Search

Background: The application of neoadjuvant immunotherapy in the treatment of esophageal cancer needs further exploration. This study aimed to investigate the safety and effectiveness of tislelizumab, an anti-PD-1 antibody, combined with chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (LA-ESCC)., Methods: In this phase II study, patients with clinical stages of II-IVA (T3-T4 and/or node positive) potentially resectable LA-ESCC were enrolled. Patients received neoadjuvant tislelizumab and chemotherapy every 3 weeks for 4 cycles before surgery and adjuvant tislelizumab for 9 months. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included R0 resection, disease free survival (DFS), adverse events (AE), and biomarkers for predicting efficacy., Results: The study included 30 patients. 25 patients completed neoadjuvant chemoimmunotherapy and underwent surgery, 96% with R0 resection. The pCR and MPR rate was 44% and 52%. The 6-month and 1-year DFS rate was 100% and 75.3%. 43.3% patients experienced severe (grade 3-4) treatment-related adverse events (TRAEs) and 5 patients developed severe immune-related adverse events (irAEs). Further exploration found that a group of peripheral lymphocyte subsets increased significantly after 2 cycles of neoadjuvant therapy in patients who achieved pCR, suggesting the importance of dynamic monitoring of circulating lymphocyte., Conclusions: The combination of perioperative tislelizumab and neoadjuvant chemotherapy has achieved an encouraging pCR rate and demonstrated a manageable safety profile in patients with potentially resectable ESCC., Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2100043772., 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 Zhou, Hua, Ge, Wang, Wang, He, Zhao, Yu, Yan, Zhao, Li and Bai.)

Purpose: Benign prostatic hyperplasia (BPH) is a urinary tract disorder that primarily affects geriatric males. Natural materials have been developed to treat and prevent symptoms of BPH. However, a few natural functional foods has been conclusively proven to cure or prevent symptoms of BPH. The study aimed to investigate the anti-proliferative mechanism of Curcumae Radix (CR) and Syzygium aromaticum (SA) extracts using RWPE-1 cells and testosterone propionate (TP)-induced BPH rats., Materials and Methods: In vitro experiments were performed to assess the synergistic anti-proliferative effects of an equal mixture of CR and SA extracts on TP-treated RWPE-1 cells. In animal experiments, TP-induced BPH rats were administrated with saline, CR and SA extracts at 50, 100, and 200 mg/kg or finasteride at 1 mg/kg daily for 6 weeks. Body weight, prostate weight, dihydrotestosterone (DHT), androgen receptor (AR), and prostate-specific antigen (PSA) levels were measured. Additionally, extracellular signal-regulated kinase and NF-κB levels, oxidative stress, and inflammatory stress responses in the prostate were also analyzed., Results: In this study, the combination of CR and SA extracts synergistically inhibited cell proliferation compared with the effect of each extract in TP-treated RWPE-1 cells. CR and SA extracts inhibited increasing of prostate weight, thickness of prostate epithelium, the level of PSA and DHT in serum. The expression of protein and gene of PSA and AR in prostate of TP-induced BPH rats were also suppressed by the administration of CR and SA extracts. Furthermore, reactive oxygen species and inflammation axis, NOX4-iNOS-COX2 and its associated representative inflammatory cytokine, interleukin-8 were also reduced in the CR and SA extracts-administered BPH rats., Conclusions: The results suggest that the combination of CR and SA extracts improves BPH through its anti-inflammatory and anti-oxidative effects, demonstrating great potential as an anti-BPH medicine., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose: Benign prostate hyperplasia (BPH) is a common age-related chronic condition. Its pathogenesis involves androgen imbalance, inflammation, oxidative stress, and endoplasmic reticulum (ER) stress. This study aims to assess the protective effect of finasteride, a 5α-reductase inhibitor, against testosterone propionate (TP)-induced BPH in rats and explore its potential mechanism of action., Materials and Methods: TP-induced BPH rats received either saline or finasteride (1 mg/kg) orally once a day for 7 weeks. Prior to sacrificing the animals, blood samples were collected. After sacrifice, prostate and tissue around the prostate were dissected from seminal vesical for further analysis. Body weight, prostate weight, dihydrotestosterone (DHT), 5α-reductase type 2 (5-AR2), and prostate-specific antigen (PSA) levels were measured. In addition, HIF-1α, VEGF, MMP-2 expressions in prostate, oxidative stress, inflammation, and ER stress responses were analyzed to understand the mechanism of action of finasteride., Results: Finasteride administration inhibited prostate enlargement, DHT, 5-AR2, and PSA levels in BPH rats. Additionally, finasteride inhibited angiogenesis markers such as HIF-1α, VEGF, and MMP-2. Moreover, components of oxidative stress, inflammation, and ER stress responses were significantly regulated by finasteride treatment., Conclusions: This study suggests that finasteride prevents BPH-associated symptoms by regulating angiogenesis, reactive oxygen species, ER stress responses, and inflammation, another mechanism to explain the effect of the 5α-reductase against BPH., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

MCM8 is a helicase, which participates in DNA replication and tumorigenesis and is upregulated in many human cancers, including lung cancer (LC); however, the function of MCM8 in LC tumour progression is unclear. In this study, we found that MCM8 was expressed at high levels in LC cells and tissues. Further, MCM8 upregulation was associated with advanced tumour grade and lymph node metastasis, and indicated poor prognosis. Silencing of MCM8 suppressed cell growth and migration in vitro and in vivo, while ectopic MCM8 expression promoted cell cycle progression, as well as cell migration, proliferation, and apoptosis. Mechanistically, DNAJC10 was identified as a downstream target of MCM8, using gene array and CO-IP assays. DNAJC10 overexpression combatted the inhibitory activity of MCM8 knockdown on LC progression, while silencing DNAJC10 alleviated the oncogenic function of MCM8 overexpression. MCM8 expression was positively correlated with that of DNAJC10 in LC samples from The Cancer Genome Atlas database, and DNAJC10 upregulation was also associated with poor overall survival of patients with LC. This study indicated that MCM8/DNAJC10 axis plays an important role in in LC development, and maybe as a new potential therapeutic target or a diagnostic biomarker for treating patients with LC., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Obesity is a common metabolic syndrome that causes a significant burden on individuals and society. Conventional therapies include lifestyle interventions, bariatric surgery, and pharmacological therapies, which are not effective and have a high risk of adverse events. Acupuncture is an effective alternative for obesity, it modulates the hypothalamus, sympathetic activity and parasympathetic activity, obesity-related hormones (leptin, ghrelin, insulin, and CCK), the brain-gut axis, inflammatory status, adipose tissue browning, muscle blood flow, hypoxia, and reactive oxygen species (ROS) to influence metabolism, eating behavior, motivation, cognition, and the reward system. However, hypothalamic regulation by acupuncture should be further demonstrated in human studies using novel techniques, such as functional MRI (fMRI), positron emission tomography (PET), electroencephalogram (EEG), and magnetoencephalography (MEG). Moreover, a longer follow-up phase of clinical trials is required to detect the long-term effects of acupuncture. Also, future studies should investigate the optimal acupuncture therapeutic option for obesity. This review aims to consolidate the recent improvements in the mechanism of acupuncture for obesity as well as discuss the future research prospects and potential of acupuncture for obesity.

The drivers and mechanisms underlying succession and the spontaneous formation of plant communities in mining wasteland remain largely unknown. This study investigated the use of nature-based restoration to facilitate the recovery of viable plant communities in mining wasteland. It was found that scientific analyses of spontaneously formed plant communities in abandoned mining areas can provide insights for nature-based restoration. A chronosequence ("space for time") approach was used to establish sites representing three successional periods with six successional stages, and 90 quadrats were constructed to investigate changes in plant species and functional diversity during succession in abandoned PbZn mining areas. A total of 140 soil samples were collected to identify changes in soil properties, including plant nutrient and heavy metal concentrations. Then, this paper used structural equation models to analyze the mechanisms that drive succession. It was found that the functional diversity of plant communities fluctuated substantially during succession. Species had similar functional traits in early and mid-succession, but traits tended to diverge during late succession. Soil bulk density and soil organic matter gradually increased during succession. Total nitrogen (N), pH, and soil Zn concentrations first increased and then decreased during succession. Concentrations of Mn and Cd gradually decreased during succession. During early succession, soil organic matter was the key factor driving plant colonization and succession. During mid-succession, soil Zn functioned as an environmental filter factor limiting the rates of succession in mining wasteland communities. During late succession, soil bulk density and competition for nutrient resources contributed to more balanced differentiation among plant species. This thesis proposed that a nature-based strategy for the stabilization of abandoned mining lands could facilitate effective plant community restoration that promotes ecosystem services and functioning., 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 © 2023 Elsevier B.V. All rights reserved.)

Graphene is a material formed with carbon atoms connected by sp 2 hybridization. It is extremely strong and very ductile, and is superhydrophobic and superlipophilic. It has important application prospects in materials science, micro and nano processing, energy, aerospace and biomedicine. Graphene also has some applications in the petroleum industry. As nanoscale materials, graphene-based materials can plug nano-pores and prevent water intrusion into clay minerals during the drilling process, they are suitable for sliding between layers and can be used as lubricants due to the two-dimensional structure. The adsorption properties of graphene-based materials allow them to improve the treatment rate when treating oily wastewater. This paper compiles recent advances in the application of graphene and its derivatives in oilfield extraction, including improving drilling fluid performance, enhanced oil recovery and oily wastewater treatment. We compare the performance advantages of graphene-based materials over other additives, and summarize the mechanism of action of graphene-based materials. The shortcomings of current research are identified and future research and improvement directions are envisaged., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: With the rapidly increasing morbidity and mortality, lung cancer has been considered one of the serious malignant tumors, affecting millions of patients globally. Currently, the pathogenesis of lung cancer remains unclear, hindering the development of effective treatment. This study aims to investigate the mechanisms of lung cancer and develop an effective therapeutic approach for intervention in preventing lung cancer progress., Methods: The USP5 levels are detected in lung cancerous and paracancerous tissue by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting methods to explore their roles in lung cancer progression. MTT, colony assay, and transwell chamber approaches are employed to measure cell viability, proliferation, and migration, respectively. Further, flow cytometry experiments are performed to examine the effect of USP5 on lung cancer. Finally, the investigations in vivo are executed using the mice subcutaneous tumor model to identify the effect of USP5 in promoting lung cancer development., Results: Notably, USP5 is highly expressed in lung cancer, USP5 overexpression promoted the proliferation and migration in the lung cancer cell lines, H1299 and A549, while knockdown of USP5 inhibited these via regulating the PARP1-mediated mTOR signaling pathway. Furthermore, the subcutaneous tumors model was established in C57BL/6 mice, and the volume of subcutaneous tumors was significantly reduced after silencing USP5, while increased after USP5 overexpression and decreased significantly with shRARP1 treatment at the same time., Conclusions: Together, USP5 could promote the progression of lung cancer cells by mTOR signaling pathway and interacting with PARP1, indicating that USP5 may become a new target for lung cancer treatment., (© 2023. The Author(s).)

One of the principal conundrums in drilling operations is addressing wellbore instability caused by shale hydration. Therefore, it is crucial to develop high-performance shale inhibitors. In this work, a hyperbranched polyethyleneimine/graphene composite (HPEI-G) was prepared by blending at 60 °C, and it was then used as a shale inhibitor. The inhibition performance of HPEI-G was verified using mud making test, linear swelling test and sedimentation test. The mechanism of HPEI-G was researched and determined using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), particle size distribution test and scanning electron microscopy (SEM). The compatibility of HPEI-G with the basic water-based drilling mud (WBM) was also verified. It can be observed from the results of the linear swelling test that 0.5 wt% HPEI-G reduced the swelling rate of montmorillonite (MMT) to 30.36%, and 1 wt% of KCl only decreased the swelling rate of MMT to 43.83%. In addition, HPEI-G is compatible with WBDF. The inhibition mechanism of HPEI-G included chemical adsorption and physical blockage. HPEI-G was adsorbed on the surface and interlayer of MMT by hydrogen bonding and electrostatic attraction, reducing the diffuse electric double layer to inhibit the hydration of MMT. The sheets of graphene in HPEI-G allowed it to stick on the surface of the shale and plug the nanopores of the shale, preventing the access of water. The inhibition effect of HPEI-G over a temperature range from room temperature to 150 °C was considered to be excellent., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: The lungs are the most common site of metastasis in patients with gestational trophoblastic neoplasia. We investigated surgical management and prognostic factors of patients with refractory gestational trophoblastic neoplasia to assess the value of lung metastasis resection., Patients and Methods: The clinical data of patients with refractory gestational trophoblastic neoplasia and lung metastasis treated at Peking Union Medical College Hospital from January 2005 to December 2020 were retrospectively analyzed. Surgical characteristics and survival outcomes were analyzed., Results: In total, 213 patients with refractory gestational trophoblastic neoplasia and lung metastasis were screened, and 148 patients who underwent unilateral lung resection were analyzed. Patients' median age was 32 years. Lobectomy was performed in 65.5% of patients, while wedge resection was performed in 34.5%. The rate of postoperative complications was 12.2%. The pathological rate was 66.2%. Video-assisted thoracoscopic surgery showed better surgical characteristics than thoracotomy did. Compared with lobectomy, wedge resection had a shorter operative time, shorter duration of chest tube placement, shorter postoperative hospital stay, and fewer postoperative complications. The median follow-up period was 36 months. During follow-up, 90.5% of patients achieved complete remission. The 5-year disease-free and overall survival rates were 80.4% and 92.6%, respectively. More previous chemotherapy courses and failure to achieve normal β-human chorionic gonadotropin levels postoperatively were predictors of poor prognosis., Conclusions: Surgical treatment of lung metastasis is valuable and safe for patients with refractory gestational trophoblastic neoplasia. The minimally invasive video-assisted thoracoscopic approach and wedge resection are recommended., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The magneto-optical resonance response of sodium atoms generated by a high-energy solid-state pulse Nd:YAG laser is studied in different external magnetic fields. We investigate the resonance fluorescence signal of sodium atoms in a simulated sea fog environment based on the laser-induced plasma (LIP) effect. By ionizing an NaCl solution spray to generate sodium atoms in an atmospheric environment, we build a Bell-Bloom magneto-optical resonance system under laboratory conditions. With the help of laser-induced breakdown spectroscopy (LIBS) and extinction spectrum, we obtain sodium atoms with a lifetime of 250 µs. A narrowband tunable continuous wave (CW) 589-nm laser tuned at the D 2 line with a modulation frequency around the Larmor frequency is used as the pump beam to polarize sodium atoms in the test magnetic field. We find that the magneto-optical resonance signals vary with different external magnetic fields and the positions of the resonance signal are consistent with the theoretical values. An intrinsic magnetometric sensitivity of 620.4 pT in a 1-Hz bandwidth is achieved.

Objective: The aim of this study was to evaluate the efficacy of acupuncture, an alternative medicine therapy, as a preventive treatment for menstruation-related migraine (MRM)., Patients and Methods: This was a prospective, multicenter, double-dummy, participant-blinded, randomized controlled clinical trial conducted in China between 1 April 2013, and 30 April 2014. The participants were enrolled from four study centers and randomized to into either the acupuncture group, which received 24 sessions of acupuncture at traditional acupoints plus placebo, or the medication group, which received sham acupuncture plus naproxen. The primary endpoint was change from the baseline average number of migraine days per perimenstrual period over cycles 1-3. The secondary endpoints included changes from the baseline average number of migraine days outside the perimenstrual period, mean number of migraine hours during and outside the perimenstrual period, mean visual analog scale score during and outside the perimenstrual period, ≥50% migraine responder rate, and the proportion of participants who used acute pain medication over cycles 1-3 and 4-6., Results: A total of 172 women with MRM were enrolled; 170 in the intention-to-treat analyses. Our primary outcome reported a significant between-group difference that favored the acupuncture group (95% CI, 0.17-0.50; P < 0.001), with the average reduction of migraine days per perimenstrual period from the baseline was 0.94 (95% CI, 0.82-1.07) in the acupuncture group and 0.61 (95% CI, 0.50-0.71) in the medication group over cycles 1-3., Conclusion: This study showed that compared to medication, acupuncture reduces the number of migraine days experienced by patients with MRM. For patients who received the acupuncture treatment over three cycles, the preventive effect of the therapy was sustained for six cycles., Clinical Trial Registration: [https://www.isrctn.com/ISRCTN57133712], identifier [ISRCTN15663606]., 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 Liu, Zhang, Liu, He, Lyu, Zeng, Zhao, Wang, Qu, Nie, Guo, Zhang, Lu, Wang, Li, Jing and Wang.)

Smart grid is regarded as an evolutionary regime of existing power grids. It integrates artificial intelligence and communication technologies to fundamentally improve the efficiency and reliability of power systems. One serious challenge for the smart grid is its vulnerability to cyber threats. In the event of a cyber attack, grid data may be missing; subsequently, load forecast and power planning that rely on these data cannot be processed by generation centers. To address this issue, this paper proposes a transfer learning-based framework for smart grid scheduling that is less reliant on local data while capable of delivering schedules with low operating cost. Specifically, the proposed framework contains (1) a power forecasting model based on transfer learning which can provide high quality load prediction with limited training data, (2) a novel adaptive time series prediction method with modeling time series from a covariate shift perspective that aims to train the forecasting model with a strong generalization capability, and (3) a day-ahead optimal economic power scheduling model considering a shared energy storage station., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Luo Zhao et al.)

Background: Mediastinal lymphadenectomy is of great importance during esophagectomy for esophageal squamous cell carcinoma. However, recurrent laryngeal nerve (RLN) injury is a severe complication caused by lymphadenectomy along the RLN. Intraoperative nerve monitoring (IONM) can effectively identify the RLN and reduce the incidence of postoperative vocal cord paralysis (VCP). Here, we describe the feasibility and effectiveness of IONM in minimally invasive McKeown esophagectomy., Methods: A total of 150 patients who underwent minimally invasive McKeown esophagectomy from 2016 to 2020 were enrolled in this study. We divided the patients into two groups: a neuromonitoring group (IONM, n = 70) and a control group (control, n = 80). Clinical data, surgical variables, and postoperative complications were retrospectively analyzed and compared., Results: There was no significant difference in baseline data between the two groups. Postoperative VCP occurred in six cases (8.6%) in the IONM group, which was lower than that in the control group (21.3%, P = 0.032). Postoperative pulmonary complications were found in five cases (7.1%) and 14 in the control group (18.8%, P = 0.037). The postoperative hospital stay in the IONM group was significantly shorter than that in the control group (8 vs. 12, median, P < 0.001). The number of RLN lymph nodes harvested in the IONM group was higher than that in the control group (13.74 ± 5.77 vs. 11.03 ± 5.78, P = 0.005). The sensitivity and specificity of IONM monitoring VCP were 83.8% and 100%, respectively. A total of 66.7% of patients with a reduction in signal showed transient VCP, whereas 100% with a loss of signal showed permanent VCP., Conclusion: IONM is feasible in minimally invasive McKeown esophagectomy. It showed advantages for distinguishing RLN and achieving thorough mediastinal lymphadenectomy with less RLN injury. Abnormal IONM signals can provide an accurate prediction of postoperative VCP incidence., (© The Author(s) 2021. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To observe the clinical therapeutic effect on post-stroke dysphagia treated with He's santong (triple promotion) acupuncture therapy through surface electromyography (sEMG)., Methods: A total of 60 patients with post-stroke dysphagia were divided into a routine treatment group and a He's santong acupuncture therapy group, using blocked randomization, 30 cases in each one. In the routine treatment group, the secondary prevention and swallowing rehabilitation training were adopted. In the He's santong acupuncture therapy group, on the base of the treatment as the routine treatment group, weitong (mild promotion, routine acupuncture at bilateral Fengchi ［GB20］, Fengfu ［GV16］, Yifeng ［TE17］, Lianquan ［CV23］, Jia-lianquan ［Extra］, Fenglong ［ST40］ and Tongli ［HT5］, needle retaining for 30 min, 5 treatments a week), wentong (warm promotion, pricking with fire needle at bilateral GB20 and CV23, twice a week) and qiangtong (strong promotion, blood-letting with three-edge needle at Jinjin ［EX-HN12］, Yuye ［EX-HN13］ and Yanhoubi ［Extra］, twice a week) treatment was added. The therapy was given consecutively for 4 weeks in each group. The score of fiberoptic endoscopic examination of swallowing (FEES) and Rosenbek-penetration-aspiration scale (PAS), the score of swallowing grading scale, the score of the modified Mann assessment of swallowing ability (MMASA) and the peak amplitude of sEMG were recorded before and after treatment in patients., Results: Compared with before treatment, the score of FEES and PAS after treatment was decreased ( P <0.05), the scores of swallowing grading scale and MMASA after treatment were increased in both routine treatment group and He's santong acupuncture therapy group ( P <0.05), the peak amplitude of sEMG was increased ( P <0.05) in the He's santong acupuncture therapy group and decreased ( P <0.05) in the routine treatment group. Compared with the routine treatment group, the score of FEES and PAS was decreased ( P <0.05), the scores of swallowing grading scale and peak amplitude of sEMG were increased in the He's santong acupuncture therapy group ( P <0.05)., Conclusion: He's santong acupuncture therapy is obviously effective on post-stroke dysphagia, which may be related to its effects in increasing the contraction of swallowing-related muscles and improving the peak amplitude of hyoid muscle group.

The morphotropic phase boundary (MPB) in lead-free ferroelectrics, starting from a quadruple point (QP), often displays large piezoelectric responses due to the flattened free-energy profiles. In this work, we found that the QP composition rendering most flattened energy profiles could also exhibit abnormally low piezoelectric constants in Hf-doped BaTiO 3 . Such an anomaly in the strength of piezoelectricity can be ascribed to the progressive influence of additional strain heterogeneity induced by the substitution of Hf 4+ for Ti 4+ in BaTiO 3 , which was overlooked previously. An intermediate level of strain heterogeneity can form an invisible ferroelectric crossover consisting of both micro- and nanodomains, resulting in a large elastic softening and high piezoelectricity. With a further increase in the level of strain heterogeneity, the extinction of regular ferroelectric domain structures and pinned polar dynamics resulted in the feeble piezoelectric outputs near the QP composition. Impressively, a giant d 33 of ∼610 pC/N has been accordingly obtained through employing a ferroelectric crossover at off-QP composition in Zr-doped BaTiO 3 , further underpinning the critical role of uncovered ferroelectric crossover on piezoelectricity along MPB. This work offers another degree of freedom in the design of high-performance eco-friendly piezoelectric ceramics.

Purpose: High-normal blood pressure has been suggested to associate with target organ damage and higher left ventricular mass index (LVMI). Our aim is to find the association between people with high-normal blood pressure and their left ventricular mass index., Materials and Methods: Given a total of 181 people with office blood pressure, 24-hour ambulatory blood pressure monitoring, 35 of them are normotensive (BP < 130/85 mm Hg), and 146 people with high-normal blood pressure (BP 130-139/85-89 mm Hg), divide the high-normal blood pressure group into dipper and nondipper according to their ABPM in 24 hours. All of them were performed with echocardiography to calculate LVMI., Results: After adjusting for potential confounding factors, mean systolic blood pressure (BP) of the nondipper group is (119 + 9) mmHg in 24 h, which is significantly higher ( p  < 0.05) than in the dipper group (116 + 11) mmHg, indicating the mean systolic BP is associated with the dipper type ( p  < 0.05); furthermore, the higher nocturnal blood pressure is associated with the nondipper group significantly ( p  < 0.05), and LVMI ((121 ± 11) g/m 2 ) of the nondipper group is also significantly higher than in the dipper group's LVMI ((108 ± 12) g/m 2 ) ( p  < 0.05). The multivariate linear regression analyses revealed significant and independent associations of LVMI with these factors: triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), and coefficient of variation of systolic and diastolic blood pressure in 24 hours., Conclusion: After multiple relevant clinical confounding factors were adjusted, patients with dipper and nondipper high-normal blood pressure had higher LVMI. Abnormalities in circadian blood pressure variability may be associated with the left ventricular hypertrophy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Fan-kai Xiao et al.)

Purpose: To evaluate the feasibility and safety of single-lumen endotracheal intubation combined with right bronchial occlusion (SLET) under artificial pneumothorax in minimally invasive McKeown esophagectomy., Methods: A total of 165 patients who underwent minimally invasive McKeown esophagectomy at Peking Union Medical College Hospital were retrospectively analyzed. In all, 48 patients received double-lumen endotracheal intubation (DLET group), and 117 patients received SLET-B (SLET-B group). Clinical data, intraoperative hemodynamics, surgical variables, and postoperative complications were analyzed and compared., Results: Compared with the DLET group, a shorter intubation time and lower tube dislocation rate were found in the SLET-B group. In the thoracic phase, with the application of artificial pneumothorax, patients in the SLET-B group had lower partial pressure of carbon dioxide (PaCO 2 ) and end-tidal carbon dioxide pressure (PetCO 2 ) values and higher pH than those in the DLET group. Patients in the SLET-B group had shorter thoracic phase times and hospital stays and less intraoperative hemorrhage than those in the DLET group. The numbers of thoracic and bilateral recurrent laryngeal lymph nodes harvested were significantly higher in the SLET-B group., Conclusion: SLET under artificial pneumothorax is feasible and safe in minimally invasive McKeown esophagectomy.

Background: Oesophageal leiomyomas are one of the most common benign oesophageal tumours. This retrospective, observational study summarized and compared the clinical outcomes of thoracoscopic enucleation of oesophageal leiomyoma between single-lumen endotracheal intubation with a bronchial blocker and double-lumen endotracheal intubation., Methods: A total of 36 patients who underwent thoracoscopic enucleation of oesophageal leiomyoma at Peking Union Medical College Hospital between 2014 and 2020 were retrospectively analysed. Fifteen patients received single-lumen endotracheal intubation combined with a right bronchial blocker (SLT-B group), and twenty-one patients received double-lumen endotracheal intubation (DLT group). Clinical data, surgical variables, and postoperative complications were analysed and compared., Results: The average tumour size in all patients was 4.3 ± 2.0 cm. The average tumour size among symptomatic patients was significantly larger than that among asymptomatic patients (5.1 ± 2.0 cm vs 3.7 ± 1.7 cm, P < 0.05). Patients in the SLT-B group had a significantly larger average tumour size than patients in the DLT group (5.4 ± 2.1 cm vs 3.5 ± 1.4 cm, P < 0.05). The SLT-B group had a significantly shorter operation time and shorter total hospital stay than the DLT group. No mucosal injury, conversion to thoracotomy, or other operative complications occurred in the SLT-B group. In the follow-up, no recurrence, dysphagia, or regurgitation was found in any of the patients., Conclusions: Compared with traditional double-lumen intubation, artificial pneumothorax-assisted single-lumen endotracheal intubation combined with a bronchial blocker for thoracoscopic oesophageal leiomyoma enucleation can achieve complete removal of larger tumours, with fewer complications and shorter hospital stays., (© 2021. The Author(s).)

Electroacupuncture (EA) is widely used in clinical practice to relieve migraine pain. 5-HT 7 receptor (5-HT 7 R) has been reported to play an excitatory role in neuronal systems and regulate hyperalgesic pain and neurogenic inflammation. 5-HT 7 R could influence phosphorylation of protein kinase A (PKA)- or extracellular signal-regulated kinase 1 / 2 (ERK 1 / 2 )-mediated signaling pathways, which mediate sensitization of nociceptive neurons via interacting with cyclic adenosine monophosphate (cAMP). In this study, we evaluated the role of 5-HT 7 R in the antihyperalgesic effects of EA and the underlying mechanism through regulation of PKA and ERK 1 / 2 in trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC). Hyperalgesia was induced in rats with dural injection of inflammatory soup (IS) to cause meningeal neurogenic inflammatory pain. Electroacupuncture was applied for 15 min every other day before IS injection. Von Frey filaments, tail-flick, hot-plate, and cold-plated tests were used to evaluate the mechanical and thermal hyperalgesia. Neuronal hyperexcitability in TNC was studied by an electrophysiological technique. The 5-HT 7 R antagonist (SB269970) or 5-HT 7 R agonist (AS19) was administered intrathecally before each IS application at 2-day intervals during the 7-day injection protocol. The changes in 5-HT 7 R and 5-HT 7 R-associated signaling pathway were examined by real-time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) analyses. When compared with IS group, mechanical and thermal pain thresholds of the IS + EA group were significantly increased. Furthermore, EA prevented the enhancement of both spontaneous activity and evoked responses of second-order trigeminovascular neurons in TNC. Remarkable decreases in 5-HT 7 R mRNA expression and protein levels were detected in the IS + EA group. More importantly, 5-HT 7 R agonist AS19 impaired the antihyperalgesic effects of EA on p-PKA and p-ERK 1 / 2 . Injecting 5-HT 7 R antagonist SB-269970 into the intrathecal space of IS rats mimicked the effects of EA antihyperalgesia and inhibited p-PKA and p-ERK 1 / 2 . Our findings indicate that 5-HT 7 R mediates the antihyperalgesic effects of EA on IS-induced migraine pain by regulating PKA and ERK 1 / 2 in TG and TNC., 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. The handling editor declared a past co-authorship with one of the authors, X-HJ., (Copyright © 2021 Liu, Xu, Qu, Zhao, Zhang, Li, Lyu, Wang, Jing and Li.)

Background: Preoperative assessment of patients is meaningful to predict survival in patients with malignant tumors. The prognostic nutritional index (PNI) is one of the most significant factors related to the prognosis in various types of cancer; however, its role in esophageal cancer is still inconclusive. The aim of this study was to identify the prognostic value of PNI in predicting overall survival (OS) in esophageal squamous cell carcinoma (ESCC). Methods : This retrospective study included 4146 ESCC patients, 3812 who underwent esophagectomy for ESCC. Other 334 had no surgery. The Preoperative PNI was measured before any therapies and calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). We classified the patients into three categories according to the PNI, >50, 45-50, and <45. Results: Our study showed that PNI was associated with age ( P <0.0001), gender( P <0.001),tumor length ( P <0.0001), T grade ( P  = 0.001), N staging ( P  = 0.017),and M staging ( P <0.0001). Multivariate analysis showed that PNI was a significant predictor of overall survival Lower PNI vs. Higher PNI group had significantly increased the hazard ratio of ESCC survival (OR = 1.2, 95% CI= 1.05-1.5, p  = 0.01). The Kaplan-Meier curve suggested that high PNI group will significantly increase the OS in both surgical and non-surgical group. Conclusion: PNI is a useful predictive factor for long-term survival in ESCC. The survival rate of ESCC can be discriminated between three groups, PNI, >50, 45-50, and <45. The prognostic value of PNI can be applied for both surgical and non-surgical ESCC patients.

In recent years, a new technique of elastic quantization imaging, the ultrasound-based shear wave elastography (SWE) is arising, which has advantages of real-time, non-invasion, rapid imaging and strong repeatability, and quantifying the elastic properties of soft tissues including thyroid gland, breast, prostate, muscle tendon, ligament, etc.. It has been gradually applied to clinical and experimental researches of acupuncture and has an extensive application prospect. The present paper briefly introduces the application of SWE in accurately locating the acupoint, Deqi from needled acupoints, acupuncture manipulations, and evaluation of efficacy of acupuncture in the treatment of musculofascial diseases.

Immune checkpoint inhibitors (ICIs) have made a breakthrough in cancer therapy. Patients treated with ICIs may develop immune-related adverse events (irAEs) due to the upregulated activity of the immune system. With the increasing use of ICIs, irAEs are more frequently reported and have become important challenges in many patients. Neurological irAEs, which include encephalitis, myelitis, aseptic meningitis, peripheral neuropathy, myasthenia gravis, and myositis, consist of a distinct group of neuroinflammatory disorders. These disorders are rare but frequently severe with high mortality and morbidity. Patients with neurological irAEs are generally responsive to immune-modulating therapy. Therefore, early recognition and treatment are the most important ways to improve their prognosis. Here, we provide a comprehensive review of neurological irAEs associated with ICIs and focus on these affecting central nervous systems., (© 2020 John Wiley & Sons Australia, Ltd.)

Objective: The aim of the present study was to investigate the biological roles and underlying mechanism of the long non-coding RNA maternally expressed gene 3 (MEG3) on osteogenic differentiation of human dental pulp stem cells (hDPSCs)., Methods: The expression levels of MEG3, microRNA-543 (miR-543), osterix, osteopontin, osteocalcin and runt-related transcription factor 2 (RUNX2) were measured by quantitative real-time PCR (qRT-PCR). Alkaline phosphatase (ALP) activity assay and alizarin red S staining (ARS) were used to measure the impacts exerted by MEG3, miR-543 on osteogenic differentiation. Cell proliferation was measured by MTT assay. In addition, the targeted relationships between miR-543, MEG3, and Smad ubiquitin regulatory factor 1 (SMURF1) were assessed through dual luciferase reporter assay., Results: During osteogenic induction, the expression of MEG3 was gradually reduced, whereas the expression of miR-543, osterix, osteopontin, osteocalcin and RUNX2 were gradually increased. Functional analysis implied that MEG3 overexpression or miR-543 inhibition reduced the cell proliferation, ALP activity, ARS levels, and decreased the expression of osteoblast-related proteins. Moreover, MEG3 promoted SMURF1 expression by directly targeting miR-543 as a competing endogenous RNA. Furthermore, overexpression of miR-543 or silencing SMURF1 could reverse the inhibitory effects of MEG3 on the osteogenic differentiation of hDPSCs., Conclusions: In conclusion, our study revealed that overexpression of MEG3 inhibited hDPSCs osteogenic differentiation via miR-543/SMURF1/RUNX2 regulatory network, which may contribute to the functional regulation and clinical applications of hDPSCs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To assess the use of video-assisted thoracoscopic surgery to treat lung metastases from refractory choriocarcinoma., Patients and Methods: We reviewed patients diagnosed with refractory choriocarcinoma who underwent lung resection by video-assisted thoracoscopic surgery combined with chemotherapy between October 2013 and August 2019 at the Peking Union Medical College Hospital. The surgical records, pathologic findings and survival rates were analyzed., Results: The study included 73 patients who underwent 78 thoracoscopic surgeries. Most patients underwent lobectomy (48.7%), and 17 patients (21.8%) underwent resection of more than one lobe. The median operation time and bleeding volume were 95 minutes and 50 mL, respectively. The median duration of chest tube use and hospital stay were 3 days and 4 days, respectively. Postoperative complications were documented in 6 patients (7.7%). The thoracic lymph nodes were harvested in 51 patients (65.4%), but none of these patients had positive nodes. A total of 69.2% of the patients had positive pathologic findings. The mean follow-up time was 30 months. During follow-up, 11 patients experienced disease relapse, and 2 of them died because of brain metastasis. The overall disease-free rate was 83.6%, and the survival rate was 97.0% after excluding those lost to follow-up. Patients with decreased postoperative β-hCG showed a higher disease-free rate during follow up ( P <0.05)., Conclusion: The minimally invasive video-assisted thoracoscopic approach is a valuable and safe treatment for refractory choriocarcinoma patients with lung metastases. Lymphadenectomy is not suggested for these patients. Patients with decreased postoperative β-hCG levels may achieve a much better prognostic result., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Zhao et al.)

Purpose: Oral squamous cell carcinoma (OSCC) is a common malignancy of the oral cavity. As the survival rate of OSCC patients is low, it is crucial to explore new markers and therapeutic targets for early diagnosis of the disease. A high level of actinin alpha 1 (ACTN1) in patients could serve as an independent prognostic factor of acute myeloid leukemia. However, the role of ACTN1 in OSCC remains unclear. In the present study, we aimed to investigate the role of ACTN1 in OSCC., Methods: ACTN1 protein levels in tissues were determined by immunohistochemical (IHC) staining. The correlation of ACTN1 expression with clinicopathological features and prognosis was analyzed. Univariate and multivariate analyses were performed. The effect of ACTN1 knockdown on cell proliferation, migration, invasion, apoptosis, epithelial-mesenchymal transition (EMT), and the cell cycle was evaluated using Western blotting, Cell Counting Kit‑8 (CCK8) assays, flow cytometry analysis, transwell assays, wound-healing assays, and nude mouse models of subcutaneous xenograft and pulmonary metastasis., Results: Based on the total score of ACTN1 IHC staining analysis, ACTN1 expression was found to be low in 10 normal mucosal tissues, 48 normal mucosal tissues adjacent to OSCC, and 19 OSCC tissues, but high in 29 OSCC tissues. ACTN1 protein levels were significantly associated with the clinical stage and node metastasis, and a high ACTN1 protein level indicated poor prognosis. Moreover, ACTN1 expression was an independent predictor of poor prognosis of OSCC. Using in vitro assays, we found that ACTN1 knockdown could induce cell cycle arrest, promote apoptosis, and inhibit EMT and cell proliferation, migration, and invasion in the OSCC cell lines, SCC-15 and HSC-3. Moreover, ACTN1 knockdown inhibited subcutaneous tumor growth and pulmonary metastasis in vivo., Conclusion: ACTN1 levels were significantly associated with the clinical stage and node metastasis, and a high ACTN1 protein level indicated poor prognosis. Moreover, ACTN1 knockdown could suppress cell proliferation and metastasis of OSCC. Our results suggested that ACTN1 may serve as a diagnostic and prognostic marker of OSCC., Competing Interests: We wish to confirm that there are no known conflicts of interest associated with this publication and no significant financial support that could have influenced the work and its outcome was extended., (© 2020 Xie et al.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.03.98). The authors have no conflicts of interest to declare.

Knee osteoarthritis is the most common type of arthritis, which is manifested by the deformation and degeneration of articular cartilage and the discomfort of patients with joint pain, which affects the quality of life of patients and aggravates the medical burden of society. The pathogenesis of knee osteoarthritis is very complex. This paper reviews the inflammatory factors and signal pathways involved in knee osteoarthritis. It is found that most of the inflammatory factors involved are interleukin, such as IL-1 β, IL-6, IL-15, IL-17, IL-18, and tumor necrosis factors, such as TNF-α. These inflammatory factors aggravate knee osteoarthritisby activating corresponding pathways and promoting the release of inflammatory mediators. The inflammatory signaling pathways involved in knee osteoarthritis are complex. Notch pathway, Wnt pathway, SDF-1 / CXCR4 pathway, TLRs pathway, MAPKs pathway, hippo Yap pathway, OPG-RANK-RANKL pathway and TGF-β pathway are all involved in the regulation of knee osteoarthritis, and the pathways related to inflammatory mechanism are mainly MAPKs pathway and TLRs pathway. Different signaling pathways can cause the destruction of articular cartilage, promote the apoptosis of chondrocytes, and finally lead to the further imbalance of homeostasis in the knee joint. At the same time, the activation of signal pathway can promote the release of inflammatory factors, so under the cascade reaction of inflammatory factors and signal pathway, knee osteoarthritis is aggravating.

Background: Isolated diaphragmatic metastasis is rarely associated with periosteal osteosarcoma., Case Presentation: A 24-year-old female patient was found to have periosteal osteosarcoma of the right humerus 11 years ago. Computed tomography showed a mass in her left chest in 2018, and thoracotomy was performed to remove the tumour. The tumour showed the same characteristics as the original periosteal osteosarcoma. Genetic analysis of the tumour sample showed a TP53 point mutation and CCNE1 gene copy number variants., Conclusions: We believe this is the first case report of haematogenous metastasis to the diaphragm of periosteal osteosarcoma, and an investigation of the genetic factors may help to unravel the underlying cause of periosteal osteosarcoma.

Long noncoding RNAs (lncRNAs) play critical roles in tumour progression and metastasis. Emerging evidence indicates that the lncRNA X inactive-specific transcript (XIST) is dysregulated in several tumor types, including non-small cell lung cancer (NSCLC). However, in NSCLC and other cancers the oncogenic mechanism of XIST remains incompletely understood. Here, we confirmed that XIST is upregulated in human NSCLC specimens, and is especially overexpressed in tumors previously treated with cisplatin (cis-diamminedichloroplatinum(II); DDP). In vitro, XIST knockdown inhibited NSCLC cell growth and promoted DDP chemosensitivity by stimulating apoptosis and pyroptosis. Moreover, XIST's oncogenic effects and ability to promote DDP chemoresistance were largely related to its binding to the TGF-β effector SMAD2, which inhibited its translocation to the nucleus and prevented the transcription of p53 and NLRP3, crucial regulators of apoptosis and pyroptosis, respectively. Using DDP-resistant NSCLC cells, mouse xenograft studies verified the oncogenic function of XIST and its ability to inhibit programmed cell death, thereby mediating DDP chemoresistance. These findings suggest that XIST expression may serve as a novel biomarker to predict DDP treatment efficacy, and may help in the design of new therapies to circumvent DDP chemoresistance in NSCLC and other tumor types.

Objective : To determine the underlying mechanism of miR-34b/c in regulating doxorubicin (Dox)-induced myocardial cell injury. Methods : The viability of mouse myocardial cells HL-1 was detected by MTT assay. The apoptosis of HL-1 cells was detected by TUNEL assay. mRNA expressions of ITCH, TNF-α and IL-6 were measured by qRT-PCR. Protein levels of ITCH, NF-κB, TNF-α and IL-6 were measured by western blot. Dual luciferase assay was performed to detect the regulation of miR-34b/c on ITCH. Mouse model of cardiomyopathy was induced by intraperitoneal injection of Dox. Results : Dox reduced HL-1 cell viability and activated NF-κB pathway in HL-1 cells. miR-34b/c expressions were gradually up-regulated and ITCH expression was gradually down-regulated in Dox-treated HL-1 cells. miR-34b/c expression had negative correlation with the mRNA expression of ITCH. Besides, ITCH was a target of miR-34b/c. miR-34b/c mimic reduced cell viability, suppressed ITCH expression, increased TNF-α and IL-6 level, and promoted NF-κB expression in nucleus and cytoplasm of HL-1 cells. Whereas silencing miR-34 protected HL-1 cells through regulating ITCH. Finally, we demonstrated miR-34 antagomir-protected myocardial cells in mouse model of cardiomyopathy. Conclusion : miR-34b/c decreased HL-1 cell viability and promoted the secretion of proinflammatory cytokines in Dox-induced myocardial cells through ITCH/NF-κB pathway.

Background: Reserpine is currently used by millions of Chinese hypertensive patients, in spite of the continued concern of its depressogenic effect, even when used in low dose. This study aimed to investigate the association between low-dose reserpine use and depression in older Chinese hypertensive patient., Methods: In this cross-sectional, case-control study, we recruited patient aged 60 years or over who had regularly taken one or two tables of "compound reserpine and triamterene tablets (CRTTs)" for more than one year (reserpine user) from 26 community health centers located in 10 provinces in China. For each patient who took CRTTs, we selected an age (within five years) and sex matched hypertensive patient who had never taken any drugs containing reserpine (non-reserpine user) as control. Depressive symptoms were evaluated using a Chinese depression scale adapted from the Zung Self-Rating Depression Scale. Demographic, clinical data and laboratory examination results within six months were collected., Results: From August 2018 to December 2018, 787 reserpine user and 787 non-reserpine user were recruited. The mean age of all study subjects was 70.3 years, with about equal numbers of males and females. The mean depression score was 40.4 in reserpine users and 40.6 in non-reserpine users ( P = 0.7). The majority of study subject had a depression score < 53 (87.6% in reserpine users and 88.2% in non-reserpine users, respectively). There were no significant differences in the prevalence of mild, moderate or severe depression in reserpine users and non-reserpine users., Conclusions: There is no association between low-dose reserpine use and depression in older hypertensive patient. The role of reserpine in the treatment and control of hypertension should be reconsidered; and further studies, especially randomized, controlled clinical trials to compare efficacy and safety of reserpine and other widely recommended anti-hypertensive agents are needed.

Background: To investigate the diagnosis and surgical therapy of delayed diaphragmatic rupture., Methods: Forty patients with traumatic diaphragmatic rupture with delayed presentation and diagnosis were collected in Peking Union Medical College Hospital from 2000 to 2018, and a retrospective analysis was performed., Results: In all forty patients, 36 (90%) patients had a traumatic past history, and 32 (80%) patients had clinical manifestations when diagnosed. Left-sided diaphragmatic rupture was found in 32 (80%) patients and right in 8 (20%) patients. One patient received emergency surgery, and 39 received selective surgery. Thirty-eight patients received thoracotomy, and 2 patients received combined thoracic-abdominal surgery. Thirty-six patients received direct diaphragm suture, and 4 patients received mesh repair. One patient had an intestinal obstruction and received enterolysis 19 days after surgery. During follow-up, 1 patient experienced recurrence 2 years later., Conclusions: Careful recording of past history and physical examination are the best approaches in diagnosing delayed presentation of traumatic diaphragmatic rupture. CT scan with reconstruction of the diaphragm is helpful in both diagnosis and differential diagnosis. Surgical therapy after diagnosis is the best treatment., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

We evaluated an immunochromatographic strip for the detection of avian avulavirus 1 (Newcastle disease virus, NDV) based on a high-affinity monoclonal antibody (mAb) that specifically recognizes the hemagglutinin-neuraminidase (HN) protein. The anti-HN mAb was labeled with colloidal gold as the detector. A chicken anti-NDV polyclonal antibody and staphylococcal protein A (SPA) were blotted on the nitrocellulose membrane for the test and control lines, respectively. The strip specifically recognized the NDV antigen with no cross-reactivity to other viruses that were examined. Furthermore, it specifically recognized a variety of NDV isolates, including virulent and attenuated strains. These results were confirmed using hemagglutination (HA) and RT-PCR assays. The NDV detection strip detected 10 4.9 EID 50 viruses/0.1 mL in the NDV-infected sample, which is comparable to the classical HA test (10 5.2 EID 50 /0.1 mL). Following experimental infection, NDV was detected using the detection strip in infected tissues as early as 36 h after experimental infection and prior to development of clinical signs and appearance of gross anatomic lesions. The diagnostic sensitivity and specificity of the NDV detection strip for NDV infection were 83.3% and 100%, respectively, as confirmed by RT-PCR.

Background: Overexpression of the murine double minute 2 (MDM2) has been explored in many tumors with high proliferation and anti-apoptosis ability. However, the role of MDM2 and its functional single nucleotide polymorphism (SNP) rs2279744 (also known as SNP309) in esophageal squamous cell carcinoma (ESCC) remains unclear., Methods: We performed a genotype study of blood samples in 360 ESCC patients and 360 healthy control individuals to determine the risk of various rs2279744 in ESCC. To further evaluate the role of rs2279744 in regulating MDM2 expression, we performed an allele-specific reporter assay and investigated whether the SNP-containing sequences functioned as an active enhancer. To examine the functional role of MDM2 on esophageal cancer cell lines, we carried out an MTS assay and flow cytometry analysis., Results: From the genotyping study, we found that GG genotype of SNP309 significantly increased the risk of ESCC in an additive model [odds ratio (OR) = 2.55, 95% confidence interval (CI) = 1.66-3.89, p = 1.50 × 10 -5 ) and in a recessive model (OR = 2.44, 95% CI = 1.69-3.51, p = 1.60 × 10 -8 ). Furthermore, the G allele was significantly associated with a higher risk of ESCC (OR = 1.56, 95% CI = 1.26-1.92, p = 2.81 × 10 -5 ). In multivariate logistic regression analysis, the GG genotype had increased the occurrence of ESCC by 2.39-fold (95% CI = 1.48-3.8). Compared to the T allele, the variant G allele had significantly higher luciferase activity on the promoter of MDM2 in both cell lines. By transfecting the gene to ESCC lines, we showed that overexpression of MDM2 significantly promote cell proliferation and anti-apoptosis., Conclusions: The MDM2 promoter SNP309 is a risk factor for esophageal cancer. MDM2 promotes the proliferation and anti-apoptosis of ESCC., (© 2019 John Wiley & Sons, Ltd.)

Background: Acupuncture has been recommended as an alternative therapy for migraine. Emerging evidence suggests that the 5-HT 7 receptor (5-HT 7 R) plays a significant facilitatory role in descending modulation in migraine pathophysiology, and that activation of 5-HT 7 R in the descending pathway is involved in migraine central sensitisation., Objective: To investigate the ability of electroacupuncture (EA) to ameliorate central sensitisation via modulation of 5-HT 7 R in the descending pain pathways using a rat model of migraine induced by repetitive dural electrical stimulation (DES)., Design: 64 male Sprague-Dawley rats were randomly divided into four groups: Normal group; DES group (receiving dural electrical stimulation only); DES+GB20 group (DES model group treated with EA at GB20); and DES+Sham group (DES model group treated with EA at a non-traditional (sham) acupuncture point). The presence of cutaneous allodynia was determined by measuring facial and hind-paw withdrawal latencies to electronic von-Frey. The expression of 5-HT 7 R in the descending pathways (periaqueductal grey, raphe magnus nucleus, and trigeminal nucleus caudalis) was assessed using immunofluorescence and Western blotting., Results: Facial and hind-paw withdrawal thresholds were significantly increased in the DES+GB20 group compared with the untreated DES group. The expression of 5-HT 7 R was significantly decreased in the DES+GB20 group compared with the DES group (one-way analysis of variance (ANOVA), P<0.05). No significant differences in behaviour or expression were found between the rats in the DES+Sham group and the untreated DES group (one-way ANOVA, P>0.05)., Conclusion: EA at GB20 may ameliorate central sensitisation in migraine by inhibiting the activation of 5-HT 7 receptors in the descending pain pathway in a rat model of migraine.

Objective: To screen out an effective substitute in the prescription of Shengjing Capsules (SJC), observe the effects of the redeveloped New SJC (NSJC) with cordyceps cephalosporium mycelia (CCM) substituted for the ingredient cordyceps sinensis in the treatment of spermatogenesis impairment (SI), and provide some experimental evidence for its application in the treatment of male infertility and sexual dysfunction., Methods: We equally randomized 192 male mice into 16 groups: normal saline control, SI model, high-, medium- and low-dose fermented cordycepin powder (FCP, 1.60, 0.80 and 0.40 g/kg), high-, medium- and low-dose CCM (1.60, 0.80 and 0.40 g/kg), high-, medium- and low-dose cordyceps mortierella mycelia (CMM, 1.60, 0.80 and 0.40 g/kg), high-, medium- and low-dose fermented cordyceps sinensis (FCS, 1.60, 0.80 and 0.40 g/kg), SJC (0.80 g/kg), and vitamin E (VE, 0.25 g/kg), with the SI model established in all the mice and the normal controls injected intraperitoneally with cyclophosphamide at 60 mg/kg qd for 5 consecutive days. After intragastrical medication with respective drugs, we obtained the body mass index (BMI), sexual organ coefficient, sperm count, sperm motility, and percentage of morphologically abnormal sperm (MAS) of the mice. We also randomly divided 70 male rats into 7 groups of equal number: normal control, SI model, high-, medium- and low-dose NSJC (1.12, 0.56 and 0.28 g/kg), SJC (0.56 g/kg), and VE (0.18 g/kg), the SI model constructed in the latter 6 groups of rats by gavage of adenine at 200 mg/kg qd for 5 consecutive days. After intragastrical medication with respective drugs, we examined the BMI, coefficients of sexual and renal organs, levels of reproductive hormones, testicular morphology, and fertility of the animals., Results: After medication, the mice in different groups showed different degrees of improvement in the cyclophosphamide-induced slow growth, significant increases in the testicular and epididymal coefficients, sperm count, motility and viability (P < 0.05 or P < 0.01), and a remarkable reduction in the percentage of MAS (P < 0.05 or P < 0.01). The effect was particularly significant in the CCM group and therefore CCM was chosen as the best substitute ingredient in the redeveloped NSJC. Compared with the rats in other groups, those treated with NSJC exhibited significant increases in the BMI, coefficients of sexual and renal organs and levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and estradiol (E2) (P < 0.05 or P < 0.01), improvement of the pathologically damaged testicular morphology, elevation of the pregnancy rate and litter size, and recovery from adenine-induced SI., Conclusions: The redeveloped New Shengjing Capsules with cordyceps cephalosporium mycelia substituted for the ingredient cordyceps sinensis can improve fertility and reverse spermatogenesis impairment in male rats. The new prescription may also be applied to the clinical treatment of male infertility and sexual dysfunction.

Introduction: Approximately 1.4%-2.2% of the global population suffers from chronic migraine. Acupuncture may serve as an alternative management for chronic migraine, where pharmacological prophylaxis is not suitable. However, the effects of acupuncture as migraine prophylaxis have not been confirmed. This study is designed as a single-blinded, double-dummy randomised controlled trial to evaluate the efficacy and safety of acupuncture compared with topiramate in patients with chronic migraine., Methods and Analysis: A total of 60 participants will be randomly assigned to two different groups. Participants will receive verum acupuncture and placebo medicine in the treatment group, while participants in the control group will be treated with sham acupuncture and real medicine (topiramate). All participants will receive a 12-week treatment and then be followed up for another 12 weeks. The primary outcome is the reduction of monthly headache days, and the secondary outcomes include the reduction of the number of days with acute headache medications, and changes of Migraine Disability Assessment, Migraine-Specific Quality of Life Questionnaire, Headache Impact Test, State-Trait Anxiety Inventory-trait, and Beck Depression Inventory-II scores from baseline to endpoints., Ethics and Dissemination: Ethical approval of this study was granted by the Research Ethical Committee of Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University (2017BL-045-01). Written informed consent will be obtained from all participants. Outcomes of the trial will be disseminated through peer-reviewed publications., Trial Registration Number: ISRCTN13563102; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aminergic neurotransmitters play important roles in the regulation of food intake. However, their effects on feeding in fish have been less explored and still unclear. In the present study, the effects of serotonin (5-HT) and dopamine (DA) on food intake were evaluated through intraventricular (ICV) administration in Chinese perch (Siniperca chuatsi) and the mRNA expression levels of neuropeptide Y (NPY), agouti gene-related protein (AgRP), and pro-opiomelanocortin (POMC) were detected. At 1 h post-injection, 5-HT significantly decreased food intake in a dose-dependent manner. The mRNA expression of NPY and AgRP were significantly decreased (p < 0.05), whereas the mRNA expression of POMC was significantly increased (p < 0.05), suggesting the involvement of NPY, AgRP, and POMC in inhibitory action of 5-HT on food intake in Chinese perch. DA significantly decreased (p < 0.05) food intake and AgRP mRNA expression at 1 h post-injection, indicating the inhibitory effect of DA on food intake might be mediated through AgRP. This might shed new light on the regulation of food intake in Chinese perch.

A 55-year-old female patient was found to have a pulmonary nodule combined with multiple lung cysts detected on CT scan. Video-assisted thoracoscopic surgery (VATS) lobectomy was performed and the nodule showed adenocarcinoma while the whole left upper lobe showed a heavy deposition of amyloid. Syphilis infection was detected and was suspected contributing to secondary pulmonary amyloidosis. Although very rare, pulmonary amyloidosis should be added to the differential diagnosis for solid pulmonary nodules. Furthermore, widespread lung cysts located apart from pulmonary nodules is especially rare in pulmonary amyloidosis secondary to syphilis infection., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Despite advances in controlled drug delivery, drug-delivery systems with controlled activatable drug release and high spatial and temporal resolution are still required. PEGylation has been extensively used to increase the circulation time of controlled drug-delivery systems, but polyethylene glycol (PEG) is unsuitable for uptake by tumor cells because it causes steric hindrance. In this study, a near-infrared (NIR)-light-regulated drug-delivery system with enhanced cellular uptake was developed using a hybrid nanoplatform (GO@Au). GO@Au modified with tumoral-acid-cleavable PEG circumvents the hindrance effect of PEG grafted onto the drug-delivery system without sacrificing the property of a long circulation time. With the application of NIR light, both GO and Au in GO@Au strongly absorb the NIR energy, leading to intense resonance, and causing the release of a significant proportion of the loaded drug. GO@Au retains most of the loaded drug without NIR. We show the feasibility of using this nanocarrier as a targeted, noninvasive remote-controlled drug-delivery system with high spatial and temporal resolution. Integrating chemotherapy and photothermal therapy functions into one system, we investigated the therapeutic effects of DOX-loaded GO@Au-PEG, with highly efficient drug loading. Our in vitro and in vivo results reveal a synergistic effect, enhancing the therapeutic effects of the drugs and reducing their adverse effects. These results highlight the great potential utility of GO@Au-PEG/DOX in the treatment of cancer.

Most migraine patients suffer from cutaneous allodynia; however, the underlying mechanisms are unclear. Calcitonin gene-related peptide (CGRP) plays an important role in the pathophysiology of migraine, and it is therefore, a potential therapeutic target for treating the pain. In the present study, a rat model of conscious migraine, induced by repeated electrical stimulation of the superior sagittal sinus, was established and treated with electroacupuncture at Fengchi (GB20) (depth of 2-3 mm, frequency of 2/15 Hz, intensity of 0.5-1.0 mA, 15 minutes/day, for 7 consecutive days). Electroacupuncture at GB20 significantly alleviated the decrease in hind paw and facial withdrawal thresholds and significantly lessened the increase in the levels of CGRP in the trigeminal ganglion, trigeminal nucleus caudalis and ventroposterior medial thalamic nucleus in rats with migraine. No CGRP-positive cells were detected in the trigeminal nucleus caudalis or ventroposterior medial thalamic nucleus by immunofluorescence. Our findings suggest that electroacupuncture treatment ameliorates migraine pain and associated cutaneous allodynia by modulating the trigeminovascular system ascending pathway, at least in part by inhibiting CGRP expression in the trigeminal ganglion., Competing Interests: Conflicts of interest: None declared.

Key Message: MKK9-MPK3/MPK6 cascade positively regulates IGSs' biosynthetic genes. Glucosinolates (GSs), secondary metabolites well known for their roles in plant defense, have been implicated to play an important role in plant abiotic stress response; however, the exact role in these processes and the underlying regulatory mechanisms remain elusive. Mitogen-activated protein kinase (MAPK) cascades are extensively involved in plant abiotic stress response. In this study, we examined the levels of four indolic glucosinolates (IGSs) in the shoots of Arabidopsis seedlings under mild osmotic stress conditions and found that 4-methoxy indolyl-3-methyl glucosinolate (4MI3G) accumulated and that MPK3 and MPK6 were activated. Loss of MPK3 or MPK6 function led to a reduction in mild osmotic stress-induced 4MI3G. Further analyses revealed that MKK9 acts upstream of MPK3 and MPK6 to promote 4MI3G accumulation. The level of 4MI3G induced by mild osmotic stress was reduced in the mkk9 mutant. Conversely, 4MI3G increased in MKK9 DD , a constitutively activate mutant of MKK9. Gene expression analyses indicated that the activated MKK9-MPK3/MPK6 cascade upregulates the IGS biosynthetic genes. Moreover, the lack of MYB51, the transcription factor controlling biosynthetic genes responsible for synthesizing the IGS core structure, or CYP81F2, the enzyme catalyzing core structure modification to 4MI3G, significantly reduced mild osmotic stress- and MKK9 DD -induced 4MI3G. Thus, our study demonstrates that mild osmotic stress promotes 4MI3G biosynthesis and the accumulation in Arabidopsis through activation of the MKK9-MPK3/MPK6 cascade and provides an MAPK-mediated signaling pathway for the IGS response to abiotic stress in plants.

Background: Malignant thymomas are rarely associated with bone metastasis and T-cell lymphocytosis., Case Presentation: A 47-year-old female patient was admitted to our hospital for ptosis. A diagnosis of malignant thymoma was made based on the thymectomy and pathological result. Peripheral T-cell lymphocytosis and bone metastasis were found later. T-cell lymphocytosis was relived after surgical and radiation therapy to the metastasis., Conclusion: Peripheral T-cell lymphocytosis is a rare paraneoplastic phenomenon associated with thymomas. This report is the first to describe an invasive thymoma with late bone metastasis accompanied with T-cell lymphocytosis. We should be aware of peripheral T-cell lymphocytosis in thymomas and it may contribute to a better understanding of the complex physiology and pathogenesis of thymoma.

Background . While electroacupuncture (EA) pretreatment in migraine has been found to attenuate pain and frequencies of attacks, the underlying mechanism of its antinociceptive effect remains poorly understood. Emerging evidence suggests that the serotonin system may be involved in migraine pathophysiology. Method . Forty male Sprague-Dawley rats were randomly assigned to Control, Model, EA, and sham acupuncture (SA) groups. HomeCageScan was used to measure the effects on spontaneous nociceptive behaviors. Radioimmunoassay and high-performance liquid chromatography were used to evaluate the expression of 5-hydroxytryptamine (HT) in the plasma and three-key structure of the descending pain modulatory system. Results . Our study showed that EA pretreatment could produce a significant reduction in resting, freezing, and grooming behavior and a significant increase in exploration behavior. Furthermore, we found that the level of 5-HT in plasma was significantly increased, and it was significantly decreased in the descending pain modulatory system in Model group. The aforementioned results were significantly reversed in EA group; that is, the level of 5-HT was increased in the rostroventromedial medulla (RVM) and trigeminal nucleus caudalis (TNC) region and decreased in the plasma. Conclusion . EA pretreatment exerts antinociceptive effects in a rat model of recurrent migraine, possibly via modulation of the serotonin system.

Recently, the rs1042713 G > A and rs1042714 C > G polymorphisms in the beta-2 adrenergic receptor (ADRB2) gene were shown to be related to atherosclerosis diseases. Therefore, we performed a systemic meta-analysis to determine whether the two functional polymorphisms are related to the risk of myocardial infarction (MI) and coronary artery disease (CAD). We identified published studies that are relevant to our topic of interest. Seven case-control studies, with a total of 6,843 subjects, were incorporated into the current meta-analysis. Our analysis showed a higher frequency of rs1042713 G > A variant in patients with MI or CAD compared to healthy controls. A similar result was also obtained with the rs1042714 C > G variant under both the allele and dominant models. Ethnicity-stratified subgroup analysis suggested that the rs1042714 C > G variant correlated with an increased risk of the two diseases in both Asians and Caucasians, while rs1042713 G > A only contributes to the risk of two diseases in Asians. In the disease type-stratified subgroups, the frequencies of both the rs1042713 G > A and rs1042714 C > G variants were higher in the cases than in the controls in both the MI and CAD subgroups. Collectively, our data contribute towards understanding the correlation between the rs1042713 G > A and rs1042714 C > G polymorphisms in ADRB2 and the susceptibility to MI and CAD.

Background: Bilirubin is a potent antioxidant and previous studies have reported the relationship between low serum bilirubin concentration and atherosclerosis., Objective: To evaluate the prognostic value of serum total bilirubin (STB) in patients with angina pectoris undergoing percutaneous coronary intervention (PCI)., Methods: In total of 1419 patients (931 men, mean age 60.9±10.5 years) with angina pectoris who had undergone successfully percutaneous coronary intervention (PCI) were included in this study. Patients were divided into 2 groups according to the median baseline STB (0.49 mg/dL in this cohort), which was measured before the PCI. Patients with a STB ≥0.49 mg/dL were classified into the high STB group and those with a STB <0.49 mg/dL were classified into the low STB group., Results: The incidence of in-hospital mortality and myocardial infraction was similar in the two groups. After a mean follow-up of 29.0±7.6 months, the incidence of death/myocardial infarction/stroke was significantly higher in low STB group compared with high STB group. Multivariate Cox regression analysis showed that low STB was an independent predictor of death/myocardial infarction/stroke (hazard ratio (HR) = 1.59, 95% confidence interval (CI) = 1.04-2.41, P = 0.031). The cumulative survival rate free from death/myocardial infarction/stroke was lower in low STB group than in high STB group (P = 0.002)., Conclusion: Low STB levels before PCI is an independent predictor of long-term adverse clinical outcomes in patients with angina pectoris.

Objective: This study aimed to validate the fully automated Pangao PG-800B68 upper-arm device according to the European Society of Hypertension International Protocol (ESH-IP) revision 2010., Materials and Methods: Sequential measurements of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were obtained in 33 participants using the standard mercury sphygmomanometer and the test device. The ESH-IP revision 2010 was followed precisely and 99 pairings of test device and reference blood pressure measurements were obtained for analysis., Results: The number of blood pressure differences within 5, 10, and 15 mmHg was 76, 95, and 98, respectively, for SBP and 79, 96, and 99, respectively, for DBP. The device achieved all the required criteria of the ESH-IP revision 2010 with a device-observer difference of -0.03±4.64 mmHg for SBP and -0.64±4.50 mmHg for DBP., Conclusion: According to the validation results on the basis of the ESH-IP revision 2010, the Pangao PG-800B68 can be recommended for clinical use and self-measurement in adults., (Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.)