Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions:an intravascular ultrasound study

OBJECTIVES To investigate whether negative remodeling(NR) detected by intravascular ultrasound(IVUS) of the side branch ostium(SBO) would affect in-stent neointimal hyperplasia(NIH) at the one-year follow-up and the clinical outcome of target lesion failure(TLF) at the long-term follow-up for patients with left main bifurcation(LMb) lesions treated with a two-stent strategy.METHODS A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention(PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre-and post-PCI and at the 1-year follow-up were enrolled in phase Ⅰ analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index(RI) for predicting NIH ≥ 50% was analyzed next. The phase Ⅱ analysis focused on the incidence of TLF as the primary endpoint at the 1-to 5-year follow-up for all 328 patients by grouping based on the cutoff value of RI.RESULTS In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic(ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893(0.778, 1.000), P = 0.002. In phase Ⅱ: the TLR rate(35.8% vs. 5.3%, P < 0.0001)was significantly higher in the several NR(s NR, defined as RI ≤ 0.85) group than in the non-s NR group.CONCLUSION The NR of LCx O is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy,and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

Predictive power of abnormal electroencephalogram for post-cerebral infarction depression

Electroencephalography is a sensitive indicator for measuring brain condition, and can reflect early changes in brain function and severity of cerebral ischemia. However, it is not yet known whether electroencephalography can predict development of post-cerebral infarc- tion depression. A total of 321 patients with ischemic stroke underwent electroencephalography and Hamilton Depression Rating Scale assessment to analyze the relationship between electroencephalography and post-cerebral infarction depression. Our results show that electroencephalograms of ischemic stroke patients with depression exhibit low-amplitude alpha activity and slow theta activity. In con- trast, electroencephalograms of ischemic stroke patients without depression show fast beta activity and slow delta activity. ＂Ihese findings confirm that low-amplitude alpha activity and slow theta activity can be considered as independent predictors for post-cerebral infarction depression.

Effects of HPV Pseudotype Virus in Cutting E6 Gene Selectively in SiHa Cells

The objectives of this study were to investigate the effects of the CRISPR/Cas9 system mediated by the HPV pseudotype virus on SiHa cytobiology behavior by cutting the HPV16 E6 gene selectively and to explore the role of this system in the treatment of cervical cancer. After designing specific gRNA sequences targeting HPV 16 E6, generating hCas9-EGFP and E6-gRNA-RFP plasmids, and preparing the pseudovirus of HPV16 carrying E6-gRNA and Cas9 plasmids, we determined the titer of the pseudotype virus using the TCID50 method. We obtained the pseudotype virus of HPV16 carrying E6-gRNA and Cas9 plasmids to transfect cervical cancer SiHa cells. Experimental subjects were divided into control group, empty virus group, E6-gRNA transfected group, Cas9 transfected group and Cas9＋E6-gRNA transfected group. The molecular size of the cutting sequence was detected using the T7E1 enzyme digestion method and agarose gel electrophoresis, and the cleavage function of CRISPR/Cas9 on the E6 gene was determined at the same time. RT-PCR and Western blotting were performed to detect the mRNA and protein expression levels of E6 in all the groups; the Transwell cell migration assay was performed to detect the cell migration ability and metastasis in all groups. Heterotopic transplantation tumors were incorporated into mice and were used to investigate the effects of the CRISPR/Cas9 system mediated by the HPV pseudovirus on the tumorigenic ability of SiHa cells by selectively cutting HPV16 E6. The HPV16 pseudotype virus carrying E6-gRNA and Cas9 plasmids could successfully infect SiHa cells, and there were two cutting zones in the Cas9＋E6- gRNA transfected group. However, the empty virus group, E6-gRNA transfected group and Cas9 transfected group had no corresponding zone. Compared with those in the control group, the empty virus group, E6-gRNA transfected group and Cas9 transfected group, the mRNA and protein expression levels of E6 in SiHa cells were downregulated in the Cas9＋E6-gRNA transfected group （P〈0.01）. In addition, the proliferation and migration abilities of SiHa cells were significantly inhibited （P〈0.01）. There were no significant differences among the other groups. In contrast to the control group, the HPV pseudotype virus carrying E6-gRNA and Cas9 plasmids could significantly delay the growth of tumor cells of the ectopic tumor transplantation model （P〈0.01）. The CRISPR/Cas9 system mediated by the HPV pseudotype virus to knockout E6 gene expression exhibited a clear inhibitory effect on the biological function of SiHa cells, which indicated that knocking out the E6 gene using the CRISPR/Cas9 system mediated by the HPV pseudotype virus had a potential effect of eliminating HPV infection and inhibiting the growth of HPV-related tumors. Taken together, these findings provide insight into a new treatment strategy for the prevention and treatment of hr-HPV infected disease, particularly in HPV-related tumors.

Meta analysis about the efficacy and safety of anti-ocular hypertension eye drops without benzalkonium chloride

Objective:To explore the safety and efficacy of eye drops without benzalkonium chloride(BAK)in treating glaucoma and ocular hypertension.Methods:The clinical case-control literatures about eye drops without BAK treating glaucoma and ocular hypertension were retrieved in PubMed,EMBASE,Cochrane and Chinese Biological and Medical database.Mela 5.0 software was used to analyze the literatures.Results:Five clinical control studies were included.The results indicated both eye drops could lower the intraocular pressure,and the intraocular pressurelowering difference between two eye drops was 0.07 mmHg(95%CI:0.04,0.19)(P>0.05).Two adverse reactions occurred more were conjunctival injection(10.78%)and allergic conjunctivitis(4.78%).The odd ratio of two eye drops occurring conjunctival injection and allergic conjunctivitis was 0.67(95%CI,0.25,1.10)and 0.82(95%CI,0.09,1.54),respectively(P<0.05)in fixed effect model.Conclusions:There is no difference between the eye drops with or without BAK in lowering intraocular pressure.but the latter is of higher safety.In consideration of the relatively small sample size of this research,more high-quality clinical research contrasts are needed as evidence.

PD-1 inhibitor plus anlotinib for metastatic castration-resistant prostate cancer: a real-world study

Management and treatment of terminal metastatic castration-resistant prostate cancer(mCRPC)remains heavily debated.We sought to investigate the efficacy of programmed cell death 1(PD-1)inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes.We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments.The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA(ctDNA)next-generation sequencing.Statistical analysis showed that 6(24.0%)patients experienced prostate-specific antigen(PSA)response and 11(44.0%)patients experienced PSA reduction.The relationship between ctDNA findings and outcomes was also analyzed.DNA-damage repair(DDR)pathways and homologous recombination repair(HRR)pathway defects indicated a comparatively longer PSA-progressionfree survival(PSA-PFS;2.5 months vs 1.2 months,P=0.027;3.3 months vs 1.2 months,P=0.017;respectively).This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC.PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.

Silicon-carbide fiber-reinforced polymer electrolyte for all-solid-state lithium-metal batteries

Silicon carbide(SiC) with various morphologies was employed as reinforcing fillers for poly(ethylene oxide)(PEO)-based solid polymer electrolytes(SPEs).Specific ally,the SiC nanoparticles with an average size of 5-10 μm endow a significant enhancement of the interaction between carbon atoms for the fillers and the oxygen atoms from the PEO-lithium bis(trifluoromethanesulfonyl)imide(LiTFSI) matrix,which provides rapid transport channels for mobile Li+and enhances the mechanical strength of SPEs.The SPEs reinforced with one-dimensional SiC nanoparticles exhibit superior Li^(+)conduction,good mechanical property,and uniform Li plating.Thus,a dendrite-free plating of lithium for 0.58 mAh at 0.1 mA·cm^(-2) and excellent cycle stability at various current densities for 250 h are achieved in Li/Li symmetric cells using SPEs electrolytes with 5.0 wt% SiC nanoparticles.Moreover,the LiFePO_(4)/Li full cells assembled using SPEs electrolytes with 5.0 wt% SiC nanoparticles provide a capacity of 151.5 mAh·g^(-1) at 0.1 mA·cm^(-2)(55℃),and maintained a Coulombic efficiency of 99% for 120 cycles.

Peripheral monocyte count： an independent diagnostic and prognostic biomarker for prostate cancer - a large Chinese cohort study

Increasing evidence indicates that inflammation may play important roles in tumorigenesis and progression, and an elevated peripheral monocyte count predicts a poor prognosis in various types of malignancies. Here, we evaluate the roles of peripheral monocyte count in the diagnosis and prognosis for prostate cancer in Chinese patients. A total of 1107 consecutive patients who had undergone prostate biopsy and 290 prostate cancer patients receiving androgen deprivation therapy as first-line therapy were retrospectively analyzed. The parameters were measured at the time of diagnosis. Univariate and multivariate logistic regression analyses were performed to identify the independent predictors of a positive biopsy. Patients were categorized in two groups using a cutoff point of 0.425 x 109 1-1 as calculated by the receiver-operating curve analysis for prognosis. Univariate and multivariate Cox regression analyses were performed to determine the associations of monocyte count with progression-free survival, cancer-specific survival, and overall survival. Multivariate logistic regression analyses showed that monocyte count, age, prostate-specific antigen （PSA）, free/total PSA, and prostate volume were independent predictors for prostate cancer. Multivariate Cox regression analyses identified an elevated monocyte count as an independent prognostic factor for worse cancer-specific survival （hazard ratio = 2.244, P 〈 0.05） and overall survival （hazard ratio = 1.995, P 〈 0.05）, but not progression-free survival （P = 0.117）. Our results indicated that an elevated monocyte count was an independent diagnostic biomarker for prostate cancer, and pretreatment peripheral monocyte count might play a significant role in the prognosis of prostate cancer patients treated with androgen deprivation therapy.

Research progress on the NLRP3 inflammasome and its role in the central nervous system

The NLRP3 inflammasome,which consists of the NLRP3（nucleotide-binding oligomerization domain（Nod）–like receptor 3） scaffold,the ASC（apoptosis-associated speck-like protein containing a CARD） adaptor and procaspase-1,is assembled after the cytoplasmic LRRs（leucine-rich repeats） of NLRP3 sense pathogens or danger signals.The NLRP3 inflammasome controls the activation of the proteolytic enzyme caspase-1.Caspase-1 in turn regulates the maturation of the proinflammasome cytokines IL-1β and IL-18,which leads to an inflammatory response.The inflammasome plays an important role in the development of Alzheimer’s disease and bacterial meningitis,and the NLRP3 inflammasome may become a new target for the prevention and treatment of central nervous system diseases.

miR-124/VAMP3 is a novel therapeutic target for mitigation of surgical trauma-induced microglial activation

Activation of microglia and the subsequently elevated inflammatory cytokine release in the brain during surgery predispose individuals to cognitive dysfunction,also known as postoperative cognitive dysfunction(POCD).miR-124 is one of the most abundant microRNAs in the brain that regulates microglial function.Elucidating the role of miR-124 in microglial activation in the context of surgery may therefore promote understanding of as well as therapeutic development for post-surgical disorders involving microglial activation.The downstream targets of miR-124 were investigated using bioinformatic screening and dual-luciferase reporter assay validation,and vesicle-associated membrane protein 3(VAMP3)was identified as a potential target.The kinetics of miR-124/VAMP3 expression was first examined in vitro in microglial cells(primary microglia and BV2 microglial cells)following lipopolysaccharide(LPS)stimulation.LPS induced a time-dependent decrease of miR-124 and upregulated the expression of VAMP3.Manipulating miR-124/VAMP3 expression by using miR-124 mimics or VAMP3-specific siRNA in LPS-stimulated BV2 microglial cells inhibited BV2 microglial activation-associated inflammatory cytokine release.To further examine the role of miR-124/VAMP3 in a surgical setting,we employed a rat surgical trauma model.Significant microglial activation and altered miR-124/VAMP3 expression were observed following surgical trauma.We also altered miR-124/VAMP3 expression in the rat surgical trauma model by administration of exogenous miR-124 and by using electroacupuncture,which is a clinically applicable treatment that modulates microglial function and minimizes postoperative disorders.We determined that electroacupuncture treatment specifically increases the expression of miR-124 in the hypothalamus and hippocampus.Increased miR-124 expression with a concomitant decrease in VAMP3 expression resulted in decreased inflammatory cytokine release related to microglial activation post-surgery.Our study indicates that miR-124/VAMP3 is involved in surgery-induced microglial activation and that targeting miR-124/VAMP3 could be a potential therapeutic strategy for postoperative disorders involving microglial activation.

Peripheral Leptin Signaling Mediates Formalin-Induced Nociception

Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a well-established obese mouse model induced by a highfat diet, we found that:(1) the acute thermal pain sensory threshold did not change in obese mice;(2) the model obese mice had fewer nociceptive responses in formalininduced inflammatory pain tests; restoring the obese mice to a chow diet for three weeks partly recovered their pain sensation;(3) leptin injection induced significant phosphorylation of STAT3 in control mice but not in obese mice,indicating the dysmodulation of topical leptin–leptin receptor signaling in these mice; and(4) leptin–leptin receptor signaling-deficient mice(ob/ob and db/db) or leptin–leptin receptor pathway blockade with a leptin receptor antagonist and the JAK2 inhibitor AG 490 in wildtype mice reduced their nociceptive responses in formalin tests. These results indicate that leptin plays a role in nociception induced by acute inflammation and that interference in the leptin–leptin receptor pathway could be a peripheral target against acute inflammatory pain.

Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1

Trigeminal neuralgia is a debilitating condition,and the pain easily spreads to other parts of the face.Here,we established a mouse model of partial transection of the infraorbital nerve(pT-ION)and found that the Connexin 36(Cx36)inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia.Mefloquine reversed the pT-IONinduced upregulation of Cx36,glutamate receptor ionotropic kainate 2(GluK2),transient receptor potential ankyrin 1(TRPA1),and phosphorylated extracellular signal regulated kinase(p-ERK)in the trigeminal ganglion.Cold allodynia but not mechanic al allodynia induced by pT-ION or by virusmediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS 102,and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanic al allodynia.In conclusion,we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2,TRPA1,and p-ERK signaling.

Investigation of an enteritis outbreak caused by Salmonella enterica serovar Aberdeen in China

Salmonella Aberdeen is a ubiquitous pathogen that can cause severe gastroenteritis and plays an important role in food-borne illness and international food-trade dispute.[1]However,the molecular biological characteristics of this organism have been rarely studied.This study was conducted in accordance with the Declaration of Helsinki and aimed to assess the epidemiological and clinical characteristics of a food-borne outbreak caused by Salmonella Aberdeen.Furthermore,the molecular biological characteristics of the outbreak isolates were detected and analyzed.From June 10 to 12,2018,an enteritis outbreak affected 75 employees in the Fushan district of Yantai,Shandong province,China,including 33 males and 42 females.The mean age of the patients was 34.2±5.3 years.