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Patients with nmoyamoya disease (MMD) who present primarily with ischemic stroke are known to have greater rates of perioperative strokes as compared with those who present with nonstroke symptoms. The optimal timing for revascularization for these patients remains unclear.From 1994 to 2015, 91 patients with MMD presented with signs and symptoms of an acute ischemic stroke with diffusion restriction correlate on magnetic resonance imaging, and these patients were subdivided into those who underwent early revascularization (90 days from last stroke), versus those who underwent delayed revascularization (≥90 days after last stroke), based on evidence that most neurological recovery after stroke occurs during the first three months. Perioperative and long-term outcomes were compared between the 2 surgical cohorts.In total, 27 patients underwent early revascularization, and 64 patients underwent delayed revascularization. Patients who underwent early revascularization had a statistically greater rate of perioperative stroke (P = 0.04) and perioperative mortality (P = 0.03), and overall complication rate (P = 0.049). At last follow-up of 5.2 ± 4.3 years, patients who underwent delayed revascularization had a lower mortality rate (P = 0.01) and a lower overall postoperative stroke incidence (P = 0.002). As a function of time, patients with MMD undergoing delayed revascularization had a statistically higher length of stroke-free survival (P = 0.005).Patients with MMD who present with ischemic stroke are more likely to have perioperative strokes, overall perioperative complications, worse long-term mortality rates, and lower rates of stroke-free survival if revascularization surgery occurred within 90 days of last stroke.

Nursing practices based on the dynamic interaction model have been shown to be superior to generic nursing practices. However, whether this model is effective in patients recovering from intracranial aneurysm surgery is not well studied.To investigate the effect of nursing based on a dynamic interaction model on functional rehabilitation of patients after aneurysm surgery.A total of 86 cases in our hospital with intracranial aneurysm from April 2019 to April 2021, were selected and divided into the study group and the control group, with 43 patients in each group. The control group received routine nursing, and the research group received nursing intervention based on a dynamic interaction model. The daily living ability (activities of daily living, ADL), cognitive function (Simple Intelligent Mental State Scale, MMSE), quality of life (Generic Quality of Life Inventory-74, GQOL-74), self-care ability (Exercise of Self-Care Agency scale), incidence of complications, and nursing satisfaction were recorded before and after intervention.Before intervention, ADL (52.09 ± 6.44), MMSE (18.03 ± 4.11), and GQOL-74 (53.68 ± 4.34) scores in the study group were not significantly different from those in the control group (ADL: 50.97 ± 7.32, MMSE: 17.59 ± 3.82, GQOL-74: 55.06 ± 3.98) (Nursing intervention based on a dynamic interaction model can improve postoperative cognitive function, daily living ability, self-care ability, quality of life, and patient satisfaction, while reducing the risk of complications.

OBJECTIVE Pediatric intracranial aneurysms are rare. Most large series in the last 15 years reported on an average of only 39 patients. The authors sought to report their institutional experience with pediatric intracranial aneurysms from 1991 to 2021 and to compare pediatric patient and aneurysm characteristics with those of a contemporaneous adult cohort. METHODS Pediatric (≤ 18 years of age) and adult patients with one or more intracranial aneurysms were identified in a prospective database. Standard epidemiological features and outcomes of each pediatric patient were retrospectively recorded. These results were compared with those of adult aneurysm patients managed at a single institution over the same time period. RESULTS From a total of 4500 patients with 5150 intracranial aneurysms admitted over 30 years, there were 47 children with 53 aneurysms and 4453 adults with 5097 aneurysms; 53.2% of children and 36.4% of adults presented with a subarachnoid hemorrhage (SAH). Pediatric aneurysms were significantly more common in males, more likely giant (≥ 25 mm), and most frequently located in the middle cerebral artery. Overall, 85.1% of the pediatric patients had a modified Rankin Scale score ≤ 2 at the last follow-up (with a mean follow-up of 65.9 months), and the pediatric mortality rate was 10.6%; all 5 patients who died had an SAH. The recurrence rate of treated aneurysms was 6.7% (1/15) in the endovascular group but 0% (0/31) in the microsurgical group. No de novo aneurysms occurred in children (mean follow-up 5.5 years). CONCLUSIONS Pediatric intracranial aneurysms are significantly different from adult aneurysms in terms of sex, presentation, location, size, and outcomes. Future prospective studies will better characterize long-term aneurysm recurrence, rebleeds, and de novo aneurysm occurrences. The authors currently favor microsurgical over endovascular treatment for pediatric aneurysms.

To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF).nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower risk LARC patients with uninvolved MRF.Patients between June 2014 and October 2020 with LARC within 12 cm from anal verge and uninvolved MRF were randomly assigned to nCT group with four cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported results of secondary end points: histopathologic response, surgical events, and toxicity.Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathological complete response (pCR) rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm (P=0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm (P=0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P=0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P=0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a non-surgical approach. Similar results were observed in subgroup analysis.nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.

Excessive autophagy-induced follicular atresia of ovarian granulosa cells might be one of the pathogenesis of Premature Ovarian Insufficiency (POI), and melatonin (MT) exerted many beneficial effects on mitochondria. However, there was little report regarding the beneficial effects of MT on excessive autophagy-induced mitochondrial and ovarian reserve function deficiency, and the mechanisms have not been clearly identified. Autophagy played a protective role in cells survival, however, high level of autophagy could lead to cell death. In this report, firstly, Chinese hamster ovary cell damage model stably expressing EGFP-LC3 was established. Next, we systematically investigated the protective effects of MT on mitochondrial and ovarian reserve function and molecular mechanisms using this cell damage model. Our results revealed that 10-9 M MT not only protected against the decline of anti-mullerian hormone (AMH) expression induced by excessive autophagy, but also rescued excessive autophagy-induced impairment of mitochondrial expression and mitochondrial membrane potential. Furthermore, MT protected against excessive autophagy-induced decrease of nucleus-encoded proteins including SDHA and mitofilin, and mitochondrial dynamic-related proteins including OPA1, MFN2, and DRP1. MT also decreased mitochondrial oxidative stress, increased antioxidant enzyme superoxide dismutase 2 (SOD2) expression and ameliorated the G2/M cell cycle arrest induced by excessive autophagy. Finally, MT inhibited excessive autophagy-induced activation of extracellular signal regulated kinase (ERK) signaling pathway. In conclusion, our study showed that MT rescued impairment of mitochondrial and ovarian reserve function, and production of mitochondrial ROS and cell cycle arrest induced by excessive autophagy through down-regulated ERK pathway, implying the potential therapeutic drug target for POI.

Background Primary duodenal tuberculosis is very rare. Due to a lack of specificity for its presenting symptoms, it is easily misdiagnosed clinically. Review of the few case reports and literature on the topic will help to improve the overall understanding of this disease and aid in differential diagnosis to improve patient outcome. Case summary A 71-year-old man with a 30-plus year history of bronchiectasis and bronchitis presented to the Gastroenterology Department of our hospital complaining of intermittent upper abdominal pain. Initial imaging examination revealed a duodenal space-occupying lesion; subsequent upper abdominal contrast-enhanced computed tomography indicated duodenal malignant tumor. Physical and laboratory examinations showed no obvious abnormalities. In order to confirm further the diagnosis, electronic endoscopy was performed and tissue biopsies were taken. Duodenal histopathology showed granuloma and necrosis. In-depth tuberculosis-related examination did not rule out tuberculosis, so we initiated treatment with anti-tuberculosis drugs. At 6 mo after the anti-tuberculosis drug course, there were no signs of new development of primary lesions by upper abdominal computed tomography, and no complications had manifested. Conclusion This case emphasizes the importance of differential diagnosis for gastrointestinal diseases. Duodenal tuberculosis requires a systematic examination and physician awareness.

Based on the literature regarding Sen’s capability approach, this work contributes to the empirical literature on multidimensional well-being by exploring whether a relationship exists between resources and how individuals convert their personal endowments. To control for conversion efficiency, differences in individual efficiency levels are estimated using the Stochastic Frontier Approach (SFA) in a production analysis, and efficiency scores are calculated at the individual level to capture the main factors leading to existing conversion inefficiency. Differences in individual living standards may also be caused by lower/higher efficiency in converting personal resources into income and well-being. Some determinants of efficiency levels for both poor and non-poor individuals are then investigated. Individual characteristics that can contribute to explaining the relationship between individuals’ resources and achieved functioning are further investigated, and an individual’s conversion efficiency is found to be positively affected by increased parental income, being married and living in an urban or eastern area. On the other hand, ageing and a larger household size decrease an individual’s conversion efficiency. Constraints in the conversion of given resource factors into achieved functioning can be caused by personal, environmental or social factors. These conversion factors determine why one individual achieves higher functioning output than someone else with the same input.

BackgroundHepatocellular carcinoma (HCC) is a highly invasive disease with a high mortality rate. Our previous study found that Chenodeoxycholic acid (CDCA) as an endogenous metabolite can enhance the anti-tumor effect. Sorafenib has limited overall efficacy as a first-line agent in HCC, and combined with CDCA may improve its efficacy.MethodsHepG2 cells and Balb/c nude mice were used respectively for in vitro and in vivo experiments. Flow cytometry, Western blotting, HE and immunohistochemical staining and immunofluorescence were used to study the effects of CDCA combined with sorafenib on HepG2 cell growth and apoptosis-related proteins. Magnetic bead coupling, protein profiling and magnetic bead immunoprecipitation were used to find the targets of CDCA action. The effect of CDCA on EGFR/Stat3 signaling pathway was further verified by knocking down Stat3 and EGFR. Finally, fluorescence confocal, and molecular docking were used to study the binding site of CDCA to EGFR.ResultsIn this study, we found that CDCA enhanced the effect of sorafenib in inhibiting the proliferation, migration and invasion of HepG2 cells. Magnetic bead immunoprecipitation and protein profiling revealed that CDCA may enhance the effect of sorafenib by affecting the EGFR/Stat3 signaling pathway. Further results from in vitro and in vivo gene knockdown experiments, confocal experiments and molecular docking showed that CDCA enhances the efficacy of sorafenib by binding to the extracellular structural domain of EGFR.ConclusionThis study reveals the mechanism that CDCA enhances the inhibitory effect of sorafenib on HepG2 cell growth in vitro and in vivo, providing a potential new combination strategy for the treatment of HCC.

Introduction Hemangioblastomas typically present throughout the neuroaxis, particularly within the cerebellum and spinal cord. A rare case of cystic hemangioblastoma within the quadrigeminal cistern is described. Case Report A 18-year-old female presented with 3 weeks of worsening headaches and vomiting. Workup revealed multiple contrast enhancing lesions throughout the neuroaxis concerning for hemangioblastoma, with the largest cystic mass within the quadrigeminal cistern causing brainstem compression and hydrocephalus. The patient experienced an acute neurologic decompensation likely due to brainstem compression and hydrocephalus, which was temporized by cyst drainage and endoscopic third ventriculostomy. After neurological stabilization and Von Hippel Lindau disease workup, she underwent a suboccipital craniotomy and resection of the hemangioblastoma via a transcystic approach. Intraoperatively, the trochlear nerve was identified and preserved. Conclusion Operative approaches to the quadrigeminal cistern typically include the infratentorial supracerebellar approach and the occipital transtentorial approach. Here, we describe a safe and efficacious transcystic approach to a quadrigeminal cistern hemangioblastoma.

An ideal type-III nodal point is generated by crossing a completely flat band and a dispersive band along a certain momentum direction. To date, the type-III nodal points found in two-dimensional (2D) materials have been mostly accidental and random rather than ideal cases, and no one mentions what kind of lattice can produce ideal nodal points. Here, we propose that ideal type-III nodal points can be obtained in a diamond-like lattice. The flat bands in the lattice originate from destructive interference of wavefunctions, and thus are intrinsic and robust. Moreover, the specific lattice can be realized in some 2D carbon networks, such as T-graphene and its derivatives. All the carbon structures possess type-III Dirac points. In two of the structures, consisting of triangular carbon rings, the type-III Dirac points are located just on the Fermi level and the Fermi surface is very clean. Our research not only opens a door to finding the ideal type-III Dirac points, but also provides 2D materials for exploring their physical properties experimentally.

Background Proton pump inhibitor (PPI) is effective for the treatment of nonerosive gastroesophageal reflux (NERD), but long-term use of PPI is prone to have complications and recurrence after withdrawal. Traditional Chinese medicine (TCM) can relieve the symptoms of reflux and improve the quality of life. The purpose of this study is to evaluate the safety and efficacy of Hewei Jiangni recipe (HWJNR) in the treatment of NERD with cold-heat complex syndrome, and clarify the mechanism of HWJNR on NERD based on the correlation analysis of intestinal flora and metabolites. Methods This is a single-center, randomized controlled, double-blind, placebo-controlled clinical trial in which 72 eligible participants with NERD and TCM syndrome of intermingled heat and cold will be randomly allocated in the ratio of 1:1 to two groups: TCM group and western medicine group. The TCM group will receive HWJNR with omeprazole enteric-coated tablets placebo, while the western medicine group will receive omeprazole enteric-coated tablets with HWJNR placebo. Each group will be treated for 8 weeks. The primary outcome is the score of gastroesophageal reflux disease (GERD) health-related quality of life questionnaire (GERD-Q). Secondary outcomes include SF-36 quality of life scale (SF-36), patient-reported outcomes (PRO) self-rating scale score, syndrome score of TCM, and adverse events. Mechanistic outcome is the correlation analysis of intestinal flora and metabolites from healthy individuals and NERD participants before and after the treatment respectively. Discussion The goal of this trial is to investigate the efficacy and safety of HWJNR in the treatment of NERD with cold-heat complex syndrome, and to study the composition structure and metabolite expression profile of intestinal flora in patients with NERD through 16SrRNA sequencing and metabolomic correlation analysis of fecal flora, which makes us identify the dominant links of treatment and reveal the potential mechanism of HWJNR. ChiCTR2000041225. Registered on 22 December 2020

Trigeminal neuralgia (TN) has been described in the literature as one of the most debilitating presentations of orofacial pain. This review summarizes over 150 years of collective clinical experience in the medical and surgical treatment of TN. Fundamentally, TN remains a clinical diagnosis that must be distinguished from other types of trigeminal neuropathic pain and/or facial pain associated with other neuralgias or headache syndromes. What is increasingly clear is that there is no catch-all medical or surgical intervention that is effective for all patients with trigeminal neuralgia, likely reflective of the fact that TN is likely a heterogenous group of disorders that jointly manifests in facial pain. The first-line treatment for TN remains anticonvulsant medical therapy. Patients who fail this have a range of surgical options available to them. In general, microvascular decompression is a safe and effective procedure with immediate and durable outcomes. Patients who are unable to tolerate general anesthesia or whose medical comorbidities preclude a suboccipital craniectomy may benefit from percutaneous methodologies including glycerol or radiofrequency ablation, or both. For patients with bleeding diathesis due to blood thinning medications who are ineligible for invasive procedures, or for those who are unwilling to undergo open surgical procedures, radiosurgery may be an excellent option—provided the patient understands that maximum pain relief will take on the order of months to achieve. Finally, peripheral neurectomies continue to provide an inexpensive and resource-sparing alternative to pain relief for patients in locations with limited economic and medical resources. Ultimately, elucidation of the molecular mechanisms underlying trigeminal neuralgia will pave the way for novel, more effective and less invasive therapies.

Several East Asian studies have examined the role of revascularization in the context of hemorrhagic moyamoya disease (MMD) and found a decrease in postoperative rehemorrhage rates. To date, no data exist comparing revascularization with conservative management in North American patients with hemorrhagic MMD.To compare the clinical outcomes of conservative management vs surgical revascularization for North American patients with hemorrhagic MMD and investigate the effect of revascularization timing.We retrospectively studied the mortality and stroke-free survival of patients with MMD presenting with hemorrhagic stroke between 1994 and 2015.The diagnosis of hemorrhagic MMD was established in 38 patients. Seventeen patients were managed conservatively, and 21 were surgically revascularized. Twelve patients underwent revascularization within 6 months of hemorrhage, and 9 underwent surgery in a delayed fashion. Six conservatively managed patients (35.3%) died within the follow-up period compared with 0 (0%) surgically revascularized patients, P = .004. Conservatively managed patients also experienced an increased number of postoperative strokes, P = .037, and shorter stroke-free survival compared with patients undergoing revascularization, P = .047. On multivariate analysis, increased age, worse baseline modified Rankin score, and conservative management were independently associated with worse neurological outcomes, P.05. Early revascularization was associated with higher rates of postoperative seizures, P = .033, and wound complications, P = .031, compared with those who underwent delayed surgery.Conservative management in a North American patient cohort was associated with greater mortality and worsened neurological outcomes compared with those undergoing revascularization. Early revascularization was associated with higher rates of postoperative seizures and wound complications, although these risks must be balanced against the risk of rehemorrhage.

Qing-E Xie,1– 3,* Xin Du,4,* Mengyao Wang,1,2,5 Fenfen Xie,3 Zuoyang Zhang,6 Yunxia Cao,1,2,5,7,8 Yajing Liu1,2,5,7,8 1Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei, 230022, People’s Republic of China; 3Department of Histology and Embryology, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China; 4 901th Hospital of PLA Joint Logistic Support Force, Heifei, 230031, Anhui, People’s Republic of China; 5Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People’s Republic of China, Hefei, 230032, Anhui, People’s Republic of China; 6Department of Pathology, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China; 7Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, 230032, Anhui, People’s Republic of China; 8Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunxia Cao; Yajing Liu Email caoyunxia6@126.com; 13385690561@163.comPurpose: Cumulative evidence has demonstrated that breast cancer was the most commonly diagnosed cancer in women. Despite growing evidence for a link between serotonin and tumorigenesis, research on the expression of serotoninergic systems in the human breast cancer cell and tissue has only rarely been reported.Methods: First, immunofluorescence staining, ELISA and Western blotting were used to detect serotonin and melatoninergic systems in various breast cancer cell types. Then, serotonin expression was evaluated in the cultures of TPBC cell line BT-474 and TNBC cell line MDA-MB-231 using immunofluorescence assay. To further explore the diagnostic role of serotonin in breast cancer, serotonin expression was conducted in the TPBC and TNBC tumor sections by immunostaining analysis.Results: Our results suggested that both human breast cancer cells and human breast epithelial cell line could synthesize serotonin and melatonin. Unlike melatonin, serotonin levels varied significantly between human breast cancer and breast epithelial cell line (p< 0.01). In addition, serotonin N-acetyltransferase (NAT) and acetylserotonin methyltransferase (ASMT), the key enzymes in the pathway of melatonin synthesis from serotonin, were also detectable. In agreement with these findings of human breast cancer cell and human breast epithelial cell line, serotonin expression was also much higher in triple-negative (PR−, ER−, HER-2−) breast cancer (TNBC) and triple-positive breast cancer (TPBC) compared to para-carcinoma tissues (PCTs).Conclusion: Here, we provided evidence that the human breast cancer cell (MCF-7, Bcap-37) and human breast epithelial cell (MCF-10A) could synthesize intrinsic serotonin and melatonin, and serotonin expression was higher in the breast cancer tissue compared with PCT. The findings suggested that serotonin might be used as a predictive marker for breast cancer patients.Keywords: serotonin, melatonin, breast cancer, serotonin N-acetyltransferase, acetylserotonin methyltransferase

This article analyzes how trade facilitation influence China’s agricultural exports to RCEP partners. Based on the data of the World Economic Forum Global Competitiveness Report and principal component analysis, we constructs a 14 index system to measure trade facilitation. Based on the export data from 2011 to 2019, the extended gravity model is used to estimate the relationship between trade facilitation and the depth and breadth of China's agricultural exports. The study shows that improving the trade facilitation of RCEP partners can significantly enhance the depth of China's agricultural exports. Specifically, the trade openness, e-commerce and financial environment of importing countries have a significant positive impact on the depth and breadth of exports. Another important finding is that China's trade facilitation has played a more active role in the depth and breadth of exports. Its infrastructure quality, e-commerce and financial environment can greatly promote China's agricultural exports.

Over the past 10 years, Oosterhof and Todorov’s valence–dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov’s methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov’s original analysis strategy, the valence–dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence–dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. Protocol registration: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease characterized by visceral hypersensitivity-related abdominal pain, in which diarrhea-predominant IBS (IBS-D) is the main subtype and has a high clinical incidence. Tongxie Anchang Decoction (TXACD) has been proved to significantly improve abdominal pain in patients with IBS-D, but its underlying therapeutic mechanism still remains unclear. In the present study, IBS-D model rats were induced by neonatal maternal separation (NMS) combined with restraint stress (RS). The therapeutic effect of TXACD was evaluated by fecal characteristics and abdominal withdrawal reflex (AWR) scores. After 14 days of intragastric administration, the colonic tissues of rats were collected to detect the protein and gene level of the NGF, TrkA, and TRPV1 using Western blotting and real-time polymerase chain reaction, respectively, and detect mast cells infiltration using toluidine blue staining. The abdominal aorta blood centrifuged was collected for detecting serum levels of SP, 5-HT, and CGRP with ELISA. The results revealed that TXACD could significantly improve visceral hypersensitivity in IBS-D rats, reflected in the decrease of AWR score and the serum levels of SP, 5-HT, and CGRP. In addition, TXACD treatment could alleviate mast cells infiltration. Moreover, the expression levels of the NGF, TrkA, and TRPV1 were repressed by TXACD. The findings of the present study indicated that the therapeutic effect of TXACD on visceral hypersensitivity might be closely related to the downregulation of the NGF/TrkA signaling pathway, the reversal of TRPV1 expression and mast cells infiltration, and the decreased release of neuroendocrine factors SP, 5-HT, and CGRP.

Summary The ability to probe the membrane potential of multiple genetically defined neurons simultaneously would have a profound impact on neuroscience research. Genetically encoded voltage indicators are a promising tool for this purpose, and recent developments have achieved a high signal-to-noise ratio in vivo with 1-photon fluorescence imaging. However, these recordings exhibit several sources of noise and signal extraction remains a challenge. We present an improved signal extraction pipeline, spike-guided penalized matrix decomposition-nonnegative matrix factorization (SGPMD-NMF), which resolves supra- and subthreshold voltages in vivo. The method incorporates biophysical and optical constraints. We validate the pipeline with simultaneous patch-clamp and optical recordings from mouse layer 1 in vivo and with simulated and composite datasets with realistic noise. We demonstrate applications to mouse hippocampus expressing paQuasAr3-s or SomArchon1, mouse cortex expressing SomArchon1 or Voltron, and zebrafish spines expressing zArchon1.

Objective The clinical symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) can be effectively improved by traditional Chinese medicine (TCM) treatment, based on the usage of specific therapies for different TCM syndromes. However, in the stage of diagnosis, the standard criteria for the classification of TCM syndrome were still deficient. Through serum metabolic profiling, this study aimed to explore potential biomarkers in IBS-D patients with different TCM syndromes, which can assist in diagnosis of the disease. Methods Serum samples were collected from healthy controls (30 cases), IBS-D patients with Liver-Stagnation and Spleen-Deficiency syndrome (LSSD, 30 cases), Yang Deficiency of Spleen and Kidney syndrome (YDSK, 11 cases) and Damp Abundance due to Spleen-Deficiency syndrome (DASD, 22 cases). Serum metabolic profiling was conducted by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential biomarkers were screened by orthogonal partial least square-discriminate analysis, while metabolic pathways undergoing alterations were identified by pathway enrichment analysis in MetaboAnalyst 4.0. Results Overall, 34 potential biomarkers were identified in LSSD group, 36 in YDSK group and 31 in DASD group. And the 13 metabolites shared by three groups were determined as the potential biomarkers of IBS-D. Glycerophospholipid metabolism was disturbed significantly in IBS-D patients, which may play a role in IBS-D through inflammation. What’s more, three TCM syndromes have the specific potential biomarkers in glycerophospholipid metabolism. Conclusion The serum metabolomics revealed that different TCM syndrome types in IBS-D may have different metabolic patterns during disease progression and glycerophospholipid metabolism was one of the pathways, whose metabolism was disturbed differently among three TCM syndromes in IBS-D. Therefore, the specific potential biomarkers in glycerophospholipid metabolism of three TCM syndromes in IBS-D can serve as the objective indicators, which can facilitate the TCM-syndrome objective classification of IBS-D.

We have fabricated and studied a system of two tunable and coupled nonlinear superconducting resonators. The nonlinearity is introduced by galvanically coupled dc superconducting quantum interference devices. We simulate the system response by means of a circuit model, which includes an additional signal path introduced by the electromagnetic environment. Furthermore, we present two methods allowing us to experimentally determine the nonlinearity. First, we fit the measured frequency and flux dependence of the transmission data to simulations based on the equivalent circuit model. Second, we fit the power dependence of the transmission data to a model that is predicted by the nonlinear equation of motion describing the system. Our results show that we are able to tune the nonlinearity of the resonators by almost two orders of magnitude via an external coil and two on-chip antennas. The studied system represents a basic building block for larger systems, allowing for quantum simulations of bosonic many-body systems with a larger number of lattice sites.

Correction to: Space Sci. Rev. (2020) 216: 103 Affiliation 2 in this article is the wrong affiliation that instead should read: “Institute of Geophysics and Planetary Physics, University of California, Los Angeles, CA, USA” which should be regarded as the final version by the reader.

BRAF and MLH1 promoter methylation testings have been proven effective prescreens for Lynch Syndrome. We aimed to compare different screening strategies for Lynch Syndrome in patients with MLH1(-) CRC. Patients with MLH1(-) CRC who had been tested for BRAF mutation and germline variants of DNA mismatch repair genes were included. We compared the sensitivities and specificities for identifying Lynch Syndrome and the cost-effectiveness of four screening approaches that used the following tests as prescreens: BRAF testing, MLH1 methylation testing, MLH1 methylation & BRAF testing, and MLH1 methylation testing & Revised Bethesda Criteria. Of 109 patients included, 23 (21.1%) were Lynch Syndrome patients. BRAF mutation and MLH1 methylation occurred in 6 (5.5%) and 40 (36.7%) patients, respectively. The sensitivity for identifying Lynch syndrome of BRAF testing was 100%, but the specificity was only 7%. MLH1 methylation testing had a lower sensitivity than BRAF testing (97.5% vs 100%), but had a markedly higher specificity (45.3% vs 7%). The combination of the two testings had a slightly higher specificity than MLH1 methylation testing alone (47.7% vs 45.3%). The MLH1 methylation testing approach had a 10% lower cost of identifying MLH1(-) Lynch syndrome carriers per case than universal genetic testing, but it missed 4.5% of patients. BRAF and MLH1 promoter methylation testings as prescreens for Lynch syndrome are less effective in Chinese patients with MLH1(-) CRC than in their Western counterparts. Universal genetic testing could be considered an up-front option for this population.

Cortical layer 1 (L1) interneurons have been proposed as a hub for attentional modulation of underlying cortex, but the transformations that this circuit implements are not known. We combined genetically targeted voltage imaging with optogenetic activation and silencing to study the mechanisms underlying sensory processing in mouse barrel cortex L1. Whisker stimuli evoked precisely timed single spikes in L1 interneurons, followed by strong lateral inhibition. A mild aversive stimulus activated cholinergic inputs and evoked a bimodal distribution of spiking responses in L1. A simple conductance-based model that only contained lateral inhibition within L1 recapitulated the sensory responses and the winner-takes-all cholinergic responses, and the model correctly predicted that the network would function as a spatial and temporal high-pass filter for excitatory inputs. Our results demonstrate that all-optical electrophysiology can reveal basic principles of neural circuit function in vivo and suggest an intuitive picture for how L1 transforms sensory and modulatory inputs. Video Abstract: [Figure presented] By simultaneously combining genetically targeted voltage imaging with optogenetic modulation of neuronal activity, Fan et al. demonstrate that all-optical electrophysiology in awake animals can be a powerful tool for revealing hidden principles of neural circuit function.

The ability to probe the membrane potential of multiple genetically defined neurons simultaneously would have a profound impact on neuroscience research. Genetically encoded voltage indicators are a promising tool for this purpose, and recent developments have achieved high signal to noise ratio in vivo with 1-photon fluorescence imaging. However, these recordings exhibit several sources of noise that present analysis challenges, namely light scattering, out-of-focus sources, motion, and blood flow. We present a novel signal extraction methodology, Spike-Guided Penalized Matrix Decomposition-Nonnegative Matrix Factorization (SGPMD-NMF), which resolves supra- and sub-threshold voltages with high fidelity, even in the presence of correlated noise. The method incorporates biophysical constraints (shared soma profiles for spiking and subthreshold dynamics) and optical constraints (smoother spatial profiles from defocused vs. in-focus sources) to cleave signal from background. We validated the pipeline using simulated and composite datasets with realistic noise properties. We demonstrate applications to mouse hippocampus expressing paQuasAr3-s or SomArchon, mouse cortex expressing SomArchon or Voltron, and zebrafish spine expressing zArchon1.

Heweijiangni decoction (HWJND) is an effective traditional Chinese medicine prescription in clinical treatment of nonerosive reflux disease (NERD). Esophageal hypersensitivity and acid contribute to the disease. However, the exact underlying mechanism of action remains unclear. In this study, we observed the effect of HWJND on esophageal morphology in a rat model of ovalbumin (OVA)-induced visceral hypersensitivity followed by acid exposure. Esophageal morphology was assessed by measuring the extent of dilated intercellular spaces (DIS), desmosome disruption, and mitochondrial fragmentation. HWJND in low, moderate, and high doses relieved DIS and desmosome disruption in esophageal epithelium compared with model group (Plt;0.05 for all doses). In addition, HWJND in high dose protected mitochondria from fragmentation (Plt;0.05). Other findings suggest that DIS and mitochondrial fragmentation are independent events, and that omeprazole protects mitochondria. Overall, HWJND significantly resists esophageal morphology changes in OVA-induced and acid exposure rat model.

The stability of neural dynamics arises through a tight coupling of excitatory (E) and inhibitory (I) signals. Genetically encoded voltage indicators (GEVIs) can report both spikes and subthreshold dynamics in vivo, but voltage only reveals the combined effects of E and I synaptic inputs, not their separate contributions individually. Here we combine optical recording of membrane voltage with simultaneous optogenetic manipulation to probe E and I individually in barrel cortex Layer 1 (L1) neurons in awake mice. Our studies reveal how the L1 microcircuit integrates thalamocortical excitation, lateral inhibition and top-down neuromodulatory inputs. We develop a simple computational model of the L1 microcircuit which captures the main features of our data. Together, these results suggest a model for computation in L1 interneurons consistent with their hypothesized role in attentional gating of the underlying cortex. Our results demonstrate that all-optical electrophysiology can reveal basic principles of neural circuit function in vivo.One Sentence SummaryAll-optical electrophysiology revealed the function in awake mice of an inhibitory microcircuit in barrel cortex Layer 1.

Common bile duct (CBD) stone is one of the most common diseases among elderly people. In recent decades, there are numerous studies regarding the safety and efficacy of laparoscopic common bile duct exploration (LCBDE). Elderly patients are often regarded as high-risk patients because they are more likely to present with age-specific deterioration of organ function and coexisting chronic diseases, which may reduce their tolerance of laparoscopic surgery. Although laparoscopic surgery for choledocholithiasis is now widely accepted as the treatment for CBD stone, its appropriateness for the treatment of elderly patients or those with coexisting high-risk patients has not been well established. Therefore, the objective of this paper is to analyze the safety and efficacy of LCBDE in elderly patients.Between January 2012 and November 2015, 376 patients underwent LCBDE in our center. Based on their ages, they were divided into two groups, and a retrospective study was performed. By making comparisons between younger group who were younger than 70 years (n = 253) and elderly group who were 70 years old or older (n = 123), the demographics, clinical characteristics, laboratory data, operative parameters and outcomes were analyzed.Before operation, elderly patients had more coexisting chronic diseases and risk factors, such as arterial hypertension, heart diseases, pulmonary diseases and previous abdominal surgery (P 0.05). In both groups, LCBDE was equally successful with a high clearance rate (100 % in elderly patients vs. 98.8 % in younger group, P = 0.554). Besides, the operating time, intraoperative blood loss, postoperative hospital stay, total costs and overall complication showed no significant difference between two groups (P 0.05). There was no major bile duct injury or death in either group.Although elderly patients are frequently confronted with coexisting disorders, LCBDE can be considered as a safe and effective technique in choledocholithiasis treatment for elderly patients.

The concept of parity describes the inversion symmetry of a system and is of fundamental relevance in the standard model, quantum information processing, and field theory. In quantum electrodynamics, parity is conserved and large field gradients are required to engineer the parity of the light-matter interaction operator. In this work, we engineer a potassium-like artificial atom represented by a specifically designed superconducting flux qubit. We control the wave function parity of the artificial atom with an effective orbital momentum provided by a resonator. By irradiating the artificial atom with spatially shaped microwave fields, we select the interaction parity in situ. In this way, we observe dipole and quadrupole selection rules for single state transitions and induce transparency via longitudinal coupling. Our work advances the design of tunable artificial multilevel atoms to a new level, which is particularly promising with respect to quantum chemistry simulations with near-term superconducting circuits., Comment: Published manuscript (6 pages, 3 figures) plus supplemental materials (8 pages, 2 figures)

Two-mode squeezing is a fascinating example of quantum entanglement manifested in cross-correlations of non-commuting observables between two subsystems. At the same time, these subsystems themselves may contain no quantum signatures in their self-correlations. These properties make two-mode squeezed (TMS) states an ideal resource for applications in quantum communication. Here, we generate propagating microwave TMS states by a beam splitter distributing single mode squeezing emitted from distinct Josephson parametric amplifiers along two output paths. We experimentally study the fundamental dephasing process of quantum cross-correlations in continuous-variable propagating TMS microwave states and accurately describe it with a theory model. In this way, we gain the insight into finite-time entanglement limits and predict high fidelities for benchmark quantum communication protocols such as remote state preparation and quantum teleportation. We acknowledge support by the German Research Foundation through FE 1564/1-1, Spanish MINECO/FEDER FIS2015-69983-P, UPV/EHU PhD grant, Basque Government Grant IT986-16, European Project AQuS (Project No. 640800), Elite Network of Bavaria through the program ExQM, the projects JST ERATO (Grant No. JPMJER1601) and JSPS KAKENHI (Grant No. 26220601 and Grant No. 15K17731). E.S. acknowledges support from a TUM August-Wilhelm Scheer Visiting Professorship and hospitality of Walther-Meissner-Institut and TUM Institute for Advanced Study. We would like to thank K. Kusuyama for assistance with part of the JPA fabrication.

Superconducting 3D microwave cavities offer state-of-the-art coherence times and a well controlled environment for superconducting qubits. In order to realize at the same time fast readout and long-lived quantum information storage, one can couple the qubit both to a low-quality readout and a high-quality storage cavity. However, such systems are bulky compared to their less coherent 2D counterparts. A more compact and scalable approach is achieved by making use of the multimode structure of a 3D cavity. In our work, we investigate such a device where a transmon qubit is capacitively coupled to two modes of a single 3D cavity. The external coupling is engineered so that the memory mode has an about 100 times larger quality factor than the readout mode. Using an all-microwave second-order protocol, we realize a lifetime enhancement of the stored state over the qubit lifetime by a factor of $6$ with a fidelity of approximately $80\%$ determined via quantum process tomography. We also find that this enhancement is not limited by fundamental constraints., 5 pages, 4 figures

A technology that simultaneously records membrane potential from multiple neurons in behaving animals will have a transformative effect on neuroscience research1,2. Genetically encoded voltage indicators are a promising tool for these purposes; however, these have so far been limited to single-cell recordings with a marginal signal-to-noise ratio in vivo3–5. Here we developed improved near-infrared voltage indicators, high-speed microscopes and targeted gene expression schemes that enabled simultaneous in vivo recordings of supra- and subthreshold voltage dynamics in multiple neurons in the hippocampus of behaving mice. The reporters revealed subcellular details of back-propagating action potentials and correlations in subthreshold voltage between multiple cells. In combination with stimulation using optogenetics, the reporters revealed changes in neuronal excitability that were dependent on the behavioural state, reflecting the interplay of excitatory and inhibitory synaptic inputs. These tools open the possibility for detailed explorations of network dynamics in the context of behaviour. A combination of improved near-infrared voltage indicators, high-speed microscopes and targeted gene expression schemes enabled simultaneous in vivo optogenetic control and recording of voltage dynamics in multiple neurons in the hippocampus of behaving mice.