Prenatal LPS leads to increases in RAS expression within the PVN and overactivation of sympathetic outflow in offspring rats.

The renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) are two major blood pressure-regulating systems. The link between the renal and cerebral RAS axes was provided by reflex activation of renal afferents and efferent sympathetic nerves. There is a self-sustaining enhancement of the brain and the intrarenal RAS. In this study, prenatal exposure to lipopolysaccharide (LPS) led to increased RAS activity in the paraventricular nucleus (PVN) and overactivation of sympathetic outflow, accompanied by increased production of reactive oxygen species (ROS) and disturbances between inhibitory and excitatory neurons in PVN. The AT1 receptor blocker losartan and α2 adrenergic receptor agonist clonidine in the PVN significantly decreased renal sympathetic nerve activity (RSNA) and synchronously reduced systolic blood pressure. Prenatal LPS stimulation caused H3 acetylation at H3K9 and H3K14 in the PVN, which suggested that epigenetic changes are involved in transmitting the prenatal adverse stimulative information to the next generation. Additionally, melatonin treatment during pregnancy reduced RAS activity and ROS levels in the PVN; balanced the activity of inhibitory and excitatory neurons in the PVN; increased urine sodium secretion; reduced RSNA and blood pressure. In conclusion, prenatal LPS leads to increased RAS expression within the PVN and overactivation of the sympathetic outflow, thereby contributing to hypertension in offspring rats. Melatonin is expected to be a promising agent for preventing prenatal LPS exposure-induced hypertension.

Investigation on uniaxial compression and fracture damage mode of prefabricated parallel double-jointed red sandstone.

As a special type of joint fracture, the fracture evolution characteristics of parallel double joints have important engineering significance for the stability analysis of fractured rock mass. In this work, a new method for calculating stress intensity factor of parallel double-jointed fractures was importantly proposed. Physical uniaxial compression tests were carried out on parallel double jointed red sandstone filled with cement mortar under different geometric parameters, and the macroscopic mechanical properties and failure characteristics of red sandstone are deeply analyzed. The results show that the larger the connectivity rate is, the smaller the peak stress and strain are. The increase of connectivity rate will affect the change rate of transverse strain in the center of rock bridge. The closer the dip angle of the joint is, the lower the peak stress is and the shorter the failure time is. The damage mode of joint tip encroachment affects the lateral displacement of the rock bridge center, and the displacement is always close to the first damage section. The closer the joint tip is to the load, the easier the end-face penetrating cracks occur. The research content can provide basic support for guaranteeing the stability of underground engineering rock mass.

Effect of hyperbaric oxygen treatment on patients with heatstroke complicated by multiple organ dysfunction:A retrospective study.

Background: The benefits of hyperbaric oxygen (HBO) in treating animals with heat stroke (HS) have been established. This study aims to retrospectively analyze the effect of HBO on multiple organ dysfunction following HS in humans. Methods: Retrospective data were collected from patients with HS admitted to our hospital in the past 7 years. Patients were categorized into groups based on whether they received HBO therapy. The study compared various factors, including sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation-Ⅱ (APACHE-Ⅱ) scores, mortality rates, neurological function scores, serum myocardial enzyme levels, liver, kidney, and coagulation function indicators, blood routine results, electrolyte levels, and modified Barthel index (MBI) score for standard daily living ability before treatment and after 2 and 4 weeks of treatment. Results: The mortality rates in the HBO and control group were 0% and 8.49%, respectively. Upon admission, the HBO group had higher SOFA and APACHE-Ⅱ scores and lower neurological, coagulation, and liver functions than those of the control group. HBO treatment significantly improved SOFA, APACHE-Ⅱ, and neurological scores while relieving levels of alanine aminotransferase, aspartate aminotransferase, creatinine, and myocardial enzymes. Additionally, it mitigating lymphocyte and platelet count decline caused by HS. The MBI score was significantly enhanced after treatment in the HBO group. Conclusions: Clinical practice advocates administering HBO therapy to patients with severe illness, organ damage, and nerve impairment. Compared with conventional treatment, combined HBO therapy demonstrated superior efficacy in alleviating multiple organ dysfunction and improving daily living ability in patients with HS.

The efficacy of gastric aspiration in reducing postoperative vomiting after oral and maxillofacial surgery: A meta-analysis.

BACKGROUND: Gastric aspiration is applied in oral and maxillofacial procedures to reduce postoperative vomiting (POV), yet its clinical benefit remains largely uncertain. Our study aimed to determine the role of gastric aspiration in the amelioration of POV by a meta-analysis. METHODS: With adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, global recognized databases, including PubMed, Embase, and Cochrane Central, were searched to obtain randomized controlled trials (RCTs) investigating the effects of gastric aspiration in oral and maxillofacial surgery. The incidence and the number of episodes of POV and the frequency of rescue antiemetic use were extracted as parametric data for pooled estimation. Funnel plots and Egger's test were utilized to assess bias. The recommendation of evidence was rated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: After detailed evaluation, 5 RCTs containing 274 participants were eventually included. The results of pooled estimation indicated that gastric aspiration could not reduce the incidence of POV (risk ratio [95% CI] = 0.94 [0.73, 1.21], P = .621), the number of episodes of POV (standard mean difference [95% CI] = -0.13 [-0.45, 0.19], P = .431) or the frequency of rescue antiemetic use (RR [95% CI] = 0.86 [0.49, 1.52], P = .609). No publication bias was detected by the funnel plot and Egger test. The overall recommendation of evidence was rated low regarding each outcome. CONCLUSION: Based on current evidence, gastric aspiration is not recommended for oral and maxillofacial surgery. Meanwhile, more large-scale high-quality RCTs are needed.

The Pharyngeal Packs for Dental and Otolaryngological Surgery: A Meta-Analysis of High-Quality Randomized Controlled Trials.

Background: Pharyngeal packs are employed to mitigate postoperative nausea and vomiting (PONV) and have become prevalent in dental and otolaryngological surgeries. However, their clinical efficacy continues to be a topic of debate. The objective of the present study was to conduct a quantitative assessment of the impact of pharyngeal packing in dental and otolaryngological surgeries through meta-analysis. Methods: We identified relevant randomized controlled trials (RCTs) through systematic searches of online databases, including PubMed, Embase, and Cochrane Central. Potential eligible studies were evaluated using the Jadad scoring system (range 0-5 points), with only high-quality RCTs (3 points or more) being included. The incidence of PONV, morbidity, and the level of throat pain were aggregated and estimated. Publication bias was evaluated using funnel plot symmetry and the Egger test. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was utilized to rate the evidence. Results: Ten high-quality RCTs comprising 1026 participants were ultimately included. Subsequent quantitative pooled estimation unveiled that the utilization of pharyngeal packing did not lead to a significant reduction in the incidence of nausea (P = .272), vomiting (P = .775), overall PONV (P = .118), or throat pain (P = .149). By contrast, the application of pharyngeal packs was found to significantly increase the level of throat pain (P = .003). No obvious publication bias was detected, and the majority of evidence was rated high or moderate. Conclusion: Based on the existing evidence, we conclude that pharyngeal packing lacks clinical benefit and is not advised for dental and otolaryngological surgeries.

Construction and identification of lncRNA/circRNA-coregulated ceRNA networks in gemcitabine-resistant bladder carcinoma.

OBJECTIVES: To explore the regulatory networks that underlie the development of chemoresistance in bladder cancer. METHODS: We analyzed profiles of differentially expressed long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs) and messenger RNA (mRNAs) in gemcitabine-resistant/sensitive bladder cancer cells using next-generation sequencing data. RESULTS: Hundreds of differentially expressed lncRNAs and miRNAs and thousands of circRNAs and mRNAs were identified. Bioinformatics analysis revealed the chromosomal localizations, classification and coexpression of mRNAs, as well as candidates for cis and trans regulation by lncRNAs. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of differentially expressed mRNAs and circRNAs indicated important functional roles of coregulated RNAs, thus establishing competing endogenous RNA (ceRNA) and protein-protein interactions networks that may underlie chemoresistance in bladder cancer. We demonstrated that lncRNA LINP1 can act as a ceRNA by inhibiting miR-193a-5p to increase TP73 expression; and that lncRNA ESRG and hsa_circ_0075881 can simultaneously bind miR-324-3p to increase ST6GAL1 expression. Modulation of ceRNA network components using ablation and overexpression approaches contributed to gemcitabine resistance in bladder cancer cells. CONCLUSIONS: These results elucidate mechanisms by which lncRNAs and circRNAs coregulate the development of bladder cancer cell resistance to gemcitabine, thus laying the foundation for future research to identify biomarkers and disease targets.

Case Report: A MiT family translocation renal cell carcinoma in the renal pelvis, calyces and upper ureter misdiagnosed as upper tract urothelial carcinoma.

Background: Upper tract urothelial carcinoma (UTUC) is the most common urothelial malignancy in the renal pelvis or ureter. Renal pelvic carcinoma accounts for 90% of all tumours in the renal pelvis, so the mass in the renal pelvis is usually considered a UTUC. Renal cell carcinoma (RCC) in the renal pelvis, calyces and upper ureter is extremely rare, especially MiT family translocation RCC, which makes this case even more uncommon. Case presentation: We report the case of a 54-year-old man had intermittent painless gross haematuria with occasional blood clots and urodynia for 2 years. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) scan showed an enlarged left kidney, and a soft tissue mass was seen in the renal pelvis, calyces and upper ureter. The patient's urine-based cytology was positive three times. Due to the severity of the upper ureteral lumen stenosis, we did not perform pathological biopsy during ureteroscopy. In the current case, clinical symptoms, imaging examinations, urine-based cytology, and ureteroscopy were combined to obtain a preoperative diagnosis of UTUC. Therefore, robot-assisted laparoscopic left radical nephroureterectomy and retroperitoneal lymphadenectomy were performed. Unexpectedly, the patient was pathologically diagnosed with MiT family translocation RCC after surgery. The surgery was uneventful. There was no intestinal tube injury or other complications perioperatively. The postoperative follow-up was satisfactory. Conclusion: MiT family translocation RCC in the renal pelvis, calyces and upper ureter is extremely rare, and can be easily confused with UTUC, resulting in the expansion of surgical scope. Preoperative ureteroscopy and biopsy or tumour punch biopsy should be used to obtain accurate pathology as far as possible, and the selection of correct surgical method is conducive to a good prognosis for patients.

Case report: A rare case of synchronous mucinous neoplasms of the renal pelvis and the appendix.

Background: Mucinous neoplasms are tumors arising in the epithelial tissue, characterized by excessive mucin secretion. They mainly emerge in the digestive system and rarely in the urinary system. They also seldom develop in the renal pelvis and the appendix asynchronously or simultaneously. The concurrence of this disease in these two regions has not yet been reported. In this case report, we discuss the diagnosis and treatment of synchronous mucinous neoplasms of the right renal pelvis and the appendix. The mucinous neoplasm of the renal pelvis was preoperatively misdiagnosed as pyonephrosis caused by renal stones, and the patient underwent laparoscopic nephrectomy. Herein, we summarize our experience with this rare case in combination with related literature. Case presentation: In this case, A 64-year-old female was admitted to our hospital with persistent pain in the right lower back for over a year. Computer tomography urography (CTU) showed that the patient was confirmed as right kidney stone with large hydronephrosis or pyonephrosis, and appendiceal mucinous neoplasm (AMN). Subsequently, the patient was transferred to the gastrointestinal surgery department. Simultaneously, electronic colonoscopy with biopsy suggested AMN. Open appendectomy plus abdominal exploration was performed after obtaining informed consent. Postoperative pathology indicated low-grade AMN (LAMN) and the incisal margin of the appendix was negative. The patient was re-admitted to the urology department, and underwent laparoscopic right nephrectomy because she was misdiagnosed with calculi and pyonephrosis of the right kidney according to the indistinctive clinical symptoms, standard examination of the gelatinous material, and imaging findings. Postoperative pathology suggested a high-grade mucinous neoplasm of the renal pelvis and mucin residing partly in the interstitium of the cyst walls. Good follow-up results were obtained for 14 months. Conclusion: Synchronous mucinous neoplasms of the renal pelvis and the appendix are indeed uncommon and have not yet been reported. Primary renal mucinous adenocarcinoma is very rare, metastasis from other organs should be first considered, especially in patients with long-term chronic inflammation, hydronephrosis, pyonephrosis, and renal stones, otherwise, misdiagnosis and treatment delay may occur. Hence, for patients with rare diseases, strict adherence to treatment principles and close follow-up are necessary to achieve favorable outcomes.

Case report: Robot-assisted laparoscopic partial nephrectomy for renal cell carcinoma in a patient with situs inversus totalis and abdominal cocoon.

Background: Situs inversus totalis (SIT) is a congenital condition wherein organs in abdominal or thoracic cavity are mirrored from their normal positions. Abdominal cocoon, is a rare disease of unknown aetiology that is characterised by total or partial small intestine encapsulation by a compact fibrocollagenous membrane. Aside from having two extremely rare conditions (SIT and Abdominal cocoon), our patient developed renal cell carcinoma (RCC), which makes this case even more uncommon. Case Presentation: We report the case of a 64-year-old man who was admitted to our hospital with an extremely rare case of localized RCC in the left kidney complicated with SIT and abdominal cocoon. Computer tomography urography (CTU) and angiography (CTA) showed that the patient was confirmed as having SIT, for the space-occupying lesion in the left kidney, clear cell RCC (ccRCC) was considered, the lesion in the right kidney was probably cystic. We diagnosed our patient as having a cT1aN0M0 left RCC, and the RENAL score was 7x. With partial nephrectomy (PN) being the preferred treatment approach, robot-assisted laparoscopic partial nephrectomy (RALPN) was performed after obtaining informed consent. After insertion of the laparoscope, adhesions were observed between the entire colon and the anterior abdominal wall. Then, abdominal cocoon was diagnosed. The surgery was uneventful, and the tumour was resected successfully while preserving the tumour capsule. No intestinal injury or any other complication occurred in the intraoperative or postoperative, and the patient recovered well after the operation. Conclusion: PN is an extremely challenging procedure in patients with SIT and abdominal cocoon. The da Vinci Xi surgical system and thorough preoperative assessment allowed the surgeon to overcome stereotyping, visual inversion, and successfully perform PN in a patient with SIT and abdominal cocoon without increasing the risk of complications and preserving as much renal function as possible. Considering the satisfactory outcomes, this report may hopefully provide a practical reference for the treatment of RCC in patients with other special conditions.

Quantitative detection of purine from food products with different water activities using needle-based surface-enhanced Raman scattering sensors.

Typically, for accurate quantitative tests of molecules, considering the actual solute concentration in the environment with different water activities (Aws) is essential. Accordingly, for effective detection of food substances, this paper proposes a non-destructive pluggable sensor to capture and monitor four free purines based on surface-enhanced Raman scattering characteristics such as sensitivity, uniformity, repeatability, and stability. In particular, we investigate the impact of Aw on the evaluation of purine detection and its deviation corrections. Furthermore, the recoveries of purine from three food products, including fish (Aw: 0.99), ham (Aw: 0.91), and bacon (Aw: 0.73), are subsequently explored to validate the reliability of the proposed method. The results indicate that the proposed non-destructive pluggable sensor performs better when the Aw is considered. Therefore, this strategy for achieving more reliable quantitative detection by rectifying deviations based on the Aw can significantly help monitor food quality.

Prevalence of Human Papillomavirus Infection in the Female Partner of Infertile Couples Undergoing IVF/ICSI-ET and Subsequent Reproductive Outcomes.

We investigated the prevalence of human papillomavirus (HPV) infection in the female partner of infertile couples and the reproductive outcomes after in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). We conducted a retrospective analysis on 8117 women from infertile couples who underwent IVF/ICSI treatment and evaluated the prevalence of HPV infection in these women. The prevalence of HPV infection in the female partner of infertile couples was 9.2% (747/8117). These HPV-infected female patients undergoing ART were divided into high-risk HPV (hrHPV) (n = 130) and low-risk HPV (lrHPV) groups (n = 94), and non-infected women patients formed the negative group (n = 126). Of the 747 cases infected with HPV, 529 showed hrHPV infection (70.82%; primarily genotypes 16, 52, 53, 58, and 59); 175 exhibited lrHPV infection (23.43%; primarily genotypes 6, 43, 44, 55, 61, and 81); and 43 cases were co-infected with hrHPV and lrHPV (5.76%). Except for the Day-3 high-quality embryo rate, there were no differences in ovum maturation, fertilization, implantation, clinical pregnancy, live birth, or miscarriage rates between women infected with HPV and non-infected women (p > 0.05); however, we noted an increased miscarriage rate after logistic regression analyses (OR, 0.16; 95% CI, 0.03−0.84; p = 0.041). For single-male-factor-induced infertility in couples (smHPV), although we likewise observed no differences in ovum maturation, fertilization, or implantation rates (p > 0.05) between the smHPV group and the negative group, we discerned diminutions in the Day-3 high-quality embryo rate (46.01% vs. 70.04%, p = 0.013), clinical pregnancy rate (46.67% vs. 57.94%, p = 0.003), and live birth rate (33.33% vs. 46.83%, p = 0.027) as well as an augmented miscarriage rate (11.11% vs. 4.76%, p = 0.003), respectively. Logistic regression analyses indicated that smHPV was a risk factor for decreased clinical pregnancy rate (OR, 4.17; 95% CI, 2.31−7.53; p < 0.001) and live birth rate (OR, 1.83; 95% CI, 0.81−2.14; p = 0.045) and elevated miscarriage rate (OR, 6.83; 95% CI, 2.22−21.00; p = 0.001). HPV infection in women was associated with increased miscarriage rate, and single-male-factor infertility influenced reproductive outcomes in couples undergoing IVF/ICSI treatment. Both were potentially due to HPV infection in the couple.

Case report: Misdiagnosis of accessory spleen in the left adrenal region as an adrenal tumour after splenectomy.

Background: Adrenal tumours are common in urology and endocrinology, and the diagnosis of adrenal tumours were mainly depends on imaging diagnosis. Howerver, misdiagnosis can still occur for some adrenal space-occupying lesions without specific manifestations or abnormal biochemical indexes. Methods: We report the case of a 55-year-old patient with a soft-tissue mass in the left adrenal region, and have no specific manifestations or abnormalities in biochemical indexes. The patient had undergone open splenectomy 20 years ago for splenic rupture caused by traffic-accident trauma, and had a 10-year special history of hypertension. Because of the uncertain nature of the mass, surgical treatment was recommended. Results: The surgeon managed to remove the left adrenal region mass. During the surgery, the adrenal source was excluded. In the histological examination, the splenic corpuscle and splenic medullary structure were seen under the microscope, and an accessory spleen was diagnosed. Conclusions: The accessory spleen was located in the adrenal region rarely, and can easily be misdiagnosed as an adrenal tumour. When the cases show abnormal adrenal space-occupying lesions in imaging examinations, non-adrenal diseases should be considered. we need to combine different imaging techniques for analysis, and think more about it, avoid misdiagnosis leading to unnecessary surgery.

CHFR-mediated degradation of RNF126 confers sensitivity to PARP inhibitors in triple-negative breast cancer cells.

Ring-finger protein 126 (RNF126), an E3 ubiquitin ligase, plays crucial roles in various biological processes, including cell proliferation, DNA damage repair, and intracellular vesicle trafficking. Whether RNF126 is modulated by posttranslational modifications is poorly understood. Here, we show that PARP1 interacts with and poly(ADP)ribosylates RNF126, which then recruits the PAR-binding E3 ubiquitin ligase CHFR to promote ubiquitination and degradation of RNF126. Moreover, RNF126 is required for the activation of ATR-Chk1 signaling induced by either irradiation (IR) or a PARP inhibitor (PARPi), and depletion of RNF126 increases the sensitivity of triple-negative breast cancer (TNBC) cells to PARPi treatment. Our findings suggest that PARPi-mediated upregulation of RNF126 protein stability contributes to TNBC cell resistance to PARPi. Therefore, targeting the E3 ubiquitin ligase RNF126 may be a novel treatment for overcoming the resistance of TNBC cells to PARPi in clinical trials.

Effect of Preeclampsia on Ultrastructure of Thyroid Gland, Hepatic Type 1 Iodothyronine Deiodinase, and Thyroid Hormone Levels in Rats.

BACKGROUND: Although hypothyroidism during pregnancy may develop grave outcomes for both mothers and offspring, management of which is still a challenge due to the insufficient understanding of this disease. The close correlation between hypothyroidism and preeclampsia is well documented, suggesting that preeclampsia is a potential risk factor for the development of maternal hypothyroidism. However, the exact role of preeclampsia in gestational hypothyroidism is still obscure. OBJECTIVE: In this study, we explored the possible mechanisms of the effect of preeclampsia on thyroid function of maternal rats. METHODS: Thirty pregnant rats were randomly divided into normal pregnancy control (NOP), preeclampsia (PE), and preeclampsia supplemented with amlodipine besylate (PEAml). NG-Nitro-L-arginine-methyl ester was used to induce preeclamptic symptoms. On gestational day 21, rats were sacrificed, and then, the ultrastructure of the thyroid gland, type 1 iodothyronine deiodinase (Dio1) expression, and serum-free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulation hormones (TSH) were assessed. RESULTS: Compared to NOP rats, results of PE rats showed that thyroid follicular cells' ultrastructure was damaged; both hepatic Dio1 mRNA and protein levels were decreased. Interestingly, these changes were ameliorated in PEAml rats. Additionally, FT4, FT3, and TSH levels have no significant differences among groups. CONCLUSION: These findings indicated that preeclampsia could disrupt synthesis, secretion, and metabolism function of thyroid hormones by damaging thyroid follicular cells and interfering Dio1 expression.

Knockdown of TRIM26 inhibits the proliferation, migration and invasion of bladder cancer cells through the Akt/GSK3ß/ß-catenin pathway.

Tripartite motif-containing protein 26 (TRIM26) is a member of the TRIM protein family and has been demonstrated to play crucial roles in several types of cancers. However, the biological role of TRIM26 in bladder cancer and the mechanism have not been studied. In this study, we investigated the expression of TRIM26 in bladder cancer tissues and their adjacent non-tumor tissues by Western blot and qRT-PCR. In vitro investigations were performed to assess the roles of TRIM26 in bladder cancer using TRIM26-silencing and TRIM26-overexpressing bladder cancer cell lines. MTT and EdU assays were performed to evaluate cell proliferation. Cell migration and invasion were determined by transwell assays. Western blot analysis was performed to detect the expression levels of p-Akt, Akt, p-GSK3ß, GSK3ß, ß-catenin and c-Myc. Our results showed that TRIM26 expression was upregulated in human bladder cancer tissues and cell lines at both mRNA and protein levels. Knockdown of TRIM26 significantly inhibited the proliferation, migration and invasion of bladder cancer cells. In contrast, TRIM26 overexpression promoted bladder cancer cell proliferation, cell migration and invasion. Furthermore, knockdown of TRIM26 significantly decreased the levels of p-Akt, p-GSK3ß, ß-catenin and c-Myc in bladder cancer cells. Additionally, induction of Akt by SC79 treatment reversed the inhibitory effects of TRIM26 knockdown on the cellular behaviors of bladder cancer cells, while inhibition of ß-catenin reversed the effects of TRIM26 overexpression on the behaviors. Finally, knockdown of TRIM26 attenuated the growth of tumor xenografts in nude mice. In conclusion, these findings demonstrated that TRIM26 exerted an oncogenic role in bladder cancer through regulation of cell proliferation, migration and invasion via the Akt/GSK3ß/ß-catenin pathway.

Variant in BCAR4 gene correlated with the breast cancer susceptibility and mRNA expression of lncRNA BCAR4 in Chinese Han population.

BACKGROUND: Long non-coding RNA (LncRNA) Breast cancer anti-estrogen resistance 4 (BCAR4) has been shown to participate in the biological progress of various cancers including breast cancer. Genetic Polymorphisms in BCAR4 may have an influence on the progress of breast cancer, but it is rarely studied. METHODS: In our epidemiology study, three tagging SNPs (rs4561483, rs11649623 and rs13334967) in lncRNA BCAR4 were selected for genotyping among 487 breast cancer cases and 489 healthy controls. And quantitative real-time PCR (qRT-PCR) was performed to evaluate the relative mRNA expression of BCAR4 in different genotypes of the significant locus rs13334967. RESULTS: We found that BCAR4 rs13334967 is associated with lower breast cancer risk both in codominant model (AT vs AA, OR 0.632, 95% CI 0.429-0.931, TT vs AA, OR 0.731, 95% CI 0.511-0.990) and dominant model (AT + TT vs AA, OR 0.798, 95% CI 0.571-0.970). The further results of qRT-PCR displayed that carriers with rs13334967 AT, TT genotype have lower BCAR4 mRNA expression compared with AA genotype. CONCLUSION: The research study implied that BCAR4 rs13334967 was correlated with the susceptibility to breast cancer and may impact the mRNA expression of BCAR4. LncRNA BCAR4 may be a potential biomarker and therapeutic target for breast cancer.

A randomized controlled Phase II trial of vinorelbine plus capecitabine versus docetaxel plus capecitabine in anthracycline-pretreated women with metastatic breast cancer.

BACKGROUND: Previous studies have shown that vinorelbine/capecitabine (NX) and docetaxel/capecitabine (TX) chemotherapy has a certain effect in advanced breast cancer. However, there are few clinical studies directly comparing TX and NX regimen chemotherapy, especially in patients with advanced breast cancer previously treated with anthracycline and taxane. The purpose of this Phase II study was to compare survival and side effects between patients with anthracycline- and taxane-resistant advanced breast cancer treated with NX and those treated with TX chemotherapy. PATIENTS AND METHODS: From February 2012 to March 2014, a total number of 97 patients were randomly assigned to NX (n = 55) or TX (n = 42). Baseline characteristics were relatively well-balanced in the two treatment arms. The clinical trial registration number (clincaltrials.gov) is NCT01635465. RESULTS: After a median follow-up of 46.0 months, there was no significant difference between the NX and TX arms in objective response rate (17.9% vs. 21.1%; P = 0.686) and progression-free survival (6 months vs. 7 months; P = 0.560). The overall survival period of the TX arm was longer than that of the NX arm (32 months vs. 27 months) but without statistical significance. Both regimens were well-tolerated. The main toxicities were neutropenia, leukopenia, and anemia. In the TX arm, hand-foot syndrome occurred more frequently than in the NX arm (P < 0.01), but frequencies of other minor adverse effects were similar between the two arms. CONCLUSION: NX and TX regimens are both alternative treatments for patients with anthracycline- and taxane-resistant advanced breast cancer, but the safety profile was more favorable and manageable with the NX regimen. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT01635465. Registered 09 July 2012.

First case of COVID-19 complicated with fulminant myocarditis: a case report and insights.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. CASE PRESENTATION: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33rd day of hospitalization. CONCLUSION: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.

Ag-Catalyzed minisci C-H difluoromethylarylation of N-heteroarenes.

A mild silver-catalyzed decarboxylative difluoromethylarylation of electron-deficient N-heteroarenes has been developed by using aryldifluoro acetic acid as difluoromethyl sources. This protocol provides an efficient and straightforward access to difluoromethylated heteroarenes in moderate to excellent yields with good selectivities. Furthermore, this reaction was applicable to bioactive heteroarenes, providing a straightforward approach for the late-stage C-H difluoromethylation of pharmacophores.

Sevoflurane-induced inflammation development: involvement of cholinergic anti-inflammatory pathway.

Chronic inflammation plays an important role in the mechanisms underpinning the development of anesthesia-induced cognitive dysfunction. However, less is known about how anesthesia causes inflammation. One possibility is that the inflammation is related to alteration of the activity of the alpha 7 nicotinic acetylcholine receptor cholinergic anti-inflammatory pathway. This study analyzed the effect of sevoflurane administration on the cognitive function by using a novel object recognition test and Y-maze test, and on acetylcholinesterase activity and expression in hippocampal tissue by using an acetylcholinesterase assay kit and quantitative real-time PCR. This study also evaluated the effect of alpha 7 nicotinic acetylcholine receptor agonist PNU-282987 and antagonist methyllycaconitine on cognitive function and the level of hippocampal tumor necrosis factor-α in aged rats exposed to sevoflurane anesthesia. We found that 3% sevoflurane significantly impaired cognitive function and increased acetylcholinesterase activity by upregulating its expression in hippocampal tissue. Sevoflurane-induced impairment of cognitive function was significantly rescued by PNU-282987 but aggravated by methyllycaconitine. In addition to impairment of cognitive function, sevoflurane also significantly increased tumor necrosis factor-α level in plasma and hippocampal tissue. Similarly, this sevoflurane-induced change of tumor necrosis factor-α level in rats was antagonized by PNU-282987 but amplified by methyllycaconitine. In conclusion, our data show that the development of inflammation in sevoflurane-induced cognitive decline is associated with the downregulation of alpha 7 nicotinic acetylcholine receptor cholinergic anti-inflammatory pathway in aged rats.