Objective To study the expression of amplified in breast cancer 1(AIB1)and ankyrin repeat domain containing11(ANKRD11/ANCO1)in human papillomavirus(HPV)positive cervical cancer and their relationship with clinicopathological characteristics and their predictive value for postoperative recurrence.Methods Cancer tissues and paracancer tissues of 94 HPV positive cervical cancer patients who visited the Third People's Hospital of Mianyang from January 2018 to January 2020 were selected,while 50 HPV negative cervical cancer tissues during this period were taken as controls.Real-time qPCR(RT-qPCR)was conducted to detect AIB1 mRNA and ANCO1 mRNA expression in cancer tissue and paracancer tissues of HPV positive cervical cancer and cancer tissue of HPV negative cervical.Pearson analysis of the correlation between AIB1 mRNA and ANCO1 mRNA expression in HPV positive cervical cancer tissues.Logistic regression analysis was used to identify the risk factors for postoperative recurrence of HPV-positive cervical cancer patients.The predictive value of AIB1 mRNA,ANCO1 mRNA,and their combination in predicting postoperative recurrence in HPV positive cervical cancer patients was analyzed by receiver operating characteristic curve.Results Compared to the adjacent tissues of HPV positive cervical cancer and cancer tissues of HPV negative cervical cancer,AIB1 mRNA(3.04±0.37 vs 0.87±0.21,1.02±0.33)in HPV positive cervical cancer tissues was higher,while ANCO1 mRNA(1.13±0.26 vs 1.91±0.35,1.82±0.36)was lower,with significant differences(t=68.499,53.137;23.649,17.434,all P<0.05).The expression of AIB1 mRNA and ANCO1 mRNA in HPV positive cervical cancer tissues showed a negative correlation(r=-0.714,P<0.001).Compared to patients with FIGO stage ⅡA～ⅡB and without lymph node metastasis,AIB1 mRNA(3.88±0.32 vs 2.04±0.41,4.46±0.33 vs 2.16±0.46)in HPV positive cervical cancer tissues with FIGO stage ⅡA and lymph node metastasis was higher,while ANCO1 mRNA(0.67±0.29 vs 1.68±0.20,0.49±0.24 vs 1.53±0.32)was lower,with significant differences(t=24.425,26.097;19.288,16.777,all P<0.001).FIGO stage ⅡA,lymph node metastasis,and high AIB1 mRNA[OR(95％CI)=1.644(1.223～2.210),1.779(1.295～2.444),1.247(1.050～1.728)]were risk factors for postoperative recurrence in HPV positive cervical cancer patients,while high ANCO1 mRNA[(OR(95％CI):0.634(0.451～0.891)]was a protective factor.The AUC(95％CI)of AIB1 mRNA and ANCO11 mRNA combined for predicting postoperative recurrence in HPV positive cervical cancer patients was 0.914(0.863～0.952),which was higher than the single indicator detection of 0.821(0.782～0.869)and 0.794(0.763～0.847),and the differences were significant(Z=4.123,4.432,all P<0.001).Conclusion The expression of AIB1 mRNA is increased and the expression of ANCO1 mRNA is reduced in HPV positive cervical cancer tissue,which are related to the occurrence and progression of cancer.The combination of the two has a high predictive value for evaluating postoperative recurrence.

Peripheral arterial disease is one of the common complications of diabetes. At present, the pathogenesis of diabetic peripheral arterial diseases is not completely clear, and there is a lack of effective treatment methods and drugs. Adipokines have profound impact on the occurrence and development of diabetes mellitus and its complications, and are directly or indirectly involved in the progression of diabetic peripheral arterial diseases. Different adipokines may inhibit or promote the occurrence of vascular diseases with the mechanisms that are complex and controversial. Adipokines are expected to be a new target for the treatment of diabetic peripheral arterial disease, which is worthy of further study. This article mainly reviews the relationship between some common adipokines and new adipokines and diabetic vascular disease, aiming to provide new methods for the clinical treatment of diabetic peripheral arterial disease.

Objective To study the mechanism of Chaihu Guizhi Decoction(CGD)in the treatment of influenza and staphylococcus aureus co-infection.Methods The co-infection model of influenza and staphylococcus aureus was established and CGD was used to intervene.The chemical components of CGD were qualitatively analyzed by UPLC-Q-Exactive/MS technology.The potential action targets of chemical components in CGD and the related targets of influenza Staphylococcus aureus co-infection were mined by network pharmacology method.The"component target disease"network was constructed.Core targets were selected according to degree ranking.Core action pathways were enriched by KEGG analysis and GO annotation analysis.The core target was verified by RT-qPCR,and the interaction between the core component and the key target was verified by molecular docking.Results CGD could significantly improve the decrease of body weight and thymus index(P<0.05)caused by co-infection.The lung index(P<0.05),relative amount of MmRNA expression(P<0.05)and bacterial load(P<0.05)were decreased,and the survival rate was improved.51 chemical constituents were identified from CGD.Through network pharmacological analysis,107 related targets corresponding to CGD treatment of bacterial pneumonia secondary to influenza were excavated.TNF,AKT1,ALB,VEGFA,MAPK3,PTGS2,STAT3,EGFR and other targets with strong correlation,mainly involved Fc epsilon RI signal pathway,GnRH signal pathway,NF-κB signal path,etc.Molecular docking study showed that the main active component of CGD,including oroxyloside,baicalein and wogonin have strong affinity with TNF,PTGS2 and EGFR targets.Compared with co-infection model group,in CGD group TNF-α、EGFR and PTGS2 increased significantly(P<0.05).Conclusion The main active ingredient of CGD is oroxyloside,baicalein and wogonin.TNF-α,PTGS2,EGFR and other targets to played a role in the treatment of influenza staphylococcus aureus co-infection.

Objective:To explore changes in high-risk sexual behaviors and associated factors in HIV-infected men who have sex with men (MSM) in industrial workers, and provide evidence for designing behavioral interventions for this population.Methods:In this observational study, HIV-infected MSM were recruited in industrial workers using convenient sampling during August to September 2021. The sample size was estimated to be 530. A questionnaire was used and combined with routine follow-up to collect socio-demographic characteristics, high-risk sexual behaviors, partner notification, viral load testing and history of sexually transmitted diseases before and after diagnosis of HIV infection. The χ2 test was used to analyze the changes in high-risk sexual behaviors before and after diagnosis and logistic regression was conducted to identify factors associated with high-risk sexual behaviors. Results:A total of 560 HIV-infected MSM in industrial workers were recruited in this study. Of whom, 32.1% (180/560) had unprotected anal intercourse (UAI) within 12 months after diagnosis . The proportions of those having UAI with casual, commercial and regular same-sex partners significantly decreased from 73.4% (381/519), 75.1% (187/249) and 69.5% (207/298) within 12 months before diagnosis to 36.2% (146/403), 40.2% (86/214) and 34.2% (67/196) within 12 months after diagnosis , respectively. Educational level of college or above (a OR=0.41, 95% CI:0.23-0.71), passive anal sex (a OR=0.40, 95% CI:0.19-0.85), both active and passive anal sex after diagnosis (a OR=0.40, 95% CI:0.20-0.83) and no unprotected oral sex (a OR=0.02, 95% CI:0.01-0.05) were negatively associated with UAI within 12 months after diagnosis. Whereas, not considering necessary to use condom consistently after having repeated undetectable viral load (a OR=3.02, 95% CI:1.37-6.69) was positively associated with UAI within 12 months after diagnosis. Conclusions:Compared with that before diagnosis of HIV infection, although the prevalence of UAI seemed to decrease in HIV-infected MSM in industrial workers after diagnosis, nearly one third of them had high-risk sexual behaviors. Therefore, relevant interventions should be strengthened to reduce high-risk sexual behaviors.

Objective:To explore the cognition of the "undetectable equals untransmittable" ("U=U") concept and associated factors among HIV-infected men who have sex with men (MSM) receiving antiviral treatment (ART) in Shenzhen, and provide evidence for designing promotion and advocacy strategies for the "U=U" concept.Methods:We recruited HIV-infected MSM receiving ART using convenient sampling method combined with routine follow-up in Shenzhen through conducting observational survey. The sample size was estimated to be 475. A questionnaire was administered to collect socio-demographic characteristics, sexual behaviors, ART, viral load testing and the cognition towards "U=U" in HIV-infected MSM. Logistic regression was used to access factors associated with acceptance of "U=U".Results:A total of 490 HIV-infected MSM receiving ART were recruited. Of whom, 60.2% (295/490) were aware of "U=U" and 50.6% (248/490) accepted "U=U". Multiple logistic regression showed that participants who had an educational level of college or above (a OR=1.76,95% CI: 1.12-2.75) were more likely to accept "U=U". Those who had no local residency (a OR=0.51,95% CI: 0.29-0.92), had viral load >0 copies/ml in the last testing (a OR=0.61,95% CI: 0.38-0.98) and were unaware of "U=U" (a OR=0.13, 95% CI: 0.09-0.21), were less likely to accept "U=U". Conclusions:HIV-infected MSM receiving ART had a low cognition level of "U=U" in Shenzhen. Promotion and advocacy on this concept through healthcare workers should be enhanced in combination with routine follow-up in order to improve their ART adherence and outcome of treatment. Furthermore, developing related guidelines on "U=U" according to the characteristics of HIV-infected individuals is warranted to improve the normalization of promotion and advocacy on "U=U".

The aim of this study was to evaluate the roles of interleukin (IL)-17A in risk stratification and prognosis of patients with sepsis-associated acute kidney injury (SAKI). Methods: We enrolled 146 sepsis patients (84 non-SAKI and 62 SAKI patients) admitted to the emergency department from November 2020 to November 2021. Patients with SAKI were differentiated based on the severity of acute kidney injury. All clinical parameters were evaluated upon admission before administering antibiotic treatment. Inflammatory cytokines were assessed using flow cytometry and the Pylon 3D automated immunoassay system (ET Healthcare). In addition, a receiver operating characteristic (ROC) curve was utilized to determine the prognostic values of IL-17A in SAKI. Results: The levels of creatinine, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor alpha, C-reactive protein, and procalcitonin (PCT) were significantly higher in the SAKI group than in the non-SAKI group (p < 0.05). The level of IL-17A revealed significant differences among stages 1, 2, and 3 in SAKI patients (p < 0.05). The mean levels of PCT, IL-4, and IL-17A were significantly higher in the non-survival group than in the survival group in SAKI patients (p < 0.05). In addition, the area under the ROC curve of IL-17A was 0.811. Moreover, the IL-17A cutoff for differentiating survivors from non-survivors was 4.7 pg/mL, of which the sensitivity and specificity were 77.4% and 71.0%, respectively. Conclusion: Elevated levels of IL-17A could predict that SAKI patients are significantly prone to worsening kidney injury with higher mortality. The usefulness of IL-17A in treating SAKI requires further research.

Complex structural variants(CSVs)are genomic alterations that have more than two breakpoints and are considered as the simultaneous occurrence of simple structural variants.How-ever,detecting the compounded mutational signals of CSVs is challenging through a commonly used model-match strategy.As a result,there has been limited progress for CSV discovery com-pared with simple structural variants.Here,we systematically analyzed the multi-breakpoint con-nection feature of CSVs,and proposed Mako,utilizing a bottom-up guided model-free strategy,to detect CSVs from paired-end short-read sequencing.Specifically,we implemented a graph-based pattern growth approach,where the graph depicts potential breakpoint connections,and pattern growth enables CSV detection without pre-defined models.Comprehensive evaluations on both simulated and real datasets revealed that Mako outperformed other algorithms.Notably,validation rates of CSVs on real data based on experimental and computational validations as well as manual inspections are around 70％,where the medians of experimental and computational breakpoint shift are 13 bp and 26 bp,respectively.Moreover,the Mako CSV subgraph effectively characterized the breakpoint connections of a CSV event and uncovered a total of 15 CSV types,including two novel types of adjacent segment swap and tandem dispersed duplication.Further analysis of these CSVs also revealed the impact of sequence homology on the formation of CSVs.Mako is publicly available at https://github.com/xjtu-omics/Mako.

We aimed to develop a whole-genome sequencing(WGS)-based copy number variant(CNV)calling algorithm with the potential of replacing chromosomal microarray assay(CMA)for clinical diagnosis.JAX-CNV is thus developed for CNV detection from WGS data.The perfor-mance of this CNV calling algorithm was evaluated in a blinded manner on 31 samples and com-pared to the 112 CNVs reported by clinically validated CMAs for these 31 samples.The result showed that JAX-CNV recalled 100％of these CNVs.Besides,JAX-CNV identified an average of 30 CNVs per individual,representing an approximately seven-fold increase compared to calls of clinically validated CMAs.Experimental validation of 24 randomly selected CNVs showed one false positive,i.e.,a false discovery rate(FDR)of 4.17％.A robustness test on lower-coverage data revealed a 100％sensitivity for CNVs larger than 300 kb(the current threshold for College of American Pathologists)down to 10×coverage.For CNVs larger than 50 kb,sensi-tivities were 100％for coverages deeper than 20×,97％for 15×,and 95％for 10×.We developed a WGS-based CNV pipeline,including this newly developed CNV caller JAX-CNV,and found it capable of detecting CMA-reported CNVs at a sensitivity of 100％with about a FDR of 4％.We propose that JAX-CNV could be further examined in a multi-institutional study to justify the transition of first-tier genetic testing from CMAs to WGS.JAX-CNV is available at https://github.com/The J acksonLaboratory/JAX-CNV.

Objective:To systematically evaluate the clinical effect of biliary stent combined with intra-biliary radiofrequency ablation and stent alone in the treatment of malignant obstructive jaundice.Methods:The PubMed, Cochrane library, Embase, HowNet, Wanfang, Weipu were systematically searched, the search time was up to February 2021. To collect and compare the clinical efficacy studies of combined intra-biliary radiofrequency ablation in the treatment of patients with malignant obstructive jaundice before biliary stent placement. After literature screening, data extraction and quality assessment conducted by two independent reviewers. Meta-analysis was performed with the patients' 1-year survival rate, 6-month patency rate after biliary stent operation, and comparative changes in postoperative complications as the main outcome indicators.Results:Finally, 9 studies were included, comprising 2 randomized controlled studies (RCT) and 7 retrospective studies, involving a total of 443 patients, with 211 cases in the biliary stent combined with intra-biliary radiofrequency ablation group and 232 cases in the stent alone group. The results of meta-analysis showed that in two joint groups compared with the stent alone group, in overall analysis, the rate of re-obstruction of the biliary tract decreased 6 months after stenting ( OR=0.24, 95% CI: 0.13-0.42) and 1-year survival rate increased ( OR=3.79, 95% CI: 2.08-6.90), the differences are statistically significant ( P<0.001), there was no statistical difference in the complications ( P=0.13). In ERCP group, the rate of re-obstruction of the biliary tract decreased 6 months after stenting ( OR=0.21, 95% CI: 0.08-0.55), and the 1-year survival rate significant increase ( OR=3.63, 95% CI: 1.76-7.48), the differences are statistically significant ( P<0.01). In PTCD group, the rate of re-obstruction of the biliary tract decreased 6 months after stenting ( OR=0.25, 95% CI: 0.12-0.51), and the 1-year survival rate significant increase ( OR=4.13, 95% CI: 1.42-12.03), the differences are statistically significant ( P<0.01). Conclusion:Compared with the stent-only group, the combined group is safe and effective in treating malignant obstructive jaundice.

ObjectiveTo investigate the effect of kaempferol on the proliferation, migration, invasion, and apoptosis of human hepatoma Bel-7402 cells and related molecular mechanism. MethodsHepatoma Bel-7402 cells cultured in vitro were randomly divided into control group and low-, middle-, and high-concentration experimental groups. The experimental groups were treated with low-, middle-, and high-concentration kaempferol (25, 50, and 100 μmol/L), and the control group was treated with an equal volume of dimethyl sulfoxide. CCK-8 assay was used to observe the effect of kaempferol on the viability of Bel-7402 cells; plate colony formation assay was used to evaluate the effect of kaempferol on cell colony formation ability; wound healing assay and Transwell chamber were used to observe the effect of kaempferol on cell migration and invasion; Western blot was used to measure the expression of apoptosis- and cycle-related proteins. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsAfter 24 hours of treatment, the cell viability was 100.00%±2.72% in the control group and 75.70%±2.42%, 62.79%±2.45%, and 43.41%±2.11%, respectively, in the low-, middle-, and high-concentration experimental groups, and compared with the control group, the experimental groups had a significant reduction in cell viability (all P＜0.05). The number of cell colonies was 923.3±35.2 in the control group and 682.7±24.4, 464.0±22.0, and 327.3±14.0, respectively, in the low-, middle-, and high-concentration experimental groups, and compared with the control group, the experimental groups had a significant reduction in cell colony formation ability (all P＜0.05). After 24 hours of treatment, the relative migration rate was 100.00%±1.11% in the control group and 63.33%±1.16%, 51.72%±3.23%, and 37.18%±2.71%, respectively, in the low-, middle-, and high-concentration experimental groups, and the number of transmembrane cells was 212.0±3.0 in the control group and 134.0±2.0, 71.0±2.0, and 34.0±1.0, respectively, in the low-, middle-, and high-concentration experimental groups; compared with the control group, the experimental groups had significant reductions in relative migration rate and number of transmembrane cells (all P＜0.05). After 48 hours of treatment, compared with the control group, the low-, middle-, and high-concentration experimental groups had a significant reduction in the expression of the anti-apoptotic protein Bcl-2 (all P＜0.05), a significant increase in the expression of the pro-apoptotic protein Bax (all P＜0.05), and a significant reduction in the expression of C＜italic/＞yclinD1 (all P＜005). ConclusionKaempferol can inhibit the proliferation, migration, and invasion of human hepatoma Bel-7402 cells and promote the apoptosis of such cells, possibly by regulating the apoptosis proteins Bax and Bcl-2 and downregulating the expression of CyclinD1.