Study on the Anti-Ulcerative Colitis Effect of Pseudo-Ginsenoside RT4 Based on Gut Microbiota, Pharmacokinetics, and Tissue Distribution.

The purpose of this study was to explore the therapeutic effect of the oral administration of pseudo-ginsenoside RT4 (RT4) on ulcerative colitis (UC), and to determine the rate of absorption and distribution of RT4 in mice with UC. Balb/c mice were induced using dextran sulfate sodium salts (DSS) to establish the UC model, and 10, 20, or 40 mg/kg of RT4 was subsequently administered via gavage. The clinical symptoms, inflammatory response, intestinal barrier, content of total short-chain fatty acids (SCFAs), and gut microbiota were investigated. Caco-2 cells were induced to establish the epithelial barrier damage model using LPS, and an intervention was performed using 4, 8, and 16 µg/mL of RT4. The inflammatory factors, transient electrical resistance (TEER), and tight-junction protein expression were determined. Finally, pharmacokinetic and tissue distribution studies following the intragastric administration of RT4 in UC mice were performed. According to the results in mice, RT4 decreased the disease activity index (DAI) score, restored the colon length, reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), and boosted the levels of immunosuppressive cytokine IL-10, increased the content of SCFAs, improved the colonic histopathology, maintained the ultrastructure of colonic mucosal epithelial cells, and corrected disturbances in the intestinal microbiota. Based on the results in caco-2 cells, RT4 reduced the levels of TNF-α, IL-6, and IL-1ß; protected integrity of monolayers; and increased tight-junction protein expression. Additionally, the main pharmacokinetic parameters (Cmax, Tmax, t1/2, Vd, CL, AUC) were obtained, the absolute bioavailability was calculated as 18.90% ± 2.70%, and the main distribution tissues were the small intestine and colon. In conclusion, RT4, with the features of slow elimination and directional distribution, could alleviate UC by inhibiting inflammatory factors, repairing the intestinal mucosal barrier, boosting the dominant intestinal microflora, and modulating the expression of SCFAs.

(-)-Syringaresinol attenuates ulcerative colitis by improving intestinal epithelial barrier function and inhibiting inflammatory responses.

BACKGROUND: (-)-Syringaresinol (SYR), a natural lignan with significant antioxidant and anti-inflammatory activities, possesses various pharmacological benefits including cardio-protective, antibacterial, anticancer, and anti-aging effects. It was shown that the effectiveness of (+)-syringaresinol diglucoside on the ulcerative colitis (UC) was attributed to the active metabolite (+)-syringaresinol (the enantiomor of SYR). However, the efficacy of SYR against UC remains unclear, and the associated molecular mechanism has not been revealed yet PURPOSE: This study aimed to assess the protective effect of SYR in UC and its underlying mechanism STUDY DESIGN AND METHODS: We examined SYR's protective impact on the intestinal epithelial barrier and its ability to inhibit inflammatory responses in both a lipopolysaccharide (LPS)-induced Caco-2 cell model and a dextran sodium sulfate (DSS)-induced UC mouse model. We also explored the potential signaling pathways regulated by SYR using transcriptome analysis and western blot assay RESULTS: In Caco-2 cells, SYR significantly increased trans-epithelial electrical resistance, reduced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ), and cyclooxygenase-2 (COX-2) levels, and enhanced cellular tight junction protein expression and distribution. In mice with UC, oral treatment with SYR (10, 20, 40 mg·kg-1) dose-dependently increased body weight, colon length, and expression of tight junction proteins, decreased disease activity index score, spleen coefficient, cytokine serum levels, bacterial translocation, and intestinal damage, and also preserved the ultrastructure of colonic mucosal cells. Transcriptomics indicated that the anti-UC effect of SYR is mediated via the PI3K-Akt/MAPK/Wnt signaling pathway. CONCLUSION: In summary, SYR effectively mitigated the development of UC by enhancing the intestinal epithelial barrier function and attenuating the inflammatory response. The plant-derived product SYR might be a potentially effective therapeutical agent against UC.

Between now and later: a mixed methods study of HPV vaccination delay among Chinese caregivers in urban Chengdu, China.

BACKGROUND: Adolescent girls in China have a low HPV vaccination rate. Although vaccination is recommended by the Chinese health authorities, the cost is not covered by the national immunisation programme. Vaccination delay, among other reasons such as supply shortage and poor affordability, may contribute to low uptake. This sequential mixed methods study aimed to identify potential factors of delayed HPV vaccination among Chinese adolescent girls. METHODS: Quantitative data about the attitudes and perceptions of HPV vaccination were collected from 100 caregivers of 14-18-year-old girls using an online survey in Chengdu, China. The survey data informed a subsequent qualitative study using four focus group discussions. We conducted a descriptive analysis of the survey data and a thematic analysis of the qualitative data. The findings were interpreted using a health behaviour model adapted from the Health Belief Model and the Andersen's Behavioural Model for Health Services Use. RESULTS: A total of 100 caregivers - 85 were mothers and 15 were fathers - participated in the survey; 21 caregivers joined focus group discussions. When asked about their intended course of action if the 9vHPV vaccine was out-of-stock, 74% chose to delay until the 9vHPV vaccine is available while 26% would consider 2vHPV or 4vHPV vaccines or seek alternative ways to procure the vaccine. Qualitative results confirmed that caregivers preferred delaying HPV vaccination for adolescent girls. The intent to delay was influenced by systemic barriers such as supply shortage and individual-level factors such as a preference for the 9vHPV vaccine, safety concerns, inadequate health communication, and the belief that adolescents were unlikely to be sexually active. CONCLUSION: In urban areas, Chinese caregivers' intent to delay vaccination in favour of 9vHPV vaccine over receiving the more accessible options was influenced by a mix of individual and contextual factors. Focussed health communication strategies are needed to accelerate HPV vaccination among adolescents.

Traditional Chinese medicine for smoking cessation: An umbrella review of systematic reviews and meta-analysis of randomized controlled trials.

INTRODUCTION: Traditional Chinese medicine (TCM) may have special advantages in facilitating smoking cessation, but consensus on effectiveness is lacking. We aim to comprehensively review, update, and refine current evidence on TCM effectiveness and safety. METHODS: Nine databases were searched from their inception up to 28 February 2023. Systematic reviews (SRs) and meta-analysis of TCM for smoking cessation were identified and retrieved. Additional databases and hand searches of RCTs from included SRs were performed for data pooling. Cochrane ROB tools and AMSTAR-2 were used to evaluate the methodological quality of RCTs and SRs, respectively. RCT data are presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI) using RevMan 5.4. RESULTS: Thirteen SRs involving 265 studies with 33081 participants were included. Among these 265 studies, 157 were duplicates (58.36%) and 52 were non-RCTs (19.62%). Combined with the remaining 56 RCTs identified through hand searches, 88 RCTs involving 12434 participants were finally included for data synthesis. All the SRs focused on acupoint stimulation, and the majority were of low or very low quality. The methodological quality of RCTs was either unclear or high risk. For continuous abstinence rate, TCM external interventions were better than placebo in 6 months to 1 year (RR=1.60; 95% CI: 1.14-2.25; I2=27%; n=5533 participants). Compared with placebo, TCM external application was effective in reducing nicotine withdrawal symptoms, and the effect was gradually stable and obvious in the fourth week (MD= -4.46; 95% CI: -5.43 - -3.49; n=165 participants). Twelve RCTs reported adverse events as outcome indicators for safety evaluation, and no serious adverse events occurred. CONCLUSIONS: Despite the methodological limitations of the original studies, our review suggests that TCM intervention shows potential effectiveness on the continuous abstinence rate. Extending the intervention time can enhance the effect of TCM on nicotine withdrawal symptoms. Referred to adverse events, more data for safety evaluation are required.

Hierarchical Nickel Cobalt Phosphide @ Carbon Nanofibers Composite Microspheres: Ultrahigh Energy Densities of Electrodes for Supercapacitors.

Supercapacitors (SCs) are widely used in energy storage devices due to their superior power density and long cycle lifetime. However, the limited energy densities of SCs hinder their industrial application to a great extent. In this study, we present a new combination of metallic phosphide-carbon composites, synthesized by directly carbonizing (Ni1-xCox)5TiO7 nanowires via thermal chemical vapor deposition (TCVD) technology. The new method uses one-dimensional (1D) (Ni1-xCox)TiO7 nanowires as precursors and supporters for the in situ growth of intertwined porous CNF microspheres. These 1D nanowires undergo microstructure transformation, resulting in the formation of CoNiP nanoparticles, which act as excellent interconnected catalytic nanoparticles for the growth of porous 3D CNF microspheres. Benefiting from the synergistic effect of a unique 1D/3D structure, the agglomeration of nanoparticles can effectively be prevented. The resulting CNF microspheres exhibit an interconnected conductive matrix and provide a large specific surface area with abundant ion/charge transport channels. Consequently, at a scanning rate of 10 mV s-1, its specific capacitance in 1.0 M Na2SO4 + 0.05 M Fe(CN)63-/4- aqueous solution is as high as 311.7 mF cm-2. Furthermore, the CoNiP@CNFs composite film-based symmetrical SCs show an ultrahigh energy density of 20.08 Wh kg-1 at a power density of 7.20 kW kg-1, along with outstanding cycling stability, with 87.2% capacity retention after 10,000 cycles in soluble redox electrolytes. This work provides a new strategy for designing and applying high-performance binary transition metal phosphide/carbon composites for next-generation energy storage devices.

Impact of Bariatric Surgery on Cardiac Function and Structure in Chinese Patients with Obesity.

Introduction: Obesity contributes to cardiac dysfunction and has an impact on atherosclerotic cardiovascular disease. Bariatric surgery (BS) is being considered a therapeutic option for patients with obesity and also can improve cardiac function. Very few studies considered the Chinese population. This study aimed to examine the effect of BS on cardiac function and structure in Chinese subjects with obesity. Methods: A single-center retrospective analysis of 143 patients with obesity was included. To observe and analyze the short-term, midterm, and long-term effects of BS on cardiovascular function and structure, the study population was divided into three groups according to the time of review. Fifty-two patients in group T1 (re-examination within 12 months); 53 patients in group T2 (re-examination within 12 to 24 months); and 38 patients in group T3 (re-examination over 24 months). The effects of BS on the cardiac function and structure were evaluated by analyzing the echocardiographic parameters. Results: After BS, body mass index (BMI) decreased from 39.7 ± 8.0 to 28.4 ± 6.4 kg/m2 (P < 0.001). Blood pressure decreased significantly. Left ventricular mass index (LVMI) decreased (43.7 ± 16.4 to 37.8 ± 13.4 g/m2.7, P < 0.001). The change in LVMI was correlated with the change in BMI (R2 = 0.14, P < 0.001). In subgroup analyses at different follow-ups, echocardiographic parameters showed varying degrees of change compared with the baseline. Conclusions: Significant weight loss by BS was associated with improved left ventricular structure and function in Chinese patients with obesity, suggesting potential favorable effects of BS on the cardiac function and structure.

Mechanisms of esophageal cancer metastasis and treatment progress.

Esophageal cancer is a prevalent tumor of the digestive tract worldwide. The detection rate of early-stage esophageal cancer is very low, and most patients are diagnosed with metastasis. Metastasis of esophageal cancer mainly includes direct diffusion metastasis, hematogenous metastasis, and lymphatic metastasis. This article reviews the metabolic process of esophageal cancer metastasis and the mechanisms by which M2 macrophages, CAF, regulatory T cells, and their released cytokines, including chemokines, interleukins, and growth factors, form an immune barrier to the anti-tumor immune response mediated by CD8+ T cells, impeding their ability to kill tumor cells during tumor immune escape. The effect of Ferroptosis on the metastasis of esophageal cancer is briefly mentioned. Moreover, the paper also summarizes common drugs and research directions in chemotherapy, immunotherapy, and targeted therapy for advanced metastatic esophageal cancer. This review aims to serve as a foundation for further investigations into the mechanism and management of esophageal cancer metastasis.

Study on the Comprehensive Phytochemicals and the Anti-Ulcerative Colitis Effect of Saussurea pulchella.

BACKGROUND: Saussurea pulchella (SP) is a traditional medicinal plant that is widely used in folk medicine because of its diverse biological activities, particularly its anti-inflammatory effects. However, the alleviation effect of SP on ulcerative colitis (UC) has not yet been realized. PURPOSE: To investigate the chemical composition and therapeutic effect of SP extract against UC. METHODS: First, qualitative and quantitative analysis of SP 75% ethanol extract was performed by UPLC-Q/TOF-MS. Second, a dextran sodium sulfate (DSS) model of UC mice was developed to study the effects of SP on the symptoms, inflammatory factors, oxidative stress indexes and colon histopathology. Third, an integration of network pharmacology with metabolomics was performed to investigate the key metabolites, biological targets and metabolisms closely related to the effect of SP. RESULTS: From the SP ethanol extract, 149 compounds were identified qualitatively and 20 were determined quantitatively. The SP could dose-dependently decrease the DAI score, spleen coefficient and the levels of TNF-α, IL-6, iNOS, MPO and MDA; increase the colon length, GSH level and SOD activity; and protect the intestinal barrier in the UC mice. Moreover, 10 metabolite biomarkers,18 targets and 5 metabolisms were found to play crucial roles in the treatment of UC with SP. CONCLUSIONS: SP 75% ethanol extract could effectively alleviate the progression of UC and, therefore, could be classified as a novel natural treatment for UC.

Robotic-assisted pulmonary lobectomy with lung cancer in a patient with situs inversus totalis.

BACKGROUND: Situs inversus totalis (SIT) is a relatively rare congenital abnormality in which the major thoracic and abdominal visceral organs are reversed from their usual positions. In patients with SIT and bronchial carcinoma, surgical difficulty increases sharply. It has been reported that the video-assisted thoracic surgery (VATS) still poses the operator to a challenge situation. The similarity of surgical positions and the flexibility of the mechanical arm in robotic surgery, may be beneficial to SIT patients due to reducing technical difficulties. Here, we present a first case of SIT patient with lung cancer, in which Da Vinci robot-assisted thoracic surgery (RATS) was performed successfully. CASE PRESENTATION: A 66-year old patient, previously diagnosed with SIT since childhood, came to our hospital with two pulmonary nodules in his left lung field. The bigger one had increased somewhat for the last 2 years of follow-up. Software Mimics was preoperatively carried out to analyze anatomical variations. RATS was conducted to complete left upper lobectomy and left middle wedge resection. The patient had no intraoperative complications and was discharged day 5 after the operation. CONCLUSIONS: This is the first report of a successful robot-assisted lung cancer resection in a patient with SIT. In such challenging cases as lung cancer and rare anomaly as SIT, RATS is more advantageous and suitable than VATS with the help of software Mimics utilized for 3D reconstruction, which can identify the anatomical abnormalities and facilitate the surgical procedures.

Design, Synthesis, and Antitumor Evaluation of Novel Mono-Carbonyl Curcumin Analogs in Hepatocellular Carcinoma Cell.

Curcumin is a polyphenolic natural product that has promising anticancer properties. However, its clinical utility is limited by its chemical instability and poor metabolic properties. In this paper, a series of new curcumin analogs were synthesized and found to be potent antiproliferative agents against the HepG2 cell line by MTT assay. In general, Group B with single ketone and group C with chalcone were markedly more cytotoxic than group A with diketone. Compound B5 was found as the most potent analog (IC50 = 11.33 µM) compared to curcumin (IC50 = 32.83 µM) and the mechanism of its cytotoxicity was investigated. The result of the wound healing assay indicated B5 strong potential to suppress HepG2 cell migration in a dose- and time-dependent manner. Subsequent assays (including JC-1 staining, Bcl-2, and caspase 3 protein levels by Western blotting) confirmed that B5 exposure induced apoptosis in HepG2 cells. Curcumin-induced comprehensive transcriptomes profile, Western blotting, molecular docking, and molecular dynamics analysis showed that the mechanism may relate to the regulation of cellular metabolic process and the expression of AKT protein. Taken together, we could conclude that curcumin and its analogs induced HepG2 cell proliferation, migration, and apoptosis via AKT signaling pathway and the mitochondrial death pathway. This study could lay the foundation for optimizing curcumin and provide valuable information for finding novel anti-HCC drugs.

HuR Affects the Radiosensitivity of Esophageal Cancer by Regulating the EMT-Related Protein Snail.

Purpose: We previously found that Hu antigen R (HuR) can regulate the proliferation and metastasis of esophageal cancer cells. This study aims to explore the effects of HuR on the radiosensitivity of esophageal cancer. Materials and Method: Analyses of CCK-8, colony formation assay, Western blot, immunofluorescence, flow cytometry, reactive oxygen species (ROS), and mitochondrial membrane potential were conducted to characterize the esophageal cancer cells. Nude mouse models were used to detect the effects of HuR in a combination of X-ray treatment on the subcutaneous xenografts of esophageal cancer. In addition, a luciferase assay was used to detect the direct interaction of HuR with Snail mRNA 3'-UTR. Results: The down-regulation of HuR combined with X-ray can significantly inhibit the proliferation and colony formation of esophageal cancer cells. Flow cytometry data showed that the down-regulation of HuR could induce a G1 phase cell cycle block in esophageal cancer cells, and aggravate X-ray-induced apoptosis, indicated by the increases of apoptosis-related proteins Bax, caspase-3 and caspase-9. Moreover, the down-regulation of HuR could significantly impair the mitochondrial membrane potential and increase the ROS production and DNA double-strand break marker γH2AX expression in esophageal cancer cells that were exposed to X-rays. In vivo data showed that the down-regulation of HuR combined with radiation significantly decreased the growth of subcutaneous xenograft tumors. Furthermore, HuR could interact with Snail. Up-regulation of Snail can reverse the EMT inhibitory effects caused by HuR down-regulation, and attenuate the tumor-inhibiting and radiosensitizing effects caused by HuR down-regulation. Conclusion: In summary, our data demonstrate that HuR effectively regulates the radiosensitivity of esophageal cancer, which may be achieved by stabilizing Snail. Thus, HuR/Snail axis is a potentially therapeutic target for the treatment of esophageal cancer.

Predictive value of two different definitions of contrast-associated acute kidney injury for long-term major adverse kidney events in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: It remains controversial whether contrast-associated acute kidney injury (CA-AKI) is associated with long-term major adverse kidney events (MAKE) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS: By the Acute Kidney Injury Network (AKIN) criteria, CA-AKI was defined as an increase in serum creatinine ≥ 0.3 mg/dL or 50% from baseline within 48 h after PCI; or an increase in serum creatinine ≥ 0.5 mg/dL or 25% within 72 h by the contrast-induced nephropathy (CIN) criteria. The primary endpoint was 1-year MAKE, defined as a composite of all-cause mortality and persistent renal dysfunction. RESULTS: A total of 402 patients were finally included in this study. The primary endpoint occurred in 29 (7.2%) patients. There was a significant association between CA-AKI and 1-year MAKE assessed by both the AKIN (hazard ratios [HR]: 11.58, 95% confidence interval [CI]: 4.29-31.24, p = 0.000) and CIN (HR: 6.45, 95% CI: 2.56-16.25, p = 0.000) definitions. However, the AKIN definition (HR: 4.95, 95% CI: 1.17-21.02, p = 0.030) was more reliable in the prediction of persistent renal dysfunction than CIN definition (HR: 4.08, 95% CI: 0.99-16.87, p = 0.052). Additionally, the area under receiver operating characteristic curve was larger for predicting 1-year MAKE with the AKIN definition than CIN definition (0.742 vs. 0.727). CONCLUSIONS: In patients with STEMI undergoing primary PCI, CA-AKI was significantly associated with 1-year MAKE. Moreover, the AKIN definition might be more reliable in the prediction of long-term prognosis.

Outcomes and quality of life after Robot-assisted lobectomy/segmentectomy for lung cancer compared to video-assisted thoracoscopic surgery: both three-port procedures performed by a single surgeon.

Background: At present, research comparing robot-assisted thoracic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) in lobectomy/segmentectomy for lung cancer is insufficient. This paper aimed to compare the safety, short-term efficacy, quality of life (QoL), and delayed complications at 6 weeks postoperatively via a retrospectively controlled study by a single surgeon. Methods: A total of 110 non-small cell lung cancer (NSCLC) cases from December 2020 to May 2021 were enrolled in this retrospective study, and were divided into RATS and VATS groups (both three-port procedures) according to the patients' preference. The propensity-score matching method was applied to control the potential differences. The patients were treated with lobectomy/segmentectomy for lung cancer by RATS or VATS, and the safety outcomes were evaluated. The follow-up was initiated after surgery, and the outcome assessments including hospitalization costs, short-term efficacy, pain and QoL, were collected and analyzed. Results: Both matched groups achieved a R0 resection rate of 100%. The average operation time of the RATS group was 21 minutes shorter than VATS (P<0.01), and the average hospitalization costs of the RATS group was 17,746 China Yuan higher than VATS (P<0.01). Furthermore, the visual analogue pain scores of the RATS group were lower than those of the VATS group at 1 day and 6 weeks postoperatively (2.53±0.86 vs. 3.88±0.88 and 0.35±0.65 vs. 0.74±0.88, respectively, P<0.05). Moreover, the core QoL scale score for cancer patients in the RATS group were higher than those of the VATS group at 6 weeks postoperatively (98.64±5.73 vs. 93.02±15.21, respectively, P<0.05). No significant differences were observed in the other indicators. Conclusions: Despite its high cost, RATS showed considerable potential for reducing the operation time and improving the QoL of patients. Meanwhile, RATS and VATS exhibited similar perioperative safety and short-term efficacy in lobectomy and segmentectomy.

Recovery Infectious Enterovirus 71 by Bac-to-Bac Expression System in vitro and in vivo.

Enterovirus 71 (EV71) is one of the most important etiological agents for hand-foot-mouth disease. Compared with coxsackievirus A16 infection, EV71 infection is often associated with severe central nervous system complications, such as encephalitis, encephalomyelitis, and acute flaccid paralysis in infants and young children. In this study, we constructed a recombinant baculovirus with T7 ribonucleic acid polymerase under the control of a cytomegalovirus promoter and simultaneously engineered the T7 promoter upstream of a full-length EV71 complementary deoxyribonucleic acid. After transduction into mammalian cells, typical cytopathic effects (CPEs) and VP1 signals were detected in cells transfected with recombinant baculovirus. Additionally, viral particles located in the cytoplasm of human rhabdomyosarcoma cells (Rd) and Vero cells were observed by electron microscope, indicating that EV71 was recovered using a Bac-to-Bac expression system in vitro. After four passages, the rescued virus had a growth curve and plaque morphology similar to those of the parental virus. Furthermore, the Vp1 gene and the protein from the mouse brain were detected by reverse transcription polymerase chain reaction and immunohistochemistry after intracerebral injection of purified recombinant baculovirus. Typical CPEs were observed after inoculation of the supernatant from mouse brain to Rd cells, revealing a reconstruction of EV71 in vivo. Thus, we established a new approach to rescue EV71 based on a baculovirus expression system in vitro and in vivo, which may provide a safe and convenient platform for fundamental research and a strategy to rescue viruses that currently lack suitable cell culture and animal models.

Conservative management versus cesarean hysterectomy in patients with placenta increta or percreta.

OBJECTIVE: To compare conservative management and cesarean hysterectomy in patients with placenta increta or percreta. MATERIALS AND METHODS: In this multicenter retrospective study, we recorded data on 2219 patients with placenta increta or percreta from 20 tertiary care centers in China from 1 January 2011 to 31 December 2015. Propensity score analysis was used to control for baseline characteristics. We divided patients into conservative management (C) and hysterectomy (H) groups. The primary outcome was operative/postoperative maternal morbidity; secondary outcomes were maternal-neonatal outcomes. RESULTS: In total, 17.9% (398/2219) of patients had placenta increta and percreta; 82.1% (1821/2219) of the patients were in group C. After propensity score matching, 140 pairs of patients from the two groups underwent one-to-one matching. Group C showed less average blood loss within 24 h of surgery (1518 ± 1275 vs. 4309 ± 2550 ml in group H, p<.001). There were more patients with blood loss >1000 ml in group H than in group C (93.6% [131/140] vs. 61.4% [86/140], p<.001). More patients received blood transfusions in group H than in group C (p=.014). There was no significant difference between the groups in terms of bladder injury, postoperative anemia, fever, and disseminated intravascular coagulation. Neonatal outcomes in the two groups were similar. CONCLUSION: Either conservative management or hysterectomy should be considered after thorough evaluation and detailed discussion of risks and benefits. A balance between bleeding control and fertility can be achieved.

Prognostic and diagnostic roles of prolyl 4-hydroxylase subunit α members in breast cancer.

Aim: We aimed to evaluate the diagnostic and prognostic values of P4HAs in breast cancer (BC) patients. Materials & methods: Kaplan-Meier plotter was used to evaluate the prognostic values of P4HAs and correlations between their expression and clinical characteristics were assessed based on The Cancer Genome Atlas and the Human Protein Atlas. Results: The current study showed that P4HAs were highly expressed in BC patients with clinical stage I compared with nontumor control and elevated P4HAs were correlated with poor survival outcomes. Subtypes analysis revealed that P4HA1 and P4HA2 were most expressed in HER2+ subtypes patients. Univariate analysis displayed that elevated P4HA1 and P4HA3 correlated with unfavorable recurrence-free survival in mutated TP53 patients. Conclusion: This study indicated the diagnostic and prognostic roles of P4HAs members and broadened the biomarker fields of early diagnosis and prognostic monitoring of BC patients.

PSMB4 inhibits cardiomyocyte apoptosis via activating NF-κB signaling pathway during myocardial ischemia/reperfusion injury.

Myocardial ischemia/reperfusion (I/R) injury induces cardiomyocyte apoptosis to deteriorate heart function. Thus, how to inhibit cardiomyocyte apoptosis is the focus of recent researches. Proteasome family member PSMB4 (proteasome subunit beta type-4) promotes cell survival. The relationship between PSMB4 and cardiomyocyte apoptosis during myocardial I/R is unknown. In this study, PSMB4 expression increased in rat myocardial I/R model, positively correlated with cleaved caspase-3 expression, negatively correlated with Bcl-2 expression. In vitro, neonatal ventricle cardiomyocyte hypoxia/reoxygenation (H/R) model was constructed to mimic myocardial I/R. PSMB4 silence promoted cardiomyocyte apoptosis and IκBα expression, inhibited the activation of NF-κB. On the contrary, PSMB4 overexpession inhibited cardiomyocyte apoptosis and IκBα expression, promoted the activation of NF-κB. Additionally, PSMB4-IκBα interaction was identified, suggesting that PSMB4 might participate in the proteasome dependent degradation of IκBα. The data indicates that PSMB4 inhibits cardiomyocyte apoptosis via activating NF-κB signaling pathway during myocardial I/R, which can supply novel molecular target for the treatment of ischemic heart disease.

MIR99AHG is a noncoding tumor suppressor gene in lung adenocarcinoma.

Little is known about noncoding tumor suppressor genes. An effective way to identify these genes is by analyzing somatic copy number variation (CNV)-related noncoding genes. By integrated bioinformatics analyses of differentially expressed long noncoding RNAs (lncRNAs) and arm-level CNVs in lung adenocarcinoma (LUAD), we identified a potential antitumor gene, MIR99AHG, encoding lncRNA MIR99AHG as well as a miR-99a/let-7c/miR-125b2 cluster on chromosome 21q. All four of these transcripts were downregulated in LUAD tissues partly due to the copy number deletion of the MIR99AHG gene. Both MIR99AHG and miR-99a expression was positively correlated with the survival of LUAD patients. MIR99AHG suppressed proliferation and metastasis and promoted autophagy both in vitro and in vivo. Mechanistically, the interaction between MIR99AHG and ANXA2 could accelerate the ANXA2-induced ATG16L+ vesicle biogenesis, thus promoting phagophore assembly. Additionally, miR-99a targeted a well-known autophagy suppressor, mammalian target of rapamycin (mTOR), thereby synergistically promoting autophagy and postponing LUAD progression with MIR99AHG. In summary, MIR99AHG emerges as a noncoding tumor suppressor gene in LUAD, providing a new strategy for antitumor therapy.

Safety analysis of application of mediastinal CO2 aeration in mediastinal esophagectomy.

BACKGROUND: In recent years, minimally invasive esophagectomy (MIE) has been used gradually in esophageal surgery. The application of CO2 aeration in minimally invasive surgeries, especially in laparoscopic surgery, has been very mature. However, the application of CO2 aeration in mediastinal esophagectomy is still in the exploration stage. This study was designed to investigate the safety of mediastinal CO2 aeration in the mediastinal esophagectomy. METHODS: A total of 15 pigs were used to construct an experimental animal model of mediastinal CO2 aeration. The effects of different inflation pressures on the circulatory respiratory function of pigs were studied by detecting the relevant physiological parameters. Heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP) were monitored before ventilating CO2 (T0), and also monitored at 30 (T1), 60 (T2), 90 (T3) min after inflation and 30 min after deflation (T4). Arterial blood was collected for PaCO2, blood lactate concentration (cLac), PaO2/FiO2, SaO2, pH value, and cardiac output (CO) was measured by esophageal ultrasound. RESULTS: The results of animal experiments showed that under 5-10 mmHg CO2 inflation pressure, circulation function indicators (CVP, MAP, HR, CO) and respiratory function indicators (PaCO2, cLac, PaO2/FiO2, SaO2, pH value) in pigs had no significant difference compared with the indicators before inflation; and under 15 mmHg CO2 inflation pressure, CVP, HR, PaCO2 and blood cLac increased, while MAP, CO, PaO2, SaO2 and pH values decreased. The visual field using mediastinoscopy under 15 and 10 mmHg CO2 inflation pressure was better than that under 5 mmHg CO2 inflation pressure. CONCLUSIONS: Mediastinal esophagectomy with 5-10 mmHg CO2 inflation pressure has no significant effect on the circulation and respiratory function of the body. Compared with the conventional non-inflated transseptal esophageal cancer (EC) surgery, it can provide a better surgical vision and reduce the difficulty of the surgery.

Mutation landscape and tumor mutation burden analysis of Chinese patients with pulmonary sarcomatoid carcinomas.

INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a group of rare tumors with the presence of both cancerous and sarcoma components in tumor. In this study, we explore their cancer genomic background and the relationship with clinical prognosis. MATERIALS AND METHODS: A cohort of 32 PSC patients were retrospectively collected from the First People's Hospital of Changzhou between 2005 and 2016. Targeted next-generation sequencing (NGS) of 416 cancer-relevant genes was performed on 32 PSC tumors. RESULTS: EGFR (28%), KRAS (22%), and MET (16%) are the most commonly mutated oncogenes, while the top mutated tumor suppressor genes are TP53 (69%) and RB1 (25%). The majority of EGFR mutations are rare mutations, some of which have not been reported before. Moreover, 4 out of 6 MET alterations are exon 14 skipping, far more frequent than in NSCLC. Interestingly, ARID1A was found to be co-mutated with TP53 at all times. The tumor mutation burden (TMB) is ranging from 3.3 to 52.2 per megabase (MB) with a median of 11.7 per MB and 13 patients have more than 20 mutations per MB. Patients mutated in BRCA2, KMT2B, SMARCA4 or TSC2 have significantly higher TMB compared to patients with wide-type genes. CONCLUSION: Our study characterizes the genetic background of Chinese PSC patients and demonstrates the importance of involving EGFR rare mutations and MET exon 14 skipping targeted therapies into clinical trials for treating PSC patients. High TMB are seen in about 40.6% Chinese patients with PSC, which could benefit from immune checkpoint inhibitors.