Extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (AMSC-EVs) have been highlighted as a cell-free therapy due to their regenerative capability to enhance tissue and organ regeneration. Herein, we aimed to examine the mechanism of PF127-hydrogel@AMSC-EVs in promoting tracheal cartilage defect repair. Based on bioinformatics methods, SCNN1B was identified as a key gene for the osteogenic differentiation of AMSCs induced by AMSC-EVs. EVs were isolated from rat AMSCs and then loaded onto thermo-sensitive PF-127 hydrogel to develop PF127-hydrogel@AMSC-EVs. It was established that PF127-hydrogel@AMSC-EVs could effectively deliver SCNN1B into AMSCs, where SCNN1B promoted AMSC osteogenic differentiation. The promotive effect was evidenced by enhanced ALP activity, extracellular matrix mineralization, and expression of s-glycosaminoglycan, RUNX2, OCN, collagen II, PERK, and ATF4. Furthermore, the in vivo experiments revealed that PF127-hydrogel@AMSC-SCNN1B-EVs stimulated tracheal cartilage regeneration in rats through PERK/ATF4 signaling axis activation. Therefore, PF127-hydrogel@AMSC-SCNN1B-EVs may be a novel cell-free biomaterial to facilitate tracheal cartilage regeneration and cartilage injury repair.

SNHG3, a long noncoding RNA (lncRNA), has been linked to poor outcomes in patients with liver hepatocellular carcinoma (LIHC). In this study, we found that SNHG3 was overexpressed in LIHC and associated with poor outcomes in patients with LIHC. Functional assays, including colony formation, spheroid formation, and in vivo assays showed that SNHG3 promoted stemness of cancer stem cells (CSC) and tumor growth in vivo by interacting with microRNA-502-3p (miR-502-3p). miR-502-3p inhibitor repressed the tumor-suppressing effects of SNHG3 depletion. Finally, by RNA pull-down, dual-luciferase reporter assay, m6A methylation level detection, and m6A-IP-qPCR assays, we found that miR-502-3p targeted YTHDF3 to regulate the translation of integrin alpha-6 (ITGA6) and targeted HBXIP to inhibit the m6A modification of ITGA6 through methyltransferase-like 3 (METTL3). Our study revealed that SNHG3 controls the YTHDF3/ITGA6 and HBXIP/METTL3/ITGA6 pathways by repressing miR-502-3p expression to sustain the self-renewal properties of CSC in LIHC.

OBJECTIVE:Cartilage injury is a common clinical condition, and treatment approaches have evolved over time from traditional conservative and surgical methods to regenerative repair. In this context, hydrogels, as widely used biomaterials in the field of cartilage repair, have garnered significant attention. Particularly, responsive hydrogels (also known as "smart hydrogels") have shown immense potential due to their ability to respond to various physicochemical properties and environmental changes. This paper aims to review the latest research developments of hydrogels in cartilage repair, utilizing a more systematic and comprehensive meta-analysis approach to evaluate the research status and application value of responsive hydrogels. The goal is to determine whether these materials demonstrate favorable therapeutic effects for subsequent clinical applications, thereby offering improved treatment methods for patients with cartilage injuries.METHOD:This study employed a systematic literature search method to summarize the research progress of responsive hydrogels by retrieving literature on the subject and review studies. The search terms included "hydrogel" and "cartilage," covering data from database inception up to October 2023. The quality of the literature was independently evaluated using Review Manager v5.4 software. Quantifiable data was statistically analyzed using the R language.RESULTS:A total of 7 articles were retrieved for further meta-analysis. In the quality assessment, the studies demonstrated reliability and accuracy. The results of the meta-analysis indicated that responsive hydrogels exhibit unique advantages and effective therapeutic outcomes in the field of cartilage repair. Subgroup analysis revealed potential influences of factors such as different types of hydrogels and animal models on treatment effects.CONCLUSION:Responsive hydrogels show significant therapeutic effects and substantial application potential in the field of cartilage repair. This study provides strong scientific evidence for their further clinical applications and research, with the hope of promoting advancements in the treatment of cartilage injuries.

Extracellular vesicles (EVs) play an important role in post-traumatic stress disorder (PTSD). This study is aimed to investigate the possible molecular mechanism of CD63 mediating CXCL8 delivery via EVs to affect astrocyte-neuron communication in PTSD. The neuron-derived EVs (NDEVs) and astrocyte-derived EVs (ADEVs) were isolated from plasma in PTSD patients. Next, the uptake of EVs by neurons was assessed. Following determination of the interaction between CD63 and CXCL8, gain- and loss-of-function experiments were performed in astrocytes. Finally, a PTSD mouse model was established using the single prolonged stress and electric foot shock to confirm the effects of plasma-derived EVs delivering CXCL8 on anxiety- and depression-like behaviors in PTSD mice. EVs derived from plasma of PTSD patients aggravated anxiety- and depression-like behaviors in PTSD mice. CXCL8 was a key gene upregulated in both NDEVs and ADEVs from plasma of PTSD patients, which could be delivered into EVs by CD63. Meanwhile, CXCL8 was also highly expressed in plasma-derived EVs. In vivo experiments also verified that plasma-derived EVs could enhance astrocyte-neuron communication by delivering CXCL8, and silencing of CXCL8 ameliorated anxiety- and depression-like behaviors in PTSD mice. Taken together, CD63 promotes delivery of CXCL8 via EVs to induce PTSD by enhancing astrocyte-neuron communication, suggesting the potential of CD63 mediating delivery of CXCL8 via EVs as a therapeutic target for PTSD.

Objective: To explore the role of miR-448 in regulating MAGEA6/AMPK signaling pathway in the biological study of hepatocellular carcinoma (HCC) tumor stem cells. Methods: Using the database, the hepatocellular carcinoma related expression chips were obtained and the regulatory mirnas of candidate genes were predicted, and the predicted results were analyzed. The effects of miR-448 and MAGEA6 on the pellet formation rate and clone formation rate of hepatocellular carcinoma stem cells were detected by immunofluorescence identification of stem cell markers and light microscope counting method. The effects of miR-448 and MAGEA6 on migration and invasion of hepatocellular carcinoma stem cells were detected by scratch and Transwell assay. Dual luciferase reporter assay to verify whether miR-448 targets MAGEA6. The expression and influence of miR-448 on MAGEA6 and AMPK pathway were detected by qRT-PCR and Western blot. Results: It was found that miR-448 may directly regulate the expression of MAGEA6. Overexpression of miR-448 inhibited the characteristics, proliferation, migration, and invasion of hepatocellular carcinoma stem cells in vitro, as well as the ability of xenograft tumor formation in vivo. However, inhibition of miR-448 showed opposite results. In addition, miR-448 directly targets MAGEA6 and regulates AMPK signaling. Silencing MAGEA6 and adding AMPK activator further verified that miR-448 activated AMPK signaling pathway by targeting MAGEA6, thus affecting characteristics, proliferation, migration and invasion of hepatoma stem cells. Conclusions: Our results reveal that miR-448 activates AMPK signaling pathway by targeting MAGEA6, thereby affecting characteristics, proliferation, migration and invasion of hepatoma stem cells. It is suggested that overexpression of miR-448 may be a new therapeutic strategy for hepatocellular carcinoma.

目的 探讨5-羟色胺转运体(5-HTTLPR)基因多态性与海南省黎、汉民族创伤后应激障碍(PTSD)患者的相关性.方法 选取2017年10月至2018年7月在海南省人民医院就诊的308例PTSD患者作为研究组,其中黎族167例,汉族141例;另选2017年10月至2018年7月间未经受创伤性事件并在我院健康体检中心体检的158例健康志愿者作为对照组.收集研究对象的一般资料,采用PTSD临床评定量表、埃森创伤问卷(ETI)评定入组患者PTSD严重程度,另采用汉诺塔(TOH)、威斯康星卡片分类测试(WCST)、连线测验(TMT)与韦氏成人智力量表(WAIS)对评定入组对象认知功能,应用多聚酶链式反应(PCR)方法检测研究对象5-HTTLPR基因多态性.结果 三组被试者的平均年龄、性别构成、婚姻状况和受教育程度比较差异均无统计学意义(P>0.05);黎族PTSD患者和汉族PTSD患者的各ETI评分与PTSD总分、TMT时间、TOH计划时间和执行时间、WCST的错误数明显高于对照组,而WAIS-RC中领悟、相似、木块图、物体拼凑及操作智商和TOH总分明显低于对照组,差异均有统计学意义(P<0.05);黎族PTSD患者各ETI评分与PTSD总分、TMT时间明显高于汉族PTSD患者,而WAIS-RC中领悟、操作智商与低于汉族PTSD患者,差异均具有统计学意义(P<0.05);黎族PTSD患者5-HTTLPR等位基因与基因型分布与对照组比较差异均无统计学意义(P>0.05),而在汉族PTSD患者与对照组中比较差异均有统计学意义(P<0.05):与LL基因型比较,SS基因型可能会增加汉族人群患PTSD的风险(OR=2.157,95％CI=1.098～4.237,P=0.024);与L等位基因比较,S等位基因可能会增加汉族人群患PTSD的风险(OR=1.456,95％CI=1.045～2.207,P=0.026);汉族PTSD患者中5-HTTLPR的SS基因型患者各ETI评分与PTSD总分、TMT时间明显高于LL基因型患者,WAIS-RC中的领悟和算术及木块图明显低于LL基因型患者,差异均具有统计学意义(P<0.05),而在黎族PTSD患者中SS基因型与LL基因型的认知功能比较差异无统计学意义(P>0.05).结论 5-HTTLPR的SS基因型和S等位基因可能增加PTSD发病风险及导致患者的认知功能损害更加严重.

Objective: To investigate the correlation between 5-HTTLPR (5-and serotonin transporter linked polymer region) gene polymorphism and BDNF (brain derived neural factor) gene polymorphism and PTSD (post traumatic stress disorders) in Li and Han nationalities in Hainan Province. Methods: 167 Hainan Li PTSD patients, 141 Hainan Han PTSD patients and 158 healthy volunteers (control group) were investigated by ETI, caps, Toh, WCST, TMT and WAIS-RC. The polymorphisms of rs6265 locus of 5-HTTLPR and BDNF genes were detected by PCR (polymerase chain reaction) and page (polycylamide gel electrophoresis), and the correlation with PTSD was analyzed. Logistic regression analysis was used to analyze the influencing factors of PTSD. Results: The ETI score, total PTSD score and TMT time of Li PTSD patients were significantly higher than those of Han PTSD patients (P 0.05). SS genotype of 5-HTTLPR and (GA + AA) genotype of rs6265 locus may increase the risk of PTSD in Hainan Han population. AA and GA + AA genotypes at rs6265 locus may increase the risk of PTSD in Li population (P < 0.05). Among Li PTSD patients, the ETI score, PTSD total score, TMT time, Toh planning time and execution time of AA genotype at rs6265 locus were significantly higher than those of GG genotype; the total scores of comprehension and operation IQ, and Toh in WAIS-RC were significantly lower than those in GG genotype (P < 0.05). Among Han PTSD patients, the ETI score, PTSD total score and TMT time of SS genotype of 5-HTTLPR were significantly higher than those of LL genotype, and the comprehension, arithmetic and block diagram in WAIS-RC were significantly lower than those of LL genotype; The ETI score, PTSD total score and TMT time of patients with (GA + AA) genotype at rs6265 locus were also significantly higher than those of patients with GG genotype. The comprehension and block diagram in WAIS-RC were significantly lower than those of patients with GG genotype. The number of WCST errors in patients with AA genotype was significantly higher than those of patients with GG genotype, and the operational IQ in WAIS-RC was significantly lower than those of patients with GG genotype (P < 0.05). Conclusion: The LL genotype of 5-HTTLPR and the GG genotype of rs6265 locus are related to PTSD of Li and Han nationalities in Hainan, which are important protective factors for PTSD of Li and Han nationalities in Hainan.

目的 探讨黑色素瘤相关抗原A6(MAGEA6)在肝细胞癌(HCC)组织中的表达及与预后的关系.方法 选取2013年2月—2016年10月海南省人民院收治入院的120例HCC患者为研究对象.分析受试者的年龄、性别、饮酒史、甲胎蛋白(AFP)、肿瘤直径、分化程度、TNM分期、肝功能Child-Pugh分级、淋巴结转移等临床资料.采用实时荧光定量聚合酶链反应检测MAGEA6和AMPK mRNA的表达,免疫组织化学法检测MAGEA6蛋白的表达.根据肿瘤组织MAGEA6 mRNA相对表达量的中位值,将HCC患者分为MAGEA6低表达组和高表达组.比较两组患者的临床病理特征,绘制两组患者的Kaplan-Meier生存曲线,采用一般多因素Cox回归分析影响HCC患者预后的独立危险因素,Pearson法分析MAGEA6 mRNA与AMPK mRNA表达的相关性.结果 肿瘤组织MAGEA6 mRNA相对表达量、MAGEA6阳性率、MAGEA6蛋白免疫组织化学法评分高于癌旁组织(P<0.05).MAGEA6低表达组与高表达组HCC患者的年龄、性别、饮酒史、分化程度、Child-Pugh分级比较,差异无统计学意义(P>0.05).两组在AFP、肿瘤直径、TNM分期、淋巴结转移方面比较,差异有统计学意义(P<0.05).MAGEA6高表达组生存率低于低表达组(P<0.05).一般多因素Cox回归分析结果显示,AFP[H^R=2.183(95％CI:1.117,4.267)]、TNM分期[H^R=2.203(95％CI:1.174,4.133)]、MAGEA6 mRNA[H^R=6.328(95％CI:1.516,26.404)]是影响HCC患者预后的独立危险因素(P<0.05).肿瘤组织AMPK mRNA相对表达量低于癌旁组织(P<0.05).AMPK mRNA与MAGEA6 mRNA表达呈负相关(r=-0.680,P=0.000).结论 MAGEA6基因在肝细胞癌中高表达,是HCC患者预后的危险因素,其可能通过AMPK信号通路在HCC中发挥促癌作用.

Department of Hepatobiliary Surgery, Hainan General Hospital, Haikou, 570311 Hainan, People’s Republic of China Background: Hepatocellular carcinoma (HCC) remains a life-threatening malignant tumor. Cancer stem cells (CSCs) harbor tumor-initiating capacity and can be used as a therapeutic target for human malignancies. Bone morphogenetic proteins (BMPs) play a regulatory role in CSCs. This study investigated the role and mechanism of BMP2 in CSCs in HCC. Methods: BMP2 expression in HCC tissues and cells, and CSCs from HepG2 cells and SMMC7721 cells (HepG2-CSCs and SMMC7721-CSCs) was measured. The association between BMP2 expression and prognosis of HCC patients was analyzed. CSCs were interfered with BMP2 to evaluate the abilities of colony and tumor sphere formation, levels of stemness-related markers, epithelial–mesenchymal transition (EMT), and invasion and migration. Levels of MAPK/ERK pathway-related proteins in HepG2-CSCs were detected after BMP2 knockdown. The effect of the activated MAPK/ERK pathway on HepG2-CSCs was assessed. Finally, the effect of BMP2 inhibition on CSCs in HCC was verified in vivo. Results: BMP2 showed obvious upregulation in HCC tissues and cells and was further upregulated in CSCs in HCC, with its higher expression indicative of worse prognosis. Silencing BMP2 inhibited colony and tumor sphere formation, levels of stemness-related markers, as well as EMT, invasion and migration of HepG2-CSCs and SMMC7721-CSCs. The MAPK/ERK pathway was suppressed after BMP2 knockdown, and its activation reversed the inhibitory effect of shBMP2 on hepatic CSCs. BMP2 accelerated tumor growth and EMT of CSCs in HCC in vivo. Conclusion: We concluded that BMP2 knockdown inhibited the EMT, proliferation and invasion of CSCs in HCC, thereby hindering the stemness maintenance via suppressing the MAPK/ERK pathway.

Background: Hepatocellular carcinoma (HCC) remains a life-threatening malignant tumor. Cancer stem cells (CSCs) harbor tumor-initiating capacity and can be used as a therapeutic target for human malignancies. Bone morphogenetic proteins (BMPs) play a regulatory role in CSCs. This study investigated the role and mechanism of BMP2 in CSCs in HCC. Methods: BMP2 expression in HCC tissues and cells, and CSCs from HepG2 cells and SMMC7721 cells (HepG2-CSCs and SMMC7721-CSCs) was measured. The association between BMP2 expression and prognosis of HCC patients was analyzed. CSCs were interfered with BMP2 to evaluate the abilities of colony and tumor sphere formation, levels of stemness-related markers, epithelial-mesenchymal transition (EMT), and invasion and migration. Levels of MAPK/ERK pathway-related proteins in HepG2-CSCs were detected after BMP2 knockdown. The effect of the activated MAPK/ERK pathway on HepG2-CSCs was assessed. Finally, the effect of BMP2 inhibition on CSCs in HCC was verified in vivo. Results: BMP2 showed obvious upregulation in HCC tissues and cells and was further upregulated in CSCs in HCC, with its higher expression indicative of worse prognosis. Silencing BMP2 inhibited colony and tumor sphere formation, levels of sternness-related markers, as well as EMT, invasion and migration of HepG2-CSCs and SMMC7721-CSCs. The MAPK/ERK pathway was suppressed after BMP2 knockdown, and its activation reversed the inhibitory effect of shBMP2 on hepatic CSCs. BMP2 accelerated tumor growth and EMT of CSCs in HCC in vivo. Conclusion: We concluded that BMP2 knockdown inhibited the EMT, proliferation and invasion of CSCs in HCC, thereby hindering the sternness maintenance via suppressing the MAPK/ERK pathway.

Objective: To investigate the effect of cognitive behavioral intervention on nurses with PTSD by using cognitive behavioral intervention. Methods: The subjects were selected by randomized control method, and the PTSD nurses were divided into control group (n = 30) and intervention group (n = 30). The intervention group used cognitive behavioral intervention; the control group did not use cognitive behavioral intervention. Nurses with PTSD in the two groups completed the basic situation survey, medical coping questionnaire (MCMQ) and anxiety self-rating form (SAS) psychological scale one month later. Results: There was no significant difference in MCMQ and SAS scores between the two groups before intervention (P > 0.05). After intervention, the scores of MCMQ and SAS in the intervention group were compared with the scores of MOCQ and SAS in the control group. The scores of the control group after intervention were significantly higher than those of the intervention group, with statistical significance (P 0.05). It shows that cognitive behavioral intervention therapy has the effect and value of improving the psychological status of nurses with PTSD. Conclusion: Cognitive behavioral intervention therapy combined with psychology for nurses with PTSD can effectively relieve their stress level, relieve their mood, and improve their positive coping ability and work efficiency.

Histone methylation plays important roles in mediating the onset and progression of various cancers, and lysine-specific demethylase 5B (KDM5B), as a histone demethylase, is reported to be an oncogene in hepatocellular carcinoma (HCC). However, the mechanism underlying its tumorigenesis remains undefined. Hence, we explored the regulatory role of KDM5B in HCC cells, aiming to identify novel therapeutic targets for HCC. Gene Expression Omnibus database and StarBase were used to predict important regulatory pathways related to HCC. Then, the expression of KDM5B and microRNA-448 (miR-448) in HCC tissues was detected by RT-qPCR and Western blot analysis. The correlation between KDM5B and miR-448 expression was analysed by Pearson's correlation coefficient and ChIP experiments, and the targeting of YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) by miR-448 was examined by luciferase assay. Additionally, the effect of KDM5B on the proliferation, migration, invasion and apoptosis as well as tumorigenicity of transfected cells was assessed using ectopic expression and depletion experiments. KDM5B was highly expressed in HCC cells and was inversely related to miR-448 expression. KDM5B demethylated H3K4me3 on the miR-448 promoter and thereby inhibited the expression of miR-448, which in turn targeted YTHDF3 and integrin subunit alpha 6 (ITGA6) to promote the malignant phenotype of HCC. Moreover, KDM5B accelerated HCC progression in nude mice via the miR-448/YTHDF3/ITGA6 axis. Our study uncovered that KDM5B regulates the YTHDF3/ITGA6 axis by inhibiting the expression of miR-448 to promote the occurrence of HCC.

Long-chain non-coding RNA HOXA11 antisense RNA (HOXA11-AS) is a kind of lncRNA discovered in recent years.Long-chain non-coding RNA (LncRNA) is an important regulatory factor of protein-coding genes, especially the disorder of LncRNA in more and more diseases which are found, including cancer.HOXA11-AS was first discovered in mouse embryo cDNA library using probes, and then it was discovered by scholars and played an important role in human cervical cancer, gastric cancer, glioma and other malignant tumor cells.Overexpression of HOXA11-AS has been found to promote cell proliferation, migration and tumor invasion, and has a carcinogenic effect.HOXA11-AS can promote tumor proliferation, metastasis and other malignant biological behaviors by interacting with miRNA and EZH2 protein, and is considered to be carcinogenic lncRNA.The discovery of HOXA11-AS provides new ideas for tumor prevention and treatment.

Background Bladder cancer (BCa) is a common malignancy characterized by high heterogeneity, yet the current treatment modalities are limited. The aim of the present investigation was to unravel the functional role of Karyopherin alpha 2 (KPNA2), a tumor facilitator identified in multiple malignancies, in the progression of BCa. Methods BCa tissues and adjacent normal tissues were surgically resected and analyzed from patients with BCa to determine the expression profile of KPNA2 and Chromobox 8 (CBX8) by RT-qPCR, Western blot analysis and immunohistochemistry. The relationship among KPNA2, CBX8 and PR domain zinc finger protein 1 (PRDM1) was explored by co-immunoprecipitation and chromatin-immunoprecipitation. The functions of KPNA2, CBX8 and PRDM1 on BCa cell proliferation, migration and invasion were evaluated. Next, a nude mouse model of BCa was established for validating the roles of KPNA2, CBX8 and PRDM1 in vivo. Results KPNA2 and CBX8 were highly expressed in BCa and are in association with dismal oncologic outcomes of patients with BCa. KPNA2 promoted nuclear import of CBX8. CBX8 downregulated PRDM1 by recruiting BCOR in the promoter region of PRDM1. Overexpression of KPNA2 promoted the malignant behaviors of BCa cells, which was counteracted by silencing of CBX8. Overexpressing PRDM1 attenuated the progression of BCa by inhibiting c-FOS expression. The tumor-promoting effects of KPNA2 via the PRDM1/c-FOS pathway were also validated in vivo. Conclusion Collectively, our findings attached great importance to the interplay between KPNA2 and CBX8 in BCa in mediating the development and progression of BCa, thus offering a promising candidate target for better BCa patient management.

MicroRNA (miRNA) is a class of endogenous non-coding and regulatory single stranded small RNA molecules, about 18 24 nucleotides in length. More than 800 miRNA coding genes have been identified in the human genome, and about 113 target genes are predicted to be regulated, which distinguishes it from most oligonucleotides and functional RNA degraded fragments. It is involved in the regulation of cell proliferation, differentiation, apoptosis and other cell activities. At the same time, it is abnormal in liver cancer, breast cancer, glioma and other tumors, becoming a new biomarker, and participating in cancer differentiation, invasion and metastasis through the interaction with multiple target genes, such as SATB1, NF-KB and 5-HT2B. Mir-448 is abnormally expressed in a variety of tumor cells, such as liver cancer and non-small cell lung cancer. mirNA-448 may play a very important role in tumors. In order to deepen the understanding of the role of mirNA-448 in tumors, this paper reviews the research progress of the role of mirNA-448 in tumors.

Objective: To explore the distribution characteristics of BDNF gene frequency in Li and Han nationalities in Hainan province. Methods: In June 2018-2019 and march to the people’s hospital of Hainan province health volunteers, 152 cases (Li 80, Han, 72), the application of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to detect the polymorphism of BDNF gene (rs6265), and compared with other countries and regions of ethnic comparison between BDNF gene frequency distribution. Results: No statistical difference was found in rs6265 genotype distribution of BDNF gene in Li and Han ethnic groups (P = 0.3358, P = 0.0892, P = 0.1549). Comparison of BDNF allele frequency between Li and other ethnic groups showed statistically significant differences with other ethnic groups in China and Europe (P = 0.0384, P = 0.0000), but not statistically significant differences with Japan (P = 0.1164). Conclusion: BDNF gene (rs6265) has polymorphism in both Li and Han ethnic groups in Hainan Province. Compared with ethnic groups in other countries and regions, the polymorphism distribution is ethnically different.

This study aimed to explore the correlations of promoter methylation and single-nucleotide polymorphism (SNP) of brain-derived neurotrophic factor (BDNF) with post-traumatic stress disorder (PTSD) in Li and Han nationalities in Hainan province. Depressionand anxiety-related questionnaires were performed for PTSD-related information collection and analysis, with 164 PTSD patients and 141 healthy controls included. Serum BDNF level was measured and the methylation of BDNF promoter was evaluated. The BDNF SNP genotyping was performed, after which the risk genotypes for PTSD were detected and analyzed using logistic regression analysis. Our study found that the PTSD incidence was different in Li and Han nationalities. Serum BDNF level in PTSD patients in Li nationality was obviously lower than that in patients in Han nationality, while the methylation of BDNF promoter was higher in patients in Li nationality. The G-712A rather than rs6265 genotypes presented significant difference between PTSD patients and healthy controls. Meanwhile, the patients in Li nationality with AG genotype at G-712A inclined to depression, and patients with GG genotype had a greater degree of PTSD. G 712A and promoter methylation of BDNF were independent risk factors for PTSD. Our study demonstrated that the differences of PTSD patients between Li and Han nationalities were attributed by SNP G-712A genotypes and promoter methylation of BDNF.

Increasing evidence has suggested the crucial role cyclin-dependent kinases (CDKs) in the biology of hepatocellular carcinoma (HCC), a lethal malignancy with high morbidity and mortality. Hence, this study explored the modulatory effect of the putative cyclin-dependent kinase 11B (CDK11B)-mediated ubiquitination on HCC stem cells. The expression of CDK11B, SAM pointed domain-containing ETS transcription factor (SPDEF) and DOT1-like histone lysine methyltransferase (DOT1L) was determined by RT-qPCR and western blot analysis in HCC tissues and cells. The interaction among CDK11B, SPDEF, miR-448, and DOT1L was analyzed by Co-IP, ubiquitination-IP and ChIP assays, whereas their effects on the biological characteristics of HCC stem cells were assessed by sphere formation and colony formation assays. An in vivo xenograft tumor model was developed for validating the regulation of CDK11B in oncogenicity of HCC stem cells. We characterized the aberrant upregulation of CDK11B and downregulation SPDEF in HCC tissues and cells. CDK11B degraded SPDEF through ubiquitin-proteasome pathway, whereas SPDEF could bind to the miR-448 promoter and inhibit the expression of DOT1L by activating miR-448, whereby promoting self-renewal of HCC stem cells. Knockdown of CDK11B attenuated the self-renewal capability of HCC stem cells and their oncogenicity in vivo. These findings highlighted that blocking the CDK11B-induced degradation of SPDEF and enhancing miR-448-dependent inhibition of DOT1L may delay the progression of HCC by restraining self-renewal capability of HCC stem cells, representing novel targets for HCC management.

Objective: To explore the pathogenesis of PTSD in the brain-derived neurotrophic factor (BDNF) gene methylation of patients with posttraumatic stress disorder (Posttraumatic Stress Disorder, PTSD) in Hainan Province, the relationship between the influence of BDNF gene methylation and the influence of PTSD. Methods: A case-control study method was adopted, strictly in accordance with DSM-IV and PTSD diagnosis, and 150 Li PTSD patients matched with gender and age of 300 Han PTSD patients were selected as the research objects. The peripheral venous whole blood of the subjects was drawn, genomic DNA was extracted, modified with bisulfite, and directly sequenced to quantitatively detect the methylation status of the CpG island in the promoter region of brain-derived neurotrophic factor (BDNF). Results: The results showed that the methylation levels of CPGl, CPG2, CPG3, CPG4, CPG5, CPG6, CPG7, CPG9, CPGl2, CPGl3, CPGl4, CPGl5, CPGl6, CPGl7, and CPGl8 in THE BDNF promoter were significantly different between the HAN PTSD group and the Li PTSD group (P Conclusion: It is suggested that CPG methylation in the promoter region of BDNF gene is closely related to patients with PTSD. There is a statistical difference in the level of CpG methylation in the promoter region of BDNF gene in PTSD between Li and Han ethnic groups in Hainan Province. CpG methylation in the promoter region of BDNF gene may be used as a biomarker for the diagnosis of PTSD.

In recent years, the incidence of lung adenocarcinoma has been increasing, and now it has become the largest type of non-small cell lung cancer (NSCLC). Currently, treatment of advanced NSCLC consists of several modalities: systemic chemotherapy, local radiation therapy, and targeted therapy (including most recently immunotherapy). In the past decade, the discovery of new molecular subtypes, the search for tumor driver gene mutations, the development of targeted molecular targeted drugs, or targeted therapy to suppress tumor angiogenesis and regulate tumor immune response have been the main directions of NSCLC research and clinical diagnosis and treatment. At present, platinum-based chemotherapy is widely used in NSCLC patients clinically. Platinum-based chemotherapy drugs can effectively prolong the survival time of patients and improve their quality of life, but the incidence of adverse reactions is still high. Therefore, it is necessary to find a drug that can improve the efficacy of patients and reduce the adverse reactions of platinum chemotherapy drugs to NSCLC patients.