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Li-Juan Hu,1 Zhong Mei,1,2 Yan-Ping Shen,1 Hao-Tian Sun,1 Zhi-Min Sheng,1 Xin-Zhong Chen,1 Xiao-Wei Qian1 1Department of Anesthesiology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Anesthesiology, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, People’s Republic of ChinaCorrespondence: Xiao-Wei Qian, Department of Anesthesiology, Women’s Hospital, Zhejiang University School of Medicine, Xueshi Road 1, Hangzhou, 310006, People’s Republic of China, Tel +86-571-87061501, Fax +86 571 87061878, Email qianxw@zju.edu.cnBackground: It is well-known that severe preeclamptic parturients have less vasopressor requirements than normotensive parturients; however, the exact dose difference is poorly documented. This study aimed to determine and compare the ED50 and ED90 of a single bolus phenylephrine for the treatment of spinal anesthesia-induced hypotension in parturients with severe preeclampsia and parturients with normotension.Methods: Seventy-five parturients with severe preeclampsia scheduled for cesarean delivery under combined spinal-epidural anesthesia were enrolled and randomly allocated to receive a single bolus of phenylephrine at five different doses (40, 50, 60, 70, and 80 μg), whereas 75 parturients with normotension were randomized to receive a single bolus of phenylephrine at five different doses (70, 80, 90, 100, and 110 μg) for the treatment of the first episode of hypotension. Phenylephrine dose values were log-transformed, the proportions of the successful interventions at each dose were converted to probits, and regression analysis was performed.Results: The ED50 and ED90 (95% CI) of bolus phenylephrine were 72.1 (61.7 to 79.9) μg and 107 (95.9– 128.6) μg in parturients with normotension. The ED50 and ED90 values in parturients with severe preeclampsia were 47.6 (41.3– 52.7) μg and 70.7 (62.9– 86.7) μg. The relative median potency was 1.51 (1.16– 2.61).Conclusion: Under this study conditions, severe preeclamptic parturients required a 34% reduction of ED50 of phenylephrine dose compared with normotensive parturients.Keywords: cesarean delivery, spinal anesthesia, hypotension, phenylephrine, preeclampsia

Sheng Chen,1,* Jin-Jun Wang,2,* Qin-Qin Wang,1 Jun-Wei Hu,1 Shuang Dong,1 Li-Juan Hu,1 Yi-Cheng Jian,1 Xin-Yan Liu,2 Gen-Mei Yang,2 Wu-Jun Xiong1 1Department of Hepatology, Tongji University School of Medicine, Shanghai East Hospital, 2Department of Gerontology, Shanghai Traditional Chinese Medicine University, Shanghai Putuo Central Hospital, Shanghai, People’s Republic of China *These authors contributed equally to this workPurpose: Several randomized controlled clinical trials have been conducted to investigate the role of carvedilol and propranolol on the effect of portal pressure in patients with cirrhosis, leading to controversial results. Current meta-analysis was performed to compare the efficacy of the two drugs on portal pressure.Patients and methods: Two-hundred and ninety eligible patients were recruited. Published studies were selected based on PubMed, the Cochrane Library, Chinese Journal Full-text Database, and Wanfang Database. The outcome measurements included the mean difference (MD) in the percentage of hepatic vein pressure gradient reduction (%HVPG reduction), the risk ratio (RR) of nonresponders in hemodynamic assessment, and the percentage of mean arterial pressure reduction (%MAP reduction). Subgroup analysis was performed.Results: Seven trials were identified (including five acute and three long-term drug administration randomized controlled trials). A summary of pooled MD between the %HVPG reduction is as follows: overall -8.62 (confidence interval [CI] -11.76, -5.48, P

The Daya Bay experiment was the first to report simultaneous measurements of reactor antineutrinos at multiple baselines leading to the discovery of ν¯e oscillations over km-baselines. Subsequent data has provided the world's most precise measurement of sin22θ13 and the effective mass splitting Δmee2. The experiment is located in Daya Bay, China where the cluster of six nuclear reactors is among the world's most prolific sources of electron antineutrinos. Multiple antineutrino detectors are deployed in three underground water pools at different distances from the reactor cores to search for deviations in the antineutrino rate and energy spectrum due to neutrino mixing. Instrumented with photomultiplier tubes, the water pools serve as shielding against natural radioactivity from the surrounding rock and provide efficient muon tagging. Arrays of resistive plate chambers over the top of each pool provide additional muon detection. The antineutrino detectors were specifically designed for measurements of the antineutrino flux with minimal systematic uncertainty. Relative detector efficiencies between the near and far detectors are known to better than 0.2%. With the unblinding of the final two detectors' baselines and target masses, a complete description and comparison of the eight antineutrino detectors can now be presented. This paper describes the Daya Bay detector systems, consisting of eight antineutrino detectors in three instrumented water pools in three underground halls, and their operation through the first year of eight detector data-taking.

This Letter reports a measurement of the flux and energy spectrum of electron antineutrinos from six 2.9 GWth nuclear reactors with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls in the Daya Bay experiment. Using 217 days of data, 296 721 and 41 589 inverse β decay (IBD) candidates were detected in the near and far halls, respectively. The measured IBD yield is (1.55±0.04) ×10(-18)  cm(2) GW(-1) day(-1) or (5.92±0.14) ×10(-43)  cm(2) fission(-1). This flux measurement is consistent with previous short-baseline reactor antineutrino experiments and is 0.946±0.022 (0.991±0.023) relative to the flux predicted with the Huber-Mueller (ILL-Vogel) fissile antineutrino model. The measured IBD positron energy spectrum deviates from both spectral predictions by more than 2σ over the full energy range with a local significance of up to ∼4σ between 4-6 MeV. A reactor antineutrino spectrum of IBD reactions is extracted from the measured positron energy spectrum for model-independent predictions.

We report a new measurement of electron antineutrino disappearance using the fully constructed Daya Bay Reactor Neutrino Experiment. The final two of eight antineutrino detectors were installed in the summer of 2012. Including the 404 days of data collected from October 2012 to November 2013 resulted in a total exposure of 6.9×10^{5} GW_{th}  ton days, a 3.6 times increase over our previous results. Improvements in energy calibration limited variations between detectors to 0.2%. Removal of six ^{241}Am-^{13}C radioactive calibration sources reduced the background by a factor of 2 for the detectors in the experimental hall furthest from the reactors. Direct prediction of the antineutrino signal in the far detectors based on the measurements in the near detectors explicitly minimized the dependence of the measurement on models of reactor antineutrino emission. The uncertainties in our estimates of sin^{2}2θ_{13} and |Δm_{ee}^{2}| were halved as a result of these improvements. An analysis of the relative antineutrino rates and energy spectra between detectors gave sin^{2}2θ_{13}=0.084±0.005 and |Δm_{ee}^{2}|=(2.42±0.11)×10^{-3}  eV^{2} in the three-neutrino framework.

The Daya Bay experiment consists of functionally identical antineutrino detectors immersed in pools of ultrapure water in three well-separated underground experimental halls near two nuclear reactor complexes. These pools serve both as shields against natural, low-energy radiation, and as water Cherenkov detectors that efficiently detect cosmic muons using arrays of photomultiplier tubes. Each pool is covered by a plane of resistive plate chambers as an additional means of detecting muons. Design, construction, operation, and performance of these muon detectors are described.

A new measurement of the $\theta_{13}$ mixing angle has been obtained at theDaya Bay Reactor Neutrino Experiment via the detection of inverse beta decaystagged by neutron capture on hydrogen. The antineutrino events for hydrogencapture are distinct from those for gadolinium capture with largely differentsystematic uncertainties, allowing a determination independent of thegadolinium-capture result and an improvement on the precision of $\theta_{13}$measurement. With a 217-day antineutrino data set obtained with sixantineutrino detectors and from six 2.9 GW$_{th}$ reactors, the rate deficitobserved at the far hall is interpreted as $\sin^22\theta_{13}=0.083\pm0.018$in the three-flavor oscillation model. When combined with thegadolinium-capture result from Daya Bay, we obtain$\sin^22\theta_{13}=0.089\pm0.008$ as the final result for thesix-antineutrino-detector configuration of the Daya Bay experiment.

A new measurement of the $\theta_{13}$ mixing angle has been obtained at theDaya Bay Reactor Neutrino Experiment via the detection of inverse beta decaystagged by neutron capture on hydrogen. The antineutrino events for hydrogencapture are distinct from those for gadolinium capture with largely differentsystematic uncertainties, allowing a determination independent of thegadolinium-capture result and an improvement on the precision of $\theta_{13}$measurement. With a 217-day antineutrino data set obtained with sixantineutrino detectors and from six 2.9 GW$_{th}$ reactors, the rate deficitobserved at the far hall is interpreted as $\sin^22\theta_{13}=0.083\pm0.018$in the three-flavor oscillation model. When combined with thegadolinium-capture result from Daya Bay, we obtain$\sin^22\theta_{13}=0.089\pm0.008$ as the final result for thesix-antineutrino-detector configuration of the Daya Bay experiment.

A search for light sterile neutrino mixing was performed with the first 217 days of data from the Daya Bay Reactor Antineutrino Experiment. The experiment's unique configuration of multiple baselines from six 2.9 GW(th) nuclear reactors to six antineutrino detectors deployed in two near (effective baselines 512 m and 561 m) and one far (1579 m) underground experimental halls makes it possible to test for oscillations to a fourth (sterile) neutrino in the 10(-3) eV(2)

A measurement of the energy dependence of antineutrino disappearance at the Daya Bay reactor neutrino experiment is reported. Electron antineutrinos (ν¯(e)) from six 2.9  GW(th) reactors were detected with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls. Using 217 days of data, 41 589 (203 809 and 92 912) antineutrino candidates were detected in the far hall (near halls). An improved measurement of the oscillation amplitude sin(2)2θ(13)=0.090(-0.009)(+0.008) and the first direct measurement of the ν¯(e) mass-squared difference |Δm(ee)2|=(2.59(-0.20)(+0.19))×10(-3)  eV2 is obtained using the observed ν¯(e) rates and energy spectra in a three-neutrino framework. This value of |Δm(ee)2| is consistent with |Δm(μμ)2| measured by muon neutrino disappearance, supporting the three-flavor oscillation model.

Although acute myeloid leukemia (AML) affects hematopoietic stem cell (HSC)-supportive microenvironment, it is largely unknown whether leukemia-modified bone marrow (BM) microenvironment can be remodeled to support normal hematopoiesis after complete remission (CR). As a key element of BM microenvironment, endothelial progenitor cells (EPCs) provide a feasible way to investigate BM microenvironment remodeling. Here, we find reduced and dysfunctional BM EPCs in AML patients, characterized by impaired angiogenesis and high ROS levels, could be partially remodeled after CR and improved by N-acetyl-L-cysteine (NAC). Importantly, HSC-supporting ability of BM EPCs is partially recovered, whereas leukemia-supporting ability is decreased in CR patients. Mechanistically, the transcriptome characteristics of leukemia-modified BM EPCs return to near-normal after CR. In a classic AML mouse and chemotherapy model, BM vasculature and normal hematopoiesis are reversed after CR. In summary, we provide further insights into how leukemia-modified BM microenvironment can be remodeled to support normal hematopoiesis after CR, which can be further improved by NAC., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Global interest in lithium-sulfur batteries as one of the most promising energy storage technologies has been sparked by their low sulfur cathode cost, high gravimetric, volumetric energy densities, abundant resources, and environmental friendliness. However, their practical application is significantly impeded by several serious issues that arise at the cathode-electrolyte interface, such as interface structure degradation including the uneven deposition of Li 2 S, unstable cathode-electrolyte interphase (CEI) layer and intermediate polysulfide shuttle effect. Thus, an optimized cathode-electrolyte interface along with optimized electrodes is required for overall improvement. Herein, we comprehensively outline the challenges and corresponding strategies, including electrolyte optimization to create a dense CEI layer, regulating the Li 2 S deposition pattern, and inhibiting the shuttle effect with regard to the solid-liquid-solid pathway, the transformation from solid-liquid-solid to solid-solid pathway, and solid-solid pathway at the cathode-electrolyte interface. In order to spur more perceptive research and hasten the widespread use of lithium-sulfur batteries, viewpoints on designing a stable interface with a deep comprehension are also put forth., Competing Interests: Declarations. Conflict of interest: The authors declare no interest conflict. They have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s).)

Introduction: Acquired vulvar lymphangioma (AVL), a rare disease caused by the dilation of superficial lymphatic vessels secondary to deep lymphatic vessel injury, is characterized by a wide range of morphological diversity and massive exudate. This morphological heterogeneity has often led to misdiagnosis or non-diagnosis. The management of AVL presents a therapeutic challenge due to the absence of a standardized treatment protocol., Case Presentation: A 53-year-old female patient, previously received surgical treatments for stage IIb cervical squamous cell carcinoma, presented with vulvar enlargement and copious amount of yellow exudate seven years post-treatment. Clinically, the patient exhibited chronic vulvar swelling, with easily-exudated nodules. The vulvar biopsy revealed lymphatic vessel dilation with lymphocyte infiltration, consistent with AVL. Due to the extensive lesions and severe exudate, staged excisions of bilateral vulvar lesions were performed at one-month intervals. Follow-up examinations of this patient for one-year post-surgery showed no evidence of recurrence., Conclusion: In this instance, AVL manifest secondary to cervical cancer surgery, as a result of damage to the deep lymphatic vessels of the vulva, with characteristic symptoms of copious amounts of exudate and vulvar lesions with diverse morphologies, which provides a cautionary note for physicians. Besides, the staged resection strategy in this case may offer insights into surgical treatment protocol for extensive AVL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hu, Fang, Lin, Kang, Lin and Xiao.)

Four undescribed coumarin derivatives, ficusalt A (1) and ficusalt B (2), a pair of racemic coumarins, (±) ficudimer A (3a/3b), along with ten known amides, were isolated from the roots of Ficus hirta. Their structures were elucidated by several spectroscopic data analyses, including HRESIMS, NMR, and X-ray single-crystal diffraction. The cytotoxic activities of all compounds against HeLa, HepG2, MCF-7, and H460 cell lines were detected using the MTT assay. Among these, 5 showed the highest activity against HeLa cells. Subsequently, the apoptotic, anti-invasive, and anti-migration effects of 5 on HeLa cells were determined by flow cytometer, transwell invasion assay, and wound-healing assay, respectively. The result suggested that 5 distinctly induced the apoptosis in HeLa cells and inhibited their invasion and migration. Further studies on anticancer mechanisms were conducted using Western blotting. As a result, 5 increased the cleavage of PARP and the expression of pro-apoptotic protein Bax. Moreover, 5 notably upregulated the phosphorylation of p38 and JNK, whereas inhibited the expression of p-ERK and p-AKT. Our results demonstrated that 5 could be a potential leading compound for further application in the treatment of cervical cancer., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The wounds failing to heal through a timely and orderly standard of care (SOC) treatment are considered as chronic wounds, which add significant burden to healthcare systems around the world. SOC treatment has been commonly applied for management of chronic wounds, but SOC alone may not be adequate to heal all ulcers effectively. Fish skin graft (FSG) is a xenogenic skin substitute which could be used for accelerating skin healing. The current study was performed with the view of evaluating the effectiveness of FSG as an adjuvant treatment of SOC for chronic ulcer treatment., Methods: Two authors independently searched the following electronic databases: PubMed, Embase, and CENTRAL, using keywords including "diabetic foot ulcer," "fish skin graft," and "wound healing." Clinical studies that evaluated the clinical outcomes of FSG in treatment of chronic ulcers were included in this meta-analysis. Random- or fixed-effect modeled meta-analyses were performed according to the heterogeneity test result (i.e., I 2 ), to analyze the clinical outcome of FSG., Results: A total of 8 studies were included in qualitative synthesis and meta-analysis, with 145 patients treated by SOC and 245 patients treated by SOC plus FSG. There was no significant difference between two groups for time to healing (MD = 1.99, 95% CI: -3.70~7.67, p = 0.493). The complete healing rate was significantly higher in FSG group compared with SOC alone (OR = 3.44, 95% CI: 2.03~5.82, p < 0.001***). Mean percentage area reduction (PAR) was reported in six studies, with a range of 71.6~97.3%. However, many of these studies did not report the value of standard deviation (SD), so we could not pool the data. No significantly different ulcer recurrence rate (RR = 0.60, 95% CI: 0.07~5.27, p = 0.645) and severe adverse events (SAEs) risk (RR = 1.67, 95% CI: 0.42~6.61, p = 0.467) were found between two groups., Conclusions: The application of FSG treatment for patients with chronic ulcers that do not respond well to SOC management could significantly increase the complete healing rate compared with SOC alone, without increased recurrence rate and SAEs risk., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Familial hypercholesterolemia (FH) is a common hereditary cholesterol metabolic disease that usually leads to an increase in the level of low-density lipoprotein cholesterol in plasma and an increase in the risk of cardiovascular disease. The lack of disease screening and diagnosis often results in FH patients being unable to receive early intervention and treatment, which may mean early occurrence of cardiovascular disease. Thus, more requirements for FH identification and management have been proposed. Recently, machine learning (ML) has made great progress in the field of medicine, including many innovative applications in cardiovascular medicine. In this review, we discussed how ML can be used for FH screening, diagnosis and risk assessment based on different data sources, such as electronic health records, plasma lipid profiles and corneal radian images. In the future, research aimed at developing ML models with better performance and accuracy will continue to overcome the limitations of ML, provide better prediction, diagnosis and management tools for FH, and ultimately achieve the goal of early diagnosis and treatment of FH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Luo, Wang, Hu, Fu, Zhang and Jiang.)

Lipase is involved in lipid hydrolysis, which is related to nematodes' energy reserves and stress resistance. However, the role of lipases in Bursaphelenchus xylophilus, a notorious plant-parasitic nematode responsible for severe damage to pine forest ecosystems, remains largely obscure. Here, we characterized a class III lipase as a candidate effector and named it BxLip-3. It was transcriptionally up-regulated in the parasitic stages of B. xylophilus and specifically expressed in the oesophageal gland cells and the intestine. In addition, BxLip-3 suppressed cell death triggered by the pathogen-associated molecular patterns PsXEG1 and BxCDP1 in Nicotiana benthamiana, and its Lipase-3 domain is essential for immunosuppression. Silencing of the BxLip-3 gene resulted in a delay in disease onset and increased the activity of antioxidant enzymes and the expression of pathogenesis-related (PR) genes. Plant chitinases are thought to be PR proteins involved in the defence system against pathogen attack. Using yeast two-hybrid and co-immunoprecipitation assays, we identified two class I chitinases in Pinus thunbergii, PtChia1-3 and PtChia1-4, as targets of BxLip-3. The expression of these two chitinases was up-regulated during B. xylophilus inoculation and inhibited by BxLip-3. Overall, this study illustrated that BxLip-3 is a crucial virulence factor that plays a critical role in the interaction between B. xylophilus and host pine., (© 2023 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Background: Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease of immune hyperactivation that arises in the context of infectious, inflammatory, or neoplastic triggers. The aim of this study was to establish a predictive model for the timely differential diagnosis of the original disease resulting in HLH by validating clinical and laboratory findings to further improve the efficacy of therapeutics for HLH., Methods: We retrospectively enrolled 175 secondary HLH patients in this study, including 92 patients with hematologic disease and 83 patients with rheumatic disease. The medical records of all identified patients were retrospectively reviewed and used to generate the predictive model. We also developed an early risk score using multivariate analysis weighted points proportional to the β regression coefficient values and calculated its sensitivity and specificity for the diagnosis of the original disease resulting in HLH., Results: The multivariate logistic analysis revealed that lower levels of hemoglobin and platelets (PLT), lower levels of ferritin, splenomegaly and Epstein-Barr virus (EBV) positivity were associated with hematologic disease, but young age and female sex were associated with rheumatic disease. The risk factors for HLH secondary to rheumatic diseases were female sex [OR 4.434 (95% CI, 1.889-10.407), P =0.001], younger age [OR 6.773 (95% CI, 2.706-16.952), P <0.001], higher PLT level [OR 6.674 (95% CI, 2.838-15.694), P <0.001], higher ferritin level [OR 5.269 (95% CI, 1.995-13.920), P =0.001], and EBV negativity [OR 27.656 (95% CI, 4.499-169.996), P <0.001]. The risk score included assessments of female sex, age, PLT count, ferritin level and EBV negativity, which can be used to predict HLH secondary to rheumatic diseases with an AUC of 0.844 (95% CI, 0.836~0.932)., Conclusion: The established predictive model was designed to help clinicians diagnose the original disease resulting in secondary HLH during routine practice, which might be improve prognosis by enabling the timely treatment of the underlying disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gao, Hu, Ma, Shi, Wang, Ma, Song, Zhu and Wang.)

Microbial graphene oxide reduction is a developing method that serves to reduce both production costs and environmental impact in the synthesis of graphene. This study demonstrates microbial graphene oxide reduction using Shewanella decolorationis NTOU1 under neutral and mild conditions (pH = 7, 35 °C, and 1 atm). Graphene oxide (GO) prepared via the modified Hummers' method is used as the sole solid electron acceptor, and the characteristics of reduced GO (rGO) are investigated. According to electron microscopic images, the surface structure of GO was clearly changed from smooth to wrinkled after reduction, and whole cells were observed to be wrapped by GO/rGO films. Distinctive appendages on the cells, similar to nanowires or flagella, were also observed. With regard to chemical-bonding changes, after a 24-h reaction of 1 mg mL -1 , GO was reduced to rGO, the C/O increased from 1.4 to 3.0, and the oxygen-containing functional groups of rGO were significantly reduced. During the GO reduction process, the number of S. decolorationis NTOU1 cells decreased from 1.65 × 10 8 to 1.03 × 10 6 CFU mL -1 , indicating the bactericide effects of GO/rGO. In experiments adding consistent concentrations of initial bacteria and lactate, it was shown that with the increase of GO additions (0.5-5.0 mg mL -1 ), the first-order reaction rate constants ( k ) of lactate metabolism and acetate production increased accordingly; in experiments adding consistent concentrations of initial bacteria and GO but different lactate levels (1 to 10 mM), the k values of lactate metabolism did not change significantly. The test results of adding different electron transfer mediators showed that riboflavin and potassium ferricyanide were able to boost GO reduction, whereas 2,6-dimethoxy-1,4-benzoquinone and 2,6-dimethyl benzoquinone completely eliminated bacterial activity.

Background: Swelling after apical microsurgery is a postoperative reaction and may reduce quality of life during healing., Aim: To evaluate periapical swelling after apical microsurgery and determine potential risk factors., Methods: Ninety-eight apical microsurgery patients were selected for this study. Before surgery, bone shadow volume and density of pathological tissue were measured by cone beam computed tomography. The other variables (age, gender, operative teeth number, fistula, preoperative swelling, drug use and preoperative root canal treatments) were assessed during examination. Swelling degree was confirmed by questionnaires for patients on postoperative days 1, 7, 14 and 21. Statistical analyses were performed to identify predictors for swelling., Results: Majority of patients reported moderate (45.9%) or severe (34.7%) swelling on day 1, and moderate (44.9%) or mild (45.9%) on postoperative day 7. Ninety-nine percent of patients had no or mild swelling on postoperative day 14. The average swelling level peaked on day 1 postoperatively and gradually decreased. Of statistical significance, age, bone shadow volume and density of pathological tissue acted as predictors of swelling ( P < 0.05). However, there was no significant difference in gender, tooth number, fistula, preoperative swelling, drug use, or preoperative root canal treatments ( P > 0.05)., Conclusion: Younger patients with larger shadow volume and density were significantly more likely to develop swelling after apical microsurgery., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Enoyl-CoA hydratase domain containing 3 (ECHDC3) increased in CD34 + progenitor cells of acute myeloid leukemia (AML) cells after chemotherapy. However, the prognostic significance and function of ECHDC3 in AML remain to be clarified., Methods: In the training cohort, 24 AML (non-acute promyelocytic leukemia, APL) patients were enrolled in Peking University People's Hospital and tested for ECHDC3 in enriched CD34 + cells at diagnosis. In the validation set, 351 bone marrow RNA-seq data of non-APL AML were obtained by two independent online datasets (TCGA-LAML and BEAT-AML). LASSO regression model was conducted to a new prediction model of ECHDC3-related genes. In addition, the ECHDC3 signature was further explored by GO, KEGG, GSEA, and immuno-infiltration analysis. By RNA interference, the function of ECHDC3 in mitochondrial DNA (mt-DNA) transcriptome and chemoresistance was further explored, and the GSE52919 database re-verified the ECHDC3 chemoresistance feature., Results: By Kaplan-Meier analysis, patients with ECHDC3 high demonstrated inferior overall survival (OS) compared to those with ECHDC3 low both in the training (2-year OS, 55.6% vs . 100%, p = 0.011) and validation cohorts (5-year OS, 9.6% vs . 24.3%, p = 0.002). In addition, ECHDC3 high predicted inferior OS in the subgroup of patients with ELN 2017 intermediated (int) risk (5-year OS, 9.5% vs . 26.3%, p = 0.039) or FLT3+NPM1- adverse (adv) risk (4-year OS, 6.4% vs . 31.8%, p = 0.003). In multivariate analysis, ECHDC3 was an independent risk factor of inferior OS (HR 1.159, 95% CI 1.013-1.326, p = 0.032). In the prediction model combining ECHDC3 and nine selected genes (RPS6KL1, RELL2, FAM64A, SPATS2L, MEIS3P1, CDCP1, CD276, IL1R2, and OLFML2A) by Lasso regression, patients with high risk showed inferior 5-year OS (9.3% vs . 23.5%, p < 0.001). Bioinformatic analysis suggested that ECHDC3 alters the bone marrow microenvironment by inducing NK, resting mast cell, and monocyte differentiation. Knocking down ECHDC3 in AML cells by RNAi promoted the death of leukemia cells with cytarabine and doxorubicin., Conclusion: These bioinformatic analyses and experimental verification indicated that high ECHDC3 expression might be a poor prognostic biomarker for non-APL AML, which might be a potential target for reverting chemoresistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Niu, Hu and Lv.)

Objective: This study aimed to explore variables associated with remission rate and survival in patients with acute myeloid leukemia (AML) after induction failure and relapse. Methods: Data of 373 consecutive patients with AML were analyzed after induction failure and relapse. Binary logistics and the Cox model regression were used to identify variables associated with remission rate and outcomes. Results: In patients with AML after induction failure and relapse, the total CR+CRi rates were 50.6% and 40.3%, respectively; among those who achieved CR/CRi, the 3-year RFS rates were 34.4% and 30.4%, respectively, and the 3-year overall survival rates were 40.1% and 31.6%, respectively. In the multivariate analyses, using CLAG or FLAG regimen as a re-induction chemotherapy regimen, age <39 years and SWOG low-risk were significantly associated with higher remission rates in patients with induction failure. Male, secondary AML, SWOG high-risk, the interval from the first remission to relapse within 12 months, and bone marrow blasts ≥20% at the time of relapse were significantly associated with lower remission rates in relapsed patients. Transplantation was significantly associated with prolonged relapse-free survival and overall survival in patients achieving hematologic remission; the SWOG low-risk group was significantly associated with longer overall survival in those with induction failure; and achieving CR (not CRi) or having female gender was associated with longer RFS or overall survival in relapsed patients. Conclusion: Reinduction chemotherapy regimen, age, gender, SWOG risk, secondary AML, the interval from the first remission to relapse, and bone marrow blast percentage at the time of relapse were significantly associated with remission rates in the patients with AML after induction failure and relapse. Transplantation, SWOG low-risk, achieving CR, or female gender were associated with longer survivals in those achieving remission.

The migratory plant-parasitic nematode Bursaphelenchus xylophilus is the pathogen of the pine wilt disease (PWD), causing serious damage to pine forests in China. During the process of plant resistance to multiple pathogens, plant immunity plays a key role. In this current study, the pathogen-associated molecular pattern (PAMP) BxCDP1 in B. xylophilus has been identified, but the host target protein of BxCDP1 and its key amino acid region inducing the plant immunity have yet to be elucidated. We found that BxCDP1 could trigger superoxide production, H 2 O 2 production, and callose deposits. A RING-H2 finger protein 1 (RHF1) of Pinus thunbergii was screened and characterized as a target protein of BxCDP1 by yeast two-hybrid and co-immunoprecipitation (Co-IP). Moreover, two peptides (namely M9 and M16) proved to be key regions of BxCDP1 to induce PAMP-triggered immunity (PTI) in Nicotiana benthamiana , which also induced the expression of pathogenesis-related (PR) genes ( PtPR-3 , PtPR-4 , and PtPR-5 ) in P. thunbergii and enhanced the resistance of the host to B. xylophilus . These results indicate that BxCDP1 plays a critical role in the interaction between B. xylophilus and P. thunbergii , and both peptides M9 and M16 have the potential to be developed and utilized as immune inducers of pines against B. xylophilus in future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Wu, Wen, Ye, Qiu, Rui and Zhang.)

Objective: The study aims to explore the efficacy and safety of low-dose chemotherapy combined with tyrosine kinase inhibitor (TKI) as an induction therapy for Philadelphia-chromosomal-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: The data of the consecutive newly diagnosed patients with Ph(+) ALL were reviewed. The efficacy and safety of low-dose chemotherapy and conventional-dose chemotherapy combined with TKI were compared. Results: A total of 217 patients with a median age of 38 (10-69) years old were included in this study. 78 patients were in the low-dose chemotherapy group, and 139 patients were in the conventional-dose chemotherapy group. There were no significant differences in the 4-week complete remission (CR) rate (98.7% vs 97.0%, P =0.766) and overall CR rate (100% vs 100%, P =1.000) between the two groups. Multivariate analyses showed that the chemotherapy intensity was not related to the disease-free survival rate and overall survival rate. However, the lower incidence of infection ( P =0.017) , the shorter duration of neutropenia ( P =0.001) and PLT<20 × 10(9)/L ( P =0.057) , and the lower red blood cell transfusion volume ( P =0.002) were more common in the low-dose chemotherapy group than in the conventional-dose chemotherapy group. Conclusions: The low-dose chemotherapy is superior to the conventional-dose chemotherapy combined with TKI as induction therapy in Ph(+) ALL with similar efficacy but is safer.

Bursaphelenchus xylophilus is the most economically important species of migratory plant-parasitic nematodes (PPNs) and causes severe damage to forestry in China. The successful infection of B. xylophilus relies on the secretion of a repertoire of effector proteins. The effectors, which suppress the host pine immune response, are key to the facilitation of B. xylophilus parasitism. An exhaustive list of candidate effectors of B. xylophilus was predicted, but not all have been identified and characterized. Here, an effector, named BxSCD3, has been implicated in the suppression of host immunity. BxSCD3 could suppress pathogen-associated molecular patterns (PAMPs) PsXEG1- and INF1-triggered cell death when it was secreted into the intracellular space in Nicotiana benthamiana. BxSCD3 was highly up-regulated in the early infection stages of B. xylophilus . BxSCD3 does not affect B. xylophilus reproduction, either at the mycophagous stage or the phytophagous stage, but it contributes to the virulence of B. xylophilus. Moreover, BxSCD3 significantly influenced the relative expression levels of defense-related (PR) genes PtPR-3 and PtPR-6 in P inus thunbergii in the early infection stage. These results suggest that BxSCD3 is an important toxic factor and plays a key role in the interaction between B. xylophilus and host pine.

Background: Bursaphelenchus xylophilus is the causal agent of pine wilt disease (PWD) that has caused enormous ecological and economic losses in China. The mechanism in the interaction between nematodes and pine remains unclear. Plant parasitic nematodes (PPNs) secrete effectors into host plant tissues. However, it is poorly studied that role of effector in the infection of pine wood nematode (PWN)., Results: We cloned, characterized and functionally validated the B. xylophilus effector BxML1, containing an MD-2-related lipid-recognition (ML) domain. This protein inhibits immune responses triggered by the molecular pattern BxCDP1 of B. xylophilus. An insitu hybridization assay demonstrated that BxML1 was expressed mainly in the dorsal glands and intestine of B. xylophilus. Subcellular localization analysis showed the presence of BxML1 in the cytoplasm and nucleus. Furthermore, number of B. xylophilus and morbidity of pine were significantly reduced in Pinus thunbergii infected with B. xylophilus when BxML was silenced. Using yeast two-hybrid (Y2H) and coimmunoprecipitation (CoIP) assays, we found that the BxML1 interacts with cyclophilin protein PtCyP1 in P. thunbergii., Conclusions: This study illustrated that BxML1 plays a critical role in the B. xylophilus-plant interaction and virulence of B. xylophilus., (© 2022. The Author(s).)

Inspired by a previously reported biomimetic synthesis study, four new naturally occurring phloroglucinol trimers 1-4 with unusual 6/5/5/6/6/6-fused hexacyclic ring systems, along with two known analogues ( 5 and 6 ) and two known biogenetically related dimers ( 10 and 11 ), were isolated from Rhodomyrtus tomentosa . Their structures and absolute configurations were unambiguously elucidated by spectroscopic analysis, X-ray diffraction, and electronic circular dichroism calculation. By mimicking two potentially alternative biosynthetic pathways, the first asymmetric syntheses of 1-4 and the racemic syntheses of 5 and 6 were achieved in only five to six steps without the need for protecting groups. Furthermore, phloroglucinol dimers 10 and 11 exhibited significant in vitro antiviral activity against the respiratory syncytial virus.

The plant-parasitic nematode Bursaphelenchus xylophilus, the causal agent of pine wilt disease (PWD), causes enormous economic loss every year. Currently, little is known about the pathogenic mechanisms of PWD. Several effectors have been identified in B. xylophilus, but their functions and host targets have yet to be elucidated. Here, we demonstrated that BxSCD1 suppresses cell death and inhibits B. xylophilus PAMP BxCDP1-triggered immunity in Nicotiana benthamiana and Pinus thunbergii. BxSCD1 was transcriptionally upregulated in the early stage of B. xylophilus infection. In situ hybridization experiments showed that BxSCD1 was specifically expressed in the dorsal glands and intestine. Cysteine residues are essential for the function of BxSCD1. Transient expression of BxSCD1 in N. benthamiana revealed that it was primarily targeted to the cytoplasm and nucleus. The morbidity was significantly reduced in P. thunbergii infected with B. xylophilus when BxSCD1 was silenced. We identified 1-aminocyclopropane-1-carboxylate oxidase 1, the actual ethylene-forming enzyme, as a host target of BxSCD1 by yeast two-hybrid and coimmunoprecipitation. Overall, this study illustrated that BxSCD1 played a critical role in the B. xylophilus-plant interaction., (© 2021 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Background: Isocenter deviation, often induced by small displacements of both the device and the patient, is a common error seen in radiotherapy. In this study, we investigated the impact of isocenter deviation on the results of the volumetric modulated arc therapy (VMAT) plan and dosimetric verification gamma passing rate in the treatment of cervical cancer., Methods: The clinical data of 15 patients with cervical cancer who were treated with VMAT were retrospectively collected and analyzed. In this study, the isocenter site modification method was adopted. The VMAT plan with isocenter deviation adjustment was set as the experimental group, while the original plan was set as the control group. The impact of isocenter deviation on the results of the VMAT plan and dosimetric verification gamma passing rate was analyzed. Applying gamma analysis with different test criterions, the impact of isocenter deviation on the gamma passing rates was evaluated, and the sensitivity of different test criterions in identifying isocenter deviation was also analyzed., Results: There was a significant difference in the average dose in the target area between experimental group and control group (P<0.05). In organs at risk (OAR) terms, isocenter deviations also caused significant differences in dose parameters between the two groups. Except that there was no significant difference in the rectal V40 between two groups when the isocenter deviation was greater than 3 mm in the y axis direction. With the increase in the isocenter deviation, there was a trend towards decreased gamma passing rates with different analysis criterions in the experimental group. The 2 mm/2% standard had the highest sensitivity for identifying isocenter deviation., Conclusions: Isocenter deviation has significant effects on the results of the volume rotation intensity modulation plan and dosimetric verification gamma passing rates in the treatment of cervical cancer. When the isocenter deviation was less than 3 mm, a higher gamma passing rate (>90%) could also be obtained under the condition of the 3 mm/3% test criterions. It is recommended that the 2 mm/2% test standard should be utilized in clinical practice., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tcr-21-1514). The authors have no conflicts of interest to declare., (2021 Translational Cancer Research. All rights reserved.)

Background: The pine wood nematode (PWN), Bursaphelenchus xylophilus, is a devastating pathogen of many Pinus species in China. The aim of this study was to understand the interactive molecular mechanism of PWN and its host by comparing differentially expressed genes and candidate effectors from three transcriptomes of B. xylophilus at different infection stages., Results: In total, 62, 69 and 46 candidate effectors were identified in three transcriptomes (2.5 h postinfection, 6, 12 and 24 h postinoculation and 6 and 15 d postinfection, respectively). In addition to uncharacterized pioneers, other candidate effectors were involved in the degradation of host tissues, suppression of host defenses, targeting plant signaling pathways, feeding and detoxification, which helped B. xylophilus survive successfully in the host. Seven candidate effectors were identified in both our study and the B. xylophilus transcriptome at 2.5 h postinfection, and one candidate effector was identified in all three transcriptomes. These common candidate effectors were upregulated at infection stages, and one of them suppressed pathogen-associated molecular pattern (PAMP) PsXEG1-triggered cell death in Nicotiana benthamiana., Conclusions: The results indicated that B. xylophilus secreted various candidate effectors, and some of them continued to function throughout all infection stages. These various candidate effectors were important to B. xylophilus infection and survival, and they functioned in different ways (such as breaking down host cell walls, suppressing host defenses, promoting feeding efficiency, promoting detoxification and playing virulence functions). The present results provide valuable resources for in-depth research on the pathogenesis of B. xylophilus from the perspective of effectors.

The risk of colitis and colorectal cancer increases markedly throughout adult life, endangering the health and lives of elderly individuals. Previous studies have proposed that bacterial translocation and infection are the main risk factors for these diseases. Therefore, in the present study, we aimed to identify the underlying mechanism by focusing on the mucus barrier function and mucin-type O-glycosylation. We evaluated alterations in the colon mucus layer in 2-, 16-, and 24-month-old mice and aged humans. Aged colons showed defective intestinal mucosal barrier and changed mucus properties. The miR-124-3p expression level was significantly increased in the aged distal colonic mucosa, which was accompanied by an increase in pathogens and bacterial translocation. Meanwhile, T-synthase, the rate-limiting enzyme in O-glycosylation, displayed an age-related decline in protein expression. Further experiments indicated that miR-124-3p modulated O-glycosylation by directly targeting T-synthase. Moreover, young mice overexpressing miR-124-3p exhibited abnormal glycosylation, early-onset, and more severe colitis. These data suggest that miR-124-3p predisposes to senile colitis by reducing T-synthase, and the miR-124-3p/T-synthase/O-glycans axis plays an essential role in maintaining the physiochemical properties of colonic mucus and intestinal homeostasis., (© 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

The migratory plant-parasitic nematode Bursaphelenchus xylophilus is the causal agent of pine wilt disease, which causes serious damage to pine forests in China. Plant immunity plays an important role in plant resistance to multiple pathogens. Activation of the plant immune system is generally determined by immune receptors, including plant pattern recognition receptors, which mediate pattern recognition. However, little is known about molecular pattern recognition in the interaction between pines and B. xylophilus. Based on the B. xylophilus transcriptome at the early stages of infection and Agrobacterium tumefaciens-mediated transient expression and infiltration of recombinant proteins produced by Pichia pastoris in many plant species, a novel molecular pattern (BxCDP1) was characterized in B. xylophilus. We found that BxCDP1 was highly up-regulated at the early infection stages of B. xylophilus, and was similar to a protein in Pararhizobium haloflavum. BxCDP1 triggered cell death in Nicotiana benthamiana when secreted into the apoplast, and this effect was dependent on brassinosteroid-insensitive 1-associated kinase 1, but independent of suppressor of BIR1-1. BxCDP1 also exhibited cell death-inducing activity in pine, Arabidopsis, tomato, pepper, and lettuce. BxCDP1 triggered reactive oxygen species production and the expression of PAMP-triggered immunity marker genes (NbAcre31, NbPTI5, and NbCyp71D20) in N. benthamiana. It also induced the expression of pathogenesis-related genes (PtPR-3, PtPR-4, and PtPR-5) in Pinus thunbergii. These results suggest that as a new B. xylophilus molecular pattern, BxCDP1 can not only be recognized by many plant species, but also triggers innate immunity in N. benthamiana and defence responses of P. thunbergii., (© 2020 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

This study aimed to determine whether and how the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide affects the chemoresistance and chemosensitivity of pancreatic cancer cells to gemcitabine in vitro and in vivo. The GLP-1R and protein kinase A (PKA) levels were compared between the human pancreatic cancer cell line PANC-1 and the gemcitabine-resistant cell line PANC-GR. The in vitro effects of liraglutide on the cell proliferation and apoptosis as well as the nuclear factor-kappa B NF-κB expression levels of PANC-GR cells were evaluated. In addition, a mouse xenograft model of human pancreatic cancer was established by s.c. injection of PANC-1 cells, and the effects of liraglutide on the chemosensitivity were evaluated in vitro and in vivo. In contrast to PANC-1 cells, PANC-GR cells exhibited lower expression levels of GLP-1R and PKA. Incubation with liraglutide dose dependently inhibited the growth, promoted the apoptosis, and increased the expression of GLP-1R and PKA of PANC-GR cells. Similar effects of liraglutide were observed in another human pancreatic cancer cell line MiaPaCa-2/MiaPaCa-2-GR. Either the GLP-1R antagonist Ex-9, the PKA inhibitor H89, or the NF-κB activator lipopolysaccharide (LPS) could abolish the antiproliferative and proapoptotic activities of liraglutide. Additionally, each of these agents could reverse the expression of NF-κB and ABCG2, which was decreased by liraglutide treatment. Furthermore, liraglutide treatment increased the chemosensitivity of pancreatic cancer cells to gemcitabine, as evidenced by in vitro and in vivo experiments. Thus, GLP-1R agonists are safe and beneficial for patients complicated with pancreatic cancer and diabetes, especially for gemcitabine-resistant pancreatic cancer.

Clinical analysis of antibiotic bone cement spacer combined with membrane induction technology in the treatment of osteomyelitis after intramedullary nail fixation operation for femoral shaft fracture was retrospectively performed on 12 cases in Department of Orthopaedics Centre, Renmin Hospital, Hubei University of Medicine from February 2013 to November 2016. The healing time of bone defect, infection recurrence and other complications were observed. Membrane induced series treatment scheme was given to all patients. Membrane-induced sequence therapy consisted of the first stage which included complete debridement, removal of the original internal fixation of intramedullary nail, intraoperative preparation of antibiotic bone cement rod into the medullary cavity and full drainage. The second stage included replacement of the interlocking intramedullary nail after infection control and autologous iliac bone graft was then used at the bone defect. Followup visits for bone situations were conducted for all the cases and the duration was 12-35 min (25.75 min on average). Fractures of all patients healed clinically. The healing duration was 4-11 min (7.33 min on average).After treatment, patients had no significant shortening of the limbs and their gait was normal at 12 months follow-up. This study is of femoral shaft fracture with no involvement of the joints and range of movement was not measured. No apparent relevant complications were seen.

Three new monoterpenoid indole alkaloids (MIAs), hunterines A-C ( 1 - 3 ), were isolated from Hunteria zeylanica. Compound 1 possesses a unique skeleton with an unprecedented azabicyclo[4.3.1]decane ring system. Compounds 2 and 3 are a pair of epimeric vobasinylindole alkaloid heterodimers. Their structures including absolute configurations were established by spectroscopic analyses, X-ray diffraction, computational calculation, and the modified Mosher's method. Plausible biogenetic pathways of 1 - 3 were also proposed. Alkaloid 1 showed moderate cytotoxic activity against the HepG2 cell line.

The pine wood nematode (PWN) Bursaphelenchus xylophilus has caused serious damage to pine forests in China. Effectors secreted by phytonematodes play a role in host infection. We identified and characterized an effector, BxSapB1, based on the B. xylophilus transcriptome at the early stages of infection and the transient expression of proteins in Nicotiana benthamiana. BxSapB1 triggered cell death in N. benthamiana when secreted into the apoplast, and this effect was independent of N. benthamiana brassinosteroid-insensitive 1-associated kinase 1 (NbBAK1) and suppressor of BIR1-1 (NbSOBIR1). The signal peptide of BxSapB1 was proven to be functional in yeast using the yeast signal sequence trap system and BxSapB1 was strongly expressed in the subventral gland cells of B. xylophilus, as revealed by in-situ hybridization. In addition, based on local BLAST analysis, the BxSapB1 showed 100% identity to BUX.s00139.62, which was identified from the B. xylophilus secretome during Pinus thunbergii infection. BxSapB1 was upregulated in a highly virulent strain and downregulated in a weakly virulent strain of PWN at the early stages of infection. RNA interference assays showed that silencing BxSapB1 resulted in decreased expression of pathogenesis-related genes (PtPR-1b, PtPR-3, and PtPR-5) as well as delayed onset of symptoms in P. thunbergii infected by B. xylophilus. The combined data suggest that BxSapB1 can trigger cell death in N. benthamiana and that it contributes to the virulence in B. xylophilus during parasitic interaction.

Objective: To investigate the effects of artesunate combined with bortezomib on the proliferation, apoptosis and autophagy of human acute myeloid leukemia cell lines MV4-11, and its mechanisms. Methods: MTT method was used to determine the anti-proliferation effect of different concentrations of artesunate, bortezomib and their combination on MV4-11 cells. The cell apoptosis were analyzed by flow cytometry. The expression of cleaved-Caspase-3, Bcl-2 family protein (Bcl-2, Mcl-1, Bim, Bax) and autophagy-related protein LC3B were assayed by Western blot. Results: Artesunate displayed a proliferation inhibition effect on MV4-11 with dose- and time-dependent manner, the IC(50) of artesunate on MV4-11 after 48 hours was 1.44 μg/ml. Bortezomib displayed a proliferation inhibition effect on MV4-11 with dose-dependent manner, the IC(50) of bortezomib on MV4-11 after 48 hours was 8.97 nmol/L. The combination of artesunate (0.75, 1.0 μg/ml) and Bortezomib (6, 8 nmol/L) showed higher inhibition on MV4-11 than artesunate or bortezomib alone in the same concentration gradient after 48 hours ( P <0.05) . The cooperation index of the two drugs were all less than 1. The 48 h apoptotic rate of artesunate (1.5 μg/ml) on MV4-11 was (15.27±2.18) %, (19.85±3.23) % of bortezomib (8 nmol/L) , (81.67±5.96) % of combination of the two drugs, significantly higher than the single group ( P <0.05) . When combination of the two drugs on MV4-11 after 24 hours, the levels of pro-apoptotic protein Bim and the cleaved activation of Caspase-3 and autophagy-related protein LC3B were up-regulated and the anti-apoptotic protein Bcl-2 expressions was down-regulated. Conclusion: Combination of artesunate with bortezomib shows a significant synergistic effects on proliferation, apoptosis and autophagy of MV4-11 cell lines, which may be associated with Bcl-2 family proteins expression.

The immune mechanism underlying graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (HSCT) remains unclear. Natural killer (NK) cells play a crucial role in mediating pathogen-specific immunity and are the first donor-derived lymphocytes reconstituted post-HSCT. However, NK cells vary at different stages after HSCT. Here, we found that the absolute NKG2A + subset cell counts and the percentages of NKG2A + among NK cells were significantly reduced in GVHD patients after HSCT compared with those from non-GVHD patients. Moreover, the reduction in NKG2A + NK cells in post-HSCT GVHD patients was ascribed to increased apoptosis and a decreased proliferation capacity while retaining a strong graft-versus-leukemia effect. In vitro assays showed that co-culture of T cells with NKG2A + NK cells significantly reduced IFN-γ secretion by T cells and increased IL-4 secretion. Moreover, the CD25 expression level was decreased, whereas the number of cells with the CD4 + CD25 + FOXP3 + phenotype was increased. In addition, the NKG2A + NK cells induced T cell apoptosis and decreased T cell proliferation during the co-culture process. Importantly, NKG2A + NK cells mainly regulated activated but not resting T cells. In vivo assays showed that the serologic IL-10 level was evidently lower in GVHD than in non-GVHD patients, whereas the IL-1β, IFN-γ, and tumor necrosis factor-α levels were higher in GVHD patients. Furthermore, the NKG2A + NK cell ratio from GVHD patients was markedly increased by the presence of exogenous IL-10 but not by other cytokines. In contrast, the NKG2A + cell ratio from non-GVHD patients was not increased by IL-10. Therefore, post-HSCT GVHD may be ascribed to the reduced induction of NKG2A + NK cells by IL-10, which further overactivates T cells., (Copyright © 2018. Published by Elsevier Inc.)

Aim: To find a stable, inexpensive, and reliable method to produce a rat meibomian gland dysfunction (MGD) model., Methods: We inserted slim guidewires into the meibomian gland orifices of twelve Brown Norway rats and fulgurized every guidewire to destroy part of the meibomian gland. We then observed the morphological changes in the eyelid margin, and compared the data of tear breakup time (TBUT), Schirmer I test, and the corneal fluorescence staining scores at different times (1, 2, 4, and 6wk). We observed pathological changes of the cornea, conjunctiva and meibomian gland, and we used real-time polymerase chain reaction to analyze epithelial growth factor (EGF), interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and Ki67., Results: In the fourth week, compared with the control group, the TBUT of the model group began to decreased ( P <0.05). The tear secretion remained stable ( P >0.05). The corneal dots were significantly increased in the fourth week when the fusion stain began to appear ( P <0.05). In the fourth week, partial meibomian gland openings had hoary secretions blocked, orifices were expanded, and there was a partial convex deformation. In the sixth week, the tissue section showed that the number of conjunctival goblet cells was decreased, epithelial cells were irregular, the epithelium was detached and rough, and meibomian glands were lost. The expressions of EGF, IL-6, IL-8, and TNF-α in corneal, conjunctival, and meibomian tissues were highly increased ( P <0.05), but no statistical difference was found in the expression of Ki67 in corneal and conjunctival tissues ( P >0.05)., Conclusion: The MGD rat model, produced via electrocauterization of meibomian gland orifices, matched clinical manifestations and cytokine levels. Our research provides a new method of achieving an MGD animal model.

Objective: To describe the characteristics of spinal cord injury (SCI) individuals in Shanghai and examine their treatment and rehabilitation for traumatic and complete SCI individuals., Design: Community-based secondary data analyses., Setting: Shanghai, China., Methods: We analyzed gender, age at injury, complications, disturbances of function, treatment, etiology, and severity of injury of SCI individuals that enrolled in "halfway houses", government-supported community co-op centers. Bivariate statistical analyses were conducted to examine the factors associated with complete and traumatic SCI., Results: We analyzed 808 SCI individuals who participated in halfway houses in Shanghai during 2009-2015. The male-to-female ratio was 2.1:1. The proportion of middle or elder age groups at injury (age 46 to 60 and age 61 or over) showed a rising trend from 1970 to 2015. The leading causes of SCIs in Shanghai were traumatic injuries (58%), followed by disease (29.5%). The proportion of traumatic injuries decreased over time, while the proportion of non-traumatic injuries rose significantly. A majority of traumatic injury individuals were aged between 16-45., Conclusion: The middle or elder age groups at injury among SCI individuals increased continuously from 1970 to 2015. The principal causes of injury in Shanghai were traumatic injuries and disease-related injuries. Men had a higher prevalence of traumatic SCI in Shanghai. Preventive measures should focus on male and middle-aged adults. As a fast-aging society in Shanghai, more effective prevention, medical care, and rehabilitation schemes should be implemented for aging SCI individuals.

Purpose: Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in Southeast Asia. Because local recurrence and distant metastasis are still the main causes of NPC treatment failure, it is urgent to identify new tumor markers and therapeutic targets for advanced NPC. Experimental Design: RNA sequencing (RNA-seq) was applied to look for interchromosome translocation in NPC. PCR, FISH, and immunoprecipitation were used to examine the fusion gene expression at RNA, DNA, and protein levels in NPC biopsies. MTT assay, colony formation assay, sphere formation assay, co-immunoprecipitation, chromatin immunoprecipitation assay, and in vivo chemoresistance assay were applied to explore the function of RARS-MAD1L1 in NPC. Results: We demonstrated that RARS-MAD1L1 was present in 10.03% (35/349) primary NPC biopsies and 10.7% (9/84) in head and neck cancer (HNC) samples. RARS-MAD1L1 overexpression increased cell proliferation, colony formation, and tumorigenicity in vitro , and the silencing of endogenous RARS-MAD1L1 reduced cancer cell growth and colony formation in vitro In addition, RARS-MAD1L1 increased the side population (SP) ratio and induced chemo- and radioresistance. Furthermore RARS-MAD1L1 interacted with AIMP2, which resulted in activation of FUBP1/c-Myc pathway. The silencing of FUBP1 or the administration of a c-Myc inhibitor abrogated the cancer stem cell (CSC)-like characteristics induced by RARS-MAD1L1. The expression of c-Myc and ABCG2 was higher in RARS-MAD1L1 -positive HNC samples than in negative samples. Conclusions: Our findings indicate that RARS-MAD1L1 might contribute to tumorigenesis, CSC-like properties, and therapeutic resistance, at least in part, through the FUBP1/c-Myc axis, implying that RARS-MAD1L1 might serve as an attractive target for therapeutic intervention for NPC. Clin Cancer Res; 24(3); 659-73. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Herein, we describe a concise catalytic approach to the first asymmetric total syntheses of myrtucommuacetalone, myrtucommuacetalone B, and callistrilones A, C, D and E. The syntheses proceed in only 5-7 steps from the readily available compound 11 , without the need for protecting groups. Key features of the syntheses include a unique organocatalytic asymmetric Friedel-Crafts-type Michael addition with high enantioselectivity and a broad substrate scope, a novel Michael-ketalization-annulation cascade reaction, and an oxidative [3 + 2] cycloaddition. Furthermore, the new compound 7 exhibited potent antibacterial activities against several multidrug-resistant strains (MRSA, VISA and VRE), and showed greater potency than vancomycin.

Background: Some esophageal cancer patients complicated with depression exhibit cognitive impairments. Frontal electroencephalogram (EEG) may be used as a reliable biomarker for prefrontal-mediated cognitive functions. This study was to investigate alterations of EEG and frontal cognitive impairment in esophageal cancer patients complicated with depression and to assess their correlation., Methods: Sixty-five esophageal cancer patients with depression (study group) and 62 healthy controls (control group) were included in this study. The study group were assigned into psychotic depressed (PD, n = 32) and nonpsychotic depressed (NPD, n = 33) subgroups based on complication with psychotic symptoms (Brief Psychiatric Rating Scale [BPRS] >35). EEG examination, Beck self-rating depression scale, and BPRS were used to assess clinical symptoms. Chi-square test, two independent sample t-test, one-way analysis of variance, and Kruskal-Wallis test were utilized to compare the variables between two groups. EEG abnormalities and scores of frontal cognitive function test were analyzed by partial correlation analysis in the PD and NPD subgroups., Results: Compared with control group, the study group displayed greater scores either in the Stroop test (19.89 ± 2.05 vs. 24.12 ± 2.19, P = 0.006) or Color Trails Test (CTT; 11.92 ± 1.01 vs. 15.02 ± 1.63, P = 0.008), and reduced score (35.05 ± 2.01 vs. 32.11 ± 2.38, P = 0.007) in the verbal fluency test (VFT). Compared to NPD subgroup, PD subgroup exhibited increased scores in Stroop test (22.89 ± 2.07 vs. 25.38 ± 2.32, P = 0.009) and CTT (13.16 ± 1.71 vs. 15.82 ± 1.13, P = 0.008). Moreover, increased scores in Stroop test and CTT as well as scores in VFT were associated with the severity of depression. The study group had an abnormal frontal EEG, such as α forward, α asymmetry, α moderation, and increased θ activity relative to control group. Similarly, compared with NPD subgroup, PD subgroup displayed α forward, α asymmetry, and α moderation. The correlation test revealed that α forward and α asymmetry were negatively associated with VFT score, but positively correlated with the scores of CTT and the Stroop test in PD subgroup. In addition, α asymmetry in NPD subgroup was positively related to CTT scores., Conclusion: This study indicated that frontal cognitive impairment in esophageal cancer patients complicated with depression is associated with EEG alterations.

The present study was performed to describe the changes of lung tissues in mice with acute myocardial infarction (AMI) and also explain the cell mechanism involved in inflammation in lung. AMI was established by left coronary ligation in mice. Then mice were divided into three groups: control group, MW1 group (sampling after surgery for one week) and MW2 group (sampling after surgery for two weeks). Afterwards, measurement of lung weight and lung histology, cell sorting in bronchoalveolar lavage (BAL) fluid and detection of several adhesive molecules, inflammatory molecules as well as enzyme associated with inflammation were performed. Moreover, dendritic cells (DCs) were isolated from bone marrow of C57B/L6 mice. After incubating with necrotic myocardium, the expression of antigen presenting molecules, co-stimulatory molecules and inflammatory molecules were detected by flow cytometry or immunohistochemistry in DCs. We also detected T-cell proliferation after incubating with necrotic myocardium-treated DCs. AMI induced pathological changes of lung tissue and increased inflammatory cell amount in BAL fluid. AMI also increased the expression of several inflammatory factors, adhesive molecules and enzymes associated with inflammation. CD11c and TLR9, which are DC surface markers, showed a significantly increased expression in mice with AMI. Additionally, necrotic myocardium significantly increased the expression of co-stimulatory factors including CD83 and CD80, inflammatory cytokines including TNF-α, IFN-γ and NF-κB in DCs. Furthermore, DCs treated with necrotic myocardium also significantly promoted T-cell proliferation. AMI induced inflammation in lung and these pathological changes were mediated by DC-associated immune response.