HIV-1 Drug Resistance Detected by Next-Generation Sequencing among ART-Naïve Individuals: A Systematic Review and Meta-Analysis.

BACKGROUND: There are an increasing number of articles focused on the prevalence and clinical impact of pretreatment HIV drug resistance (PDR) detected by Sanger sequencing (SGS). PDR may contribute to the increased likelihood of virologic failure and the emergence of new resistance mutations. As SGS is gradually replaced by next-generation sequencing (NGS), it is necessary to assess the levels of PDR using NGS in ART-naïve patients systematically. NGS can detect the viral variants (low-abundance drug-resistant HIV-1 variants (LA-DRVs)) of virus quasi-species at levels below 20% that SGS may fail to detect. NGS has the potential to optimize current HIV drug resistance surveillance methods and inform future research directions. As the NGS technique has high sensitivity, it is highly likely that the level of pretreatment resistance would be underestimated using conventional techniques. METHODS: For the systematic review and meta-analysis, we searched for original studies published in PubMed, Web of Science, Scopus, and Embase before 30 March 2023 that focused exclusively on the application of NGS in the detection of HIV drug resistance. Pooled prevalence estimates were calculated using a random effects model using the 'meta' package in R (version 4.2.3). We described drug resistance detected at five thresholds (>1%, 2%, 5%, 10%, and 20% of virus quasi-species). Chi-squared tests were used to analyze differences between the overall prevalence of PDR reported by SGS and NGS. RESULTS: A total of 39 eligible studies were selected. The studies included a total of 15,242 ART-naïve individuals living with HIV. The prevalence of PDR was inversely correlated with the mutation detection threshold. The overall prevalence of PDR was 29.74% at the 1% threshold, 22.43% at the 2% threshold, 15.47% at the 5% threshold, 12.95% at the 10% threshold, and 11.08% at the 20% threshold. The prevalence of PDR to INSTIs was 1.22% (95%CI: 0.58-2.57), which is the lowest among the values for all antiretroviral drugs. The prevalence of LA-DRVs was 9.45%. At the 2% and 20% detection threshold, the prevalence of PDR was 22.43% and 11.08%, respectively. Resistance to PIs and INSTIs increased 5.52-fold and 7.08-fold, respectively, in those with a PDR threshold of 2% compared with those with PDR at 20%. However, resistance to NRTIs and NNRTIs increased 2.50-fold and 2.37-fold, respectively. There was a significant difference between the 2% and 5% threshold for detecting HIV drug resistance. There was no statistically significant difference between the results reported by SGS and NGS when using the 20% threshold for reporting resistance mutations. CONCLUSION: In this study, we found that next-generation sequencing facilitates a more sensitive detection of HIV-1 drug resistance than SGS. The high prevalence of PDR emphasizes the importance of baseline resistance and assessing the threshold for optimal clinical detection using NGS.

Prevention and Control Are Not a Regional Matter: A Spatial Correlation and Molecular Linkage Analysis Based on Newly Reported HIV/AIDS Patients in 2021 in Jiangsu, China.

HIV-related spatial analysis studies in China are relatively few, and Jiangsu Province has not reported the relevant data in recent years. To describe the spatial distribution and molecular linkage characteristics of HIV-infected patients, this article combined descriptive epidemiology, spatial analysis, and molecular epidemiology methods to analyze patient reporting, patient mobility information, and HIV sequence information simultaneously. The results showed that HIV reporting profiles differed among Jiangsu cities, with the reporting rate in southern Jiangsu being above average. There was a spatial autocorrelation (Global Moran I = 0.5426, p < 0.05), with Chang Zhou showing a High-High aggregation pattern. Chang Zhou and Wu Xi were identified as hotspots for HIV reporting and access to molecular transmission networks. Some infected individuals still showed cross-city or even cross-province mobility after diagnosis, and three were linked with individuals in the destination cities within the largest molecular transmission cluster, involving 196 patients. The cross-city or cross-province mobility of patients may result in a potential HIV transmission risk, suggesting that combining timely social network surveys, building an extensive transmission network across cities and provinces, and taking critical regions and key populations as entry points could contribute to improved prevention and control efficiency and promote achievement of the 95-95-95 target and cascade.

HPV Infection Profiles among People Living with HIV and HPV Vaccine Acceptance among Individuals with Different HIV Infection Statuses in China: A Systematic Meta-Analysis.

To understand the HPV infection profiles among Chinese HIV/AIDS patients and the HPV vaccine acceptance among unvaccinated Chinese people with different HIV infection statuses after the HPV vaccine launch in China, this study searched Web of Science, PubMed, Cochrane Library, Embase, Scopus, CNKI, WANFANG, SinoMed, and VIP databases up to 23 June 2023, according to the registered protocol (CRD42023449913). A total of 58 studies were included. The results showed that the HPV infection rate among Chinese HIV/AIDS patients was 52.54% (95% CI: 42.11-62.86%) and higher in males than in females (74.55% vs. 41.04%); meanwhile, the rate was higher in the anus than in the cervix (69.22% vs. 41.71%). Although there was no statistical difference, the high-risk HPV infection rate (38.98%) was higher than low-risk HPV (23.86%), and single infections were more common (28.84%) than multiple infections (19.23%). HPV vaccine acceptance among the unvaccinated Chinese population was 59.19% (95% CI: 52.50-65.89%), and was slightly higher among HIV-infected rather than non-HIV-infected individuals (67.72% vs. 59.58%). There was a difference in acceptance among respondents from different regions. Although the difference in acceptance rate between males and females was not statistically significant (61.10% vs. 61.18%), MSM had a higher acceptance rate than non-MSM (84.28% vs. 59.05%). HPV infection is prevalent among HIV patients, demonstrating the need to increase the frequency of HPV screening for PLWH. The HPV vaccine acceptance rate is higher than that of non-HIV-infected individuals. Male acceptance is almost the same as female's, with MSM acceptance higher than non-MSM, suggesting that using MSM, especially MSM in PLWH, as an entry point may be a practical avenue to explore to further expand the scope of HPV vaccination.

Innovate emergency governance mechanism of urban communities in response to major public health events: A qualitative study from multiple principals in Guangzhou, China.

Since the end of 2019, the sudden outbreak of COVID-19 has challenged the emergency governance systems of various countries. As the cornerstone of national governance, China's community emergency governance mainly adopts top-down organizational mobilization and rapid response, which is typical abnormal governance. In responding to major public health events, China's national system has developed certain advantages in some respects. However, the current pandemic is still serious in many places, and new mutant strains are constantly appearing. Some drawbacks of such system and mechanism are gradually emerging. In the process of preventing and controlling the pandemic, China's urban communities have continuously improved the joint mechanism, and played the role of multiple principals in collaborative and co-governance. The current work of pandemic prevention and control has entered a period of normalization. What is the collaborative mechanism of multiple principals (Subdistrict headquarter, Community committee, Owners' committee, Community hospital, Local police station, Property management company, etc.) in urban communities participating in emergencies and how to seek ways to further improve the mechanism? Therefore, taking the community practice and actions in Guangzhou, China as an example, the present study employed a qualitative design, proposed to better community emergency governance mechanisms from the aspects of preparedness, response, communication and recovery, so as to provide a reference for other grassroots organizations.

Integrated Sustainable Development of Culture into Tourist Map Design: A Case from Foshan, China.

As the fourth pillar of sustainable development, culture is widely recognized as contributing to human wellbeing. The distinctive culture of cities is an important driving force for attracting visitors to destinations for tourism consumption. Since historical cities have important cultural and historical values, the design of their tourist maps needs not only geographic positioning and artistic aesthetics, but also a systematic design method to present the connotation of regional cultures, so as to enhance the local cultural identity of hosts and the cultural cognition of visitors, and to drive the local tourism economy, improve the regional environment, promote cultural transmission and inheritance with the help of tourist map design in terms of cultural sustainability, which ultimately achieves sustainable development of human wellbeing. Taking Foshan, a national historical city, as an example, combined with the cultural gene and the cultural hierarchy theory, this study analyzes and summarizes the regional culture of Foshan from three aspects: material cultural gene, intangible cultural gene and spiritual cultural gene. This study also comprehensively presents the geographical information and historical or humanistic characteristics of the city through direct translation, narrative translation, and metaphor translation, which provide theoretical support and practical guidance for the integration of regional cultures into tourist map design.

Analysis of Risk Factors for Pneumonia Death in ICU Environment Based on Logistic Regression.

Objective: To explore the risk and protect factors for death of pneumonia patients in intensive care unit (ICU), we conducted this logistic regression research. Methods: We collected demographic and nursing care data for 80 patients form Wuhan fourth hospital, in which 40 patients were dead and the other 40 patients were alive. Difference analysis, Pearson's correlation matrix, and logistic regression were conducted to explore the risk and protective factors for living status of pneumonia patients in ICU. Results: A total of 40 individuals were dead from pneumonia in ICU. The demographic and nursing information had no difference between death and living groups except age. After that, correlation analysis showed that there were correlations between living status, age, and marriage. Logistic regression showed that age (odds ratio (OR) = 0.94, P < 0.05) and no education (OR = 0.21, P < 0.05) may be harmful for pneumonia patients living status while high-quality nursing (OR = 2.72, P < 0.05) may be helpful for pneumonia patients living status. Conclusion: High-quality care plays an important role in protecting the survival of patients with pneumonia, and old age and uneducated may be the risk factors for the death of patients with pneumonia.

[Identification of a novel TSC2 gene variant in a patient with tuberous sclerosis complex].

OBJECTIVE: To explore the genetic basis for a patient diagnosed with tuberous sclerosis complex (TSC). METHODS: Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Next generation sequencing (NGS) was carried out to detect potential variant, and the result was verified by Sanger sequencing. RESULTS: The patient was found to harbor a heterozygous c.1053delG (p.Glu352SerfsX10) frameshifting variant of the TSC2 gene. The same variant was not found in his unaffected parents and 100 unrelated healthy controls. Based on the American College of Medical Genetics and Genomics guidelines, the variant was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION: The novel c.1053delG (p.Glu352SerfsX10) frameshifting variant of the TSC2 gene probably underlay the TSC in this patient.

Stressful life events and poor sleep quality: a cross-sectional survey in the Chinese governmental employees.

Evidence has shown that stressful life events are associated with sleep quality, yet studies on employees are scarce. In the present study, we explored the association between stressful life events and sleep quality in Chinese governmental employees. The cross-sectional data on 10,994 Chinese governmental employees aged 20-60 years were derived from a cohort study on chronic diseases of governmental employees in Hunan Province, China. Logistic regression models were used to calculate the adjusted odds ratio (OR) and the 95% confidence interval (CI). Of the participants, 3517 (32.0%) reported poor sleep quality in the past month. Participants who experienced more than two life events in the past year were associated with 3 times (OR: 3.681, 95%CI:3.287-4.123) greater likelihood of poor sleep quality. Negative life events, but not positive life events, were significantly associated with poor sleep quality. Regarding the types of events, economic-related life events were associated with poor sleep quality only in employees aged 20-35 years. Regarding the specific life events, work stress, job dissatisfaction, pregnancy or wife pregnancy,quality in Chinese governmental employees. discord with spouse's parents, separation from spouse due to work, bad relationship between spouse, unsatisfied sex life, misunderstood, blamed, false accusation or argument, and lifestyle changes were significantly associated with poor sleep quality. When stratified by sex, age and occupational position, the association of specific events and sleep quality were different. The present study showed that cumulative life events, negative life events and several specific events were significantly associated with poor sleep quality on Chinese governmental employees.

[Corrigendum] GINS2 is a novel prognostic biomarker and promotes tumor progression in early­stage cervical cancer.

Subsequently to the publication of the above article, the authors have realized that Figs. 2 and 6 each contained an incorrectly assembled data panel: Essentially, a couple of the data panels had been inadvertently selected twice for these figures. The corrected versions of Figs 2 and 6, including the correct data for the H&E staining of the tissue of patient 4 in Fig. 2C and the invaded cells of RNAi#2 of the Siha cell line in Fig. 6C, are shown below and on the next page. All the authors agree to the publication of this Corrigendum, and they thank the Editor of Oncology Reports for allowing them the opportunity to publish it. Furthermore, they apologize to the readership for any inconvenience caused. [The original article was published in Oncology Reports 37: 2652­2662, 2017; DOI: 10.3892/or.2017.5573].

Transcriptomic profiles of human HaCaT cells in response to angelica polysaccharide.

The aim of this study was to explore the anti-psoriatic effect and potential mechanism of Angelica polysaccharide (APS) on an in vitro HaCaT cell model. MTS assay was performed to determine whether APS has the ability to inhibit the proliferation of HaCaT cells. RNA-sequencing (RNA-seq) was performed to investigate the underlying mechanism of APS. Quantitative real-time PCR (qRT-PCR) was used to verify the accuracy of RNA-seq data. Our MTS assay results demonstrated that APS time- and concentration-dependently inhibits the proliferation of HaCaT cells. The anti-proliferation property of APS suggests that APS may have anti-psoriatic effect. In the RNA-seq part, comparison between the CK group (i.e., Control group) and ASP groups revealed dramatic differences [468 differentially expressed genes (DEGs) for CK group vs. ASP50 group; 563 DEGs for CK group vs. ASP100 group; 532 DEGs for CK group vs. ASP200 group]. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrich analysis performed on all DEGs failed to find any significant enriched GO terms or KEGG pathways to explain the anti-proliferative effect of APS. All DEGs were then classified into 20 expression profiles by trend analysis. Interestingly, cell proliferation-related GO terms were mostly dispersed in the profile 2 and 17. DEGs enriched in these terms were then analyzed. After literature retrieval, DEGs such as SERPINE1, SMAD6, CTGF, and TGF-ß were suspected to closely relevant to the anti-proliferation effect of APS. qRT-PCR results showed similar expression trend with RNA-seq data for 8 out of 10 genes, indicating our sequence data are reliable.

Catheter ablation of supraventricular tachycardia in patients with dextrocardia and situs inversus.

BACKGROUND: Dextrocardia with situs inversus is a rare cardiac positional anomaly. Catheter ablation procedures performed in this set of patients have not been sufficiently reported. METHODS: A total of 10 patients with dextrocardia and situs inversus who received catheter ablation for supraventricular tachycardia (SVT) were included from a cohort of over 20 000 cases of catheter ablation for SVT in three centers from 2005 to 2016. All patients underwent electrophysiologic study and catheter ablation of SVT. Ablation targets were selected based on different tachycardia mechanisms with the primary endpoint of noninduction of tachycardia. RESULTS: The average age was 32.4 ± 5.6 years. Congenitally corrected transposition of great arteries (TGA) with situs inversus and D-looping of the ventricles and aorta (congenitally corrected TGA {I,D,D}) was found in four patients, while the other six patients exhibited mirror-image dextrocardia {I,L,L}. The mechanisms of SVT were atrioventricular nodal reentrant tachycardia in four patients, atrioventricular reentrant tachycardia in three, typical atrial flutter in one, intra-atrial reentrant tachycardia in one, and focal atrial tachycardia in one. Immediate procedural success was achieved in 9 out of 10 patients with no procedural complications. During a follow-up period of 6.3 ± 3.5 years on average, all patients remained free from recurrent tachycardia. CONCLUSIONS: For patients with dextrocardia and situs inversus, catheter ablation of SVT is safe and feasible. Differences in catheter maneuver and fluroscopy projection, along with difficulties in distorted anatomy are major obstacles for successful ablation.

Electrocardiographic and electrophysiologic differentiation between atriofascicular, long atrioventricular, and short atrioventricular decrementally conducting accessory pathways.

Aims: We aimed to examine the electrocardiographic and electrophysiologic characteristics of anterograde-conducting decremental accessory pathways (DAP) and to identify surrogate criteria to distinguish short atrioventricular (SAV) DAP from atriofascicular (AF) AP and long atrioventricular (LAV) DAP. Methods and results: We identified all patients with DAPs and analysed electrocardiographic and electrophysiologic characteristics. Distal insertion sites were examined using existing criteria, including V-H interval, ventricular activation at the right ventricular apex, and around tricuspid annulus during antidromic atrioventricular re-entrant tachycardia (A-AVRT) or complete pre-excitation and evaluated the AV node-like properties according to the response to adenosine and radiofrequency ablation. Out of 45 patients with DAPs, 28 (62.2%) had SAV-DAP (13 with definite AF-AP, 2 with definite LAV-DAP, 2 indeterminate). In all, 50% of SAV-DAPs and 53.3% of AF-AP/LAV-DAPs had 'rS' pattern in lead III. Longer QRS duration (159.9 ± 17.4 ms vs. 139.2 ± 14.3 ms, P < 0.0001) during full pre-excitation or A-AVRT differentiated SAV-DAP from AF-AP. The QRS-V(His) interval was longer for those with SAV-DAP compared vs. AF-AP/LAV-DAP (45.3 ± 2.4 ms vs. 22.9 ± 2.5 ms, P < 0.0001) and a cut-off value of 33.0 ms differentiated the two (sensitivity 81.3%, specificity 87.5%). Conclusion: The majority of the SAV-DAPs are located at the TA free wall. An 'rS' pattern in lead III is frequently seen in SAV-DAP as well as AF-AP/LAV-DAPs. Measuring the QRS-V(His) interval would be helpful to distinguish SAV-DAP from AF-AP/LAV-DAP.

GINS2 is a novel prognostic biomarker and promotes tumor progression in early-stage cervical cancer.

GINS complex subunit 2 (GINS2), a member of the GINS complex, is involved in DNA replication. GINS2 is upregulated in a variety of aggressive tumors. However, its role in cervical cancer carcinogenesis remains to be elucidated. We investigated the clinical significance of GINS2 in patients with early-stage cervical cancer and its biological functions in cervical cancer progression. GINS2 expression was analyzed in cervical cancer cell lines and in 8 matched cervical cancer samples at the mRNA and protein levels using real-time PCR and western blotting, respectively. GINS2 protein expression in 155 paraffin-embedded cervical cancer specimens was validated using immunohistochemistry. Statistical analysis was used to evaluate its clinicopathological significance. Short hairpin RNA interference, anchorage-independent growth ability, colony formation assay, wound healing ability, Transwell assays and western blotting were used to determine the effects of GINS2 on the aggressive phenotype of cervical cancer cells. There was obvious upregulation of GINS2 in the cervical cancer cell lines and tumor specimens compared to that in the normal cervical tissues. Significant correlations were identified between GINS2 expression and squamous cell carcinoma antigen (SCC-Ag; P<0.001), deep stromal invasion (P=0.021), vital status (P<0.001), recurrence (P<0.001) and pelvic lymph node metastasis (PLNM; P<0.001). Moreover, patients with higher GINS2 expression had shorter overall survival (OS) compared to patients with low GINS2 expression. Multivariate analysis revealed that GINS2 may serve as an independent risk factor of poor prognosis in early-stage cervical cancer. In addition, GINS2 downregulation markedly suppressed cell proliferation and tumorigenic ability, as well as cell migration and invasion. Our findings suggest that GINS2 is a novel indicator of PLNM and a valuable prognostic biomarker in early-stage cervical cancer, and subsequently is a valuable molecular target for cervical cancer diagnosis and treatment.

Very long-term outcome of catheter ablation of post-incisional atrial tachycardia: Role of incisional and non-incisional scar.

BACKGROUND: The arrhythmogenicity of right atrial (RA) incisional scar after cardiac surgery could result in atrial tachycardia (AT). Radiofrequency catheter ablation is effective in the treatment of such tachycardia. However, data regarding long-term outcomes are limited. METHODS AND RESULTS: A total of 105 patients with prior RA incision who underwent radiofrequency catheter ablation of AT were included. In the first procedure, electroanatomic mapping (EAM) revealed a total of 139 ATs in 105 patients, including 88 cavotricuspid isthmus dependent atrial flutters (IDAFs), 5 mitral annulus reentrant tachycardias (MARTs), 44 intra-atrial reentrant tachycardias (IARTs) and 2 focal ATs (FATs). AT was successfully eliminated in 101 (96.1%) patients. During a mean follow-up period of 90 ± 36 months, recurrent AT was observed in 23 patients and 21 underwent a second ablation. A total of 23 ATs were identified in redo procedures including 4 IDAFs, 2 MARTs, 12 IARTs and 5 FATs. The time to recurrence was significantly different among various AT types. Acute success was achieved in 20 of 23 redo procedures. Taking a total of 21 patients presenting atrial fibrillation during follow-up into account, 85 patients (81.9%) were in sinus rhythm. No complications except for a case of RA compartmentation occurred. CONCLUSION: RA incisional scar played an essential role in promoting both IDAF and IART, while non-incisional scar contributed to a substantial rate of late recurrent AT in forms of both macroreentry and small reentry. Catheter ablation using EAM system resulted in a high success rate during long-term follow-up.

PBOV1 correlates with progression of ovarian cancer and inhibits proliferation of ovarian cancer cells.

Prostate and breast cancer overexpressed 1 (PBOV1) is significantly upregulated in prostate, breast and bladder cancer, while its expression status in ovarian cancer and its clinical significance are unclear. We examined the expression levels of PBOV1 mRNA and protein in ovarian cancer cell lines and primary tissues using real-time PCR and western blotting. Immunohistochemistry was employed to analyze PBOV1 expression in 17 normal ovaries, 13 cystadenoma tissues, 14 borderline tumor tissues, and 165 clinicopathologically characterized ovarian cancers. There was negative PBOV1 expression in the 17 normal ovarian epithelial tissues. Compared to the normal ovarian epithelial cells, PBOV1 mRNA and protein were overexpressed in ovarian cancer cell lines. There was high PBOV1 protein expression in the ovarian cancer tissues from 59 of the 165 (35.8%) patients; PBOV1 expression was weak in 106 (64.2%) patients. Notably, there were significant negative associations between high PBOV1 expression and ascending histological grade, late pT/pN/pM, and International Federation of Gynecology and Obstetrics (FIGO) stage (P<0.05). Patients with high PBOV1 expression had longer overall survival; patients with low PBOV1 expression had shorter survival. Multivariate analysis revealed that PBOV1 upregulation is an independent prognostic indicator for ovarian cancer and might serve as a tumor-suppressor gene. Furthermore, PBOV1 overexpression inhibited ovarian cancer cell proliferation and tumorigenesis in vitro and in a tumor transplantation nude mouse model. In conclusion, our results suggest that PBOV1 may play an important role in suppressing ovarian cancer proliferation and carcinogenesis. PBOV1 may be a novel and useful prognostic marker and potential target for treating human ovarian cancer.

Overexpressed CISD2 has prognostic value in human gastric cancer and promotes gastric cancer cell proliferation and tumorigenesis via AKT signaling pathway.

CDGSH iron sulfur domain 2 (CISD2) is localized in the outer mitochondrial membrane and mediates mitochondrial integrity and lifespan in mammals, but its role in cancer is unknown. In the current study, we reported that CISD2 mRNA and protein expression levels were significantly upregulated in gastric cancer cells compared to normal gastric epithelial cells (P < 0.001). Immunohistochemical analysis of 261 paraffin-embedded archived gastric cancer tissues showed that high CISD2 expression was significantly associated with clinical stage, TNM classifications, venous invasion and lymphatic invasion. Univariate and multivariate analysis indicated that high CISD2 expression was an independent prognostic factor for poorer overall survival in the entire cohort. Overexpressing CISD2 promoted, while silencing CISD2 inhibited, the proliferation of gastric cancer cells. Furthermore, we found that silencing endogenous CISD2 also significantly inhibited the proliferation and tumorigenicity of MGC-803 and SGC-7901 cells not only in vitro but also in vivo in NOD/SCID mice (P < 0.05). Furthermore, we found that CISD2 affected cell proliferation and tumorigenicity of gastric cancer cells through mediating the G1-to-S phase transition. Moreover, we demonstrated that the pro-proliferative effect of CISD2 on gastric cancer cells was associated with downregulation of cyclin-dependent kinase inhibitor p21Cip1 and p27Kip1, and activation of AKT signaling. The findings of this study indicate that CISD2 may promote proliferation and tumorigenicity, potentially representing a novel prognostic marker for overall survival in gastric cancer.

Successful radiofrequency ablation of a right posteroseptal accessory pathway through an anomalous inferior vena cava and azygos continuation in a patient with incomplete situs inversus.

We present a 43-year-old patient with paroxysmal supraventricular tachycardia. In the process of catheter ablation, we found interruption of the inferior vena cava with azygos continuation with incomplete situs inversus. In this patient, we adopted the lower approach via the anomalous inferior vena cava and azygos continuation to achieve stability of radiofrequency catheter for right posteroseptal accessory pathway, and successfully abolished the preexcitation.