Comparison of smokers' mortality with non-smokers following out-of-hospital cardiac arrests: a systematic review and meta-analysis.

OBJECTIVE: Although some studies have linked smoking to mortality after out-of-hospital cardiac arrests (OHCAs), data regarding smoking and mortality after OHCAs have not yet been discussed in a meta-analysis. Thus, this study conducted this systematic review to clarify the association. METHODS: The study searched Medline-PubMed, Web of Science, Embase and Cochrane libraries between January 1972 and July 2022 for studies that evaluated the association between smoking and mortality after OHCAs. Studies that reportedly showed relative risk estimates with 95% confidence intervals (CIs) were included. RESULTS: Incorporating a collective of five studies comprising 2477 participants, the analysis revealed a lower mortality risk among smokers in the aftermath of OHCAs compared with non-smokers (odds ratio: 0.77; 95% CI 0.61-0.96; P < 0.05). Egger's test showed no publication bias in the relationship between smoking and mortality after OHCAs. CONCLUSIONS: After experiencing OHCAs, smokers had lower mortality than non-smokers. However, due to the lack of data, this 'smoker's paradox' still needs other covariate effects and further studies to be considered valid.

Small-molecule agonist AdipoRon alleviates diabetic retinopathy through the AdipoR1/AMPK/EGR4 pathway.

BACKGROUND: Diabetes mellitus (DM) is a progressive disease that involves multiple organs due to increased blood glucose, and diabetic retinopathy (DR) is the main complication of DM in the eyes and causes irreversible vision loss. In the pathogenesis of diabetic vascular disease, oxidative stress caused by hyperglycemia plays an important role in Müller cell impairment. In recent years, AdipoRon, an adiponectin analog that demonstrated important physiological functions in obesity, diabetes, inflammation, and cardiovascular diseases, demonstrated cellular protection from apoptosis and reduced inflammatory damage through a receptor-dependent mechanism. Here, we investigated how AdipoRon reduced oxidative stress and apoptosis in Müller glia in a high glucose environment. RESULTS: By binding to adiponectin receptor 1 on Müller glia, AdipoRon activated 5' adenosine monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase phosphorylation downstream, thereby alleviating oxidative stress and eventual apoptosis of cells and tissues. Transcriptome sequencing revealed that AdipoRon promoted the synthesis and expression of early growth response factor 4 (EGR4) and inhibited the cellular protective effects of AdipoRon in a high-glucose environment by reducing the expression of EGR4. This indicated that AdipoRon played a protective role through the EGR4 and classical AMPK pathways. CONCLUSIONS: This provides a new target for the early treatment of DR.

Hypoxia Induces Tumor-Derived Exosome SNHG16 to Mediate Nasopharyngeal Carcinoma Progression through the miR-23b-5p/MCM6 Pathway.

This study aims to investigate the mechanism of tumor-derived exosomal (EVs) SNHG16 in promoting the progression of nasopharyngeal carcinoma (NPC). QRT-PCR was used to detect the expression of SNHG16, miR-23b-5p and MCM6 in NPC. MTT, flow cytometry and transwell were used to detect the effects of them on the proliferation, cycle, apoptosis and invasion ability of NPC. Transmission electron microscopy, Western blotting and BCA were used to verify the regulation of exosome secretion under different oxygen environments. Our results showed that hypoxia induces tumor-derived exosome SNHG16 to mediate NPC progression through the miR-23b-5p/MCM6 pathway.

Efficacy and pregnancy outcomes of focused ultrasound for cervical high-grade squamous intraepithelial lesions.

OBJECTIVE: To investigate the efficacy and adverse effects of focused ultrasound (FU) in the treatment of high-grade squamous intraepithelial lesions (HSIL) and follow up on pregnancy outcomes in patients. METHODS: This retrospective study recruited 57 patients aged 20-40 years with cervical HSIL combined with HR-HPV infection who received FU treatment between September 2019 and April 2022. Clinical data of the patients were obtained from hospital records. HSIL cure rate and cumulative HR-HPV clearance rate were assessed after treatment. Patients were followed up on fertility and pregnancy outcomes after treatment by telephone interviews until April 1, 2023. RESULTS: During a 6-month follow-up, the HSIL cure rate was 73.7%, and a statistical difference between CIN2 and CIN3 (75.6% vs. 66.7%, p = 0.713) was not present. HSIL -recurrence was not observed during the follow-up period, and the median follow-up duration was 12 months. The cumulative HR-HPV clearance rates at the 6- and 12-month follow-ups were 56.1% and 75.4%, respectively. The median clearance time of HR-HPV was 6 (95% confidence interval, 5.46-6.54) months. The clearance rate was higher in HPV16/18 than in non-HPV16/18 (86.7% vs. 62.9%, p = 0.038). After treatment, the successful pregnancy rate in patients with fertility intentions and spontaneous abortion rate were 73.9% and 5.9%, respectively. Preterm birth, preterm premature rupture of membranes, or low-birth-weight infants were not observed. CONCLUSION: FU treatment can regress HSIL and accelerate HR-HPV clearance in young women of childbearing age with cervical HSIL associated with HR-HPV infection, and has no significant adverse effects on pregnancy outcomes.

Changes in cervical cytokine profiles following focused ultrasound treatment for high-risk human papillomavirus infection-related low-grade cervical lesions.

OBJECTIVE: To evaluate the changes of cervical soluble immune markers after focused ultrasound (FU) treatment to explore the underlying local immune effects of FU in the treatment of high-risk human papillomavirus (HR-HPV) infection-related low-grade squamous intraepithelial lesion (LSIL). METHODS: A total of 35 patients diagnosed with HR-HPV infection-related histological LSIL who met the inclusion criteria were enrolled in this prospective study and treated with FU. The authors used cytometric bead array to measure T-helper type 1 (Th1) cytokine (interleukin [IL] 2, tumor necrosis factor, and interferon γ) and Th2 cytokine (IL-4, IL-5, IL-6, and IL-10) levels in the cervicovaginal lavage of patients before and 3 months after FU treatment. RESULTS: After FU treatment, the concentrations of Th2 cytokines IL-5 and IL-6 were significantly lower than those before FU treatment (P = 0.044 and P = 0.028, respectively). HR-HPV infection was cleared in 27 patients, with a clearance rate of 77.1% (27 of 35). The concentration of IL-4 in patients with HR-HPV clearance after FU treatment was significantly lower than that in patients without HR-HPV clearance (P = 0.045). CONCLUSION: FU can inhibit the production of certain Th2 cytokines and may improve the local immune status of the cervix, thereby eliminating HR-HPV infection.

Improvement of vaginal probiotics Lactobacillus crispatus on intrauterine adhesion in mice model and in clinical practice.

BACKGROUND: Intrauterine adhesion (IUA) is a frequent acquired endometrial condition, for which there is no effective preventive or treatment. Previous studies have found that vaginal microbiota dysregulation is closely related to endometrial fibrosis and IUA. Therefore, we wondered whether restoration of vaginal microbiota by vaginal administration of L. crispatus could prevent endometrial fibrosis and ameliorate IUA. RESULTS: First, we created a mechanically injured mouse model of IUA and restored the mice's vaginal microbiota by the addition of L. crispatus convolvulus. The observations suggested that intrauterine injections of L. crispatus significantly decreased the degree of uterine fibrosis, the levels of IL-1ß and TNF-α in blood, and downregulated the TGF-ß1/SMADs signaling pathway in IUA mice. A therapy with L. crispatus considerably raised the abundance of the helpful bacteria Lactobacillus and Oscillospira and restored the balance of the vaginal microbiota in IUA mice, according to high-throughput sequencing. Then we conducted a randomized controlled trial to compare the therapeutic effect of L. crispatus with estrogen after transcervical resection of adhesion (TCRA). And the results showed that vaginal probiotics had a better potential to prevent intrauterine adhesion than estrogen. CONCLUSIONS: This study confirmed that L. crispatus could restore vaginal microbiota after intrauterine surgery, inhibit endometrial fibrosis, and finally play a preventive and therapeutic role in IUA. At the same time, it is a new exploration for the treatment of gynecological diseases with vaginal probiotics. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn/ , identifier (ChiCTR1900022522), registration time: 15/04/2019.

Changes in vaginal microbiome after focused ultrasound treatment of high-risk human papillomavirus infection-related low-grade cervical lesions.

BACKGROUND: In this study, the changes of vaginal microbiome after focused ultrasound (FU) treatment were evaluated to explore the possible mechanism of FU in the treatment of high-risk human papillomavirus (HR-HPV) infection. METHODS: This study was nested in the FU arm of a prospective cohort study. A total of 37 patients diagnosed with HR-HPV infection-related cervical low-grade squamous intraepithelial lesion (LSIL) who met the inclusion criteria were enrolled in this study from October 2020 to November 2021, and these patients were treated with FU. We used 16S ribosomal RNA (16S rRNA) gene amplicon sequencing to profile the vaginal microbiota composition of patients before and 3 months after FU treatment. RESULTS: After FU treatment, HR-HPV was cleared in 24 patients, with a clearance rate of 75.0% (24/32). Lactobacillus iners was the predominant species among all samples. No significant difference was found in alpha-diversity index before and 3 months after FU treatment (P > 0.05), but the rarefaction curves showed that the vaginal microbial diversity before FU treatment was higher than that after FU treatment. Linear discriminant analysis (LDA) effect size (LEfSe) showed that Bifidobacterium contributed the most to the difference between the two groups at the genus level, and the abundance after FU treatment was significantly higher than that before treatment (P = 0.000). CONCLUSIONS: The decrease of vaginal microbial diversity may be related to the clearance of HR-HPV infection, and FU treatment contributed to the decrease of vaginal microbial diversity. Increased Bifidobacterium abundance in the vaginal microbiome may be associated with clearance of HR-HPV infection, and FU treatment may contribute to the increase in Bifidobacterium abundance. TRIAL REGISTRATION NUMBER:  This study was registered in the Chinese Clinical Trial Registry on 23/11/2020 (ChiCTR2000040162).

High-Intensity Focused Ultrasound for Patients With Cervical Intraepithelial Neoplasia 2/3: A Prospective One-Arm Study.

The aim of this study was to ascertain the safety of high-intensity focused ultrasound (HIFU) for high-grade cervical intraepithelial neoplasia grade 2/3 (CIN 2/3) in patients with fertility requirements. This was a prospective one-arm study. Consecutive CIN 2/3 patients diagnosed with histopathology were screened, enrolled and treated from September 2019 to September 2020 in the Affiliated Hospital of North Sichuan Medical College. All patients were treated with a combination of HIFU and antiviral treatment with REBACIN. The scheduled follow-up visits were 1 week, 1 mo, 3 mo, 6 mo and 12 mo after surgery. The primary outcomes included cure and human papillomavirus clearance rates. We screened 287 consecutive CIN 2/3 patients in our hospital, 29 of whom were enrolled and treated in this study. The cure rate reached 82.8% at 7 mo after treatment and 96.6% within 1 y. The HPV-negative rate reached 72.4% (21/29) around 6 mo after treatment, with mild side effects during and after the procedure. Our study suggests that in CIN 2/3 study participants with fertility requirements, HIFU + REBACIN therapy is a safe and effective therapeutic option with a high cure rate, HPV clearance and few side effects.

Association between cigarette smoking and mortality in patients with hip fracture: A systematic review and meta-analysis.

INTRODUCTION: Hip fracture is associated with substantial morbidity and mortality, especially among the elderly. Current evidence on the association between cigarette smoking and mortality in hip-fracture patients is controversial. We performed a systematic review and meta-analysis of studies on this association. METHODS: The databases Medline/PubMed, Embase, Web of Science, and Cochrane Library were searched for studies that estimated the effect of smoking on the risk of mortality in hip-fracture patients. Pooled analyses were conducted of the associations, expressed in relative risk (RR) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic. Study quality was assessed by the modified Newcastle-Ottawa Scale (NOS) and publication bias was evaluated by a funnel plot, Begg's and Egger's tests. Subgroup analyses were performed by study design, race/ethnicity, age ≥60 years, smoking status, and follow-up period. RESULTS: A total of six articles involving 3739 hip-fracture patients were included in the meta-analysis. Our results indicate that ever-active smoking was significantly associated with an increased risk of death in hip-fracture patients (pooled RR=1.26; 95% CI: 1.08-1.46). In further subgroup analysis, the risk of death was significantly higher in ever-active smokers than in never smokers in White participants (pooled RR=1.23; 95% CI: 1.05-1.44) and elderly aged ≥60 years (pooled RR=1.19; 95% CI: 1.01-1.40), with no significant association in Asian participants (pooled RR=1.42; 95% CI: 0.95-2.11). Current smokers had more risk of death than never smokers (pooled RR=1.26; 95% CI: 1.08-1.46). The association was significant in follow-up periods of ≤1 year (pooled hazard ratio, HR=1.34; 95% CI: 1.05-1.71), 3 years (pooled HR=1.22; 95% CI: 1.05-1.43), and 5 years (pooled HR=1.26; 95% CI: 1.08-1.46). CONCLUSIONS: Cigarette smoking is associated with an increased risk of mortality in hip-fracture patients, especially in elderly patients aged ≥60 years, current smokers, and White participants. With the extension of follow-up period, the effect on mortality of smoking is profound and lasting.

SMYD3 regulates the abnormal proliferation of non-small-cell lung cancer cells via the H3K4me3/ANO1 axis.

Non-small-cell lung cancer (NSCLC) is the most prevalent type of lung cancer. This study evaluated the mechanism of histone methyltransferase SET and MYND domain-containing 3 (SMYD3) in the abnormal proliferation of NSCLC cells. The human bronchial epithelial cell (HBEC) line (16HBE) and NSCLC cell lines (H1299, A549, H460, and H1650) were collected. A549 and H1650 cells were transfected with si-SMYD3 and Anoctamin-1 (ANO1) and their negative controls or treated with BCI-121, or A549 cells were treated with CPI-455. SMYD3, H3 lysine 4 tri-methylation (H3K4me3), and ANO1 levels in the cells were detected. The proliferation ability of A549 and H1650 cells were examined. We found that SMYD3, H3K4me3, and ANO1 were highly expressed in NSCLC cell lines. Silencing SMYD3 or SMYD3 activity in A549 and H1650 cells inhibited the cell proliferation ability and decreased H3K4me3 level and ANO1 mRNA level in the cells. H3K4me3 upregulation orANO1 overexpression reversed the inhibitory effects of silencing SMYD3 on the abnormal proliferation of NSCLC cells. Chromatin-Immunoprecipitation (Ch-IP) assay detected that SMYD3 bound to and enriched in the ANO1 promoter region, and the ANO1 promoter region was enriched with H3K4me3. Collectively, SMYD3 promoted ANO1 transcription by upregulating H3K4me3 in the ANO1 promoter region, thus facilitating the abnormal proliferation of NSCLC cells.

Focused ultrasound for high-risk human papillomavirus infection-related low-grade cervical lesions: a prospective cohort study.

OBJECTIVES: To assess the efficacy and safety of focused ultrasound (FU) for high-risk human papillomavirus (HR-HPV) infection-related cervical low-grade squamous intraepithelial lesions (LSIL). METHODS: Of 185 patients who met the inclusion criteria for this prospective study from October 2020 to November 2021, 95 received FU and 90 were followed up only. At the six-month follow-up, the HR-HPV clearance and LSIL regression rates of the groups were compared and factors affecting HR-HPV clearance were analyzed. The safety and side effects of FU were evaluated. RESULTS: No significant difference was found in the baseline clinical data between the two groups (p > 0.05). At the six-month follow-up, the HR-HPV clearance rates were 75.6% in the FU group and 25.6% in the observation group (p = 0.000). The LSIL regression rates were 89.5% in the FU group and 56.4% in the observation group (p = 0.000). Multivariate logistic regression analysis showed that the HR-HPV clearance rate in the FU group was 9.03 times higher than that in the observation group (95% confidence interval [CI], 3.75-21.73, p = 0.000), and the clearance rate of single-type HR-HPV infections was 5.28 times higher than that of multi-type infections (95% CI, 1.83-15.23, p = 0.002). The mean intraoperative bleeding was 1.8 ± 0.6 (1-3) mL; the mean intraoperative pain score was 2.6 ± 1.0 (1-6). CONCLUSIONS: For patients with HR-HPV infection-related histological LSIL, FU can eliminate HR-HPV infection and cause lesions to regress in a short time, with few adverse effects and good tolerance.

Association between smoking and risk of death in patients with sepsis: A systematic review and meta-analysis.

INTRODUCTION: Although some research papers have suggested that smoking may increase mortality in patients with sepsis, no evidence has been produced in this regard. This systematic research evaluated the risk of death in patients with sepsis who were smokers to facilitate better clinical decision making. METHODS: This is a systematic review registered in PROPERO (CRD42022296654). Searches were conducted to identify suitable studies from the databases of PubMed, Embase, Web of Science and the Cochrane Controlled Register of Trials from January 1980 to June 2021. Two independent reviewers screened the articles using keywords and extracted the data. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of evidence. The primary endpoints included the mortality of patients with sepsis. RESULTS: Five studies involving 2694 participants were included in our study. Among the five included articles, three studies had an NOS score of 6, while the other two had an NOS score of 7. The results showed that a significantly higher risk of death was observed in smokers with sepsis compared with non-smokers with sepsis (hazard ratio, HR=1.62; 95% CI: 1.11-2.37, p=0.01). Among the patients followed for more than 2 months, the mortality rate of smokers was significantly higher (2.33 times) than that of non-smokers (HR=2.33; 95% CI: 1.83-2.96, p<0.01). The difference in mortality did not reach statistical significance when the follow-up period was shorter than 2 months (HR=1.22; 95% CI: 0.96-1.56, p=0.10). CONCLUSIONS: Smoking increased mortality in patients with sepsis when the follow-up period was longer than 2 months.

Targeting RPL23 restores chemosensitivity of cisplatin-resistant ovarian carcinoma by inhibiting EMT.

Chemoresistance is the inevitable outcome of chemotherapy for epithelial ovarian carcinoma (EOC), and its mechanism is still not fully understood. This study explored the role of ribosomal protein L23 (RPL23) in cisplatin resistance of EOC. WGCNA based on TCGA and GEO was used to screen and analyze target genes related to EOC chemotherapy sensitivity. Clinical samples of cisplatin resistance were collected to detect the expression of target genes. Cisplatin resistance was induced in EOC cell lines A2780 and SKOV3. The cell abilities of invasion, migration and adhesion were observed. Western blotting was used to detect protein expressions. Bioinformatics analysis showed that RPL23 may be related to EOC chemotherapy sensitivity, and was highly expressed in clinical samples and cell lines of cisplatin-resistant. After A2780 and SKOV3 were resistant to cisplatin, the inhibitory abilities of therapeutic dose of cisplatin on their invasion, migration and adhesion were significantly attenuated, and N-cadherin and vimentin were significantly up-regulated while E-cadherin was significantly down-regulated. However, above phenomena were significantly reversed after RPL23 knockdown. Taken together, the overexpressed RPL23 may lead to platinum resistance by inducing epithelial-mesenchymal transition (EMT) in EOC. Targeting knockdown RPL23 would restore the sensitivity of EOC cells to cisplatin by inhibiting EMT, suggesting that RPL23 is a potential therapeutic target for EOC after platinum resistance.

Abnormal spindle-like microcephaly-associated protein promotes proliferation by regulating cell cycle in epithelial ovarian cancer.

Background: Epithelial ovarian cancer (EOC) ranks first for female gynecological tumor-related deaths. Due to the limited efficacy of traditional chemotherapy strategies, potential therapeutic targets are urgently needed. Previous studies have reported a relationship between abnormal spindle-like microcephaly-associated protein (ASPM) and ovarian cancer based on immunohistochemistry (IHC) and bioinformatics analysis. However, the potential role of ASPM in the proliferation of ovarian cancer cells and its molecular mechanism remain to be elucidated. Therefore, we aimed to further investigate the potential role of ASPM and its underlying mechanism in EOC using integrated online databases, clinical samples, and cell models. Methods: We used online databases (Gene Expression Profiling Interactive Analysis, Cbioportal and Kaplan-Meier Plotter) to analyze differential ASPM expression in ovarian carcinoma and explore its prognostic value in ovarian cancer (OvCa) patients. Immunohistochemistry staining based on a clinical tissue microarray (TMA) comprised 75 cases of EOC tissue and 5 cases of adjacent normal ovary tissue was used to detect the ASPM expression and analyze the relationship between ASPM expression and EOC characteristics. Various cell function experiments related to tumorigenesis were performed including the CCK8 assay, 5-ethynyl-2'-deoxyuridine (EdU), colony formation assay and Transwell assay in EOC cell models (A2780 and OVCAR3) with knocked down ASPM by small interfering RNA (siRNA) to observe its role. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was conducted to determine the signaling pathways in which ASPM was involved in the pathogenesis of ovarian cancer. Analysis of cell cycle distribution using flow cytometry was further performed to verify the pathways. Results: The expression profile based on data from The Cancer Genome Atlas (TCGA) database confirmed ASPM expression in EOC was higher compared with normal tissue, and further analysis suggested that higher expression was correlated with worse patient prognosis. Immunohistochemical analysis further indicated that ASPM was highly expressed in OvCa tissues and associated with a higher pathological stage, grade, and positive lymphatic metastasis. Cell models with knocked down ASPM by small interfering RNA (siRNA) significantly inhibited proliferation and migration. KEGG pathway enrichment and cell cycle analysis showed that ASPM silencing could inhibit ovarian cancer cell proliferation via synthesis (S) phase arrest. Conclusions: Our study confirmed that ASPM promoted proliferation and caused S phase arrest in EOC cells. ASPM may become a potential molecular marker for early screening and a valuable therapeutic target in EOC. Keywords: Abnormal spindle-like microcephaly-associated protein (ASPM); epithelial ovarian cancer (EOC); prognosis; proliferation.

GP73-mediated secretion of AFP and GP73 promotes proliferation and metastasis of hepatocellular carcinoma cells.

Golgi protein 73 (GP73) and alpha fetoprotein (AFP) serve as biomarkers for the diagnosis of hepatocellular carcinoma (HCC), and their serum levels correlate with patients' outcomes. However, the mechanisms underlying these correlations are unknown. Here we show that GP73 increased the secretion of AFP through direct binding to AFP, thereby promoting the proliferation and metastasis of HCC cells that expressed AFP and its receptor (AFPR). Extracellular GP73 contributed to the proliferation and metastasis of HCC cells independent of AFP and AFPR. Moreover, extracellular AFP and GP73 synergized to enhance the malignant phenotype of HCC cells. Furthermore, extracellular GP73 and AFP inhibited the antitumor effects of sorafenib and synergistically increased the drug resistance of HCC cells. These findings, which reveal the mechanism of GP73-mediated secretion of AFP and its effects on the malignant phenotype of HCC cells, provide a comprehensive theoretical basis for the diagnosis and treatment of HCC and identify potential drug targets.

Short- and medium-term outcomes after uniportal and multiportal video-assisted thoracic surgery lobectomy in elderly patients with non-small cell lung cancer.

PURPOSE: To investigate the short- and medium-term outcomes following treatment with uniportal video-assisted thoracic surgery lobectomy (uniportal VATS) in elderly patients with non-small cell lung cancer (NSCLC). METHODS: We conducted a retrospective analysis on the clinical and follow-up data of 74 elderly patients with NSCLC who underwent uniportal VATS between January 2015 and January 2020. One-to-one propensity score matching (PSM) was employed to select 71 elderly patients with NSCLC who underwent multiportal video-assisted thoracoscopic lobectomy (multiportal VATS) during the same period. RESULTS: The baseline characteristics of the two patient groups were comparable, with no statistically significant differences in postoperative complications, operation time, conversion to thoracotomy, or lymph node dissection. The amount of intraoperative blood loss and postoperative pain were lower in the uniportal VATS group than in the multiportal VATS group. The 3-year overall survival and disease-free survival of the two groups were similar. CONCLUSIONS: Uniportal VATS achieved similar short- and medium-term outcomes as Multiportal VATS in elderly patients with NSCLC.

Cauliflower mosaic virus P6 Dysfunctions Histone Deacetylase HD2C to Promote Virus Infection.

Histone deacetylases (HDACs) are vital epigenetic modifiers not only in regulating plant development but also in abiotic- and biotic-stress responses. Though to date, the functions of HD2C-an HD2-type HDAC-In plant development and abiotic stress have been intensively explored, its function in biotic stress remains unknown. In this study, we have identified HD2C as an interaction partner of the Cauliflower mosaic virus (CaMV) P6 protein. It functions as a positive regulator in defending against CaMV infection. The hd2c mutants show enhanced susceptibility to CaMV infection. In support, the accumulation of viral DNA, viral transcripts, and the deposition of histone acetylation on the viral minichromosomes are increased in hd2c mutants. P6 interferes with the interaction between HD2C and HDA6, and P6 overexpression lines have similar phenotypes with hd2c mutants. In further investigations, P6 overexpression lines, together with CaMV infection plants, are more sensitive to ABA and NaCl with a concomitant increasing expression of ABA/NaCl-regulated genes. Moreover, the global levels of histone acetylation are increased in P6 overexpression lines and CaMV infection plants. Collectively, our results suggest that P6 dysfunctions histone deacetylase HD2C by physical interaction to promote CaMV infection.

Alpha-fetoprotein/endoplasmic reticulum stress signaling mitigates injury in hepatoma cells.

Alpha-fetoprotein (AFP) and endoplasmic reticulum (ER) stress play multiple roles in hepatocellular carcinoma. Here, we analyzed the crosstalk between AFP and ER stress in human hepatoma cells. We induced ER stress in human hepatoma cell lines (HepG2 and SK-Hep1 cells) with thapsigargin (TG, an ER stress inducer), and mitigated ER stress with 4-phenylbutyrate acid (4-PBA, an ER stress inhibitor). AFP expression was knocked down by AFP short hairpin RNA and rescued by the pCI-AFP vector. AFP expression and ER stress were examined, and their roles in apoptosis, necroptosis, and proliferation were analyzed. TG significantly induced ER stress, apoptosis, necroptosis, and intracellular AFP protein levels, and reduced proliferation and AFP mRNA expression as well as supernatant AFP protein levels in HepG2 and SK-Hep1 cells. 4-PBA pretreatment partially reversed those changes in HepG2 cells. By contrast to AFP overexpression, knockdown of AFP significantly exacerbated TG-induced ER stress, apoptosis, and necroptosis, and decreased proliferation and the expression of activating transcription factor 6 alpha. In conclusion, ER stress causes the accumulation of AFP protein, which may be related to the reduction of AFP secretion. Accumulated AFP mitigates apoptosis and necroptosis and restores the proliferation of hepatoma cells by reducing ER stress.

Effectiveness of focused ultrasound for high risk human papillomavirus infection-related cervical lesions.

OBJECTIVE: The purpose of this study was to compare the efficacy of focused ultrasound (FU) and interferon drug therapy for cervical intraepithelial neoplasia 1 (CIN1) and chronic cervicitis associated with high risk human papillomavirus (HR-HPV) infection, as well as analyze the influencing factors. METHODS: A retrospective cohort study was performed from January 2017 to December 2019. A total of 592 patients were enrolled, of which 300 patients were treated with FU and 292 patients were treated with interferon drugs. Kaplan-Meier curves and a COX regression model were used to compare the curative effects of the two therapeutic methods using HR-HPV clearance as the main outcome. The relationship between age, HR-HPV infection type, pathological type, preoperative HR-HPV status and HR-HPV clearance were also analyzed. RESULTS: The median time for HR-HPV clearance was 6.00 months (95% CI: 5.24-6.76) in the FU group and 26.00 months (95% CI: 22.32-29.68) in the medication group. A significant difference was observed between the two groups (χ2 =198.902, p = 0.000). The HR-HPV clearance rate was 4.927 (95% CI 3.840-6.321; p = 0.000) times higher in the patients treated with FU than those treated with interferon drugs. In the FU group, no significant difference was observed in HR-HPV clearance rate between CIN1 and chronic cervicitis (χ2=0.660, p = 0.416), which was also insignificant between HR-HPV persistent and non-persistent infections (χ2=0.751, p = 0.386). CONCLUSION: FU therapy can eliminate HR-HPV infections in a short period of time. Moreover, the treatment efficacy of FU was significantly superior to that of interferon drugs.

Cysteine-Rich Intestinal Protein 1 Served as an Epithelial Ovarian Cancer Marker via Promoting Wnt/ß-Catenin-Mediated EMT and Tumour Metastasis.

OBJECTIVE: To explore the expression, functions, and the possible mechanisms of cysteine-rich intestinal protein 1 (CRIP1) in epithelial ovarian cancer. METHODS: Using open microarray datasets from The Cancer Genome Atlas (TCGA), we identified the tumorigenic genes in ovarian cancer. Then, we detected CRIP1 expression in 26 pairs of epithelial ovarian cancer tissue samples by immunohistochemistry (IHC) and performed a correlation analysis between CRIP1 and the clinicopathological features. In addition, epithelial ovarian cancer cell lines A2780 and OVCAR3 were used to examine CRIP1 expression by western blot and qRT-PCR. Various cell function experiments related to tumorigenesis were performed including the CCK8 assay, EdU, Annexin V-FITC/PI apoptosis assay, wound healing, and Transwell assay. In addition, the expression of epithelial-mesenchymal transition (EMT) markers was detected by western blot to illustrate the relationship between CRIP1 and EMT. Furthermore, KEGG pathway enrichment analysis and western blot were conducted to reveal the signaling pathways in which CRIP1 is involved in ovarian cancer pathogenesis. RESULTS: CRIP1 was identified as an oncogene from the TCGA database. The IHC score demonstrated that the CRIP1 protein was expressed at a higher level in tumours than in tumour-adjacent tissues and was associated with a higher pathological stage, grade, and positive lymphatic metastasis. In cell models, CRIP1 was overexpressed in serous epithelial ovarian cancer. Cell function experiments showed that the knockdown of CRIP1 did not significantly affect cell proliferation or apoptosis but could exert an inhibitory effect on cell migration and invasion, and also induce changes in EMT markers. Furthermore, KEGG pathway enrichment analysis and western blot showed that CRIP1 could induce ovarian cancer cell metastasis through activation of the Wnt/ß-catenin pathway. CONCLUSION: This study is the first to demonstrate that CRIP1 acts as an oncogene and may promote tumour metastasis by regulating the EMT-related Wnt/ß-catenin signaling pathway, suggesting that CRIP1 may be an important biomarker for ovarian cancer metastasis and progression.