kidney yang deficiency syndrome.Methods The rat model of spleen-kidney yang deficiency syndrome was established by gastric gavage of Radix et Rhizoma Rhei decoction combined with injection of hydrocortisone for 17 continuous days.And then we detected the activities of 6 kinds of phase Ⅰ drug-metabolic enzymes of CYP2C19,CYP2D6,CYP2C9,CYP1A2,CYP2C8,CYP3A4,and 4 kinds of phase Ⅱ drugmetabolic enzymes of phenol sulfotransferase (PST),uridine diphosphate glucuronosyl transferase 1 (UGT1),glutathione transferase (GST),estrogen sulfotransferase (SULT1E1) in the spleen.Results Compared with the normal control group,the activities of PST,UGT1,GST and SULT1E1 in the model group were significantly decreased (P ＜ 0.05 or P ＜ 0.01),and the activity of CYP1A2 was significantly increased (P ＜ 0.01),while CYP2C19,CYP2D6,CYP2C8,CYP3A4,CYP2C9 enzymes showed no obvious changes(P ＞ 0.05).Conclusion The activities of splenic drug-metabolic enzymes,in particular the phase Ⅱ enzymes,are significantly varied under the state of spleen-kidney yang deficiency.

Meta-analysis of The olfaction effectiveness of glucocorticoid in the management of chronic rhinosinusitis with nasal polyposis / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To evaluate the effectiveness of glucocorticoid in the management of olfaction in patients with chronic rhinosinusitis accompanied with nasal polyposis.@*METHOD@#The published studies of the effectiveness of glucocorticoid in the management of chronic rhinosinusitis with nasal polyposis were searched in the Medline, Cochrane, EMBASE, Springer and CNKI databases(from the date of establishment of the databases to December 2014). The trails selection based on inclusion criteria and the quality of the included studies was assessed and meta-analysis was performed with RevMan 5. 3 software.@*RESULT@#A total of 5 trials involving 325 patients were included. The Meta-analysis showed that oral glucocorticoid showed more significant improvement in subjective olfaction scores compared to placebo [SMD = -2.22, 95% CI (-3.94 - -0. 49), P 0.05], [SMD = 0.28, 95% CI (-0.08-0.64) P > 0.05].@*CONCLUSION@#According to current evidence, oral glucocorticoid can significantly improve subjective and objective olfaction among patients with CRSwNP, but nasal glucocorticoid cannot improve subjective or objective olfaction dysfunction.

Comparetive study of conventional vs. zero-balanced ultrafiltration in concentration of serum pro-inflammatory factors and incidence of acute kidney injury after cardio-pulmonary bypass proce-dures / 临床外科杂志

Objective To compare the impact of conventional vs. zero-balanced ultrafiltration on serum pro-inflammatory factors,acute kidney injury and clinical prognosis after cardio-pulmonary bypass procedure. Methods Forty patients receiving cardiac surgery under cardio-pulmonary bypass procedures in Xiangyang Central Hospital during January 2013 to June 2013 were randomly divided into conventional ultrafiltration group(group A,n=20)and zero-balanced ultrafiltration group(group B,n=20). Blood and urine samples were collected on different time points( pre-operation,T0;pre-ultrafiltration,T1;immediately after ultrafiltration,T2;24 hours post-operation,T3;48 hours post-operation,T4;7 days post-operation, T5). TNF-α,IL-6,KIM-1,CysC,serum creatinine and urea nitrogen were detected and compared. Pre-and post-operative clinical data were also collected. Results There was no difference in baseline data or intra-operative data(p>0. 05). TNF-αand IL-6 started to increase when the operation began. Compared with conventional ultrafiltration,zero-balanced ultrafiltration alleviated the increase of TNF-α and IL-6,espe-cially on T2,T3,and T4(pgrade I)in group A and 2 patients experienced in group B(p<0. 01). There were significant differences of ventilation time,total complication incidence and ICU stay time be-tween two groups. There was no difference in other complications,post-operative days in hospital or death rate within 30 days. Conclusion Though there is a trend of more patients receving renal replacement therapy,no statistical difference has been achieved. In conclusion,zero-balanced ultrafiltration can effec-tively decrease the concentration of serum pro-inflammatory factors,alleviate acute kidney injury and improve the clinical prognosis after cardio-pulmonary bypass procedures. It is a safe and reliable method valuable for promotion.

New progression of lobaplatin in the treatment of gynecologic cancer / 国际肿瘤学杂志

Lobaplatin is the third generation platinum anticancer drug,and has been listed for the clinical treatment of advanced breast cancer,small cell lung cancer and chronic myeloid leukemia.Studies have shown that lobaplatin as the latest third generation platinum anticancer drug,has good water solubility,broadspectrum anti-tumor,strong anti-tumor activity,no cross-resistance with other platinum drugs,low toxicity and many other features.Lobaplatin has shown a clear advantage.

Hepatocyte apoptosis and mitochondrial permeability transition pore opening in rats with nonalcoholic fatty liver / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of hepatocyte apoptosis and mitochondrial permeability transition pore (MPTP) opening in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).</p><p><b>METHODS</b>Thirty male SD rats were randomized into normal diet group and high-fat diet group. At 4, 8 and 12 week of feeding. The hepatocyte apoptosis index (AI) was measured using flow cytometry, and MPTP opening was evaluated with ultraviolet spectrophotometry. Immunohistochemistry was employed to detect hepatic expressions of Bcl-2 and Bax, and Western blotting was used to detect Bax protein expression changes.</p><p><b>RESULTS</b>High-fat feeding resulted in significantly increased hepatocyte AI at 4-12 weeks and gradually increased MPTP opening. In the high-fat diet group, hepatic Bcl-2 expression was detected but the positive cell number remained stable, whereas Bax-positive cell number increased steadily with time with progressively increased intensity of Bax protein expression, resulting in gradually decreased Bcl-2/Bax ratio.</p><p><b>CONCLUSION</b>Hepatocyte apoptosis occurs in the rat model of NAFLD in close correlation with mitochondrial damage. Increased MPTP opening as the result of increased Bax expression and aberrant Bcl-2/Bax ratio is an important mechanism of hepatocyte mitochondrial damage in NAFLD.</p>