Long-term sky islands generate highly divergent lineages of a narrowly distributed stream salamander (Pachyhynobius shangchengensis) in mid-latitude mountains of East Asia.

BACKGROUND: Climate oscillation may have a profound effect on species distributions, gene flow patterns and population demography. In response to environmental change, those species restricted to montane habitats experienced expansions and contractions along elevation gradients, which can drive differentiation among sky islands. RESULTS: The Shangcheng stout salamander (Pachyhynobius shangchengensis) is a cool stream amphibian restricted to high-elevation areas in the Dabie Mountains, East China. In the present study, we used mtDNA genes (Cyt b and ND2) of 193 individuals and 12 nuclear microsatellite loci genotyped on 370 individuals, representing 6 populations (JTX, KHJ, MW, TTZ, BYM and KJY) across the taxon's distribution area, to investigate their genetic variation and evolutionary history of P. shangchengensis. Most populations showed unusually high levels of genetic diversity. Phylogenetic analyses revealed five monophyletic clades with divergence times ranging from 3.96 to 1.4 Mya. Accordingly, significant genetic differentiation was present between these populations. Bayesian skyline plot analyses provided that all populations underwent long-term population expansions since the last inter-glacial (0.13 Mya ~ 0.12 Mya). Msvar analyses found recent signals of population decline for two northern populations (JTX and KHJ) reflecting a strong bottleneck (approximately 15-fold decrease) during the mid-Holocene (about 6000 years ago). Ecological niche modelling has shown a discontinuity in suitable habitats for P. shangchengensis under different historical climatic conditions. CONCLUSIONS: Our results suggest that the niche conservatism of P. shangchengensis and sky island effects may have led to long-term isolation between populations. In sky island refuges, the mid-latitude Dabie Mountains have provided a long-term stable environment for P. shangchengensis, which has led to the accumulation of genetic diversity and has promoted genetic divergence.

[Molecular Cloning,Sequence Analysis,and Expression of Pepsinogens C Gene from Adult Alligator Sinensis Stomach].

Objective To investigate the molecular clone and structural features of pepsinogen C(PGC) gene in the stomach of Alligator sinensis,explore the phylogenetic relationships and tissue distribution,and analyze the variation of PGC expression in the stomachs of adult Alligator sinensis at different life stages. Methods The full-length cDNA of PGC gene of Alligator sinensis was cloned by reverse transcription polymerase chain reaction and rapid amplification of cDNA ends and then sequenced.The physical and chemical parameters and advanced structures of the PGC protein were predicted by bioinformatics methods and tools.The PGC amino acid sequences of the Alligator sinensis and other vertebrates were compared by Clustal X software.The neighbor-joining phylogenetic tree was built by MEGA 6 software.Immunohistochemistry was used to locate PGC in the gastric mucosa of Alligator sinensis.The variation of the PGC mRNA levels in the stomach at different life stages was detected by quantitative real-time polymerase chain reaction.Results Reverse transcription polymerase chain reaction and rapid amplification of cDNA ends revealed a 1568 bp cDNA full-length sequence containing 1167 bp open reading frame,which encoded 388 amino acids.The PGC gene of Alligator sinensis had been deposited in the GenBank Data Libraries under the accession number of KY799383.Bioinformatics analysis predicted that the Alligator sinensis PGC had a theoretical relative molecular mass of 41 998 with a theoretical isoelectric point of 4.16.In addition,the three-dimensional structure of the PGC was constructed by homology modeling to predict its active site with two essential aspartyl residues and six essential cysteine residues involved in forming three disulphide bonds.The neighbor-joining phylogenetic tree of vertebrates from the amino acids sequences of PGC showed all crocodiles were clustered as a group,and the PGC of Alligator sinensis was the closest to Alligator mississippiensis.Alligator sinensis PGC was specifically expressed in the gastric mucosa,and its expressions significantly differed during reproduction and hibernation significantly(P<0.05).Conclusions Alligator sinensis PGC gene is highly conserved in evolution.Its protein is a gastric specific digestive proteinase that belongs to a aspartic proteinase family.

Risk of Congenital Syphilis (CS) Following Treatment of Maternal Syphilis: Results of a CS Control Program in China.

Background: Early screening for syphilis among pregnant women and the effective treatment of maternal syphilis is fundamental to prevent congenital syphilis (CS). Methods: We obtained data from the Shenzhen Program for Prevention of CS (SPPCS) and estimated incidence rates of CS among infants born to syphilis-seropositive women treated with different regimens or untreated for maternal syphilis. Results: A total of 4746 matched cases of syphilis-seropositive mothers and their infants were included for analyses, and 162 infants were diagnosed with CS, providing an overall incidence of 3.41% (95% confidence interval [CI], 2.91%-3.98%). Among infants born to syphilis-seropositive women who had syphilis and were adequately treated before pregnancy, the incidence was 0.22% (95% CI, .05%-.66%). There were 159 cases of CS occurring in 3519 infants born to women who were syphilis-seropositive during their pregnancies, for an incidence of 4.52% (95% CI, 3.84%-5.28%). The incidence of CS was 1.82%-11.90% lower among infants born to the women treated with early benzathine penicillin G (BPG) compared with those treated with late BPG (adjusted odds ratio [aOR], 8.06 [95% CI, 2.93-22.21]; P < .001), other antibiotics (aOR, 7.71 [95% CI, .86-69.28]; P = .068), or those untreated (aOR, 68.28 [95% CI, 29.64-157.28]; P < .001). The incidence rates were 0.22% (95% CI, .06%-.80%) and 0.59% (95% CI, .35%-1.02%) in infants born to women treated with 2 courses and 1 course of BPG, respectively, corresponding to a risk difference of 0.37% (aOR, 1.74; 95% CI, .37-8.26). Conclusions: Treatment of syphilis-seropositive pregnant women with 1 course of intramuscular BPG before 28 gestational weeks is critical for prevention of CS.

Neuroprotective effects of human umbilical cord-derived mesenchymal stromal cells combined with nimodipine against radiation-induced brain injury through inhibition of apoptosis.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) possess the ability to repair brain injuries. Additionally, nimodipine is a neuroprotective agent that increases cerebral blood flow and may help with the homing of MSCs to the injury site. Here we investigate the effectiveness of a combined human umbilical cord-derived MSCs and nimodipine therapy in radiation-induced brain injury (RIBI). METHODS: Female mice received whole brain irradiation (WBI) and were treated with saline, nimodipine, hUC-MSCs, or hUC-MSCs combined with nimodipine. Body weight was measured weekly. An open field test for locomotor activity and a step-down avoidance test for learning and memory function were conducted at week 4 and week 12 post-WBI. The histological damage was evaluated by hematoxylin and eosin staining and glial fibrillary acidic protein immunohistochemistry. Quantitative polymerase chain reaction and Western blotting were used to detect apoptosis-related mediators (p53, Bax and Bcl-2). RESULTS: In mice receiving the hUC-MSCs or the combined treatment, their body weight recovered, their locomotor and cognitive ability improved, and the percentage of necrotic neurons and astrocytes was reduced. The combined therapy was significantly (P < 0.05) more effective than hUC-MSCs alone; these mice showed decreased expression of pro-apoptotic indicators (p53, Bax) and increased expression of an anti-apoptotic indicator (Bcl-2), which may protect brain cells. CONCLUSIONS: We demonstrated that hUC-MSCs therapy helps recover body weight loss and behavior dysfunction in a mice model of RIBI. Moreover, the effectiveness of the combined hUC-MSCs and nimodipine therapy is due to apoptosis inhibition and enhancing homing of MSCs to the injured brain.

Perspectives on biologically active camptothecin derivatives.

Camptothecins (CPTs) are cytotoxic natural alkaloids that specifically target DNA topoisomerase I. Research on CPTs has undergone a significant evolution from the initial discovery of CPT in the late 1960s through the study of synthetic small-molecule derivatives to investigation of macromolecular constructs and formulations. Over the past years, intensive medicinal chemistry efforts have generated numerous CPT derivatives. Three derivatives, topotecan, irinotecan, and belotecan, are currently prescribed as anticancer drugs, and several related compounds are now in clinical trials. Interest in other biological effects, besides anticancer activity, of CPTs is also growing exponentially, as indicated by the large number of publications on the subject during the last decades. Therefore, the main focus of the present review is to provide an ample but condensed overview on various biological activities of CPT derivatives, in addition to continued up-to-date coverage of anticancer effects.

Effect of serum choice on replicative senescence in mesenchymal stromal cells.

BACKGROUND AIMS: Multipotent mesenchymal stromal cells (MSCs) are promising candidates for innovative cell therapeutic applications. Before their use, however, they usually need to be expanded in vitro with serum-supplemented media. MSCs can undergo replicative senescence during in vitro expansion, but it is not yet clear how serum supplements influence this process. METHODS: In the present study, we compared how media supplemented with fetal bovine serum (FBS) or calf serum (CS) affected morphology, proliferation, differentiation, senescence and other functional characteristics of human umbilical cord-derived MSCs (UC-MSCs). RESULTS: UC-MSCs cultured in both FBS- and CS-containing media were able to differentiate along osteogenic and adipogenic lineages but ultimately reached proliferation arrest. However, senescence-associated characteristics, such as ß-galactosidase activity, reactive oxygen species levels, proliferation rate and gene expression, demonstrate that UC-MSCs grown with FBS have better proliferation potential and differentiation capacity. In contrast, UC-MSCs grown with CS have a higher proportion of apoptotic cells and senescent characteristics. Possible mechanisms for the observed phenotypes include changes in gene expression (Bax, p16, p21 and p53) and cytokine production (interleukin-6 and interleukin-8). CONCLUSIONS: This study demonstrates that FBS-supplemented media provides a better microenvironment for the expansion of UC-MSCs in vitro than CS-supplemented media. This work provides insight into MSCs generation practices for use in basic research and clinical therapies.

Synthesis, biological activities, and quantitative structure-activity relationship (QSAR) study of novel camptothecin analogues.

In continuation of our program aimed at the development of natural product-based pesticidal agents, three series of novel camptothecin derivatives were designed, synthesized, and evaluated for their biological activities against T. Cinnabarinus, B. brassicae, and B. xylophilus. All of the derivatives showed good-to-excellent activity against three insect species tested, with LC50 values ranging from 0.00761 to 0.35496 mmol/L. Remarkably, all of the compounds were more potent than CPT against T. Cinnabarinus, and compounds 4d and 4c displayed superior activity (LC50 0.00761 mmol/L and 0.00942 mmol/L, respectively) compared with CPT (LC50 0.19719 mmol/L) against T. Cinnabarinus. Based on the observed bioactivities, preliminary structure-activity relationship (SAR) correlations were also discussed. Furthermore, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model using comparative molecular field analysis (CoMFA) was built. The model gave statistically significant results with the cross-validated q2 values of 0.580 and correlation coefficient r2 of 0.991 and  of 0.993. The QSAR analysis indicated that the size of the substituents play an important in the activity of 7-modified camptothecin derivatives. These findings will pave the way for further design, structural optimization, and development of camptothecin-derived compounds as pesticidal agents.

Design and synthesis of new 7-(N-substituted-methyl)-camptothecin derivatives as potent cytotoxic agents.

A series of novel 7-(N-substituted-methyl)-camptothecin derivatives was designed, synthesized, and evaluated for in vitro cytotoxicity against four human tumor cell lines, A-549, MDA-MB-231, KB, and KBvin. All of the derivatives showed promising in vitro cytotoxic activity against the tested tumor cell lines, with IC50 values ranging from 0.0023 to 1.11 µM, and were as or more potent than topotecan. Compounds 9d, 9e, and 9r exhibited the highest antiproliferative activity among all prepared derivatives. Furthermore, all of the compounds were more potent than paclitaxel against the multidrug-resistant (MDR) KBvin subline. With a concise efficient synthesis and potent cytotoxic profiles, especially significant activity towards KBvin, compounds 9d, 9e, and 9r merit further development as a new generation of camptothecin-derived anticancer clinical trial candidates.

Design and synthesis of novel spin-labeled camptothecin derivatives as potent cytotoxic agents.

In our continuing search for natural product-based spin-labeled antitumor drugs, 20 novel spin-labeled camptothecin derivatives were synthesized via a Cu-catalyzed one pot reaction and evaluated for cytotoxicity against four human tumor cell lines (A-549, MDA-MB-231, KB, and KBvin). Eighteen of the target compounds (9a, 9b, 9d-9k, 9m-9t) exhibited significant in vitro antiproliferative activity against these four tested tumor cell lines. Compounds 9e and 9j (IC50 0.057 and 0.072µM, respectively) displayed the greatest cytotoxicity against the multidrug-resistant (MDR) KBvin cell line and merit further development into preclinical and clinical drug candidates for treating cancer including MDR phenotype.

High-resolution magnetic resonance vessel wall imaging in ischemic stroke and carotid artery atherosclerotic stenosis: A review.

Ischemic stroke is a significant burden on human health worldwide. Carotid Atherosclerosis stenosis plays an important role in the comprehensive assessment and prevention of ischemic stroke patients. High-resolution vessel wall magnetic resonance imaging has emerged as a successful technique for assessing carotid atherosclerosis stenosis. This advanced imaging modality has shown promise in effectively displaying a wide range of characteristics associated with the condition, leading to a comprehensive evaluation. High-resolution vessel wall magnetic resonance imaging not only enables a comprehensive evaluation of the instability of carotid atherosclerosis stenosis plaques but also provides valuable information for understanding the pathogenesis and predicting the prognosis of ischemic stroke patients. The purpose of this article is to review the application of high-resolution magnetic resonance imaging in ischemic stroke and carotid atherosclerotic stenosis.

Gay saunas and the risks of HIV and syphilis transmissions in China--results of a meta-analysis.

INTRODUCTION: Previous studies suggest the risk of human immunodeficiency virus (HIV) transmission among men who have sex with men (MSM) is associated with characteristics of venues. However, very few studies have systematically compared HIV/sexually transmitted disease (STD) prevalence among MSM according to key venue type for sourcing sex partners. AIMS: The aim of this study was to investigate the associations between HIV/syphilis prevalence and the types of venues, namely saunas, parks, gay bars, and the Internet, which are mostly used for sourcing male sex partners by MSM in China. METHODS: Meta-analyses using fixed-effect and random-effect methods were conducted. Secondary data were obtained from 10 concurrent surveys conducted in 10 cities basing on a common protocol. Pairwise comparisons (e.g., "saunas" vs. "parks") were made. MAIN OUTCOMES MEASURES: Odds ratios (OR) for HIV/syphilis infection in relations to venue type for partner sourcing. RESULTS: The distribution of the most commonly used source to recruit male sex partner was 59.32% (Internet), 18.47% (gay bars), 14.18% (gay saunas), and 8.02% (parks). The median prevalence of HIV/syphilis was 10.49% and 19.38% (gay saunas), 2.12% and 16.25% (parks), 6.06% and 15.45% (Internet), and 4.41% and 11.90% (gay bars). We found significant between-group differences when comparing "sauna" against "Internet" (HIV: OR= 2.27, 95% confidence interval [CI] = 1.65-3.12; syphilis: OR = 1.61, 95% CI= 1.07-2.41), "sauna" against "bars" (HIV: OR= 1.65, 95% CI= 1.14-2.39; syphilis: OR= 1.35, 95% CI= 1.02-1.78), and "parks" against "Internet" (syphilis: OR= 1.55, 95% CI= 1.12-2.15) as the main source to recruit male sex partners. Other pairwise comparisons were not statistically significant. CONCLUSIONS: The results of this study suggest that those sourcing partners mainly from gay saunas have higher prevalence of HIV/syphilis when compared with those doing so via the Internet or gay bars. Venue based (sauna-based) interventions using socio-ecological approaches are greatly warranted in order to reduce HIV and syphilis prevalence among MSM in China.

Hemodynamics combined with inflammatory indicators exploring relationships between ischemic stroke and symptomatic middle cerebral artery atherosclerotic stenosis.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke, and high-resolution vessel wall imaging (HR-VWI) can be used to assess the plaque characteristics of ICAS. This study combined HR-VWI, hemodynamics, and peripheral blood inflammatory indicators to investigate the role of these factors in symptomatic intracranial atherosclerotic stenosis (sICAS) and their inter-relationships. METHODS: Patients diagnosed with atherosclerotic middle cerebral artery stenosis were recruited retrospectively from June 2018 to July 2022. Plaque enhancement was qualitatively and quantitatively analyzed, and the degree of plaque enhancement was graded according to the plaque-to-pituitary stalk contrast ratio (CR). Computational fluid dynamics models were constructed, and then hemodynamic parameters, including wall shear stress (WSS) and pressure ratio (PR), were measured and recorded. Univariate and multivariable analyses were performed to identify factors that can predict sICAS. In addition, the correlation analysis between the plaque characteristics on HR-VWI, hemodynamic parameters, and peripheral blood inflammatory indicators was performed to investigate the interrelationships between these factors. RESULTS: Thirty-two patients were included. A higher proportion of plaque enhancement, maximum WSS, and WSS ratio (WSSR) were significantly associated with sICAS. The multiple logistic regression analysis showed that only the WSSR was an independent risk factor for sICAS. The correlation analysis revealed that both the CR and plaque burden showed linear positive correlation with the WSSR (R = 0.411, P = 0.022; R = 0.474, P = 0.007, respectively), and showed linear negative correlation with the lymphocyte to monocyte ratio (R = 0.382, P = 0.031; R = 0.716, P < 0.001, respectively). CONCLUSIONS: The plaque enhancement and WSSR were significantly associated with sICAS, WSSR was an independent risk factor for sICAS. Plaque enhancement and plaque burden showed linear correlation with the WSSR and lymphocyte-to-monocyte ratio (LMR). Hemodynamics and inflammation combined to promote plaque progression.

Qualitative and quantitative plaque enhancement on high-resolution vessel wall imaging predicts symptomatic intracranial atherosclerotic stenosis.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke (IS), and high-resolution vessel wall imaging (HR-VWI) can be used to assess the plaque characteristics of ICAS. This study aimed to qualitatively and quantitatively assess plaque enhancement of ICAS and to investigate the relationship between plaque enhancement, plaque morphological features, and IS. METHODS: Data from adult patients with ICAS from April 2018 to July 2022 were retrospectively collected, and all patients underwent HR-VWI examination. Plaque enhancement was qualitatively and quantitatively assessed, and the plaque-to-pituitary stalk contrast ratio (CR) indicated the degree of plaque enhancement. Plaque characteristics, such as plaque burden and area, were quantitatively measured using HR-VWI. Furthermore, receiver-operating characteristic (ROC) analysis was performed to assess the ability of CR to discriminate plaque enhancement. The patients were divided into a symptomatic ICAS group and an asymptomatic ICAS group according to the clinical and imaging characteristics. Univariate and multivariate analyses were performed to investigate which factors were significantly associated with plaque enhancement and symptomatic ICAS. The plaque burden and CR were compared using linear regression. RESULTS: A total of 91 patients with ICAS were enrolled in this study. ICAS plaque burden was significantly associated with plaque enhancement (p = .037), and plaque burden was linearly positively correlated with CR (R = 0.357, p = .001). ROC analysis showed that the cutoff value of CR for plaque enhancement was 0.56 (specificity of 81.8%). Both plaque enhancement and plaque burden were significantly associated with symptomatic ICAS, and only plaque enhancement was an independent risk factor after multivariate analysis. CONCLUSION: Plaque burden was an independent risk factor for plaque enhancement and showed a linear positive correlation with CR. The cutoff value of CR for plaque enhancement was 0.56, and CR ≥ 0.56 was significantly associated with symptomatic ICAS, which was independently associated with plaque enhancement.

Evaluation of trabecular meshwork-specific promoters in vitro and in vivo using scAAV2 vectors expressing C3 transferase.

AIM: To evaluate the potential of two trabecular meshwork (TM)-specific promoters, Chitinase 3-like 1 (Ch3L1) and matrix gla protein (MGP), for improving specificity and safety in glaucoma gene therapy based on self-complementary AAV2 (scAAV2) vector technologies. METHODS: An scAAV2 vector with C3 transferase (C3) as the reporter gene (scAAV2-C3) was selected. The scAAV2-C3 vectors were driven by Ch3L1 (scAAV2-Ch3L1-C3), MGP (scAAV2-MGP-C3), enhanced MGP (scAAV2-eMGP-C3) and cytomegalovirus (scAAV2-CMV-C3), respectively. The cultured primary human TM cells were treated with each vector at different multiplicities of infections. Changes in cell morphology were observed by phase contrast microscopy. Actin stress fibers and Rho GTPases/Rho-associated protein kinase pathway-related molecules were assessed by immunofluorescence staining, real-time quantitative polymerase chain reaction and Western blot. Each vector was injected intracamerally into the one eye of each rat at low and high doses respectively. In vivo green fluorescence was visualized by a Micron III Retinal Imaging Microscope. Intraocular pressure (IOP) was monitored using a rebound tonometer. Ocular responses were evaluated by slit-lamp microscopy. Ocular histopathology analysis was examined by hematoxylin and eosin staining. RESULTS: In TM cell culture studies, the vector-mediated C3 expression induced morphologic changes, disruption of actin cytoskeleton and reduction of fibronectin expression in TM cells by inhibiting the Rho GTPases/Rho-associated protein kinase signaling pathway. At the same dose, these changes were significant in TM cells treated with scAAV2-CMV-C3 or scAAV2-Ch3L1-C3, but not in cells treated with scAAV2-eMGP-C3 or scAAV2-MGP-C3. At low-injected dose, the IOP was significantly decreased in the scAAV2-Ch3L1-C3-injected eyes but not in scAAV2-MGP-C3-injected and scAAV2-eMGP-C3-injected eyes. At high-injected dose, significant IOP reduction was observed in the scAAV2-eMGP-C3-injected eyes but not in scAAV2-MGP-C3-injected eyes. Similar to scAAV2-CMV-C3, scAAV2-Ch3L1-C3 vector showed efficient transduction both in the TM and corneal endothelium. In anterior segment tissues of scAAV2-eMGP-C3-injected eyes, no obvious morphological changes were found except for the TM. Inflammation was absent. CONCLUSION: In scAAV2-transduced TM cells, the promoter-driven efficiency of Ch3L1 is close to that of cytomegalovirus, but obviously higher than that of MGP. In the anterior chamber of rat eye, the transgene expression pattern of scAAV2 vector is presumably affected by MGP promoter, but not by Ch3L1 promoter. These findings would provide a useful reference for improvement of specificity and safety in glaucoma gene therapy using scAAV2 vector.

The lymphocyte-to-monocyte ratio predicts intracranial atherosclerotic stenosis plaque instability.

Background and purpose: Gadolinium enhancement on high-resolution vessel wall imaging (HR-VWI) is an imaging marker of intracranial atherosclerotic stenosis (ICAS) plaque instability. This study aimed to evaluate the relationships between hematological inflammatory indicators and the enhancement of ICAS plaques and to search for hematological indicators that can predict ICAS plaque instability. Methods: Consecutive adult patients diagnosed with ICAS from April 2018 to December 2021 were recruited retrospectively, and every patient underwent HR-VWI. Plaque enhancement was measured qualitatively and quantitatively. The plaque-to-pituitary stalk contrast ratio (CR) indicated the degree of plaque enhancement. Clinical and laboratory data, including the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII), were recorded. The hematological inflammatory indicators were compared between ICAS patients with and without plaque enhancement and between patients with and without symptomatic plaque. The hematological inflammatory indicators and the CR were compared using linear regression. Furthermore, receiver operating characteristic curve analysis was performed to assess the discriminative abilities of the inflammatory indicators to predict plaque instability. Results: Fifty-nine patients were included. The NLR, SII and LMR were significantly correlated with plaque enhancement. The LMR was independently associated with plaque enhancement, and a linear negative correlation was observed between the LMR and CR (R = 0.716, P < 0.001). The NLR, LMR, plaque enhancement and CR were significantly associated with symptomatic ICAS, and the LMR and plaque enhancement were independent risk factors for symptomatic ICAS. The optimal cutoff value of the admission LMR to distinguish symptomatic plaque from asymptomatic plaque was 4.0 (80.0% sensitivity and 70.6% specificity). Conclusion: The LMR was independently associated with ICAS plaque enhancement and showed a linear negative correlation with CR. The LMR and plaque enhancement were independent risk factors for symptomatic ICAS. An LMR ≤ 4.0 may predict ICAS plaque instability.

A Double Suspension Technique for Laparoscopic Isolated Caudate Lobectomy.

Background: Laparoscopic isolated caudate lobectomy is still a challenging procedure for hepatobiliary surgeons because of its deep location and narrow operating space. Hilar exposure and adequate operation space play an important role during laparoscopic caudate lobectomy. Very few references are available on this technique, and in this study, we present a new suspension technique to assist laparoscopic caudate lobectomy. Materials and Methods: The data of patients with caudate hepatic tumors who underwent laparoscopic isolated caudate lobectomy with or without the double suspension technique at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. Results: A total of 25 patients underwent laparoscopic isolated caudate lobectomy at Eastern Hepatobiliary Surgery Hospital between June 2016 and March 2022. Eight patients had perioperative complications, and no patient died within 30 days after surgery. There were no significant differences between the two groups in terms of conversion rate (8.3% versus 7.7%; P = .954), complication rate (25.0% versus 38.5%; P = .480), length of stay (8.0 [6.0-11.0] days versus 9.0 [6.0-19.0] days; P = .098), and postoperative liver function changes. Patients who underwent resection in the suspension group had shorter operation time (154.9 ± 44.3 minutes versus 224 ± 86.3 minutes; P = .018), inferior vena cava dissection time (30.1 ± 5.4 minutes versus 44.8 ± 7.4 minutes; P < .001), and less bleeding (125.0 [20-800.0] mL versus 350 [80-850.0] mL, P = .011). Conclusions: This double suspension technique is a safe and feasible method to assist laparoscopic caudate lobectomy. It provides clear exposure and adequate surgical space, thereby shortening the operation time and reducing intraoperative blood loss.

Circular RNA hsa_circ_0007990 as a blood biomarker for unruptured intracranial aneurysm with aneurysm wall enhancement.

Background: Circular RNAs (circRNAs) may involve the formation and rupture of intracranial aneurysms (IA). Inflammation plays a vital role in the development and progression of IA, which can be reflected by aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI). This study aims to evaluate the role of circRNAs as the blood inflammatory biomarker for unruptured IA (UIA) patients with AWE on HR-VWI. Methods: We analyzed the circRNA expression profiles in the peripheral blood samples among subjects from saccular UIA with AWE, UIA without AWE, and healthy controls by the circRNA microarray. The differential expression of hsa_circ_0007990 was assessed. We constructed the hsa_circ_0007990-microRNA-mRNA network and the regulatory axis of hub genes associated with the AWE in UIA. Results: Eighteen patients harboring saccular UIAs with HR VWI and five healthy controls were included. We found 412 differentially expressed circRNAs between UIA patients and healthy controls by circRNA microarray. Two hundred thirty-one circRNAs were significantly differentially expressed in UIA patients with AWE compared with those without AWE. Twelve upregulated circRNAs were associated with AWE of UIA, including hsa_circ_0007990, hsa_circ_0114507, hsa_circ_0020460, hsa_circ_0053944, hsa_circ_0000758, hsa_circ_0000034, hsa_circ_0009127, hsa_circ_0052793, hsa_circ_0000301 and hsa_circ_0000729. The expression of hsa_circ_0007990 was increased gradually in the healthy control, UIA without AWE, and UIA with AWE confirmed by RT-PCR (P<0.001). We predicted 4 RNA binding proteins (Ago2, DGCR8, EIF4A3, PTB) and period circadian regulator 1 as an encoding protein with hsa_circ_0007990. The hsa_circ_0007990-microRNA-mRNA network containing five microRNAs (miR-4717-5p, miR-1275, miR-150-3p, miR-18a-5p, miR-18b-5p), and 97 mRNAs was constructed. The five hub genes (hypoxia-inducible factor 1 subunit alpha, estrogen receptor 1, forkhead box O1, insulin-like growth factor 1, CREB binding protein) were involved in the inflammatory response. Conclusion: Differentially expressed blood circRNAs associated with AWE on HR-VWI may be the novel inflammatory biomarkers for assessing UIA patients. The mechanism of hsa_circRNA_0007990 for UIA progression needs to investigate further.

Neutrophil-to-Lymphocyte Ratio Is Associated With Circumferential Wall Enhancement of Unruptured Intracranial Aneurysm.

Background and Purpose: Neutrophil-lymphocyte ratio (NLR) predicts clinical outcomes in patients with stroke. Aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI) is an inflammation marker for intracranial aneurysm (IA). This study aims to evaluate the association of NLR as a peripheral blood inflammatory marker with circumferential AWE in patients with IA. Methods: We analyzed data of consecutive patients harboring IAs between September 2017 and December 2021 at our institution. The peripheral blood inflammatory indicators were compared between patients with ruptured and unruptured IAs. The presence of circumferential AWE in unruptured IA was identified and quantitatively measured using the aneurysm-to-pituitary stalk contrast ratio (CRstalk) on HR-VWI. We used the optimal cutoff value of 0.5 for CRstalk to differentiate circumferential AWE in unruptured IAs. We assessed the relationship of clinical, laboratory, and radiological characteristics with circumferential AWE and CRstalk ≥0.5 in unruptured IAs. Results: The study group was composed of one hundred and twenty-five patients with 142 IAs. NLR level at admission was significantly higher in patients with ruptured IAs than those with unruptured IAs (7.55 vs. 1.81; P < 0.001). AWE on HR-VWI was present in 30 patients with unruptured IAs (38.5%), including 12 with focal AWE and 18 with circumferential AWE. NLR (odds ratio (OR), 2.168; 95% CI, 1.149-4.088) and size (odds ratio, 1.370; 95% CI, 1.126-1.667) were independently associated with circumferential AWE in unruptured IA. NLR was also independently associated with circumferential AWE in small unruptured IA (<7 mm). Furthermore, NLR level at admission was associated with CRstalk ≥.5 in patients with unruptured IA. The optimal cutoff value of NLR for circumferential AWE was 1.86. Conclusion: NLR is a valuable peripheral blood inflammatory marker is more often in the rupture status of IA and was associated with circumferential AWE on HR-VWI in unruptured IA.

Circumferential wall enhancement with contrast ratio measurement in unruptured intracranial aneurysm for aneurysm instability.

BACKGROUND: Aneurysm wall enhancement on high-resolution vessel wall imaging (HR-VWI) may represent vessel wall inflammation for unruptured intracranial aneurysms (UIAs). Further evidence for the role of circumferential aneurysm wall enhancement (CAWE) in evaluating the instability of UIAs is required, especially in small aneurysms (<7 mm). METHODS: We analyzed patients with saccular UIAs who prospectively underwent HR-VWI on a 3.0 T MRI scanner in our center from September 2017 to August 2021. The presence of AWE was identified and quantitatively measured using the aneurysm-to-pituitary stalk contrast ratio (CRstalk) with maximal signal intensity value. The PHASES and ELAPSS scores were used to assess the risk of aneurysm rupture and growth. We evaluated the association of CAWE and CRstalk value with intracranial aneurysm instability. RESULTS: One hundred patients with 109 saccular UIAs were included in this study. Eighty-three UIAs (76.1%) had a size smaller than 7 mm. PHASES and ELAPSS scores were significantly higher in UIAs with CAWE than in UIAs without CAWE (p < .01). The association of CAWE with PHASES and ELAPSS scores remained in small UIAs (<7 mm). The optimal cutoff value of CRstalk for CAWE was 0.5. PHASES and ELAPSS scores were significantly higher in UIAs with CRstalk ≥0.5 than in UIAs with CRstalk <0.5 (p < .01). CONCLUSIONS: CAWE on HR-VWI is a valuable imaging marker for aneurysm instability in UIAs. CRstalk value ≥0.5 may be associated with a higher risk of intracranial aneurysm rupture and growth.