Search

Suicidal ideation (SI) is severe comorbidity of depression that has been extensively studied in the past. Residence differences between SI have rarely been systematically studied, especially in parental rearing behavior. This large-scale explored the residence differences in the prevalence and correlation of SI adolescent patients with depression.A total of 1417 patients with depression were recruited, and their demographic data and clinical data were collected. The Children's Depression Inventory (CDI) and the Egna Minnen Beträffande Uppfostran (EMBU) scale were used to assess depression, and parental rearing behavior, respectively.The prevalence of suicidal ideation was higher in urban patients than in rural patients (43.7 % vs.37.7 %, P 0.05). Patients with SI scored higher on total CDI scores, parental punishment, parental rejection, and paternal overprotection compared to their respective patients without SI. In the urban group, patients with SI had lower parental emotional warmth scores and higher parental intervention scores compared to patients without SI. Logistic regression analysis showed that total CDI score, gender, alcohol consumption, father's emotional warmth, father's rejection, and mother's intervention were significantly associated with SI in urban patients (P 0.05); total CDI score and mother's rejection were significantly associated with SI in rural patients (P 0.05).No causal relationship could be drawn due to the cross-sectional design.The results of this study showed significant residential differences in risk and associated factors for SI among adolescents with depression. Focusing on the parenting styles of adolescent patients can help with the early identification and intervention of SI.

Patients with advanced gastric cancer experience rapid disease progression with limited survival, high mortality, and a lack of surgical options. Thus, radiochemotherapy or a combination of chemotherapeutics with targeted therapy is the mainstay of treatment. In comparison to the treatment of other malignant tumors, in gastric cancer, the development of molecularly targeted drugs has been relatively slow. Currently, there are two major classes of molecularly targeted drug regimens that have achieved a certain efficacy in clinical practice: anti-vascular endothelial growth factor (anti-VEGF) therapy and anti-epidermal growth factor receptor (anti-EGFR) therapy. Trastuzumab has been approved as the standard of care for first-line treatment in advanced human epidermal growth factor receptor 2 (HER2)-positive gastric cancer. Ramucirumab in combination with paclitaxel is the recommended regimen for second-line treatment, and apatinib is recommended as third-line treatment. This review summarizes the current status of targeted therapies in the treatment of gastric cancer and gives a perspective on the future.

Congenital heart disease (CHD) is a worldwide problem with high morbidity and mortality. Early diagnosis of congenital heart disease is still a challenge in clinical work. In recent years, few studies indicated that placental methylation may be predictors of CHD. More studies are needed to confirm the association between placental methylation and CHD. The aim of this study was to investigate the association between prenatal placental DNA methylation and CHD. Placental tissues were obtained from four fetuses during the second trimester with isolated, non-syndromic congenital heart disease, including three cases with double outlet right ventricle (DORV) and one case with tetralogy of Fallot (TOF), and four unaffected fetuses as controls. The Illumina Infinium Human Methylation 850K BeadChip assay was employed to identify differential methylation sites (DMSs) and differential methylation regions (DMRs). Differential methylation was evaluated by comparing the β-values for individual CpG loci in cases vs. controls. In addition, the function of genes was assessed through KEGG enrichment analysis, Gene Ontology (GO) analysis and KEGG pathway analysis. Compared with the control group, we identified 9625 differential methylation genes on 26,202 DMSs (p 0.05), of which 6997 were hyper-methylation and 2628 were hypo-methylation. The top 30 terms of GO biological process and KEGG enrichment analysis of DMSs were connected with multiple important pathways of heart development and disease. Ten differentially methylated regions and the genes related to DMRs, such as TLL1, CRABP1, FDFT1, and PCK2, were identified. The deformity caused by the loss of function of these genes is remarkably consistent with the clinical phenotype of our cases. The DNA methylation level of placental tissue is closely associated with fetal congenital heart disease.

Object. In this study, bioinformatics analysis of differentially expressed genes (DEGs) and signaling pathway activities in different progression stages of chronic lymphocytic leukemia (CLL) and pre- and post-chemoimmunotherapy (CIT) treatment was performed. This may provide novel ideas for molecular diagnosis and individualized treatment strategies for CLL patients. Methods. Data from single-cell RNA sequencing (RNA-seq) of CLL patients were obtained from the Gene Expression Omnibus database. The R package was utilized to analyze the data, and the relation of results was predicted via the GeneMANIA website. The information of 7 samples covered three stages: observation stage, pretreatment by CIT with rituximab, fludarabine, and cyclophosphamide (pre-CIT), and post-CIT. The differentially expressed genes (DEGs) were identified, and functional enrichment analyses were performed. B cell subpopulations and pseudotime trajectories analysis was conducted. Results. A total of 70,659 DEGs were identified. Each patient’s DEGs presented their own characteristics, with low similarity. Therefore, it is difficult to identify potential hub genes. Similarly, pathway enrichment analysis showed significant tumor heterogeneity among CLL patients. Analysis of relapsed post-CIT compared to the observation stage suggested that the TP53 pathway should be taken seriously as it is closely related to treatment strategy and patient prognosis. Conclusions. Tumor heterogeneity may be a more common manifestation of CLL. Individualized treatment should be considered for CLL. TP53 abnormality and its regulatory factors should still be the focus of CLL diagnosis and treatment.

As a toxic substance on human health produced in food thermal treatment, simple analytical approaches are highly desired for the detection of acrylamide (ACR) in foods. With the aid of exonuclease III (Exo III), a simple fluorescence sensor was proposed based on carboxyfluorescein-labeled double-stranded DNA (FAM-dsDNA) and a cationic conjugated polymer (PFP). Fluorescence resonance energy transfer (FRET) efficiency between FAM and PFP was changed with and without ACR. When ACR was present, ACR and single-stranded DNA (P1, ssDNA) formed an adduct, allowing free FAM-labeled complementarity strand DNA (P2, FAM-csDNA) to appear in the solution and avoiding the digestion of P2 by Exo III. After the addition of PFP, the interaction of PFP and FAM induced strong FRET. Under optimized conditions, ACR was detected with a limit of detection (LOD) of 0.16 μM. According to this biosensor, a LOD of 1.3 μM in water extract samples was observed with a good recovery rate (95-110 %).

A quantitative analysis was performed to evaluate the morphologic changes of the retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) in patients with Parkinson's disease (PD).Thirty PD patients were enrolled, and they were allocated to the mild-to-moderate PD group (n = 15) or severe PD group (n = 15) according to the severity of PD. Twenty healthy volunteers (20 eyes) were included as controls. Optical coherence tomography (OCT) was used to measure the thickness of mean RNFL and each of the sectors: temporal-upper (TU), superior-temporal (ST), superior-nasal (SN), nasal-upper (NU), nasal-lower (NL), inferior-nasal (IN), inferior-temporal (IT), temporal-lower (TL). The thickness of macular GCC, superior GCC, and inferior GCC was also measured.No difference was found between the three groups with respect to age, sex and disease course (p 0.05). The mean RNFL thickness was 118.15 ± 10.25 µm in the control group, 96.12 ± 9.45 µm in the mild-to-moderate PD group, and 80.48 ± 10.35 µm in the severe PD group. Significant differences were found in the mean RNFL thickness and thickness of TU, IN, IT and TL sectors among the three groups (p 0.05). These values, mean RNFL, TU, IN, IT, and TL, were lower in both the PD groups than those in the control, among them the severe PD group had the lowest values. A quantitative analysis of the macula GCC was also performed. Overall, there were significant differences in mean macula, superior, and inferior GCC thickness among the three groups (p 0.05). The two PD groups had lower values of mean macula, superior, and inferior GCC thickness than that in the controls (p 0.05); and the severe PD group had lowest values of these parameters.In this study, significant thinning of RNFL and macular GCC was found in PD patients. The more serious the illness, the more the thickness becomes thinner. The OCT measurement was found useful in detecting the structural alterations in the retina of PD. The technique may be useful in follow-up of the disease progression after further validation.

Ying Zhao,1,* Shiyuan Lin,1,2,* Ruiyue Fang,1 Yaling Shi,1 Wei Wu,1 Wei Zhang,1 Hui Chen1 1College of Pharmacy, Guilin Medical University, Guilin, 541199, People’s Republic of China; 2Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Chen; Wei Zhang, College of Pharmacy, Guilin Medical University, No. 1 Zhiyuan Road, Guilin, 541199, People’s Republic of China, Email chenhui_gl@163.com; 22437564@qq.comIntroduction: In the previous study, nanoparticles coated with trimethyl chitosan (TMC) derivatives (PPTT-NPs) could promote the oral bioavailability of panax notoginseng saponins (PNS). Herein, we chose PPTT-NPs as a model drug to study the property and mechanism of intestinal absorption in vitro and in vivo.Methods: The stability of PPTT-NPs was evaluated using simulated gastric fluid and simulated intestinal fluid. The uptake and transport of PPTT-NPs were investigated in Caco-2 and Caco-2&HT29 co-culture cells. The biosafety, intestinal permeability, adhesion, and absorption mechanism of PPTT-NPs were investigated using SD rats in vivo. The live imaging and biodistribution of PPTT-NPs were observed by IVIS. Furthermore, the effects on CYP3A4 of PPTT-NPs were investigated using testosterone as the probe substrate.Results: The results of the stability assay showed that PPTT-NPs had a strong tolerance to the pH and digestive enzymes in the gastrointestinal environment. In vitro cell experiments showed that the uptake of drugs exhibited a time-dependent. When the ratio of TMC-VB12 and TMC-Cys was 1:3, the uptake capacity of PPTT-NPs was the highest. PPTT-NPs could enhance the paracellular transport of drugs by reversibly opening a tight junction. Animal experiments demonstrated that PPTT-NPs have good biological safety. PPTT-NPs had good adhesion and permeability to small intestinal mucosa. Meanwhile, PPTT-NPs needed energy and various protein to participate in the uptake of drugs. The live imaging of NPs illustrated that PPTT-NPs could prolong the residence time in the intestine. Moreover, TMC-VB12 and TMC-Cys could reduce the metabolism of drugs by inhibiting CYP3A4 to a certain extent.Conclusion: The results show that TMC-VB12 and TMC-Cys are effective in the transport of PPTT-NPs. PPTT-NPs can increase the intestinal adhesion of drugs and exert high permeation by intestinal enterocytes which demonstrate significant and efficient potential for oral delivery of the BCS III drugs.Graphical Abstract: Keywords: Panax notoginseng saponins, TMC derivatives, nanoparticles, oral absorption, Caco-2&HT29 co-culture cells

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

The non-O1/non-O139 Vibrio cholerae caused outbreaks or sporadic cases of gastroenteritis that was rarely seen in good sanitary condition. It was described a case of systemic multiple organ lesions that worsened because of non-O1/non-O139 V. cholerae, suggesting that serogroups have a potential virulence in enhancing pathogenicity with patients with underlying diseases compared with a healthy population.Samples are identified by strain culture, polymerase chain reaction (PCR) virulence identification, and whole genome sequencing.A middle-aged man was diagnosed with cytotoxin-producing and nontoxin V. cholerae non-O1/non-O139 serogroups. Although lacking the CT toxin encoded by ctxAB gene, the pathogenesis of cholera relies on the synergistic action of many other genes, especially virulence genes.This case suggested that the laborers engaging in agricultural production are at potential risk of V. cholerae infection by exposure of open wounds to contaminated water . However, epidemiological investigation should focus on the objective cause of the change of working environment. Furthermore, common diseases can possibly enhance the virulence of non-O1/non-O139 serogroups by attacking the tight junction of small intestinal epithelial cells, further triggering bacteremia, a process that may lead to death within 48-72 hours, which requires great attention.

Human infection caused by an uncommon Salmonella enterica subsp. diarizonae (hereafter S. diarizonae) is rising. However, knowledge concerning S. diarizonae is still limited. This study aimed to investigate the genomic features of S. diarizonae S499 isolated from a child patient with gastroenteritis symptom in China.The antimicrobial susceptibility of S. diarizonae S499 was determined by microdilution broth assay. Whole genome was sequenced using Illumina HiSeq X-10 and PacBio RS II platforms and was de novo assembled using Unicycler and SPAdes. Conjugation experiment was performed by a broth mating method.S. diarizonae S499 was a multi-drug resistant (MDR) isolate and showed resistance to all cephalosporin drugs tested. Six plasmids (pS0499A, pS0499B, pS0499C, pS0499D, pS0499E and pS0499F) were identified. A rare gene cassette IS26-blaThis article reported the genome features of S. diarizonae S499, which contained four resistant plasmids including a novel plasmid pS0499A with a novel gene cassette rearrangement. These data could contribute to a better understanding of the antimicrobial resistance mechanisms and transmission dynamics of S. diarizonae.

Wuling capsule has been used in treatment of insomnia disorder in China for decades, but the reported treatment efficacy of different studies was not consistent. This study intended to evaluate the efficacy and safety of Wuling capsule for insomnia disorder, so as to provide evidence for clinical application.Eight databases (MEDLINE, EMBASE, Ovid, Cochrane Library, Chinese National Knowledge Infrastructure, VIP information database, Chinese Biomedical Database and Wanfang) were searched from inception to September 14, 2021. Randomized controlled trials (RCTs) comparing Wuling capsule with controls in adults with insomnia disorder were eligible. The primary outcome was sleep quality assessed by Pittsburgh Sleep Quality Index (PSQI), and the secondary outcomes were severity of insomnia disorder measured by Sleep Dysfunction Rating Scale (SDRS) and adverse events. This study was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0.Nineteen RCTs with a total of 1850 participants were included. In terms of sleep quality assessed by PSQI, Wuling capsule significantly lowered PSQI score (MD: -1.92, 95% CI: [-2.34, -1.50], P 0.00001, IWuling capsule can safely and effectively improve sleep quality in patients with insomnia disorder. However, these findings require careful recommendation due to the high heterogeneity and high risk of bias in the included trials. Clinical trials with higher quality designs are needed.

Renal-clearable nanomedicines are considered the next generation of nanomedicines, and show potential application for future clinical translations. However, it is important to determine whether self-assembly can form large aggregates that accrue in tumors and then tailor the size of these assemblies to be excreted renally. In this paper, a renal-clearable nanomedicine based on quanterrylene bisimide-mannose conjugates (

A study addressing the influence of type 2 diabetes on the prognosis of acute-on-chronic liver failure patients was reviewed. Some statistical deficiencies were found in the reviewed article, and the sample size was too small to support the study. In addition, age should have been considered as one of the prognostic factors.

Alcoholic liver disease (ALD), with its increasing morbidity and mortality, has seriously and extensively affected the health of people worldwide. Caffeic Acid Dimethyl Ether (CADE) significantly inhibits alcohol-induced hepatic steatosis

Introduction Gut microbiota has been implicated in the pharmacological activities of many natural products. As an effective hypolipidemic agent, berberine (BBR)’s clinical application is greatly impeded by the obvious inter-individual response variation. To date, little evidence exists on the causality between gut microbes and its therapeutic effects, and the linkage of bacteria alterations to the inter-individual response variation. Objectives This study aims to confirm the causal role of the gut microbiota in BBR’s anti-hyperlipidemic effect and identify key bacteria that can predict its effectiveness. Methods The correlation between gut microbiota and BBR’s inter-individual response variation was studied in hyperlipidemic patients. The causal role of gut microbes in BBR’s anti-hyperlipidemic effects was subsequently assessed by altered administration routes, co-treatment with antibiotics, fecal microbiota transplantation, and metagenomic analysis. Results Three-month clinical study showed that BBR was effectively to decrease serum lipids but displayed an obvious response variation. The cholesterol-lowering but not triglyceride-decreasing effect of BBR was closely related to its modulation on gut microbiota. Interestingly, the baseline levels of Alistipes and Blautia could accurately predict its anti-hypercholesterolemic efficiency in the following treatment. Causality experiments in mice further confirmed that the gut microbiome is both necessary and sufficient to mediate the lipid-lowering effect of BBR. The absence of Blautia substantially abolished BBR's cholesterol-decreasing efficacy. Conclusion The gut microbiota is necessary and sufficient for BBR’s hyperlipidemia-ameliorating effect. The baseline composition of gut microbes can be an effective predictor for its pharmacotherapeutic efficacy, providing a novel way to achieve personalized therapy.

There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC.This phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non-inferiority in progression-free survival (PFS) for XELOX as compared with EOX on an intention-to-treat basis.Between April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5-6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0-6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812-1.203; PThis non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.

Objective To retrospectively investigate the relationship between apolipoprotein E (APOE) gene polymorphism and in-stent restenosis (ISR) after stenting at the beginning of the vertebral artery. Methods The study included 155 patients who successfully underwent stenting at the beginning of the vertebral artery and had postoperative digital subtraction angiography or computed tomography angiography. Based on the follow-up results, they were divided into the restenosis (ISR) group and non-restenosis (non-ISR) group. The clinical information and APOE genotypes of both groups were analyzed. A binary logistic regression model was used to analyze independent risk factors for ISR. Results After 1 year of follow-up, 49 (31.6%) patients had ISR and 106 (68.4%) did not. Binary logistic regression analysis showed that serum low-density lipoprotein cholesterol (LDL-C), serum lipoprotein-related phospholipase A2 (Lp-PLA2), and E3/E4 genotype were independent risk factors for ISR after stenting at the beginning of the vertebral artery. In addition, the LDL-C level of patients with the E3/E4 genotype was higher compared to the E3/E3 genotype group (P Conclusions APOE gene polymorphism is associated with ISR, and the E3/E4 genotype is an independent risk factor for ISR after stenting at the beginning of the vertebral artery. Further genetic studies can identify risk genotypes to facilitate the early prediction and identification of high-risk patients with ISR.

Reverse flow Retrograde flow (RF) of blood in the aortic isthmus can be observed in different types of fetal heart disease (FHD), including abnormalities in heart structure and function. This study sought to investigate the relationship between RF and blood flow parameters, and develop a computational fluid dynamics (CFD) model to understand the mechanisms underlying this observation.A total of 281 fetuses (gestational age [GA] 26.6±.3 weeks) with FHD and 2803 normal fetuses (GA: 26.1±.1 weeks) by fetal echocardiography collected from May 2016 to December 2018. Principal component analysis (PCA) was performed to find the relationship and the CFD model reconstructed from 3D/4D spatio-temporal image correlation (STIC) images to simulate hemodynamics.There was a significant difference in the percentages of RF between the study (80/201 (39%)) and control (29/2803 (1%)) groups (p 0.05). The RF occur when the aorta flow rate (left heart) is reduced to 60% by CFD stimulation. Pearson correlation analysis showed significant correlations between flow rate and wall shear stress(WSS) (r = .883, p = 0.047) variables at the AI.Volumetric flow rate of AO or left heart was the main component of the cause of RF. The hemodynamics of the cardiovascular system have highly complex behavior hinge on the turbulent nature of circulating blood flow.

Yogurt consumption shows a wide range of effects on the gut microbial composition, and correlation of components in yogurt with the changes of gut microbia remains largely uncharacterized. We aimed to determine the effect of brown yogurt (SSN) on the composition of the gut microbiota and to explore the effects of the major components. We performed a randomized study of 70 healthy adults to compare the effects of SSN and standard probiotic-containing yogurt (YJD) during a 28-day intervention and a 10-day follow-up period. The results showed that the SSN group showed significant increases in the butyrate-producer

Periodontitis is a chronic inflammatory disease that affects tooth-supporting tissues and even leads to tooth loss. NLRP3 inflammasomes play a critical role in periodontitis pathogenesis. Aberrant activation or overexpression of NLRP3 inflammasomes in cellular players, including osteoclasts, osteoblasts, periodontal ligament fibroblasts, and leukocytes often contributes to cellular dysfunction and environment abnormality, thus resulting in the disorganization of ligament and alveolar bone. In this review, we mainly focus on the negative regulation of NLRP3 inflammasome in periodontitis and highlight the importance of NLRP3 inflammasome as a candidate therapeutic target in periodontitis treatment. Then we elucidate the development status of NLRP3 inflammasome inhibitors and show their application potential for treating periodontitis. In summary, this review reveals the recent progress and perspectives of NLRP3 inflammasome and the therapeutic potential of NLRP3 inflammasome inhibitors in periodontitis.

In this review, we discussed an interesting case infected with "COVID-19" (Corona Virus Disease 2019). The patients with Hodgkin's lymphoma recovered after infection with COVID-19. It may be that COVID-19 activates the patient's immune system, or it may be a coincidence. COVID-19 spike protein can interact with CD147 and use it as an entry to invade host cells. CD147 is a partner of SLC3A2, which is the chaperone subunit of cystine/glutamate reverse transporter (system XC). The catalytic subunit of system XC is SLC7A11. SLC7A11 mediated cysteine uptake plays a key role in ferroptosis. Through literature review and data analysis, we suggest that CD147, as a new potential COVID-19 infection entry, may also lead to ferroptosis of host cells. Our hypothesis is that spike protein of COVID-19 induced ferroptosis in host cells via CD147/SLC3A2/SLC7A11 complex. This is another explanation for the cancer patient recovered after COVID-19 infection.

Most patients with ovarian cancer (OC) get remission after undergoing cytoreductive surgery and platinum-based standard chemotherapy, but more than 50% of patients with advanced OC relapse within the first 5 years after treatment and develop resistance to standard chemotherapy. The production of medicinal properties is the main reason for the poor prognosis and high mortality of OC patients. Cisplatin (DDP) resistance is a major cause for poor prognosis of OC patients. PTPRZ1 can regulate the growth and apoptosis of ovarian cancer cells, while the molecular mechanism remains unknown. This study was designed to investigate the roles of PTPRZ1 in DDP-resistant OC cells and possible mechanism. PTPRZ1 expression in OC tissues and normal tissues was analyzed by GEPIA database and verified by Real-time Quantitative Reverse Transcription PCR (RT-PCR) assay. PTPRZ1 expression in normal ovarian cancer cells and DDP-resistant OC cells was also analyzed. Subsequently, RT-PCR, Western blot, MTT experiment and flow cytometry were used to assess the effects of PTPRZ1-PI3K/AKT/mTOR regulating axis on DDP resistance of OC. PTPRZ1 expression was abnormally low in OC tissues, and notably reduced in DDP-resistant OC cells. MTT experiment and flow cytometer indicated that overexpression of PTPRZ1 enhanced the DDP sensitivity of OC cells and promoted the cell apoptosis. Moreover, the results of our research showed that PTPRZ1 might exert its biological effects through blocking PI3K/AKT/mTOR pathway. PTPRZ1 overexpression inhibitied OC tumor growth and resistance to DDP in vivo. Overall, PTPRZ1 might suppress the DDP resistance of OC and induce the cytotoxicity by blocking PI3K/AKT/mTOR pathway.

Graves’ disease (GD) is a kind of autoimmune diseases. The development of GD is closely related to the imbalance of Th1/Th2 generated by the differentiation of CD4(+) T cells. This study was sought to clarify the role of lncRNA RUNX1-IT1 and explore the mechanism of its function. The expressions of RUNX1-IT1 and Neural cell adhesion molecule (NrCAM) in the peripheral blood of GD patients were detected by qRT-PCR and Western blot. We performed RNA pull down, RIP, and ChIP experiments to verify the correlation between p53 and RUNX1-IT1, p53 and NrCAM. The levels of Th1 cells differentiation markers were detected by Flow cytometry assay and ELISA. The expressions of lncRNA RUNX1-IT1 and NrCAM were most significantly up-regulated in CD4(+) T cells of GD patients, and NrCAM expression was significantly positively correlated with RUNX1-IT1 expression. Furthermore, p53 was a potential transcription factor of NrCAM, which could interact with NrCAM. NrCAM level was up-regulated after the overexpression of p53 in CD4(+) T cells, while knockdown of RUNX1-IT1 reversed this effect. Down-regulation of NrCAM and RUNX1-IT1 could decrease the mRNA and protein levels of transcriptional regulator T-bet and CXC chemokine ligand 10 (CXCL10) in CD4(+) T cells. Our results suggested that RUNX1-IT1 regulated the expressions of the important Th1 factor T-bet, CXCL10, and interferon γ (IFN-γ) by regulating NrCAM transcription, thus participating in the occurrence and development of specific autoimmune disease GD.

AIM: The purpose of this project was to connect nursing students from schools of nursing in China and the United States for co-learning using virtual simulations. BACKGROUND: With technology and international partnerships, nursing programs can offer global education without students traveling to other countries. METHOD: Virtual simulations were produced by each school for the project. Students completed them in two synchronous 1.5-hour virtual sessions, one month apart. At the end of each session, students completed the Simulation Effectiveness Tool-Modified (SET-M) and Nurses Clinical Reasoning Scale (NCRS). RESULTS: Scores on the SET-M ranged from 75.0 to 100 percent on simulation 1 (video vignettes focused on prioritization) and 88.9 to 100 percent on simulation 2 (computer-based obstetrics case). Most students strongly agreed or agreed that the simulation improved their clinical reasoning skills. CONCLUSION: Virtual simulations allowed students to learn together and develop an awareness of differences in nursing practices across countries.

Infertility has become a global public health issue. In vitro fertilization and embryo transfer (IVF-ET) is widely performed as an infertility treatment. However, a significant number of infertile women continue to experience serial implantation failure, despite the high quality of the transferred embryos. Jian-Pi-An-Tai formula is an experience formula in treating threatened abortion in our team. It has also been used to treat infertile women after embryo transfer and shows superiority compared to single use of conventional western medicine. However, the of evidence on its effective in treating infertile women undergo IVF-ET is lacking.This randomized controlled trial (RCT) will be carried out in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University planning to recruit 180 infertile patients undergoing IVF-ET with the type of deficiency of both the spleen and kidney. The control group will be treated by conventional western medicine and the treatment group will use conventional western medicine plus Jian-Pi-An-Tai formula. The primary outcomes will include Embryo implantation rate, Clinical pregnancy rate, Persistent pregnancy rate; and the secondary outcomes will include TCM symptom score and reproductive hormones. Safety evaluation will be recorded during the whole study. All data in this RCT will be analyzed by SPSS 23.0 software. This study has been approved by the Research Ethics Committee of the Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University (2022KY130).The results of this RCT will contribute to provide scientific and rigorous evidence for the efficacy and safety of Jian-Pi-An-Tai formula in treating infertile women undergo IVF-ET. And the results from this RCT will be published in a relevant journal after finished.

Aim Hypothyroxinemia might be easily ignored, due to attention is typically paid to individuals with elevated thyroid stimulating hormone (TSH). In this study, we aimed to evaluate the association of oxcarbazepine use as adjuvant for treatment of schizophrenia with hypothyroxinemia and central set point of thyroid homeostasis. Methods This retrospective cohort study was conducted in the "Second Affiliated Hospital of Xinxiang Medical University". Inpatients with a diagnosis of schizophrenia admitted between January 2016 and October 2019 with normal thyroid function at admission were included. Oxcarbazepine use was the exposure measure. Newly developed hypothyroxinemia was the primary outcome measure and parameters of thyroid homeostasis central set point as measured by "TSH index" and "thyroid feedback quantile-based index (TFQI)" were the secondary outcome measures. Results A total of 1,207 eligible patients were included. The occurrence of hypothyroxinemia in patients who received oxcarbazepine was higher (35/107, 32.7%) than in those patients who did not (152/1099, 13.8%), with adjusted relative risk of 2.24 and 95% confidence interval of 1.57 and 3.17. Oxcarbazepine use was associated with greater reduction in TSH index (adjusted β -0.33 and 95% confidence interval -0.48, -0.19) and TFQI (adjusted β -0.24 and 95% confidence interval -0.31, -0.16). Conclusion Oxcarbazepine use was independently associated with increased risk of developing hypothyroxinemia, and greater reduction in TSH index and TFQI, suggesting that impaired central set point of thyroid homeostasis might be involved in the mechanism of oxcarbazepine induced hypothyroxinemia.

Purpose: This study sought to compare enamel surface morphology and orthodontic bracket re-bonding strength after phosphoric acid- or erbium-doped yttrium aluminum garnet (Er:YAG) laser-mediated re...

Background This study aimed to determine the risk factors of early intraventricular hemorrhage (IVH) in very-low-birth-weight (VLBW) premature infants in China to guide early interventions and improve the survival and quality of life of these infants. Methods Data on 421 VLBW premature infants admitted to the neonatal intensive care unit of Tianjin Central Hospital of Gynecology Obstetrics between July 2017 and July 2019 were retrospectively evaluated. Data on head ultrasound results, maternal pregnancy complications, and perinatal conditions were reviewed to evaluate the association between maternal and neonatal factors and the development and severity of IVH. Results Univariate analysis showed that the incidence of early IVH was significantly higher in neonates with early gestational age, delivered after spontaneous labor, low birth weight, 5-minute Apgar score ≤ 7, invasive mechanical ventilation, and early onset sepsis (χ2 = 11.087, 16.868, 4.779, 11.170, 6.655, and 6.260, respectively; P 2 = 4.373, P = 0.037). In addition, severe IVH was significantly associated with early gestational age, low birth weight, 5-minute Apgar score ≤ 7, and neonatal sepsis (χ2 = 11.599, 8.263, 11.172, and 7.749, respectively; P P = 0.024). Conclusion Appropriate mode of delivery may effectively reduce the incidence of IVH in VLBW premature infants. The antenatal glucocorticoid use may also protect against severe IVH. The focus on steroid prophylaxis, mode of delivery and prevention of perinatal asphyxia should be stressed in China.

MicroRNA-1290 (miR-1290) has been reported to be involved in many diseases and play a key role during the development process. However, the role of miR-1290 in atherosclerosis (AS) is still unclear. The current study showed that the expressions of miR-1290 were high in serum of patients with hyperlipidemia. The functional role of miR-1290 were then investigated in human umbilical vein endothelial cells (HUVECs). Here, we found that miR-1290 expressions were notably enhanced in HUVECs mediated by IL-8. miR-1290 inhibitor repressed monocytic THP-1 cells adhesion to HUVECs by regulating ICAM-1 and VCAM-1, inhibited proliferation through regulating cyclinD1 and PCNA, and inhibited inflammatory response by regulating IL-1β. Mechanistically, we verified that miR-1290 mimic was able to directly target the 3′-UTR of GSK-3β mRNA using luciferase reporter assay. Knockdown of GSK-3β (si-GSK-3β) promoted HUVECs adhesion and the expression of IL-1β, and partially restore the depression effect of miR-1290 inhibitor on HUVECs adhesion and inflammation. In contrast, si-GSK-3β inhibited the proliferation of HUVECs and the expression of cyclinD1 and PCNA. In summary, our study revealed that miR-1290 promotes IL-8-mediated the adhesion of HUVECs by targeting GSK-3β. However, GSK-3β is not the target protein for miR-1290 to regulate the proliferation of HUVECs. Our findings may provide potential target in atherosclerosis treatment.

Cefepime exhibits a broad spectrum of antimicrobial activity and thus is a widely used treatment for severe bacterial infections. Adverse effects on the central nervous system (CNS) have been reported in patients treated with cefepime. Current explanation for the adverse neurobehavioral effect of cefepime is mainly attributed to its ability to cross the blood-brain barrier and competitively bind to the GABAergic receptor; however, the underlying mechanism is largely unknown. In this study, mice were intraperitoneally administered 80 mg/kg cefepime for different periods, followed by neurobehavioral tests and a brain lipidomic analysis. LC/MS-MS-based metabolomics was used to investigate the effect of cefepime on the brain lipidomic profile and metabolic pathways. Repeated cefepime treatment time-dependently caused anxiety-like behaviors, which were accompanied by reduced locomotor activity in the open field test. Cefepime profoundly altered the lipid profile, acyl chain length, and unsaturation of fatty acids in the corpus striatum, and glycerophospholipids accounted for a large proportion of those significantly modified lipids. In addition, cefepime treatment caused obvious alteration in the lipid-enriched membrane structure, neurites, mitochondria, and synaptic vesicles of primary cultured striatal neurons; moreover, the spontaneous electrical activity of striatal neurons was significantly reduced. Collectively, cefepime reprograms glycerophospholipid metabolism in the corpus striatum, which may interfere with neuronal structure and activity, eventually leading to aberrant neurobehaviors in mice.

This study aimed to assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with modified FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as an alternative treatment option in advanced hepatocellular carcinoma (HCC) patients with failed or unsuitability for transarterial chemoembolization (TACE). MATERIALS AND METHODS: From September 2018 to January 2020, 87 advanced HCC patients who progressed on TACE or were not eligible for TACE received HAIC treatment with modified FOLFOX. The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), tumor response assessed by Response Evaluation Criteria in Solid Tumors 1.1, and adverse events graded according to CTCAE 5.0. Based on prognostic factors determined by multivariate analysis, a nomogram was developed to predict patient survival.The median OS and PFS were 9.0 months (95%CI 7.6-10.4) and 3.7 months (95%CI 3.1-4.3), respectively. The objective response rate was 13.8%, with a disease control rate of 48.3%. Grade 3 adverse events were observed, such as infection (9.2%), thrombocytopenia (5.7%), hyperbilirubinemia (3.4%), abdominal pain (2.3%) and alanine aminotransferase increase (2.3%). Albumin, AST, and extrahepatic metastasis were incorporated to construct a new nomogram that could stratify patients into three prognostic subgroups, including low-, intermediate-, and high-risk groups, with significant differences in 9-month OS rates (71%, 42% and 6%, respectively; p0.001). The nomogram was better than the Okuda, AJCC, and CLIP staging systems for OS prediction.These findings support the feasibility of HAIC with modified FOLFOX as an alternative treatment strategy for advanced HCC when TACE is ineffective or unsuitable.

To observe the clinical efficacy of moxibustion on rheumatoid arthritis (RA) and its effect on related negative emotions, and to explore the possible mechanism.A total of 70 patients with RA were randomized into an observation group (35 cases, 1 case dropped off) and a control group (35 cases, 2 cases dropped off). Conventional western medication therapy was adopted in the control group. On the basis of the treatment in the control group, moxibustion at Zusanli (ST 36), Shenshu (BL 23) andCompared before treatment, the scores of VAS and DAS28 were decreased after treatment in both groups (Moxibustion can improve the clinical symptoms and negative emotions in patients with RA by regulating the inflammatory reactions.

Oligovascular coupling contributes to white matter vascular homeostasis. However, little is known about the effects of oligovascular interaction on oligodendrocyte precursor cell (OPC) changes in chronic cerebral ischemia. Here, using a mouse of bilateral carotid artery stenosis, we show a gradual accumulation of OPCs on vasculature with impaired oligodendrogenesis. Mechanistically, chronic ischemia induces a substantial loss of endothelial caveolin-1 (Cav-1), leading to vascular secretion of heat shock protein 90α (HSP90α). Endothelial-specific over-expression of Cav-1 or genetic knockdown of vascular HSP90α restores normal vascular-OPC interaction, promotes oligodendrogenesis and attenuates ischemic myelin damage. miR-3074(−1)−3p is identified as a direct inducer of Cav-1 reduction in mice and humans. Endothelial uptake of nanoparticle-antagomir improves myelin damage and cognitive deficits dependent on Cav-1. In summary, our findings demonstrate that vascular abnormality may compromise oligodendrogenesis and myelin regeneration through endothelial Cav-1, which may provide an intercellular mechanism in ischemic demyelination.

Suboptimal health status (SHS) is a reversible stage between health and illness that is characterized by health complaints, low energy, general weakness, and chronic fatigue. The Suboptimal Health Status Questionnaire-25 (SHSQ-25) has been validated in three major populations (African, Asian, and Caucasian) and is internationally recognized as a reliable and robust tool for health estimation in general populations. This study focused on the development of K-SHSQ-25, a Korean version of the SHSQ-25, from its English version.The SHSQ-25 was translated from English to Korean according to international guidelines set forth by the World Health Organization (WHO) for health instrument translation between different languages. A subsequent cross-sectional survey involved 460 healthy South Korean participants (aged 18-83 years; 65.4% females) to answer the 25 questions focusing on the health perspectives of 5 domains, 1) fatigue, 2) cardiovascular health, 3) digestive tract, 4) immune system and 5) mental health. The K-SHSQ-25 was further validated using tests for reliability, internal consistency, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA).The version of K-SHSQ-25 achieved linguistic, cultural, and conceptual equivalence to the English version. The intraclass correlation coefficient (ICC) of test-retest reliability for individual items ranged from 0.88 to 0.99. Reliability estimates based on internal consistency reached a Cronbach's α of 0.953; the Cronbach's α for each domain ranged from 0.76 to 0.94. Regarding construct validity, the EFA of the K-SHSQ-25 generally replicated the multidimensional structure (fatigue, cardiovascular, digestive, immune system, and mental health) and 25 questions. The CFA revealed that the root mean square error of approximation (RMSEA), goodness-of-fit index (GFI) and adjusted goodness of fit index (AGFI) were excellent (RMSEA = 0.0690.08, GFI = 0.9290.90, AGFI = 0.9070.90). The five domains of the K-SHSQ-25 showed significant correlations with each other (r = 0.59-0.81, P0.001). The cut-off point of K-SHSQ-25 for SHS was determined as an SHS score of 25. The prevalence of SHS in this study was 60.0% (276/460), with 47.8% (76/159) for males and 58.5% for females (176/301).Our results indicate that the Korean version of SHSQ-25, K-SHSQ-25, is a transcultural equivalent, robust, valid, and reliable assessment tool for evaluating SHS in the Korean-speaking population.

To evaluate the safety of the 15-valent pneumococcal conjugate vaccine (PCV15 (by LvZhuCo. Ltd)) in healthy infants aged 2 months (minimum to 6 weeks) and 3 months old. This phase I clinical trial enrolled 80 subjects in Laishui County, Hebei Province, China. The total population was divided into 4 age groups on average: 20 adults (≥18 years) and 20 children (1-5 years) all received one vaccine dose; 20 infants (3 months) received the vaccine according to a 3-dose schedule at 0, 1, and 2 months. Twenty infants (2 months, minimum of 6 weeks old) received the vaccine according to a 3-dose schedule of 0, 2, and 4 months. The adverse events (AEs) until 30 days after each dose and serious adverse events (SAEs) until 6 months after the whole dose were reported. The solicited and unsolicited AE frequencies and laboratory indices were similar among the treatment groups. No vaccine-related SAEs were reported. Most vaccine-related adverse events consisting of systemic and local reactions were fever and pain. One hypersensitivity manifested as systemic urticaria that occurred on the third day after the second dose in the 2-month group. The 15-valent pneumococcal conjugate vaccine was generally well tolerated in infants.

OBJECTIVE To investigate the relationship between mild congenital pulmonary airway malformation (CPAM) and its long-term prognosis in childhood and to explore whether surgery is necessary. METHODS We conducted a retrospective cohort of fetuses with mild CPAM diagnosed prenatally with available long-term outcomes in childhood from 2004 to 2016. The patients were divided into two groups according to the fetal CPAM-to-volume ratio (CVR) of less than 1.0 and 1.0-1.6. The primary outcome was a postnatal composite outcome including CPAM-associated respiratory symptoms and surgical resection of the lesion. The secondary outcomes included neonatal asphyxia, perinatal morbidity and mortality. RESULTS Forty-two fetuses were identified as having CVR

Deaf and hard of hearing (DHH) students face great challenges in becoming proficient readers. Vocabulary knowledge is consistently considered to be an important factor affecting DHH students’ reading ability. However, the mechanism that underlies the relationship between vocabulary knowledge and reading comprehension in DHH students remains unclear. Thus, the aim of this study was to determine the roles of word segmentation and reading fluency in the contribution of vocabulary knowledge to Chinese DHH students’ reading comprehension. A battery of tasks were administered to 116 Chinese DHH students from Grades 4 to 6 (mean age = 14.66 years). The results showed that vocabulary knowledge contributed to reading comprehension significantly in Chinese DHH students, and word segmentation and reading fluency played mediating roles in this relationship. Besides, the chain mediation effect of word segmentation and reading fluency was also significant. Revealing these mechanisms, which underlie the relationship between vocabulary knowledge and reading comprehension, is helpful to tailor remediation for DHH students.

The objective of this study was to explore a new method for the differential diagnosis between fetal double aortic arch (DAA) and right aortic arch with mirror-image branches (RAA-MB). Clinical data and prenatal echocardiographic features of the DAA (n = 22) and RAA-MB (n = 65) confirmed by postnatal or autopsy findings were analyzed retrospectively. The angles between the two aortic arches in the DAA group and between the right aortic arch and the mirror branch were measured. The differences between the two groups and differential diagnosis value of the angles were compared and analyzed based on the receiver operating characteristic curve. The proportion of left-sided ductal arteriosus (100%) was higher in the DAA group than that (32.3%) in the RAA-MB group, (P

SARM1, an executioner in axon degeneration, is an autoinhibitory NAD-consuming enzyme, composed of multiple domains. NMN and its analogs, CZ-48 and VMN, are the only known activators, which can release the inhibitory ARM domain from the enzymatic TIR domain. Here, we document that acid can also activate SARM1, even more efficiently than NMN, possibly via the protonation of the negative residues. Systematic mutagenesis revealed that a single mutation, E689Q in TIR, led to the constitutive activation of SARM1. It forms a salt bridge with R216 in the neighboring ARM, maintaining the autoinhibitory structure. Using this 'acid activation' protocol, mutation K597E was found to inhibit activation, while H685A eliminated SARM1 catalytic activity, revealing two distinct inhibitory mechanisms. The protocol has also been applied to differentiate two classes of chemical inhibitors. NAD, dHNN, disulfiram, CHAPS, and TRX-100 mainly inhibited the activation process, while nicotinamide and Tweens mainly inhibited SARM1 catalysis. Taken together, we demonstrate a new mechanism for SARM1 activation and decipher two distinct inhibitory mechanisms of SARM1.

Aims Hypothyroxinaemia could be easily neglected if attention is paid only to patients with elevated thyroid-stimulating hormone. We aimed to assess the association between mirtazapine use and hypothyroxinaemia in patients affected by major depressive disorder. Methods We conducted a retrospective cohort study in the Second Affiliated Hospital of Xinxiang Medical University between January 2016 and December 2018. Patients affected by major depression disorder and admitted to the hospital for treatment during the study period and who had thyroid tests at admission and after treatment were included. Mirtazapine use during hospitalization was the exposure measure and newly developed hypothyroxinaemia was as the primary outcome and structure parameters of thyroid homeostasis were the secondary outcomes of this study. Log-binomial model was used to estimate the association between mirtazapine use and hypothyroxinaemia, after adjusting for potential confounding factors. Results A total of 220 eligible patients were included in the final analysis. The incidence of hypothyroxinaemia in patients who used mirtazapine was higher (37.5%) than those patients who did not use (19.7%). The relative risk of developing hypothyroxinaemia was 1.70 (95% confidence interval: 1.21-2.43) for mirtazapine use, after adjusting for confounding factors. The degree of reduction in thyroid feedback quantile-based index in mirtazapine group was significantly greater than that in nonmirtazapine group. Conclusion Mirtazapine use was associated with the increased risk of developing hypothyroxinaemia. The underlying mechanism may be involved the changed central set point of thyroid homeostasis, in which pituitary was in a possibly impaired sensitivity to the lower level of thyroid hormones.

The orchid Dendrobium officinale grows throughout southeast China and southeast Asian countries and is used to treat inflammation and diabetes in traditional Chinese medicine. Tie pi feng dou is a well-known traditional Chinese medicine made from the dried D. officinale stems. Processing alters the physicochemical properties of TPFD; however, it is unclear how processing affects the quality and medicinal value of this plant. Here, we analyzed and compared the chemical composition of fresh stems of D. officinale and TPFD and explored possible explanations for the enhanced medicinal efficacy of processed D. officinale stems using qualitative and quantitative methods. To identify the components of FSD and TPFD, we used ultra-high-performance liquid chromatography combined with mass spectrometry in negative and positive ion modes and interpreted the data using the Human Metabolome Database and multivariate statistical analysis. We detected 23,709 peaks and identified 2352 metabolites; 370 of these metabolites were differentially abundant between FSD and TPFD (245 more abundant in TPFD than in FSD, and 125 less abundant), including organooxygen compounds, prenol lipids, flavonoids, carboxylic acids and their derivatives, and fatty acyls. Of these, 43 chemical markers clearly distinguished between FSD and TPFD samples, as confirmed using orthogonal partial least squares discriminant analysis. A pharmacological activity analysis showed that, compared with FSD, TPFD had significantly higher levels of some metabolites with anti-inflammatory activity, consistent with its use to treat inflammation. In addition to revealing the basis of the medicinal efficacy of TPFD, this study supports the benefits of the traditional usage of D. officinale.

OBJECTIVE: To evaluate the value of high intensity stimulation training of semicircular canal of SRM-Ⅳ vertigo diagnosis and treatment system in the rehabilitation of vestibular neuritis. METHODS: To analyze 68 patients with vestibular neuritis treated in Department of Otorhinolaryngology Head and Neck Surgery, Shijiazhuang People's Hospital from January 2020 to January 2021, conduct spontaneous nystagmus and head toss test, and perform spontaneous nystagmus and rotation test of SRM-Ⅳvertigo system, compare the positive rate of the side of disease was between the two. To randomly divide 68 patients into treatment group 1, 2 and control group, the control group with drugs, treatment group 1 with drugs and vestibular rehabilitation training exercise, treatment group 2 with additional high intensity stimulation training of semicircular canal at one week after onset, on the basis of drug therapy and vestibular rehabilitation training exercise. At 2 weeks and 1 month, through swivel chair test negative rate, DHI score, compare the efficacy of the three groups. RESULTS: Spontaneous nystagmus combined with head toss test confirmed 80.9% of the side of the disease, spontaneous nystagmus and rotation test of SRM-Ⅳ vertigo system confirmed 100%, the difference is statistically significant(P < 0.05). Compared with the control group and the treatment group 1, the negative conversion rate of the rotation test in the treatment group 2 at the second week and the first month of treatment, the difference is statistically significant(P < 0.05, the second week χ(2)=6.474, the first month χ(2)=6.245); the DHI score of treatment group 2 was statistically significant compared with that of control group and treatment group 1 at the second week and first month of treatment(P < 0.05, the second week F=13.578, the first month F=28.599). CONCLUSION: SRM-Ⅳ vertigo diagnosis and treatment system semicircular canal high intensity stimulation training has a certain role in the rehabilitation treatment of vestibular neuritis. It is simple to operate, patient tolerance and compliance are good, and it is worth promoting.

Epimedium has gained widespread clinical application in Traditional Chinese Medicine, with the functions of promoting bone reproduction, regulating cell cycle and inhibiting osteoclastic activity. However, its precise cellular pharmacological therapeutic mechanism on osteoporosis (OP) remains elusive. This study aims to elucidate the molecular mechanism of epimedium in the treatment of OP based on system bioinformatic approach. Predicted targets of epimedium were collected from TCMSP, BATMAN-TCM and ETCM databases. Differentially expressed mRNAs of OP patients were obtained from Gene Expression Omnibus database by performing Limma package of R software. Epimedium-OP common targets were obtained by Venn diagram package for further analysis. The protein-protein interaction network was constructed using Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out by using clusterProfiler package. Molecular docking analysis was conducted by AutoDock 4.2 software to validate the binding affinity between epimedium and top 3 proteins based on the result of protein-protein interaction. A total of 241 unique identified epimedium targets were screened from databases, of which 62 overlapped with the targets of OP and were considered potential therapeutic targets. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that these targets were positive regulation of cell cycle, cellular response to oxidative stress and positive regulation of cell cycle process as well as cellular senescence, FoxO, PI3K-Akt, and NF-kappa B signaling pathways. Molecular docking showed that epimedium have a good binding activity with key targets. Our study demonstrated the multitarget and multi-pathway characteristics of epimedium on OP, which elucidates the potential mechanisms of epimedium against OP and provides theoretical basis for further drug development.

Optogenetically engineered cell population obtained by heterogeneous gene expression plays a vital role in life science, medicine, and biohybrid robotics, and purification and characterization are essential to enhance its application performance. However, the existing cell purification methods suffer from complex sample preparation or inevitable damage and pollution. The efficient and nondestructive label-free purification and characterization of the optogenetically engineered cells, HEK293-ChR2 cells, is provided here using an optically-induced dielectrophoresis (ODEP)-based approach. The distinctive crossover frequencies of the engineered cells and the unmodified cells enable effective separation due to the opposite DEP forces on them. The ODEP-based approach can greatly improve the purity of the separated cell population and especially, the ratio of the engineered cells in the separated cell population can be enhanced by 275% at a low transfection rate. The size and the membrane capacitance of the separated cell population decreases and increases, respectively, as the ratio of the engineered cells grows in the cell population, indicating that successful expression of ChR2 in a single HEK293 cell makes its size and membrane capacitance smaller and larger, respectively. The results of biohybrid imaging with the optogenetically engineered cells demonstrated that cell purification can improve the imaging quality. This work proves that the separation and purification of engineered cells are of great significance for their application in practice.

Sensitive, accurate, and simultaneous determination of nitrobenzene compounds (NBs) in environmental water samples is of great significance due to their high risk to human health. In this work, a new triazine-based hyper-crosslinked polymer named CC-Py was constructed via the Friedel-Crafts reaction between cyanuric chloride (CC), pyridine (Py) and 1,2-dichloroethane. Due to its excellent stability, high surface area and hydrophilic-lipophilic (amphiphilic) structure, the CC-Py exhibited a high affinity toward the NBs (nitrobenzene, 2-nitrotoluene, 2,6-dimethylnitrobenzene, 3-nitrotoluene, 4-nitrotoluene, 3-nitrochlorobenzene, 4-nitrochlorobenzene, 2-nitrochlorobenzene, 2,4-dimethylnitrobenzene, 3-nitrobromobenzene, 4-nitrobromobenzene and 4-nitroiodobenzene). Then, a CC-Py based solid-phase microextraction coupled with gas chromatography-flame ionization detection was developed to detect the twelve NBs in real water samples. The results showed that the method had low limits of detection (0.20-0.50 μg L

Background Intraoperative intraocular pressure (IOP) elevation is a risk factor for postoperative blindness. Surgical position is associated with intraoperative IOP elevation. In China, there are few studies on the effect of various surgical positions on intraoperative IOP. This study was conducted to explore IOP change and its related factors in four common surgical positions in China. Methods This was a cross-sectional observational study. A total of 325 surgical patients who had non-ocular surgery from January 2019 to December 2019 in the hospital, were enrolled in this study. During their surgeries for general anesthesia, these participants were placed in lithotomy position/lateral position/prone position/supine position according to their surgery requirement. IOP was measured by icareTA03 handheld portable tonometer at 9 different time points from admission to exiting the operation room. And general information, postural position, and surgery information were collected through a uniform questionnaire. Multivariate analysis was performed to explore the related factors of IOP change. Results IOP of both eyes on lithotomy position, lateral position, and supine position showed statistical differences by ANOVA test at each time point (p p P p p Conclusion IOP in the four surgical positions showed different change patterns with the surgical process and position change. Nurses should assist the surgeon to reduce the head-down angle without interfering with the surgical operation and strengthen the inspection of IOP on patients with long-time surgery, to avoid intraoperative rapid IOP changes.

Molecular markers for the detection of lymph node micrometastases of malignant tumors have been extensively investigated. However, epigenetic signatures have rarely been reported for identification of metastatic lymph nodes and disease relapse. Septin 9 is the most frequently reported hypermethylated gene in colorectal cancer (CRC). This study aimed to assess the clinical relevance of Septin 9 methylation in regional lymph nodes in recurrence/metastases of CRC.We analyzed Septin 9 methylation of DNA from resected lymph nodes in 75 CRC patients with or without tumor recurrence using quantitative methylation-sensitive PCR (qMS-PCR).Of the 30 histologically negative lymph node CRC patients without recurrence (group 1), methylated Septin 9 was detected in 3 (10 %) cases. The positivity rate of methylated Septin 9 in group 2 containing 30 histologically node-negative CRC patients with recurrence was 30 % (9/30). For group 3, lymphatic invasion as well as tumor recurrence, 11 (73 %) out of 15 subjects had Septin 9 methylation-positive lymph nodes. Moreover, patients in group 3 had a higher level of methylated Septin 9 compared to subjects in group 1 and group 2 (p 0.05). In addition, CRC patients with Septin 9 methylation in lymph nodes had significantly reduced survival (Log-rank P 0.0001).Our data support the predictive role of Septin 9 methylation analysis of lymph node micrometastases for tumor relapse after surgery.

Understanding immune cell phenotypes in the tumor microenvironment (TME) is essential for explaining and predicting progression of non-small cell lung cancer (NSCLC) and its response to immunotherapy. Here we describe the single-cell transcriptomics of CD45+ immune cells from tumors, normal tissues and blood of NSCLC patients. We identified three clusters of immune cells exerting immunosuppressive effects: CD8+ T cells with exhausted phenotype, tumor-associated macrophages (TAMs) with a pro-inflammatory M2 phenotype, and regulatory B cells (B regs) with tumor-promoting characteristics. We identified genes that may be mediating T cell phenotypes, including the transcription factors ONECUT2 and ETV4 in exhausted CD8+ T cells, TIGIT and CTL4 high expression in regulatory T cells. Our results highlight the heterogeneity of CD45+ immune cells in the TME and provide testable hypotheses about the cell types and genes that define the TME.

Extracellular vesicles (EVs) have shown promise as potential therapeutics for the treatment of various diseases. However, their rapid clearance after administration could be a limitation in certain therapeutic settings. To solve this, an engineering strategy is employed to decorate albumin onto the surface of the EVs through surface display of albumin binding domains (ABDs). ABDs were either included in the extracellular loops of select EV-enriched tetraspanins (CD63, CD9 and CD81) or directly fused to the extracellular terminal of single transmembrane EV-sorting domains, such as Lamp2B. These engineered EVs exert robust binding capacity to human serum albumins (HSA) in vitro and mouse serum albumins (MSA) after injection in mice. By binding to MSA, circulating time of EVs dramatically increases after different routes of injection in different strains of mice. Moreover, these engineered EVs show considerable lymph node (LN) and solid tumour accumulation, which can be utilized when using EVs for immunomodulation, cancer- and/or immunotherapy. The increased circulation time of EVs may also be important when combined with tissue-specific targeting ligands and could provide significant benefit for their therapeutic use in a variety of disease indications.