Objective To explore the relationship between the types of bicuspid aortic valves(BAV)and the outcome of functional mitral regurgitation(FMR)and the affecting factors of FMR.Methods From Jun 2018 to Sep 2022,patients with severe BAV aortic valve stenosis(AS)complicated with FMR underwent post transcatheter aortic valve replacement(TAVR)in Zhongshan Hospital,Fudan University were retrospectively analyzed.The baseline information and imaging data of different BAV patients were collected.Logistic regression was used to analyze the factors affecting the outcome of FMR(improvement and non-improvement).Result A total of 100 patients with TAVR were included,including 49 patients with type 0 of BAV and 51 patients with type 1 of BAV.Compared with patients of type 1,patients of type 0 had younger age[(72.78±6.09)y vs.(77.00±8.35)y,P=0.050],lower male ratio(47%vs.73%,P= 0.009)higher BMI[(23.19±2.62)kg/m2 vs.(21.99±3.13)kg/m2,P=0.041],and lower incidence of aortic regurgitation(69%vs.92%,P=0.040).Compared with the non-improvement group,the improvement group had a lower incidence of coronary heart disease(5%vs.18%,P=0.042),higher incidence of pulmonary hypertension(20%vs.2%,P=0.007),larger left ventricular diastolic diameter[(51.98±6.74)mm vs.(48.04±7.72)mm,P=0.009]and higher maximum flow velocity[(4.86±0.95)cm/s vs.(4.47±0.75)cm/s,P= 0.023]of the aortic valve.The results of Logistic regression analysis showed that preoperative pulmonary hypertension,left ventricular end-diastolic diameter and maximum valvular flow velocity of BAV patients were the potential affecting factors of FMR improvement after TAVR.Conclusion No significant difference was found in FMR improvement between BAV patients of type 0 and type 1 after TAVR.For BAV patients with AS,preoperative pulmonary hypertension,larger left ventricular end-diastolic diameter,and faster aortic valve flow velocity were associated with higher FMR improvement rate.

Objective To compare the clinical efficacies of video-assisted thoracoscopic segmentectomy versus lobectomy for early-stage non-small cell lung cancer.Methods The clinical data of 234 patients with stage ⅠA non-small cell lung cancer and undergoing different surgical methods under video-assisted thoracoscopy admitted to Chongqing Dianjiang General Hospital were retrospectively analyzed,and the patients were divided into the lung segment group and the lung lobe group according to their surgical methods.The clinical characteristics of the patients in the two groups were balanced by a 1-to-1 ratio matching through the propensity score matching method,and each group finally included 63 cases.The perioperative indicators containing operation time,intraoperative blood loss,postoperative thoracic drainage tube indwelling time,thoracic drainage volumes 24 hours and 48 hours after operation and postoperative hospital stay were compared of patients between the two groups.The incidence of postoperative complications such as air leakage>6 days,pulmonary infection,atelectasis,hemoptysis,and hoarseness in the two groups was collected.Results There was no significant difference in the operation time,intraoperative blood loss,thoracic drainage volumes 24 hours and 48 hours after operation,postoperative thoracic drainage tube indwelling time or incidence of postoperative complications of patients between the two groups(P>0.05).The postoperative hospital stay of patients in the lung segment group was shorter than that in the lung lobe group,with statistically significant difference(P=0.003).Conclusion For patients with stage ⅠA non-small cell lung cancer,video-assisted thoracoscopic segmentectomy has similar perioperative efficacy to lobectomy,while segmentectomy has a more significant advantage in shortening the hospital stay.

Objective To explore the regulation of Chaihuang Qingyi Huoxue Granule on intestinal microecological changes in rats with severe acute pancreatitis (SAP) and the potential mechanism for its treatment of SAP. Methods Forty-eight rats were randomly divided into sham operation group (SHAM),SAP model group (SAP),and Chaihuang Qingyi Huoxue Granule (CH)group,with 16 rats in each group. Each group was further divided into 12 h and 24 h subgroups. The SAP model was induced by retrograde injection of 5％ sodium taurocholate into the pancreaticobiliary duct through duodenal wall. The SHAM and SAP groups received normal saline by gavage,while the CH group received 1.2 g·kg-1 Chaihuang Qingyi Huoxue Granule solution by gavage every six hours. At 12 h and 24 h after operation,eight rats from each group were sacrificed to collect abdominal aortic blood,pancreatic and ileal tissues for analysis. Ascites,pancreatic and ileal tissues were observed. Serum amylase(AMY) and lipase (LPS) levels were measured biochemically. Pathological changes in pancreatic and ileal tissues were investigated by HE staining. Claudin-1 protein expression in ileal tissue was detected by Western Blot. Changes in the intestinal flora of ileocecal contents were analyzed by 16S rDNA high-throughput sequencing. Results Compared to the SHAM group at the same time points,the SAP group exhibited extensive pancreatic edema and necrosis. Serum AMY and LPS levels,pancreatic and ileal histopathological scores increased,and Claudin-1 protein expression in ileal tissue markedly decreased (all P<0.05). The differences in abundance of microbial community increased,while the evenness of community composition reduced. The microbial richness showed no significant change (P>0.05),but the microbial diversity decreased(P<0.05). Proteobacteria were dominant intestinal bacteria. Relative abundances of Oscillospira,Ruminococcus,Bifidobacterium,and Bacteroides S24-7 decreased,whereas relative abundances of Shigella and Allobaculum increased. The differences in abundance of microbial community reduced,and the evenness of community composition increased. The microbial richness showed no significant change(P>0.05),but the microbial diversity increased (P<0.05). Firmicutes and Bacteroidetes were the dominant intestinal bacteria. Relative abundances of Oscillospira,Ruminococcus,Bifidobacterium,and Bacteroides S24-7 increased,whereas relative abundances of Shigella and Allobaculum decreased. After the intervention of CH,pathological damage in ileal tissue was improved. The expression of Claudin-1 protein in the intestinal mucosal barrier increased compared to the model group(P<0.05). The differences in abundance of microbial community reduced,and the evenness of community composition increased. CH group showed an increase in some beneficial bacteria and decrease in pathogenic bacteria compared to model group. Conclusion Chaihuang Qingyi Huoxue Granule may reduce pancreas injury in rats with SAP,which may be involved in modulating the intestinal microecology and improving intestinal mucosal barrier function.

OBJECTIVE To establish a determination method for the related substances of LPM3480392, a novel Gi protein-biased opioid receptor(MOR) agonist. METHODS The separation was carried out with Waters Symmetry Shield RP18 (150 mm×4.6 mm, 3.5 μm) by gradient elution method, using a mixture of 0.002 5 mol·L–1 sodium 1-octanesulfonate monohydrate in 0.01 mol·L–1 potassium dihydrogen phosphate-water solution(containing 0.1% triethylamine, adjusted pH to 2.50 with phosphate acid) and acetonitrile as the mobile phase at a flow rate of 1.0 mL·min–1 and the UV detection wavelength was set at 210 nm. RESULTS The chromatographic peaks of LPM3480392 and impurity A, impurity B, impurity C, impurity E and impurity F could be completely separated, the linear relationship of LPM3480392 was good in 0.064 9−5.191 2 μg·mL–1, while impurity A, impurity B, impurity C, impurity E and impurity F showed good linear relationship within 0.066 6−7.610 4 μg·mL–1, 0.166 0−3.794 0 μg·mL–1, 0.209 2−4.463 2 μg·mL–1, 0.167 9−7.672 6 μg·mL–1 and 0.016 4−7.505 7 μg·mL–1, respectively. The recovery rate was within 93.0%−103.2%. CONCLUSION The method is suitable for the determination of related substances in LPM3480392, and can provide valuable reference for the follow-up research and development of LPM3480392.

Microplastics(MPs)are emerging contaminants in aquatic environments characterized by their polar structure,small particle size(Typically less than 5 mm),large surface area,good stability,and resistance to biodegradation.They pose adverse effects on the normal physiological activities of aquatic organisms and can accumulate in biota,including humans.Therefore,there is an urgent need for rapid and accurate quantitative analysis of MPs in water environments.In this study,Raman spectroscopy combined with partial least squares(PLS)was employed for rapid and accurate quantitative analysis of polyethylene(PE)and polystyrene(PS)MPs in real water samples.Initially,33 simulated water samples containing different concentrations of MPs were prepared,and their Raman spectra were collected.Six spectral preprocessing methods(Normalization,multiplicative scatter correction,standard normal variate transformation,first derivative,second derivative,and wavelet transform)were investigated for their impact on the predictive performance of PLS calibration models.Subsequently,three variable selection methods including synergy interval partial least squares(SiPLS),variable importance in projection(VIP)and mutual information(MI)were employed to optimize the input variables of the PLS calibration model.The predictive capability of the PLS calibration model was evaluated and validated using leave-one-out cross-validation.Under the optimal conditions of spectral preprocessing,variable selection,input variables and latent variables,the wavelet transform-partial least squares(WT-PLS)calibration model based on distilled water was established,and the contents of PE and PS in real water samples were predicted with prediction correlation coefficients(R2p)of 0.9540 and 0.8472 for PE and PS,respectively,and prediction errors(Errorp)of 0.0690 and 0.1126,respectively.Furthermore,a mixed sample MI-PLS calibration model was developed,demonstrating the best predictive performance in real water samples(With R2p values of 0.9776 and 0.9755 for PE and PS,respectively,and Errorp values of 0.0360 and 0.0392,respectively).This method provided a novel approach and new methodology for quantitative analysis of MPs and other organic pollutants in real water samples.

Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Viral myocarditis(VMC)is the leading cause of dilated cardiomyopathy,which can lead to heart failure and sudden cardiac death.With the development of high-throughput sequencing technology,non-coding RNA(ncRNA)plays an important role in the occurrence and development of VMC.ncRNA promotes the occurrence and development of VMC by regulating viral replication,immune cell function,myocardial cell death,myocardial interstitial fibrosis,and other pathological processes.This article reviews the research progress of ncRNA in VMC and provides new ideas for the pathogenesis,diagnosis,and treatment of VMC.

Background::Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2, a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression. Methods::Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2-associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC. Results::NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro. NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models. Conclusions::Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Objective To analyze the research status, hotspots of biofilms and periodontitis from 2013 to 2023 by bibliometric methods. Methods The literatures related to biofilms and periodontitis were searched in the Web of Science (Wos) database, and visualization software such as VOSviewer and CiteSpace were used to analyze the countries or regions, authors, institutions, journals and keywords. Results A total of 1 821 papers were included, and the results showed that the number of published papers increased year by year. The top three countries with the highest number of publications were the United States, Brazil and China; the top three institutions were Universidade de São Paulo, Harvard University and Forsyth Institute; the authors with the highest number of publications were Feres and Magda; among the top ten journals in terms of the number of publications, Journal of Periodontology had the highest number of publications (87 papers), followed by Plos One (69 papers) and Clinical Oral Investigations (51 papers). Oxidative stress, markers, adjunctive therapy and drug delivery were the main research hotspots; the frontiers mainly focused on quorum sensing, photodynamic therapy, reactive oxygen species, copper nanoparticles, and optical coherence tomography. Conclusion Researches on biofilms and periodontitis are growing year by year, and future research directions can focus on oxidative stress, adjuvant therapies, quorum sensing and photodynamic therapy.