Modelling the transmission dynamics and optimal control strategies for HIV infection in China.

In order to end the AIDS epidemic by 2030 that was put forward by the Joint United Nations Programme on HIV/AIDS in 2014, China needs to take more effective measures to achieve the three 90% goals (90-90-90). We establish a compartmental model to study the dynamics of HIV transmission with control strategies. The analytical results show the existence and stability of the disease-free equilibrium and endemic equilibrium. An optimal control model is constructed to evaluate the impacts of control measures. The simulation results show that the optimal control strategy proposed in this work can eradicate AIDS by 2030. The cost-effectiveness analysis indicates that the cost of the control strategy that combines screening for latent individuals and enhancing education for unaware infected individuals is the lowest. Our findings can provide guidance for public health authorities on effective mitigation strategies to achieve the goals proposed by the United Nations Program on HIV/AIDS.

Altered EEG Brain Networks in Patients with Acute Peripheral Herpes Zoster.

OBJECTIVE: To investigate whether the brain networks changed in patients with acute peripheral herpes zoster (HZ). METHODS: We reviewed the EEG database in Jianyang People's Hospital. Patients with acute HZ (n=71) were enrolled from January 2016 to December 2020. Each included subject underwent a ten-minute and 16-channel EEG examination. Five epochs of 10-second EEG data in resting-state were collected from each HZ patient. Five 10-second resting-state EEG epochs from sex- and age-matched healthy controls (HC, n=71) who reported no history of neurological or psychiatric disorders and visited the hospital for routine physical examinations were collected. Brain network and graph theory analysis based on phase locking value parameter and functional ICA were performed using a self-writing Matlab code and the LORETA KEY tool. RESULTS: Compared with the HC group, the HZ patients showed significant altered brain networks. The graph theory analysis revealed that the clustering coefficient and local efficiency of full band in HZ patients were lower than those in HC group (P<0.05). In beta band, the global efficiency and local efficiency of HZ patients group decreased, compared with healthy group (P<0.05). The functional ICA showed that three components showed significant differences between the two groups. In component 2, HZ patients showed excess superior frontal gyrus (BA10) neuro oscillation in delta band and less medial frontal gyrus (BA 11) neuro oscillation in beta and gamma bands than that in HCs. And for component 3, the alpha band of the HZ patients presented increased neuro activities in superior frontal gyrus (BA 11) and decreased neuro activities in occipital lobe (BA 18). In component 4, the inferior frontal gyrus (BA 47) showed excess activity in the left hemisphere and reduced activity in the right hemisphere in delta band, compared with HC group. CONCLUSION: Altered brain networks exist in resting-state EEG data of patients with acute HZ. The changes of EEG brain networks in HZ patients are characterized by decreased global efficiency and local efficiency in beta band. Moreover, the spontaneous oscillation of some brain regions involving pain management and the connectivity of default mode network changed in HZ patients. Our study provided novel understanding of HZ from an electrophysiological view, and led to converging evidence for treatment of HZ with neural regulation in future.

Identification of 40S ribosomal protein S8 as a novel biomarker for alcohol­associated hepatocellular carcinoma using weighted gene co­expression network analysis.

Alcohol­associated hepatocellular carcinoma (HCC) is a subtype of HCC with poor prognosis. The present study aimed to identify key biomarkers for alcohol­associated HCC. The gene data profiles and corresponding clinical traits of patients with alcohol­associated HCC were downloaded from The Cancer Genome Atlas (TCGA) database. Firstly, good genes and good samples were identified, which were subsequently used to conduct weighted gene co­expression network analysis (WGCNA). Hub genes in the significant modules were selected following Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and from constructing a protein­protein interaction (PPI) network. Real hub genes among hub genes were determined following progression, survival analysis and gene set enrichment analysis (GSEA), as well as reverse transcription­quantitative PCR and immunohistochemical staining of non­alcohol­ and alcohol­associated HCC samples. In total, 64 good samples of alcohol­associated HCC with height score <160 were selected, from which 15,195 good genes were identified and used to conduct WGCNA; 8 gene co­expressed modules were identified using WGCNA, while 3 modules (including pink, magenta and turquoise) were significantly associated with Child­Pugh score, T­stage and body weight. Following GO and KEGG analysis and construction of the PPI network, a total of 30 hub genes were identified in the aforementioned 3 gene co­expressed modules, while 16 hub genes (including AURKB, BUB1, BUB1B, CCNB1, CCNB2, CDC20, CDCA8, CDK1, PLK1, RPS5, RPS7, RPS8, RPS14, RPS27, RPSA and TOP2A) were associated with the development of alcohol­associated HCC, and had a significant prognosis value. Among these genes, only RPS8 was highly expressed in alcohol­associated HCC, but not in non­alcohol­associated HCC, while RPS5 was not significantly associated in either alcohol­ or non­alcohol­associated HCC. GSEA demonstrated that 10 pathways, including RNA polymerase and ribosome pathways were enriched in alcohol­associated HCC samples where RPS8 was highly expressed. Taken together, the results of the present study demonstrate that RPS8 may be a novel biomarker for the diagnosis of patients with alcohol­associated HCC.

Linc00261 inhibits metastasis and the WNT signaling pathway of pancreatic cancer by regulating a miR­552­5p/FOXO3 axis.

The biological function of long non­coding RNA00261 (Linc00261) has been widely investigated in various types of cancer. The aim of the present study was to explore the role of Linc00261 in pancreatic cancer (PC). The expression of Linc00261 in patients with PC and PC cell lines was assessed using reverse transcription­quantitative PCR and the association of Linc00261 expression with survival was analyzed in the online database, GEPIA. The effects of Linc00261 on PC cell metastasis in vitro and in vivo were determined using a wound healing assay, Transwell invasion assays and a nude mouse model of liver metastasis. The relationship between Linc00261, the miR­552­5p/forkhead box O3 (FOXO3) axis and the Wnt signaling pathway were determined using bioinformatics analysis, dual luciferase assay and western blotting. Linc00261 expression was significantly decreased in PC tissues and cell lines, and reduced expression was associated with less favorable outcomes in patients with PC. Linc00261 overexpression inhibited migration and invasion of PC cells in vitro, whereas knockdown of Linc00261 increased migration and invasion. Linc00261 overexpression also decreased metastasis of PC cells in vivo. Linc00261 was revealed to directly bind to microRNA (miR)­552­5p and to decrease the expression of miR­552­5p. In addition, Linc00261 overexpression increased the expression of FOXO3, a target gene of miR­552­5p, as well as inhibited the Wnt signaling pathway. Overexpression of miR­552­5p in Linc00261­overexpressing PC cells increased migration and invasion, as well as decreased the expression of FOXO3 and members of the Wnt signaling pathway. Collectively, the present study demonstrated that Linc00261 inhibited metastasis and the Wnt signaling pathway of PC by regulating the miR­552­5p/FOXO3 axis. Linc00261 may suppress the development of PC, and serve as a potential biomarker and effective target for the diagnosis and treatment of PC.

MicroRNA­137 suppresses the proliferation, migration and invasion of cholangiocarcinoma cells by targeting WNT2B.

It is widely known that abnormal regulation of microRNAs (miRNAs/miRs) may contribute to the occurrence or development of tumors. The objective of the present study was to elucidate the function and underlying mechanism of miR­137 in the progression of cholangiocarcinoma (CCA). The expression levels of miR­137 in CCA tissues and cell lines were measured using reverse transcription­quantitative PCR. The role of miR­137 in the proliferation of CCA cells was assessed using the Cell Counting Kit­8 assay, colony formation assay and cell cycle distribution analysis, while its effects on the migration and invasion of CCA cells were evaluated using Transwell assays. The function of miR­137 on CCA growth in vivo was also investigated using a xenograft mouse model. Furthermore, the association between miR­137 and Wnt family member 2B (WNT2B) was analyzed using bioinformatics, double luciferase assay and western blotting. It was verified that the expression of miR­137 was low in CCA tissues and cell lines, whereas increased expression of miR­137 significantly suppressed cell proliferation, decreased colony formation ability and induced G1 phase arrest. miR­137 overexpression suppressed the migration and invasion ability of TFK­1 and HuCCT1 cells. Furthermore, the results of the xenograft mouse model assays revealed that miR­137 overexpression decreased tumor growth in vivo. The results of bioinformatics analysis and dual luciferase reporter assays demonstrated that WNT2B is directly regulated by miR­137. The expression of WNT2B and Wnt­pathway­related proteins was decreased when miR­137 was overexpressed. Restoring the expression of WNT2B notably reversed the inhibitory effect of miR­137 on CCA cells. Therefore, the findings of the present study demonstrated that miR­137 acts as a suppressor in CCA and inhibits CCA cell proliferation, migration and invasion through suppressing the expression of WNT2B.