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Lianyuan Tao,1,2 Li Su,3 Chunhui Yuan,1 Zhaolai Ma,1 Lingfu Zhang,1 Shiping Bo,4 Yunyun Niu,4 Sijia Lu,4 Dianrong Xiu11Department of General Surgery, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, People’s Republic of China; 3Medical and Health Analytical Center, Peking University Health Science Center, Beijing 100191, People’s Republic of China; 4Department of Clinical Research, Yikon Genomics Co. Ltd., Shanghai, People’s Republic of ChinaPurpose: The aim of this study was to evaluate the value of flow cytometry (FCM) detection of portal vein circulating tumor cells (CTCs) in predicting postoperative metastasis.Methods: Samples of portal venous blood and peripheral blood were collected from 39 patients during surgery, and CTCs were detected by FCM, with confirmation by laser confocal microscopy and single-cell sequencing.Results: Among all patients, a portal EpCAM+CD45- percentage ≥24.5×10−4 (P=0.06), peripheral EpCAM+CD45- count ≥97/5 mL (P=0.034), peripheral EpCAM+CD45- percentage ≥4.4×10−4 (P=0.042), and CA242≥3.5 U/mL (P=0.027) were significant predictors of metastasis. Further analysis showed that the portal EpCAM+CD45- ratio ≥24.5×10−4 is a predictor of metastasis (P=0.025) in pancreatic cancer after curative resection.Conclusion: CTCs detected by FCM in portal venous blood are of significant value for the prediction of postoperative metastasis in pancreatic or periampullary tumors.Keywords: circulating tumor cells, flow cytometry, portal vein, pancreatic cancer, metastases

Lingfu Zhang,1 Lianyuan Tao,1 Limei Guo,2 Jun Zhan,3 Chunhui Yuan,1 Zhaolai Ma,1 Bin Jiang,1 Dianrong Xiu1 1Department of General Surgery, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Pathology, Peking University Third Hospital, Beijing, People’s Republic of China; 3Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing, People’s Republic of China Background: Recent studies demonstrated that granulocyte colony-stimulating factor (G-CSF), regularly used for the prevention of neutropenia, is engaged in cancer progression. However, the role of G-CSF in pancreatic ductal adenocarcinoma (PDAC) is not clear. The aim of the present study was to investigate the expression and prognostic value of G-CSF in patients with PDAC.Materials and methods: The localization and expression of G-CSF in PDAC were examined by immunohistochemistry (IHC). The analysis of the levels of G-CSF in plasma was evaluated using ELISA kit. The correlation between G-CSF expression and patients’ survival was assessed by Kaplan–Meier analysis.Results: In IHC specimens, G-CSF was discovered predominantly in the cell cytoplasm and expressed in most of PDAC, while in plasma, the systemic level of G-CSF is no different between normal patients and pancreatic cancer patients. In 100 PDAC cases with IHC, patients with grades 2 and 3 were defined as the high expression group (41 patients, 41%), and those with grades 0 and 1 as the low expression group (59 patients, 59%). Significant correlation was noted between high G-CSF expression and neural invasion (P = 0.042) or early recurrence (P

Catechol-O-methyltransferase (COMT) Val158Met (rs4680) polymorphism plays a crucial role in regulating brain dopamine level. Converging evidence from Caucasian samples showed that, compared with rs4680 Val allele, the Met allele was linked to lower COMT activity, which in turn was linked to better cognitive performance such as working memory (WM) and to a larger hippocampus (a brain region important for WM). However, some behavioral studies have shown that the function of rs4680 appears to vary across different ethnic groups, with Chinese subjects showing an opposite pattern as that for Caucasians (i.e. the Val allele is linked to better cognitive functions related to WM in Chinese). Using a sample of healthy Han Chinese college students (ages from 19 to 21 years), this study investigated the association of COMT Val158Met genotype with behavioral data on a two-back WM task (n = 443, 189M/254F) and T1 MRI data (n = 320, 134M/186F). Results showed that, compared to the Met allele, the Val allele was associated with larger hippocampal volume (the right hippocampus: β = -0.118, t = -2.367, P = 0.019, and the left hippocampus: β = -0.099, t = -1.949, P = 0.052) and better WM performance (β = -0.110, t = -2.315, P = 0.021). These results add to the growing literature on differentiated effects of COMT rs4680 polymorphism on WM across populations and offer a brain structural mechanism for such population-specific genetic effects.

Objectives To investigate the clinical epidemiological characteristics and occurrence of post-traumatic stress symptoms (PTSS) in patients with traumatic fractures, we sought to analyze the factors that influence the prognosis of a length of hospital stay (LOS) and provide valuable insights to prevent PTSS in fracture patients and improve their prognosis. Methods Inpatients with traumatic fractures were recruited from a third-class comprehensive general hospital in southwest China between November 2019 and October 2020. Case data of traumatic fracture patients were collected, and a questionnaire that included general information and basic fracture details was completed. The post-traumatic stress disorder Self-rating Scale was used to assess PTSS among the fracture inpatients. Results A total of 204 inpatients who experienced traumatic fractures were included in this study. Falls accounted for the largest proportion of traumatic fractures. A Cox's regression analysis revealed that serious injury [Hazard Ratio (HR) = 2.44, 95% Confidence Interval (CI): 1.33–4.46], critical illness during hospitalization (HR = 1.70, 95% CI: 1.13–2.54), and undergoing two surgeries (HR = 1.87, 95% CI: 1.20–2.93) were risk factors for longer LOS. Among the fracture patients, 30.39% exhibited positive PTSD symptoms, and physical activity during the fracture [Odds Ratio (OR) = 0.63, 95% CI: 0.45–0.88] and increased pain (OR = 3.34, 95% CI: 1.82–6.11) were identified as influencing factors. Conclusions Given the high detection rate of PTSS following traumatic fractures, it is crucial for relevant departments to implement targeted measures to protect high risk individuals. Furthermore, strengthening the care provided to the patients' physical and mental health is urgently needed to reduce the incidence of PTSS.

Photocatalyzed alkylsulfonylation of unactivated alkenes using DABCO. (SO2)2 and thianthrenium salts via a distal heteroaryl migration process has been developed, which provides a new means of synthesizing a variety of valuable alkylsulfonyl-substituted compounds. These alkylsulfonyl radicals couple with unactivated alkenes to undergo efficient intermolecular reactions, followed by distal heteroaryl migration. This mild catalytic method is tolerant of functional groups and affords medicinally relevant alkylsulfonylated heterocycles.

As an important component of transcellular pathway, Caveolae enables the transcellular transport of substances without disrupting cellular homeostasis. In kidney, albumin crosses glomerular filtration barrier (GFB) via Caveolae. Transcellular transport of albumin plays a crucial role in the pathology of proteinuria. Thus the importance of Caveolae cannot be overstated. However, the acting mechanism of Caveolae affecting transcellular albumin transport in kidney and their signaling pathways have remained largely elusive. This review summarized the latest studies on the regulation of Caveolae affecting transcellular albumin transport. Thus elucidating the relevant mechanisms of action and understanding the pathways of influence may provide potential therapeutic targets in the prevention and alleviation of proteinuria

Tissue regeneration requires exogenous and endogenous signals, and there is increasing evidence that the exogenous microenvironment may play an even more dominant role in the complex process of coordinated multiple cells. The short-distance peripheral nerve showed a spontaneous regenerative phenomenon, which was initiated by the guiding role of macrophages. However, it cannot sufficiently restore long-distance nerve injury by itself. Based on this principle, we firstly constructed a proinflammatory model to prove that abnormal M2 expression reduce the guidance and repair effect of long-distance nerves. Furthermore, a bionic peptide hydrogel scaffold based on self-assembly was developed to envelop M2-derived regenerative cytokines and extracellular vesicles (EVs). The cytokines and EVs were quantified to mimic the guidance and regenerative microenvironment in a direct and mild manner. The bionic scaffold promoted M2 transformation in situ and led to proliferation and migration of Schwann cells, neuron growth and motor function recovery. Meanwhile, the peptide scaffold combined with CX3CL1 recruited more blood-derived M2 macrophages to promote long-distance nerve reconstruction. Overall, we systematically confirmed the important role of M2 in regulating and restoring the injury peripheral nerve. This bionic peptide hydrogel scaffold mimicked and remodeled the local environment for M2 transformation and recruitment, favoring long-distance peripheral nerve regeneration. It can help to explicate regulative effect of M2 may be a cause not just a consequence in nerve repair and tissue integration, which facilitating the development of pro-regenerative biomaterials.

An experiment was conducted to determine the effects of pressure loss, combined spacing, and.coefficients of uniformity on the dynamic fluidic sprinkler. Spline interpolation was used to convert the radial water volume into grid-type data and various pressure conditions were used to simulate the three-dimensional water distribution under square and triangular combinations of sprinklers. For each of the combinations of the sprinklers, experiments were performed at operating pressures of 0.15, 0.2, 0.25, and 0.3 MPa, respectively. To find the optimum spatial distribution of sprinklers, three different sprinkler intervals, 1R, 1.2R, and 1.4R, were performed for the square and triangular combinations. The droplet size distributions were also measured along a radial transect from the sprinkler for each operational pressure using the Thies Clima Laser Precipitation Monitor. The results demonstrated that the average values of the inclination angles of the water droplet trajectory curves were 60.78° and 68.85° as the pressure rose from 0.15 MPa to 0.3 MPa. When the pressure exceeds 0.2 MPa, the square combination's distribution uniformity coefficients of 25% low and high values were higher than those of the triangle combination. Triangular combination coefficients of uniformity (CU) values initially decreased and then increased as sprinkler spacing increased, with the CU value under 1.4R spacing reaching 73.85%. At a 1.2R interval, the CU value of a triangular combination was 8.49% lower than that of a square combination, which is a significant difference. Peak irrigation values for the square combination, when the pressure was changed from 0.1 to 0.3 MPa, were 29.97, 22.9, 19.8, 19.91, and 19.21 mm h−1, respectively. The CU values at 0.2, 0.25, and 0.3 MPa decreased at rates of 0.07%, 1.36%, and 0.8%, respectively, when the pressure was reduced by 10%.

Abstract Background Circulating tumor cells (CTCs), an indispensable liquid biopsy classifier, can provide extra information for the diagnosis and prognosis of hepatocellular carcinoma (HCC). Methods We systematically analyzed the peripheral blood of preoperative HCC patients (n = 270) for CTC number, Ki67 index reflecting the proliferative CTC percentage (PCP), and CTC clusters correlated with the characteristics of malignant HCC tumors. Results Driver gene mutations were found with high levels of consistency between CTCs and primary tumors (n = 73). CTC number and PCP were associated with tumor size, microvascular invasion (MVI), presence or absence of multiple tumors, and thrombosis significantly. CTC number and PCP robustly separated patients with and without relapse, with a sensitivity of 88.89%/81.48% and a specificity of 72.73%/94.81% in the training set (n = 104) and corresponding values of 80.00%/86.67% and 78.38%/89.19% in the validation set (n = 52), showing a better performance than that associated with the alpha‐fetoprotein (AFP) level. CTC number, PCP, CTC clusters, and MVI were independent significant risk factors for HCC recurrence (P = 0.0375, P

Compared to conventional artificial nerve guide conduits (NGCs) prepared using natural polymers or synthetic polymers, acellular nerve grafts (ACNGs) derived from natural nerves with eliminated immune components have natural bionic advantages in composition and structure that polymer materials do not have. To further optimize the repair effect of ACNGs, in this study, we used a composite technology based on supercritical carbon dioxide (scCO2) extraction to process the peripheral nerve of a large mammal, the Yorkshire pig, and obtained an innovative Acellular nerve xenografts (ANXs, namely, CD + scCO2 NG). After scCO2 extraction, the fat and DNA content in CD + scCO2 NG has been removed to the greatest extent, which can better supported cell adhesion and proliferation, inducing an extremely weak inflammatory response. Interestingly, the protein in the CD + scCO2 NG was primarily involved in signaling pathways related to axon guidance. Moreover, compared with the pure chemical decellularized nerve graft (CD NG), the DRG axons grew naturally on the CD + scCO2 NG membrane and extended long distances. In vivo studies further revealed that the regenerated nerve axons had basically crossed the CD + scCO2 NG 3 weeks after surgery. 12 weeks after surgery, CD + scCO2 NG was similar to autologous nerves in improving the quality of nerve regeneration, target muscle morphology and motor function recovery and was significantly better than hollow NGCs and CD NG. Therefore, we believe that the fully decellularized and fat-free porcine ACNGs may be the most promising “bridge” for repairing human nerve defects at this stage and for some time to come.

Objectives: Teicoplanin has been extensively used in the treatment for infections caused by gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). However, current teicoplanin treatment is challenging due to relatively low and variable concentrations under standard dosage regimens. This study aimed to investigate the population pharmacokinetics (PPK) characteristics of teicoplanin in adult sepsis patients and provide recommendations for optimal teicoplanin dosing regimens.Methods: A total of 249 serum concentration samples from 59 septic patients were prospectively collected in the intensive care unit (ICU). Teicoplanin concentrations were detected, and patients’ clinical data were recorded. PPK analysis was performed using a non-linear, mixed-effect modeling approach. Monte Carlo simulations were performed to evaluate currently recommended dosing and other dosage regimens. The optimal dosing regimens were defined and compared by different pharmacokinetic/pharmacodynamic parameters, including trough concentration (Cmin), the ratio of 24-h area under the concentration-time curve to the minimum inhibitory concentration (AUC0-24/MIC), as well as the probability of target attainment (PTA) and the cumulative fraction of response (CFR) against MRSA.Results: A two-compartment model adequately described the data. The final model parameter estimates for clearance, central compartment volume of distribution, intercompartmental clearance and peripheral compartment volume were 1.03 L/h, 20.1 L, 3.12 L/h and 101 L, respectively. Glomerular filtration rate (GFR) was the only covariate that significantly affected teicoplanin clearance. Model-based simulations revealed that 3 or 5 loading doses of 12/15 mg/kg every 12 h followed by a maintenance dose of 12/15 mg/kg every 24 h–72 h for patients with different renal functions were required to achieve a target Cmin of 15 mg/L and a target AUC0-24/MIC of 610. For MRSA infections, PTAs and CFRs were not satisfactory for simulated regimens. Prolonging the dosing interval may be easier to achieve the target AUC0-24/MIC than reducing the unit dose for renal insufficient patients.Conclusion: A PPK model for teicoplanin in adult septic patients was successfully developed. Model-based simulations revealed that current standard doses may result in undertherapeutic Cmin and AUC, and a single dose of at least 12 mg/kg may be needed. AUC0-24/MIC should be preferred as the PK/PD indicator of teicoplanin, if AUC estimation is unavailable, in addition to routine detection of teicoplanin Cmin on Day 4, follow-up therapeutic drug monitoring at steady-state is recommended.

Background Radix Ardisia (Jab Bik Lik Jib) is a common Miao medicine and is widely distributed in the Guizhou region of southern China. The botanical origin of Radix Ardisia includes the dry root and rhizome of Ardisia Crenata Sims (ACS) or Ardisia Crispa (Thunb.) A.DC. (AC), which are closely related species morphologically. However, the secondary metabolites in their roots are different from one another, especially the flavonoids, and these differences have not been thoroughly explored at the molecular level. This project preliminarily identified regulatory molecular mechanisms in the biosynthetic pathways of the flavonoids between ACS and AC using a multi-omics association analysis. Methods In this study, we determined the total levels of saponin, flavonoid, and phenolic in Radix Ardisia from different origins. Integrated transcriptome and metabolome analyses were used to identify the differentially expressed genes (DEGs) and differentially expressed metabolites (DEM). We also performed conjoint analyses on DEGs and DEMs to ascertain the degree pathways, and explore the regulation of flavonoid biosynthesis. Results The total flavonoid and phenolic levels in ACS were significantly higher than in AC (P

Abstract Background The efficacy of bevacizumab combined with erlotinib (B + E) for the treatment of advanced hepatocellular carcinoma, especially for sorafenib-refractory patients, has been observed and evaluated in several trials. We conducted this single arm meta-analysis to generally assess the benefit and risk with B + E for advanced hepatocellular carcinoma. Methods The PubMed, Cochrane Library, Embase, ScienceDirect, Web of Science and Scopus databases were searched for related studies. The main outcomes were objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS) and adverse effects (AEs). Results Eight phase II clinical trials including 342 hepatocellular carcinoma patients were analyzed. The pooled ORR was 12.6% (95% CI: 6.3–19.0%), and the pooled DCR was 54.5% (95% CI: 48.9–66.8%). The 16-week PFS rate was 50.2% (95% CI: 38.2–62.2%). The 6- and 12-month OS rates were 77.8% (95% CI: 71.3–84.2%) and 44.9% (95% CI: 36.8–53.0%). The main grade 3–4 AEs were fatigue (11.9%), diarrhea (9.0%), hypertension (6.7%), acne (5.8%) and hemorrhage (5.3%). The only RCT showed that the B + E regimen had a consistent response and equable median OS but fewer toxicities (grade 3–4 AEs: 19% vs. 27%) than sorafenib. Subgroup analysis showed that as a second-line treatment, the B + E regimen had substantial value with a favorable PFS-16w (P = 0.012), OS-12 m (P = 0.048) and a favorable tendency of ORR (P = 0.089), but obvious toxicities in the second-line setting could not be neglected. Conclusion Bevacizumab combined with erlotinib is effective for treating hepatocellular carcinoma patients, especially sorafenib-refractory patients. More well-designed and large-scale RCTs are warranted to prove our findings.

Background: Mitochondrial disease is a term used to describe a set of heterogeneous genetic diseases caused by impaired structure or function of mitochondria. Pyruvate therapy for mitochondrial disease is promising from a clinical point of view. Methods: According to PRISMA guidelines, the following databases were searched to identify studies regarding pyruvate therapy for mitochondrial disease: PubMed, EMBASE, Cochrane Library, and Clinicaltrials . The search was up to April 2019. The endpoints were specific biomarkers (plasma level of lactate, plasma level of pyruvate, L/P ratio) and clinical rating scales [Japanese mitochondrial disease-rating scale (JMDRS), Newcastle Mitochondrial Disease Adult Scale (NMDAS), and others]. Two researchers independently screened articles, extracted data, and assessed the quality of the studies. Results: A total of six studies were included. Considerable differences were noted between studies in terms of study design, patient information, and outcome measures. The collected evidence may indicate an effective potential of pyruvate therapy on the improvement of mitochondrial disease. The majority of the common adverse events of pyruvate therapy were diarrhea and short irritation of the stomach. Conclusion: Pyruvate therapy with no serious adverse events may be a potential therapeutic candidate for patients with incurable mitochondrial diseases, such as Leigh syndrome. However, recent evidence taken from case series and case reports, and theoretical supports of basic research are not sufficient. The use of global registries to collect patient data and more adaptive trial designs with larger numbers of participants are necessary to clarify the efficacy of pyruvate therapy.

Objectives To investigate the complications and survival of elderly patients with end-stage renal disease (ESRD) who received urgent-start peritoneal dialysis (USPD) or urgent-start haemodialysis (USHD), and to explore the value of peritoneal dialysis (PD) as the emergent dialysis method for elderly patients with ESRD.Design Retrospective cohort study.Setting Two tertiary care hospitals in Shanghai, China.Participants Chinese patients (n=542) >65 years of age with estimated glomerular filtration rate ≤15 mL/min/m2 who received urgent-start dialysis between 1 January 2005 and 31 December 2015, and with at least 3 months of treatment. Patients who converted to other dialysis methods, regardless of the initial dialysis method, were excluded, as well as those with comorbidities that could significantly affect their dialysis outcomes.Primary and secondary outcome measures Dialysis-related complications and survival were compared. Patients were followed until death, stopped PD, transfer to other dialysis centres, loss to follow-up or 31 December 2016.Results There were 309 patients in the USPD group and 233 in the USHD group. The rate of dialysis-related complications within 30 days after catheter implantation was significantly lower in the USPD group compared with the USHD group (4.5% vs 10.7%, p=0.031). The 6-month and 1, 2 and 3-year survival rates were 95.3%, 91.4%, 86.6% and 64.8% in the USPD group, and 92.2%, 85.7%, 70.2% and 57.8% in the USHD group, respectively (p=0.023). The multivariable Cox regression analysis showed that USHD (HR=2.220, 95% CI 1.298 to 3.790; p=0.004), age (HR=1.025, 95% CI 1.013 to 1.043, p

There is a growing interest to understand impacts of latent infection age and infection age on viral infection dynamics by using ordinary and partial differential equations. On one hand, activation of latently infected cells needs specificity antigen, and latently infected CD4+ T cells are often heterogeneous, which depends on how frequently they encountered antigens, how much time they need to be preferentially activated and quickly removed from the reservoir. On the other hand, infection age plays an important role in modeling the death rate and virus production rate of infected cells. By rigorous analysis for the model, this paper is devoted to the global dynamics of an HIV infection model subject to latency age and infection age from theoretical point of view, where the model formulation, basic reproduction number computation, and rigorous mathematical analysis, such as relative compactness and persistence of the solution semiflow, and existence of a global attractor are involved. By constructing Lyapunov functions, the global dynamics of a threshold type is established. The method developed here is applicable to broader contexts of investigating viral infection subject to age structure.

Abstract Stathmin‐1 is a microtubule depolymerization protein that regulates cell division, growth, migration, and invasion. Overexpression of stathmin‐1 has been observed to be associated with metastasis, poor prognosis, and chemoresistance in various human cancers. Our previous studies found that serum stathmin‐1 was significantly elevated in patients with esophageal squamous cell carcinoma (ESCC) by ELISAs. Here, we constructed high‐affinity monoclonal antibodies and then developed a competitive AlphaLISA for rapid, accurate quantitation of stathmin‐1 in serum. Compared to ELISA, our homogeneous AlphaLISA showed better sensitivity and accuracy, a lower limit of detection, and a wider linear range. The measurements of nearly 1000 clinical samples showed that serum stathmin‐1 level increased dramatically in patients with squamous cell carcinoma (SCC), especially in ESCC, with a sensitivity and a specificity of 81% and 94%, respectively. Even for early stage ESCC, stathmin‐1 achieved an area under the receiver operating characteristic curve (AUC) of 0.88. Meanwhile, raised concentrations of stathmin‐1 were associated with lymph node metastasis and advanced cancer stage. Notably, various types of SCC showed significantly higher AUCs in serum stathmin‐1 detection compared to adenocarcinoma. Furthermore, we confirmed that stathmin‐1 was enriched in the oncogenic exosomes, which can explain the reason why it enters into the blood to serve as a tumor surrogate. In conclusion, this large‐scale and systematic study of serum stathmin‐1 measured by our newly established AlphaLISA showed that stathmin‐1 is a very promising diagnostic and predictive marker for SCC in the clinic, especially for ESCC.

Lianyuan Tao, Chunhui Yuan, Zhaolai Ma, Bin Jiang, Dianrong Xiu Department of General Surgery, Peking University Third Hospital, Beijing, People’s Republic of China Introduction: Pancreatic cancer is a lethal disease with a very poor prognosis. This study investigates survival of patients diagnosed with metastatic pancreatic cancer (mPC) based on local treatment of the primary tumor. Methods: Patients diagnosed with stage IV mPC between 2004 and 2013 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Cancer-specific survival (CSS) and overall survival (OS) were examined. CSS and OS were examined by using the Kaplan–Meier method with the log-rank test. Multivariable survival analyses of CSS and OS were conducted using the Cox proportional hazard model. Results: A total of 28918 patients with mPC were included in this analysis. There were 467 patients who received surgical resection (1.6%) and 28451 patients who did not (98.4%). Patients who were younger than 70 years (odds ratio [OR]=1.45, 95% CI=1.04–2.03, p=0.03), diagnosed from 2004 to 2008 (OR=1.49, 95% CI=1.25–1.80, p50 years (HR=1.25, 95% CI=1.09–1.42, p=0.001), male (HR=1.121, 95% CI=1.09–1.15, p

Introduction: In resting conditions, breathing is typically characterized by an active inspiratory phase and a passive expiratory phase. Expiration may become active through abdominal (ABD) muscle recruitment during periods of increased inspiratory requirements. This respiratory rhythm is thought to be controlled by three coupled oscillators: preBötzinger complex (preBötC) for generating inspiration, the parafacial respiratory group (pFRG) for generating active expiration, and the post-inspiratory complex (PiCo) which is thought to control the post-inspiratory phase. Research addressing the role of pFRG in ventilation and rhythm generation across sleep states is limited. Recent work in our laboratory reports the occurrence of ABD recruitment during REM sleep, despite the induction of muscle paralysis during this sleep state. This ABD recruitment was associated with a stabilization of breathing in healthy rats. Because pFRG generates active expiration through the engagement of ABD muscles, we hypothesize that the expiratory oscillator is also responsible for the ABD recruitment observed during REM sleep in healthy rats. Objective: To demonstrate of the parafacial respiratory group in the recruitment of abdominal activity across sleep states. Material and Methods: To test this hypothesis, we inhibited and activated the pFRG oscillator using a chemogenetic approach (DREADDs) while simultaneously recording EEG, airflow, DIA, ABD and neck EMG of transfected rats across sleep/wake cycles. Results: Manipulation of pFRG activity does not affect the sleep architecture. However, activity of pFRG seems to have an effect in the occurrence of ABD recruitment events during REM sleep. Inhibition of pFRG (N=7) significantly reduced the number of REM events with ABD recruitment and the intensity of these events (described as the ABD to DIA ratio), whereas activation of this oscillator (N=8) resulted in an increase of the number of REM events in which ABD recruitment was observed and the intensity of those events. Interestingly, modulation of pFRG activity did not seem to affect the occurrence of ABD recruitment during NREM sleep. Conclusions: The occurrence of ABD recruitment during sleep may be state dependent. Further research investigating the mechanisms behind the recruitment of ABD activity specifically during REM and NREM sleep will be necessary.

Background: Obstructive sleep apnea syndrome (OSAS) has been shown to generate hypertension and endothelial dysfunction. Retinal vessel is the only vessel that can be observed directly and noninvasively; retinal vascular abnormalities can serve as a predictive marker for the occurrence, clinical course, and prognosis of cardiovascular and cerebrovascular diseases. The objective of this study was to identify the effect of OSAS severity on the morphological changes of retinal vessels. Methods: Adult patients complained of snoring were included in this study. The patients' general information, polysomnography, and fundus photography parameters including central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) were collected. Patients were divided into four groups according to their apnea-hypopnea index (AHI) results: Group I, AHI ≤5/h; Group II, 5/h < AHI ≤30/h; Group III, 30/h < AHI ≤60/h; and Group IV, AHI> 60/h. Results: A total of 133 patients were included in this study with 111 males (83.5%) and 22 females (16.5%). Mean age was 41.6 ± 9.9 years, and the mean body mass index was 28.1 ± 4.0 kg/m2. AHI ranged between 0 and 130.8/h with a mean of 39.1 ± 30.7/h. There were 24, 34, 35, and 40 patients in Group I, Group II, Group III, and Group IV, respectively. Significant differences were found for AHI (F = 388.368, P< 0.001), minimal pulse oxygen saturation (F = 91.902, P< 0.001), and arousal index (F = 31.014, P< 0.001) among four groups; no significant differences were found for CRAE (F = 0.460, P = 0.599) and CRVE (F = 0.404, P = 0.586) among groups; there were significant differences for AVR between Group I and Group IV (63.6 ± 5.1% vs. 67.2 ± 5.5%, P = 0.010) Group II and Group IV (64.5 ± 6.0% vs. 67.2 ± 5.5%, P = 0.030), and Group III and Group IV (64.7 ± 4.1% vs. 67.2 ± 5.5%, P = 0.043). A main group-by-AHI effect was found on the AVR: patients with higher AHI showed higher AVR results (r = 0.225, P = 0.009). Multivariate logistic regression analysis was used for multi-variable factors. A group-by-age effect was found on the AVR: younger patients showed higher AVR results (β = −0.001, P = 0.020). Conclusions: This study indicated that increased AVR of retinal vessel can be observed in extremely severe OSAS patients. For patients with OSAS, retinal vascular abnormalities may become an early indication for further cardiovascular abnormalities.

Background: Obstructive sleep apnea/hypopnea syndrome (OSAHS) and laryngopharyngeal reflux (LPR) disease have a high comorbidity rate, but the potential causal relation between the two diseases remains unclear. Our objectives were to investigate the esophageal functional changes in OSAHS patients and determine whether OSAHS affects LPR by affecting esophageal functions. Methods: Thirty-six OSAHS patients and 10 healthy controls underwent 24-h double-probed combined esophageal multichannel intraluminal impedance and pH monitoring simultaneously with polysomnography. High-resolution impedance manometry was applied to obtain a detailed evaluation of pharyngeal and esophageal motility. Results: There were 13 OSAHS patients (36.1%) without LPR (OSAHS group) and 23 (63.9%) with both OSAHS and LPR (OSAHS and LPR group). Significant differences were found in the onset velocity of liquid swallows (OVL, P = 0.029) and the percent relaxation of the lower esophageal sphincter (LES) during viscous swallows (P = 0.049) between the OSAHS and control groups. The percent relaxation of LES during viscous swallows was found to be negatively correlated with upright distal acid percent time (P = 0.016, R = −0.507), and OVL was found to be negatively correlated with recumbent distal acid percent time (P = 0.006, R = −0.557) in the OSAHS and LPR group. Conclusions: OSAHS patients experience esophageal functional changes, and linear correlations were found between the changed esophageal functional parameters and reflux indicators, which might be the reason that LPR showed a high comorbidity with OSAHS and why the severity of the two diseases is correlated.

Dormancy mechanisms in seeds and buds arrest growth until environmental conditions are optimal for development. A genotype-specific period of chilling is usually required to release dormancy, but the underlying molecular mechanisms are still not fully understood. To discover transcriptional pathways associated with dormancy release common to seed stratification and bud endodormancy, we explored the chilling-dependent expression of 11 genes involved in endoplasmic reticulum stress and the unfolded protein response signal pathways. We propose that endoplasmic reticulum stress and the unfolded protein response impact on seed as well as bud germination and development by chilling-dependent mechanisms. The emerging discovery of similarities between seed stratification and bud endodormancy status indicate that these two processes are probably regulated by common endoplasmic reticulum stress and unfolded protein response signalling pathways. Clarification of regulatory pathways common to both seed and bud dormancy may enhance understanding of the mechanisms underlying dormancy and breeding programs may benefit from earlier prediction of chilling requirements for uniform blooming of novel genotypes of deciduous fruit tree species.

Area coverage is one of the key issues for wireless sensor networks. It aims at selecting a minimum number of sensor nodes to cover the whole sensing region and maximizing the lifetime of the network. In this paper, we discuss the energy-efficient area coverage problem considering boundary effects in a new perspective, that is, transforming the area coverage problem to the target coverage problem and then achieving full area coverage by covering all the targets in the converted target coverage problem. Thus, the coverage of every point in the sensing region is transformed to the coverage of a fraction of targets. Two schemes for the converted target coverage are proposed, which can generate cover sets covering all the targets. The network constructed by sensor nodes in the cover set is proved to be connected. Compared with the previous algorithms, simulation results show that the proposed algorithm can prolong the lifetime of the network.

Abstract Background To assess the feasibility and efficacy of using 125I seed implantation under intraoperative ultrasound guidance for unresectable pancreatic carcinoma. Methods Fourteen patients with pancreatic carcinoma that underwent laparotomy and considered unresectable were included in this study. Nine patients were pathologically diagnosed with Stage II disease, five patients with Stage III disease. Fourteen patients were treated with 125I seed implantation guided by intraoperative ultrasound and received D90 of 125I seeds ranging from 60 to 140 Gy with a median of 120 Gy. Five patients received an additional 35–50 Gy from external beam radiotherapy after seed implantation and six patients received 2–6 cycles of chemotherapy. Results 87.5% (7/8) of patients received partial to complete pain relief. The response rate of tumor was 78.6%, One-, two-and three-year survival rates were 33.9% and 16.9%, 7.8%, with local control of disease achieved in 78.6% (11/14), and the median survival was 10 months (95% CI: 7.7–12.3). Conclusion There were no deaths related to 125I seed implant. In this preliminary investigation, 125I seed implant provided excellent palliation of pain relief, local control and prolong the survival of patients with stage II and III disease to some extent.

The distribution and diversity of woody vegetation are crucial for understanding the structure and ecology of urban forests. As urbanization accelerates, the construction and composition of urban forests vary significantly along the urban-rural gradient. Qingdao's urban forests offer an opportunity to test the relationship between the diversity of woody plants and the urban-rural gradient. We classified the urban-rural gradient using imperviousness and construction time, then investigated the diversity of woody plants in Qingdao's urban forests under different urban-rural gradients and tested the reasonableness of their allocation. Correlation analysis found that the diversity index of woody plants in urban forests was highly connected to the urban-rural gradient (by imperviousness: r Margalef Index  = -0.589, r Shannon-Wiener Index  = -0.373, r Pielou Index  = -0.170, r Simpson Index  = 0.272/by construction time: r Margalef Index  = -0.530, r Shannon-Wiener Index  = -0.360, r Pielou Index  = -0.148, r Simpson Index  = 0.272/0.174). With a decrease in urbanization density, the Margalef ( H ), Shannon-Wiener ( H' ), and Simpson ( D ) indices all decreased while the Pielou ( E ) index increased. The four diversity indices showed a substantial correlation with one another, but not with the Margalef and Pielou indices. The analysis utilizing the 10/20/30 rule of empirical demonstrates a clear irrationality in allocating shrub species in Qingdao's urban forests, and the distribution of tree species is reasonable. Based on the study results, strategies for optimizing and enhancing urban forests in Qingdao are proposed for different urban-rural gradients, respectively. This study can provide a scientific framework for urban biodiversity conservation and management in Qingdao and serve as a guide for urban forests and greening with comparable climates., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Objective: To explore the effectiveness of minimally invasive surgical treatment for pancreatic acinar cell carcinoma (PACC). Methods: Six patients with PACC diagnosed in Peking University Third Hospital from January 2010 to September 2022 were retrospectively selected. Preoperative evaluation was performed on whether the lesions were eligible for surgery, including whether radical resection of liver metastases could be performed. Laparoscopic or Da Vinci robot-assisted resection was performed on six patients, and spleen retention was determined according to the original lesions and the relationship with peripheral blood vessels and tissues, while simultaneous resection was performed on cases of peripheral organ tissue invasion. The patients' basic information, preoperative general conditions, preoperative diagnosis and tumor stage, minimally invasive surgery methods, postoperative complications, pathological results, tumor stage and follow-up data were collected and analyzed to explore the effectiveness of minimally invasive surgery. Results: Among the six patients, four were males and two were females, with the age of 25-69 years. Five patients had abdominal pain and distension before surgery, five patients had tumors located at the tail of the pancreatic body, and one patient had tumors located at the head of the pancreas. Preoperative imaging (enhanced CT and MRI) was performed to measure the tumor diameter (2.8-10.0 cm). Tumor markers were elevated in two patients before surgery, and six patients underwent surgery through laparoscopy or robotic platform. No complications such as postoperative pancreatic fistula and bleeding were clinically relevant during and after surgery. There were two cases with concurrent or heterochronous liver metastasis, two cases with lymph node metastasis and nodular metastasis, four cases with tumor invasion of surrounding organs (stomach, spleen or duodenum), and three cases with vascular cancer thrombi. The follow-up time of the six patients was 12 to 165 months, and one patient underwent three operations due to postoperative liver metastasis and residual pancreatic recurrence, and the results were satisfactory. All the six patients survived at the last follow-up. Conclusions: PACC is prone to invade the surrounding organs, and has a large tumor diameter. Radical surgery for PACC can be completed through minimally invasive surgery, and satisfactory oncology prognosis can be obtained. In addition, some PACC patients with recurrence and metastasis can still be treated by surgery.

Objective: Currently, pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases (PNELM) receiving surufatinib treatment was unsatisfying. Our objective was to examine the association between radiological characteristics and efficacy/prognosis., Methods: We enrolled patients with liver metastases in the phase III, SANET-p trial (NCT02589821) and obtained contrast-enhanced computed tomography (CECT) images. Qualitative and quantitative parameters including hepatic tumor margins, lesion volumes, enhancement pattern, localization types, and enhancement ratios were evaluated. The progression-free survival (PFS) and hazard ratio (HR) were calculated using Cox's proportional hazard model. Efficacy was analyzed by logistic-regression models., Results: Among 152 patients who had baseline CECT assessments and were included in this analysis, the surufatinib group showed statistically superior efficacy in terms of median PFS compared to placebo across various qualitative and quantitative parameters. In the multivariable analysis of patients receiving surufatinib (N=100), those with higher arterial phase standardized enhancement ratio-peri-lesion (ASER-peri) exhibited longer PFS [HR=0.039; 95% confidence interval (95% CI): 0.003-0.483; P=0.012]. Furthermore, patients with a high enhancement pattern experienced an improvement in the objective response ratio [31.3% vs . 14.7%, odds ratio (OR)=3.488; 95% CI: 1.024-11.875; P=0.046], and well-defined tumor margins were associated with a higher disease control rate (DCR) (89.3% vs . 68.2%, OR=4.535; 95% CI: 1.285-16.011; P=0.019) compared to poorly-defined margins., Conclusions: These pre-treatment radiological features, namely high ASER-peri, high enhancement pattern, and well-defined tumor margins, have the potential to serve as predictive markers of efficacy in patients with PNELM receiving surufatinib., (Copyright ©2023 Chinese Journal of Cancer Research. All rights reserved.)

Multicolor two-photon endomicroscopy has become a highly competitive tool for functional imaging in biomedical researches. However, to make the imaging system miniature and applicable for freely behaving animal brain activity, metalenses have received much attention in compact imaging systems. For high resolution multicolor imaging and maximizing fluorescence collection, there is a challenge metalenses faced to achieve large numerical aperture (NA) and focus the NIR excitation and VIS emission lights of multiple fluorophores to the same distance simultaneously because of the limitation of the group delay range of the meta-units. In this paper, we proposed a high NA and polarization-insensitive ultra-broadband achromatic metalens specifically for achromatically focusing the excitation and emission light of multiple fluorophores commonly used in neuroscience studies. TiO 2 and Si meta-unit libraries composed of heights, widths and the corresponding phase and group delay were constructed, and the optimal meta-units were selected by particle swarm optimization algorithm to engineer the dispersion of metalens in the VIS band and NIR band, respectively. Combining dispersion engineering with spatial multiplexing, the proposed metalens achieved the maximal effective NA up to 0.8 and large achromatic bandwidth ranging from 500 nm to 1050 nm, which exhibited the coefficient of variation of focal lengths was only 3.41%. The proposed achromatic metalens could successfully achromatically focus different fluorescence with any polarization, which was suitable for most fluorophores. Our results firmly establish that the proposed metalens can open the door to high resolution and minimally invasive multicolor two-photon functional imaging in intravital deep brain.

Introduction: Postoperative pancreatic fistula (POPF) remains one of the main complications following pancreatic resection. Despite pancreatic fistula having a low postoperative mortality rate, the readmission and intervention rates in patients with pancreatic fistula are still considerable. Although there are several studies on pancreatic fistula development after pancreaticoduodenectomy, there are only a few studies on the feeding protocols applied after distal pancreatectomy or enucleation of pancreatic tumours. We designed this trial to test the hypothesis that early feeding does not increase the incidence of POPF and positively influences the long-term prognosis in patients who undergo distal pancreatectomy or enucleation of pancreatic tumours., Methods and Analysis: This is a prospective randomised controlled trial that will be conducted in a single centre. A total of 106 patients undergoing distal pancreatectomy or enucleation of pancreatic tumours will be recruited after providing informed consent. They will be randomly assigned to either an early or late feeding group. The early feeding group will begin enteral nutrition on postoperative day (POD) 3, and the late feeding group will begin enteral nutrition on POD7. The primary outcome is the incidence of POPF. The secondary outcomes include the length of postoperative hospital stay, postoperative complications, and indicators of long-term prognosis., Ethics and Dissemination: Peking University Third Hospital Medical Science Research Ethics Committee approved the study (M2021395). Findings will be disseminated in a peer-reviewed journal and in national and/or international meetings to guide future practice., Trial Registration Number: ChiCTR2100053978., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)