UFMylation of HRD1 regulates endoplasmic reticulum homeostasis.

Ubiquitin fold modifier 1 is a small ubiquitin-like protein modifier that is essential for embryonic development of metazoans. Although UFMylation has been connected to endoplasmic reticulum homeostasis, the underlying mechanisms and the relevant cellular targets are largely unknown. Here, we show that HRD1, a ubiquitin ligase of ER-associated protein degradation (ERAD), is a novel substrate of UFM1 conjugation. HRD1 interacts with UFMylation components UFL1 and DDRGK1 and is UFMylated at Lys610 residue. In UFL1-depleted cells, the stability of HRD1 is increased and its ubiquitination modification is reduced. In the event of ER stress, the UFMylation and ubiquitination modification of HRD1 is gradually inhibited over time. Alteration of HRD1 Lys610 residue to arginine impairs its ability to degrade unfolded or misfolded proteins to disturb protein processing in ER. These results suggest that UFMylation of HRD1 facilitates ERAD function to maintain ER homeostasis.

Effect of COVID-19 outbreak on the treatment time of patients with acute ST-segment elevation myocardial infarction.

OBJECTIVE: To explore the effect of COVID-19 outbreak on the treatment time of patients with ST-segment elevation myocardial infarction (STEMI) in Hangzhou, China. METHODS: We retrospectively reviewed the data of STEMI patients admitted to the Hangzhou Chest Pain Center (CPC) during a COVID-19 epidemic period in 2020 (24 cases) and the same period in 2019 (29 cases). General characteristics of the patients were recorded, analyzed, and compared. Moreover, we compared the groups for the time from symptom onset to the first medical contact (SO-to-FMC), time from first medical contact to balloon expansion (FMC-to-B), time from hospital door entry to first balloon expansion (D-to-B), and catheter room activation time. The groups were also compared for postoperative cardiac color Doppler ultrasonographic left ventricular ejection fraction (LVEF),the incidence of major adverse cardiovascular and cerebrovascular events (MACCE),Kaplan-Meier survival curves during the 28 days after the operation. RESULTS: The times of SO-to-FMC, D-to-B, and catheter room activation in the 2020 group were significantly longer than those in the 2019 group (P < 0.05). The cumulative mortality after the surgery in the 2020 group was significantly higher than the 2019 group (P < 0.05). CONCLUSION: The pre-hospital and in-hospital treatment times of STEMI patients during the COVID-19 epidemic were longer than those before the epidemic. Cumulative mortality was showed in Kaplan-Meier survival curves after the surgery in the 2020 group was significantly different higher than the 2019 group during the 28 days.The diagnosis and treatment process of STEMI patients during an epidemic should be optimized to improve their prognosis.

Efficacy and safety of left atrial appendage occlusion in atrial fibrillation patients with chronic kidney disease: a systematic review and meta-analysis.

Atrial fibrillation (AF) is the most common arrhythmia among the elderly, and more frequently occur in those with chronic kidney disease (CKD). Left atrial appendage occlusion (LAAO) is used as a mechanical alternative approach for prevention of AF-related thromboembolisms. This meta-analysis was conducted to provide suggestions for the clinical application of LAAO in AF patients with CKD. The incidence of perioperative adverse events and other clinical effects after operation was by a single rate meta-analysis. Results showed that incidence of adverse events in the perioperative period after LAAO was generally low, with only pericardial effusion / tamponade (1.90%) and mortality rate (1.10%). During the follow-up period, the incidence of stroke/transient ischemic attack (TIA) and bleeding were 2.17% and 4.53%, respectively. A low incidence rate of adverse events was found in the perioperative period following LAAO. These results indicate that LAAO more effectively prevents the occurrence of stroke/TIA and minimizes bleeding events than oral anticoagulants.

Effect of CD14 polymorphisms on the risk of cardiovascular disease: evidence from a meta-analysis.

BACKGROUND: CD14 polymorphisms are associated with an increased risk of cardiovascular events. So far, many studies have been conducted, whereas the results were not always consistent. MATERIALS AND METHODS: Twenty-six articles involving thirty-seven datasets were recruited to evaluate the association between rs2569190 (9413 patients and 7337 controls), C-159T (4813 patients and 2852 controls) polymorphisms and cardiovascular diseases in a meta-analysis. The random or fixed effect models were used to evaluate the pooled odds ratios (ORs) and their corresponding 95% confidence intervals. RESULTS: The strongest association was observed between rs2569190 and CVD in overall population (T vs. C, OR = 1.169, 95% CI: 1.087-1.257, p = 2.44 × 10- 5). Analysis after stratification by ethnicity indicated that rs2569190 was related to CVD in East Asian population (T vs. C, OR = 1.370, 95% CI; 1.226-1.531, p = 2.86 × 10- 8) and a potential relationship in European (T vs. C, OR = 1.100, 95% CI: 1.019-1.189, p = 0.015). In the stratification of endpoints, the associations were found in CHD subgroup (T vs. C, OR = 1.357, 95% CI: 1.157-1.592, p = 2.47 × 10- 7) and in AMI subgroup (T vs. C, OR = 1.152, 95% CI: 1.036-1.281, p = 0.009). However, we did not find any association between C-159T polymorphism with cardiovascular disease under any model. CONCLUSIONS: The SNP rs2569190 significantly contribute to susceptibility and development of cardiovascular disease, particularly in the East Asian population and in the subtype CHD group, in addition, a potential association was observed in the AMI group, T allele acts as a risk factor for cardiovascular disease.

Pneumomediastinum and pneumoperitoneum on computed tomography after peroral endoscopic myotomy (POEM): postoperative changes or complications?

BACKGROUND: Many of the acute alterations after peroral endoscopic myotomy (POEM) may be of little clinical significance, while others may herald major clinical problems. The question whether pneumomediastinum/pneumoperitoneum is a normal postoperative finding after POEM, or should be regarded as a sign of a complication needs to be evaluated. Familiarity with these findings in computed tomography (CT) is essential for radiologists. PURPOSE: To evaluate whether or not pneumomediastinum/pneumoperitoneum detected by chest CT is a sign of a complication after POEM using CO2 insufflation for esophageal achalasia. MATERIAL AND METHODS: One hundred and eight patients with esophageal achalasia who underwent chest CT within 30 hours after POEM were included. CT findings were retrospectively reviewed by two radiologists in consensus. The correlation between pneumomediastinum and/or pneumoperitoneum shown on CT and the development of complications was analyzed. RESULTS: Abnormal findings were identified on post-treatment CT, including pneumomediastinum and/or pneumoperitoneum (53.7%, 58/108), pneumothorax (0.9%, 1/108), subcutaneous emphysema (29.6%, 32/108), pleural effusion (69.4%, 75/108), segmental atelectasis of lung tissue (29.6%, 32/108), minor inflammation of lungs (69.4%, 75/108), and ascites (0.9%, 1/108). Pneumomediastinum and pneumoperitoneum were observed simultaneously in 29 cases. The incidence rate of mild complications was high (79.6%, 86/108), while the rate of severe complications was low (2.8%, 3/108). There was no significant correlation between the occurrence of pneumomediastinum and/or pneumoperitoneum on CT and the development of complications (P = 0.542), or the development of severe complications including delayed hemorrhage, esophageal perforation, and retroperitoneal abscess. CONCLUSION: Pneumomediastinum and pneumoperitoneum detected by CT occur frequently after POEM and may be regarded as normal postoperative changes.

LncRNA AFAP1-AS1 Promotes Oral Squamous Cell Carcinoma Development by Ubiquitin-Mediated Proteolysis.

BACKGROUND AND PURPOSE: Long noncoding RNA (lncRNA) dysregulation has been reported to play a pivotal role in the development of cancers. In this study, we aimed to screen the key lncRNA in oral squamous cell carcinoma (OSCC) via bioinformatics analysis and further validate the function of lncRNA in vitro and in vivo. METHODS: Bioinformatics analysis was conducted to identify differentially expressed lncRNAs between control and OSCC samples. Quantitative real-time-polymerase chain reaction was employed to detect the expression of differentially expressed lncRNAs in human tongue squamous cell carcinoma and human oral keratinocytes cell lines. The biological function of lncRNA and its mechanism were examined via the experimental assessment of the cell lines with the lncRNA overexpressed and silenced. Additionally, to further explore the function of lncRNA in the progression of OSCC, xenograft tumour mouse models were established using 25 mice (5 groups, each with 5 mice). Tumour formation was observed at 2 weeks after the cell injection, and the tumours were resected at 5 weeks post-implantation. RESULTS: Two lncRNAs, LINC00958 and AFAP1-AS1, were found to be correlated with the prognosis of OSCC. The results of the quantitative real-time-polymerase chain reaction indicated that the 2 lncRNAs were highly expressed in OSCC. In combination with the previous literature, we found AFAP1-AS1 to be a potentially important biomarker for OSCC. Thus, we further investigated its biological function and found that AFAP1-AS1 silencing inhibited cell proliferation, migration, and invasion whereas AFAP1-AS1 overexpression reversed the effect of AFAP1-AS1 silencing (P < .05). Mechanism analysis revealed that AFAP1-AS1 regulated the development of OSCC through the ubiquitin-mediated proteolysis pathway. CONCLUSIONS: AFAP1-AS1 is an oncogene that aggravates the development of OSCC via the ubiquitin-mediated proteolysis pathway. It also provides a novel potential therapy for OSCC.

[Expression and clinicopathological significance of serine-257/threonine-261 phosphorylated MKK4 in colorectal carcinoma].

OBJECTIVE: As an activator of JNK and p38, phosphorylated MKK4 is considered to be associated with tumor progression and prognosis. This study was to examine the expression of pMKK4 and evaluate its prognostic significance in colorectal carcinoma. METHODS: A total of 343 cases of colorectal cancer were followed up to analyze the associations between the expression of pMKK4 and various clinicopathological factors. The expression of Serine-257/Threonine-261 pMKK4 was detected immunohistochemically by tissue microarray. RESULTS: The staining of pMKK4 was present in cytoplasm of colorectal carcinoma. And the expression of pMKK4 was correlated with invasion depth (P = 0.003), differentiation (P = 0.018), lymph node metastasis (P < 0.001), metastasis (P < 0.001), hepatic metastasis (P = 0.039) and TNM stage (P < 0.001). The patients with strong pMKK4 staining had a better overall survival than those with lowered levels (Log rank = 4.531, P = 0.033). Univariate analysis indicated that the expression of pMKK4 was correlated with either overall survival (HR = 0.785, P = 0.035) or relapse-free survival (HR = 0.788, P = 0.044). In multivariate analysis, there was no prognostic significance of pMKK4 after adjusting for invasion depth, differentiation, lymph node metastasis, metastasis, liver metastasis and TNM stage. CONCLUSIONS: The down-regulation of S257/T261 pMKK4 is associated with more advanced stages and it plays an important role in tumor progression. A high-level expression of pMKK4 indicates favorable clinical outcomes, but it is not an independent predictor.

The diagnostic value of electrocardiogram-based machine learning in long QT syndrome: a systematic review and meta-analysis.

Introduction: To perform a meta-analysis to discover the performance of ML algorithms in identifying Congenital long QT syndrome (LQTS). Methods: The searched databases included Cochrane, EMBASE, Web of Science, and PubMed. Our study considered all English-language studies that reported the detection of LQTS using ML algorithms. Quality was assessed using QUADAS-2 and QUADAS-AI tools. The bivariate mixed effects models were used in our study. Based on genotype data for LQTS, we performed a subgroup analysis. Results: Out of 536 studies, 8 met all inclusion criteria. The pooled area under the receiving operating curve (SAUROC) for detecting LQTS was 0.95 (95% CI: 0.31-1.00); sensitivity was 0.87 (95% CI: 0.83-0.90), and specificity was 0.91 (95% CI: 0.88-0.93). Additionally, diagnostic odd ratio (DOR) was 65 (95% CI: 39-109). The positive likelihood ratio (PLR) was 9.3 (95% CI: 7.0-12.3) and the negative likelihood ratio (NLR) was 0.14 (95% CI: 0.11-0.20), with very low heterogeneity (I2 = 16%). Discussion: We found that machine learning can be used to detect features of rare cardiovascular disease like LQTS, thus increasing our understanding of intelligent interpretation of ECG. To improve ML performance in the classification of LQTS subtypes, further research is required. Systematic Review Registration: identifier PROSPERO CRD42022360122.

Comparison of depressive symptoms among healthcare workers in high-risk versus low-risk areas during the first month of the COVID-19 pandemic in China.

Introduction: The psychological health of healthcare workers (HCWs) has become a significant concern, particularly during the initial stage of a pandemic. This study compared the depressive symptoms among HCWs in high-risk areas (HRAs) and low-risk areas (LRAs) with matching demographics. Methods: A cross-sectional study was employed to compare the depressive symptoms (Patient Health Questionnaire score ≥ 10), workplace environment characteristics, the Health Belief Model (HBM) and socio-demographics of the HCWs working in HRAs and LRAs in several accessible regions (mainly Hubei Province and Guangdong-Hong Kong-Macao Greater-Bay-Area) in China. Eight hundred eighty-five HCWs were recruited for unmatched analysis between March 6 and April 2, 2020. After matching with occupation and years of service using a 1:2 ratio, 146 HCWs in HRAs and 290 HCWs in LRAs were selected for matched analysis. Subgroup analyzes were performed using two individual logistic regressions to delineate the associated factors in LRAs and HRAs, respectively. Results: HCWs in LRAs (Prevalence = 23.7%) had 1.96 times higher odds of depressive symptoms than those in HRAs (Prevalence = 15.1%) after adjusting for occupation and years of service (p < 0.001). Significant differences in workplace environment characteristics (p < 0.001) and the 5-dimension of the HBM of HCWs (p < 0.001 to p = 0.025) were found between HRAs and LRAs.Logistic regression showed that workers with years of service between 10 and 20 years (OR:6.27), ever had contact with COVID-19 patients (OR:14.33) and had higher scores of "perceived barrier" of HBM (OR:4.48) predicted depressive symptoms in HRAs while working in pneumology departments and infectious disease units (OR:0.06), and high "self-efficacy" in the HBM (OR:0.13) was a protective factor against depressive symptoms.Contrarily, in LRAs, those HCWs who worked in ICUs (OR:2.59), had higher scores of "perceived susceptibility toward the COVID-19 outbreak" (OR:1.41), "perceived severity of the pandemic" (OR:1.25), and "perceived barriers of wearing masks" (OR:1.43) in the HBM predicted depressive symptoms. High "cues to action" (OR:0.79), and better "knowledge" (OR:0.79) in the HBM were protective factors against depressive symptoms. Conclusion: The risk of depressive symptoms of HCWS was double in LRAs than in HRAs in the first month of the COVID-19 pandemic. Furthermore, salient predictors for depressive symptoms among HCWs in HRAs and LRAs were very different.

Impact of image integration on catheter ablation for atrial fibrillation using three-dimensional electroanatomic mapping: a meta-analysis.

BACKGROUND: Studies comparing the procedural and clinical outcomes of catheter ablation for atrial fibrillation (AF) guided by CartoMerge and that by Carto have achieved mixed results (Carto, Biosense Webster, Diamond Bar, CA, USA). We collected these studies and conducted a meta-analysis to determine whether CartoMerge results in better procedural and clinical outcomes. METHODS AND RESULTS: Three randomized controlled trials and two controlled observational studies were collected for analysis. The clinical and procedural outcomes of interest were AF recurrence after catheter ablation, major complications, procedure durations, and fluoroscopy time. Meta-analysis was performed using RevMan 5.0.18 software (The Cochrane Collaboration, Copenhagen, Denmark) and pooled estimates of effect were reported as risk ratios with 95% confidence intervals (CI). The overall results of this meta-analysis indicate that catheter ablation for AF guided by CartoMerge is insignificantly associated with a decreased risk of recurrences (RR = 0.76; 95% CI: 0.55-1.04; P = 0.09) and major complications (RR = 0.73; 95% CI: 0.37-1.45; P = 0.37) compared with that by Carto. CONCLUSION: The image integration using CartoMerge guiding catheter ablation for AF does not improve the main clinical outcomes significantly compared with that by Carto in centers with experienced operators.

Transanal total mesorectal excision combined with intersphincteric resection has similar long-term oncological outcomes to laparoscopic abdominoperineal resection in low rectal cancer: a propensity score-matched cohort study.

Background: Transanal total mesorectal excision (taTME) or intersphincteric resection (ISR) has recently proven to be a valid and safe surgical procedure for low rectal cancer. However, studies focusing on the combination of these two technologies are limited. This study aimed to evaluate perioperative results, long-term oncologic outcomes, and anorectal functions of patients with low rectal cancer undergoing taTME combined with ISR, by comparing with those of patients undergoing laparoscopic abdominoperineal resection (laAPR). Methods: After 1:1 propensity score matching, 200 patients with low rectal cancer who underwent laAPR (n = 100) or taTME combined with ISR (n = 100) between September 2013 and November 2019 were included. Patient demographics, clinicopathological characteristics, oncological outcomes, and anal functional results were analysed. Results: Patients in the taTME-combined-with-ISR group had less intraoperative blood loss (79.6 ± 72.6 vs 107.3 ± 65.1 mL, P = 0.005) and a lower rate of post-operative complications (22.0% vs 44.0%, P < 0.001) than those in the laAPR group. The overall local recurrence rates were 7.0% in both groups within 3 years after surgery. The 3-year disease-free survival rates were 86.3% in the taTME-combined-with-ISR group and 75.1% in the laAPR group (P = 0.056), while the 3-year overall survival rates were 96.7% and 94.2%, respectively (P = 0.319). There were 39 patients (45.3%) in the taTME-combined-with-ISR group who developed major low anterior resection syndrome, whereas 61 patients (70.9%) had good post-operative anal function (Wexner incontinence score ≤ 10). Conclusion: We found similar long-term oncological outcomes for patients with low rectal cancer undergoing laAPR and those undergoing taTME combined with ISR. Patients receiving taTME combined with ISR had acceptable post-operative anorectal function.

Exploring the impact of the COVID-19 epidemic on the medical emergency calls and calls for cardiovascular diseases in Hangzhou, China.

AIMS: We aimed to evaluate the impact of the COVID-19 epidemic on emergency and cardiovascular disease-related calls in Hangzhou, China. METHODS: We conducted a single-center retrospective study, collecting data on emergency calls to the Hangzhou Emergency Center (HEC) during the COVID-19 epidemic (January 20, 2020, to March 15, 2020). Data were compared with the same period in 2019. RESULTS: Compared to 2019, the number of emergency calls has dropped by 21.63%, ambulance calls by 29.02%, rescue calls by 22.57%, and cardiovascular disease-related emergency calls by 32.86%. The numbers of emergency, ambulance, and rescue calls in 2020 were significantly lower than in 2019. CONCLUSIONS: During the COVID-19 epidemic in Hangzhou, the numbers of emergency and cardiovascular disease-related calls have decreased significantly. These results point to a severe social problem that requires the attention of the medical community and the government.

Protective effects of the aqueous extract of Scutellaria baicalensis against acrolein-induced oxidative stress in cultured human umbilical vein endothelial cells.

CONTEXT: Scutellaria baicalensis Georgi (Labiatae) (SbG), one of the fifty fundamental herbs of Chinese herbology, has been reported to have anti-asthmatic, antifungal, antioxidative, and anti-inflammatory activities. OBJECTIVE: This study was designed to determine the protective effects of the extract of SbG against the acrolein-induced oxidative stress in cultured human umbilical vein endothelial cells (HUVEC). MATERIALS AND METHODS: The MTT reduction assay was employed to determine cell viability. The total cellular glutathione (GSH) level was detected using a colorimetric GSH assay kit. Cellular GSH production was conducted by detecting the mRNA expression levels of γ-glutamylcysteine ligase catalytic subunit and modifier subunit. RESULTS: Concentration-dependent cytotoxic effects of acrolein were observed while SbG could effectively protect the acrolein-induced oxidative damage. The protective mechanism was investigated, showing that the increased GSH content in the SbG-incubated HUVE cells was associated with the protective effects of SbG-treated cells. Further RT-PCR data confirmed the elevated mRNA expressions of GSH synthesis enzymes. DISCUSSION AND CONCLUSION: The current study strongly indicated that SbG could be a potential antioxidant against oxidative stress in treating cardiovascular diseases.

Screening the Influence of Biomarkers for Metabolic Syndrome in Occupational Population Based on the Lasso Algorithm.

Aim: Metabolic syndrome (MS) screening is essential for the early detection of the occupational population. This study aimed to screen out biomarkers related to MS and establish a risk assessment and prediction model for the routine physical examination of an occupational population. Methods: The least absolute shrinkage and selection operator (Lasso) regression algorithm of machine learning was used to screen biomarkers related to MS. Then, the accuracy of the logistic regression model was further verified based on the Lasso regression algorithm. The areas under the receiving operating characteristic curves were used to evaluate the selection accuracy of biomarkers in identifying MS subjects with risk. The screened biomarkers were used to establish a logistic regression model and calculate the odds ratio (OR) of the corresponding biomarkers. A nomogram risk prediction model was established based on the selected biomarkers, and the consistency index (C-index) and calibration curve were derived. Results: A total of 2,844 occupational workers were included, and 10 biomarkers related to MS were screened. The number of non-MS cases was 2,189 and that of MS was 655. The area under the curve (AUC) value for non-Lasso and Lasso logistic regression was 0.652 and 0.907, respectively. The established risk assessment model revealed that the main risk biomarkers were absolute basophil count (OR: 3.38, CI:1.05-6.85), platelet packed volume (OR: 2.63, CI:2.31-3.79), leukocyte count (OR: 2.01, CI:1.79-2.19), red blood cell count (OR: 1.99, CI:1.80-2.71), and alanine aminotransferase level (OR: 1.53, CI:1.12-1.98). Furthermore, favorable results with C-indexes (0.840) and calibration curves closer to ideal curves indicated the accurate predictive ability of this nomogram. Conclusions: The risk assessment model based on the Lasso logistic regression algorithm helped identify MS with high accuracy in physically examining an occupational population.

COVID-19 Vaccination Acceptance Among Healthcare Workers and Non-healthcare Workers in China: A Survey.

Background: The coronavirus pneumonia is still spreading around the world. Much progress has been made in vaccine development, and vaccination will become an inevitable trend in the fight against this pandemic. However, the public acceptance of COVID-19 vaccination still remains uncertain. Methods: An anonymous questionnaire was used in Wen Juan Xing survey platform. All the respondents were divided into healthcare workers and non-healthcare workers. Multinomial logistic regression analyses were performed to identify the key sociodemographic, cognitive, and attitude associations among the samples of healthcare workers and non-healthcare workers. Results: A total of 2,580 respondents completed the questionnaire, including 1,329 healthcare workers and 1,251 non-healthcare workers. This study showed that 76.98% of healthcare workers accepted the COVID-19 vaccine, 18.28% workers were hesitant, and 4.74% workers were resistant. Among the non-healthcare workers, 56.19% workers received the COVID-19 vaccine, 37.57% workers were hesitant, and 6.24% workers were resistant. Among the healthcare workers, compared with vaccine recipients, vaccine-hesitant individuals were more likely to be female (AOR = 1.52, 95% CI: 1.12-2.07); vaccine-resistant individuals were more likely to live in the suburbs (AOR = 2.81, 95% CI: 1.44-3.99) with an income of 10,000 RMB or greater (AOR = 2.00, 95% CI: 1.03-3.90). Among the non-healthcare workers, vaccine-hesitant individuals were more likely to be female (AOR = 1.66, 95% CI: 1.31-2.11); vaccine-resistant individuals were also more likely to be female (AOR = 1.87, 95% CI: 1.16-3.02) and older than 65 years (AOR = 4.96, 95% CI: 1.40-7.62). There are great differences between healthcare workers and non-healthcare workers in their cognition and attitude toward vaccines. Conclusions: Our study shows that healthcare workers are more willing to be vaccinated than non-healthcare workers. Current vaccine safety issues continue to be a major factor affecting public acceptance, and to expand vaccine coverage in response to the COVID-19 pandemic, appropriate vaccination strategies and immunization programs are essential, especially for non-healthcare workers.

Overview on new progress of hereditary diffuse gastric cancer with CDH1 variants.

Hereditary diffuse gastric cancer (HDGC), comprising 1%-3% of gastric malignances, has been associated with CDH1 variants. Accumulating evidence has demonstrated more than 100 germline CDH1 variant types. E-cadherin encoded by the CDH1 gene serves as a tumor suppressor protein. CDH1 promoter hypermethylation and other molecular mechanisms resulting in E-cadherin dysfunction are involved in the tumorigenesis of HDGC. Histopathology exhibits characteristic signet ring cells, and immunohistochemical staining may show negativity for E-cadherin and other signaling proteins. Early HDGC is difficult to detect by endoscopy due to the development of lesions beneath the mucosa. Prophylactic gastrectomy is the most recommended treatment for pathogenic CDH1 variant carriers. Recent studies have promoted the progression of promising molecular-targeted therapies and management strategies. This review summarizes recent advances in CDH1 variant types, tumorigenesis mechanisms, diagnosis, and therapy, as well as clinical implications for future gene therapies.

Extraovarian Brenner tumor in the uterus: a case report and review of literature.

BACKGROUND: Extraovarian Brenner tumors (EOBTs) are extremely rare and can be observed incidentally in both female and male patients, raising concerns regarding the origin of Brenner tumors. CASE PRESENTATION: A 53-year-old postmenopausal woman presented with a nodular lesion in the left side of the corpus uteri, which was found at a routine health check. Macroscopically, the lesion appeared as a solid nodule with a yellowish-gray cut surface, approximately 6 cm in greatest diameter. Microscopically, the lesion consisted of well-defined epithelial nests and spindled stromal cells. Parenchymal cells expressed CK7, GATA3, CK5/6, 34ßE12, and p63. A single layer of cavity-lined cells with umbrella-like shape showed apical Uroplakin III positivity. Stromal cells were positive for SMA, ER, and PR. The final diagnosis was EOBT and the patient was followed for 2 months with no recurrence. CONCLUSIONS: We report here the third case of EOBTs in the uterus. The combination of morphologic and immunohistochemical results supported the involvement of urothelial metaplasia in the development of EOBTs. The similarities between EOBTs and Walthard nests made Müllerian epithelium an attractive candidate as the cellular origin. Changes of tissue structure or sex hormones imbalance may lead to the translocation of Müllerian remnants to distant organs, explaining the pathogenesis of EOBTs.

The impact of Community intervention on the time from Symptom onset to first medical contact with acute coronary syndrome.

OBJECTIVE: Patient delay in the recognition of and response to the symptoms of acute coronary syndrome (ACS) is a worldwide problem. A community education program about chest pain was implemented in China, and was aimed at providing better community intervention. In this study, the impact of this program on the time of symptom onset to the first medical contact (SO-to-FMC) in ACS patients was investigated, as was the incidence of major adverse cardiac and cerebrovascular events (MACCE) in these patients. METHODS: A total of 10 local communities were included in this study. A 9-month intensive community education program about chest pain was conducted in these communities. The data on the demographics, mode of transportation, procedures, clinical outcomes, and discharge diagnoses of all ACS patients in these communities were collected. RESULTS: The study communities had a combined population of 361,609, and all community population sizes ranged from 12,823 to 66,127. The average SO-to-FMC time of the control period was 510 min, whereas, following community intervention, the average SO-to-FMC time was 256 min (P <  0.001). Furthermore, comparative analyses revealed that, following discharge from the hospital, the 1.5-year MACCE-free survival rate was higher in the community intervention group than in the control group (95.0 % vs. 90.5 %, P =  0.025), and the 1.5-year mortality rate was lower in the community intervention group than in the control group (3.3 % vs. 6.3 %, P =  0.03). CONCLUSIONS AND PRACTICAL IMPLICATIONS: The Hangzhou Chest Pain Science Education Project(HCPSEP) was found to reduce the SO-to-FMC time and improve the outcome of ACS patients. This indicates that a scientific, educational program on chest pain can be effective in improving the knowledge and alertness of the local residents about chest pain. This type of program may be recognized and carried out in other regions.

Epithelioid sarcoma of the scalp: a case report and literature review.

Epithelioid sarcoma (ES) is an aggressive mesenchymal tumor exhibiting bi-directional phenotypes. According to its proclivity for different sites, ES can be subdivided into two categories: distal and proximal variants. Proximal ES often affects the truncal tissue, thighs, head, and neck. Accumulating evidence indicates that several locations in the head, including the orbital, gingival, and nasal cavities, are involved in ES. However, the underlying mechanisms of ES carcinogenesis and progression are largely unknown, including and especially the reason why the tumor cells are positive for both epithelial and mesenchymal classical markers. Thus, we wish to share a rare case of ES in the scalp and its clinical and molecular features. Only 9 cases to date have been reported. An 80-years-old man had sustained a painful swollen mass in his scalp for three months. A diagnosis of epithelioid sarcoma was established based on the combination of the histopathological and immunohistochemical findings. The tumor cells were positive for both mesenchymal (vimentin and S100) and epithelial markers (pan-cytokeratin). This case suggests that ES can be derived from the soft tissue of the scalp. The tumor cells co-expressed biomarkers of epithelial and mesenchymal cells, suggesting the mesenchymal-epithelial transition (MET) may be involved.

Relationship between alcohol use, blood pressure and hypertension: an association study and a Mendelian randomisation study.

BACKGROUND: Past studies have found a strong relationship between alcohol drinking and human health. METHODS: In this study, we first tested the association of rs671 with alcohol use in 2349 participants in southeast China. We then evaluated the causal impact between alcohol use and cardiovascular traits through a Mendelian randomisation (MR) analysis. RESULTS: We found strong evidence for the association of rs671 in the ALDH2 gene with alcohol drinking (p=6.08×10-47; ORadj G=4.50, 95% CI 3.67 to 5.52). We found that female G carriers of rs671 had a higher proportion of non-drinkers than male G carriers (88.01% vs 38.70%). In non-drinkers, the female G allele frequency was higher than the male G allele frequency (71.1% vs 55.2%). MR analysis suggested that alcohol use had a causal effect on blood pressure (increasing 9.46 mm Hg for systolic blood pressure (p=9.67×10-4) and 7.50 mm Hg for diastolic blood pressure (p=9.62×10-5)), and on hypertension in men (p=0.011; OR =1.19, 95% CI 1.04 to 1.36) and in pooled samples (p=0.013; OR =1.20, 95% CI 1.04 to 1.39), but not in women. We did not observe a causal effect of alcohol use on body mass index and lipid levels; further studies are needed to clarify the non-causal relationship. CONCLUSIONS: Compared to never-drinkers, current and previous alcohol use had a causal effect on blood pressure and hypertension in pooled samples and in men. These results reflect Chinese culture which does not encourage women to drink.