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Ashwagandha (W. somnifera L) is a popular ethnomedicinal herb endowed with potential pharmacotherapeutic properties. In this study the ethanol extract (EE) and water extract (WE) of ashwagandha roots were qualitatively analysed using high performance liquid chromatography (HPLC), the results showed EE containing withanoside IV (a), physagulin D (b), 27-hydroxywithanone (c), withanoside V (d), withaferin A (e), withastramonolide (f), withanolide A (g), withanone (h), and withanolide B (i) as major bioactive compounds. Antioxidant potential was studied using four in vitro free radical scavenging assays and EE displayed higher antioxidant effect compared to WE for all assays. The EE also showed enzyme inhibitory effect against lipoxygenase (5-LOX) >cyclooxygenases-1 (COX-1) compared to cyclooxygenases-2 (COX-2) and to that of WE. Furthermore, EE demonstrated a potential cytotoxic effect on proliferation of A549 cells in vitro, showing IC50 values, 394.8 (24 h), 171.9 (48 h) and 126.1 (72 h) μg/mL, respectively. EE extract also exhibited induction of apoptosis in dose dependent manner confirmed with the production of ROS in A549 cells through flow cytometric analysis. The obtained results demonstrated that ashwagandha EE with high concentration of bioactive compounds could act as potential drug candidates against pro-inflammatory enzymes involved in development of inflammation and progression of lung cancer. Further, extensive research is needed to investigate the ashwagandha bioactive compounds responsible for treating inflammation, oxidative stress and lung cancer.

Background Theta burst stimulation (TBS), a patterned repetitive transcranial magnetic stimulation (rTMS) protocol with shorter simulation duration and lower stimulus intensity, could be a better protocol for individuals with autism spectrum disorder (ASD). Our study aimed to explore the impacts of intermittent TBS (iTBS) over the bilateral posterior superior temporal sulcus (pSTS) on intellectually able adults with ASD. Material and methods In this randomized, single-blinded, sham-controlled crossover trial, 13 adults with ASD completed iTBS for 5 consecutive days over the bilateral pSTS and inion (as a sham control) in a 16-weeks interval and in a randomly assigned order. The neuropsychological function was measured with the Wisconsin Card Sorting Test (WCST) for cognitive flexibility while the clinical outcomes were measured with both self-rate and parents-rate Autism Spectrum Quotient (AQ) before and after 5-day iTBS interventions. Results The results revealed significantly immediate effects of multi-session iTBS over the bilateral pSTS on parent-rate autistic symptoms in adults with ASD. The post-hoc analysis revealed the impacts of multi-session iTBS on cognitive flexibility were affected by baseline social-communicative impairment and baseline cognitive performance. Besides, the impacts of multi-session iTBS on clinical symptoms was affected by the concurrent psychotropic medication use and baseline autistic symptoms. Conclusions Given the caveat of the small sample size and discrepancy of multiple informants, this pilot study suggests the therapeutic potential of 5-day multi-session iTBS over the pSTS in adults with ASD. Individual factors modulating the response to rTMS should be explicitly considered in the future trial.

Background Atherosclerosis is a chronic inflammatory disease in which macrophage polarization plays an important role in contribution to atherosclerotic plaque formation and stability. Here we tested the effect of miR-92 regulation on the development of atherosclerosis beyond tumorigenesis and explored the potential mechanism. Methods and results In the present study, bone marrow derived macrophages (BMDMs), mouse peritoneal macrophages (MPMs), and human macrophages were used to test the expression of miR-92. Here we noticed miR-92 levels were enhanced in classic M1 macrophage but decreased in alternative M2 macrophage, respectively. In vitro, we demonstrated that macrophages transfected with miR-92 inhibitor attenuated proinflammatory cytokine secretion represented by polarized M1 markers but promoted anti-inflammatory state that was indicative of an M2 phenotype. Mechanistically, miR-92 was found to directly interact with KLF4 and we further identified a requirement role of KLF4 in mediating the effect of miR-92 silencing macrophage polarization. Concomitantly, miR-92 inhibition treated ApoE-/- mice promoted macrophage polarization toward alternative M2 macrophage, thus protecting against atherosclerotic plaque formation and preventing a vulnerable phenotype. Conclusion miR-92 inhibition promoted alternative macrophage activation and attenuated atherosclerosis regression partially regulated in a KLF4-dependent manner, which indicated that miR-92/KLF4 axis may serve as a promising strategy for prevention of atherosclerotic diseases.

BACKGROUND Many studies have investigated treatment-related sequelae in Hodgkin's lymphoma (HL) in high-prevalence areas, but very few have been conducted in low-prevalence areas, including Taiwan and Japan. MATERIALS AND METHODS We retrospectively reviewed 101 HL patients who had received mediastinal radiotherapy between January 1997 and April 2013. RESULTS Nine patients had cardiac events and nine patients developed second malignancies. Univariate analysis showed that bulkiness of disease was significantly associated with higher incidence of cardiac events (HR 7.70, 95% CI 1.60-38.00, p = 0.012). Disease stage and cumulative dose of radiotherapy were significantly correlated with incidence of radiation pneumonitis (HR 1.40, 95% CI 1.00-2.10, p = 0.043 and HR 1.10, 95% CI 1.00-1.20, p = 0.009, respectively). All cases of grade III-IV radiation pneumonitis happened in patients receiving a radiation dose higher than 35 Gy and developed within 4 months after radiotherapy. CONCLUSIONS Despite the similar incidence rates of treatment-related sequelae among HL survivors between areas with high and low prevalence of HL, cardiac events and second malignancies cannot be overlooked in HL survivors in low-prevalence areas.

Previously, we published that 4′-azid-2′-deoxy-2′-fluorarabinoside (FNC), a novel cytosine nucleoside analog, has good anti-viral and anti-tumor activity. This study aimed to further explore the role and molecular mechanism of FNC in non-small cell lung cancer (NSCLC). FNC was tested in the NSCLC H460 cell line, the Lewis mouse model, and the H460 cell xenograft model. The effects of FNC were assessed by cell viability, transwell migration, and wound scratch analyses of cell migration and invasion. Apoptosis was assessed by flow cytometry. Proteins expression was assessed by western blot and immunohistochemistry staining (IHC). FNC inhibits the proliferation and metastasis of H460 cells in a time- and dose-dependent manner. FNC treatment showed efficacy and low toxicity in the Lewis mouse lung cancer model as well as in the H460 cell xenograft model. Further, FNC induced H460 cell apoptosis through the activation of the mitochondrial pathway. Notably, FNC inhibited invasion by increasing E-cadherin protein and reducing the protein expression of VEGF, MMP-2, MMP-9, and CD31. FNC inhibits NSCLC by activating the mitochondrial apoptosis pathway and regulating the expressions of multiple proteins related to cell adhesion and invasion, highlighting its potential as an NSCLC therapeutic.

Objective To provide a general description of women with postpartum urinary incontinence (PPUI), and investigate the effect of different types of PPUI with varied severity on affected women's quality of life. Methods We performed a cross-sectional study in China that included 130 women with reported symptoms of PPUI. At the sixth to eighth week postpartum, we analyzed sociodemographic and clinical characteristics and compared women's quality of life (measured using the I-QOL and IIQ-7) by severity of PPUI (measured using the ICI-Q-SF), types of PPUI, stages of prolapse, and age. Results 81 of the (62.3%) participating women were classified as mild PPUI, 43 as (33.1%) moderate, and 6 as (4.6%) severe, with 80 of these (61.5%) were grouped into stress urinary incontinence (SUI). With the symptoms of PPUI becoming more severer the total I-QOL score decreased significantly, and the total IIQ-7 score increased. Women with MUI reported lower scores for I-QOL and behavioral impacts, and higher scores of IIQ-7 than those with SUI. Conclusions We found that more severe symptoms of UI and prolapse more negatively affected the quality of life of postpartum women, and women with MUI experienced a lower QOL.

Qinghuan Li,1,* Yi Liang,1,* Zeng Liu,2 Chuanyun Yu1 1Oncology Radiotherapy Center, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of China; 2Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuanyun Yu Tel/Fax +86-710-2813559Email yuchuanyunxy@163.comZeng Liu Email liu8901@126.comBackground: Head and neck squamous cell carcinoma (HNSCC) ranks the sixth most common cancer worldwide. This study aims to evaluate the associations of GWAS-identified HNSCC risk loci with progression, efficacy and toxicity of radiotherapy of HNSCC treated with radiotherapy.Methods: Six GWAS-identified risk loci were genotyped and evaluated. Multivariate logistic regression was used to determine the associations of these SNPs with progression, efficacy and toxicity of radiotherapy of HNSCC treated with radiotherapy.Results: We found that rs259919 was significantly associated with higher TNM stage (allele A vs G: OR=1.49; 95% CI: 1.09– 2.03; P=0.012), while rs3135001 was significantly associated with better efficacy of radiotherapy (allele T vs C: OR=1.80, 95% CIs=1.19– 2.73, P=0.005). Both SNP rs1265081 (allele A vs C: OR=1.41, 95% CIs=1.08– 1.86, P=0.012) and rs3135001 (allele T vs allele C: OR=0.53, 95% CIs=0.35– 0.79, P=0.002) were significantly associated with the occurrence of grade 3– 4 oral mucositis.Conclusion: We identified that three GWAS-identified HNSCC risk loci were significantly associated with progression, efficacy and toxicity of radiotherapy of HNSCC. Our findings strengthen the understanding of the essential role of genetic background in the progression and therapeutic effects of HNSCC.Keywords: progression, genetic, radiotherapy, HNSCC, efficacy, toxicity

Deep-ultraviolet (DUV) photodetection has garnered extensive research interest for its vital applications in many military and civil fields. In this work, we present the synthesis of a large-area two-dimensional (2D) PdTe2 multilayer, which can be directly transferred onto a GaN substrate to construct a vertical heterostructure for visible-blind DUV photodetection. Upon 265 nm light irradiation, the heterostructure displays a distinct photovoltaic behavior, enabling it to serve as a self-driven photodetector. The important photoresponse parameters, such as ${I}_{light}/{I}_{dark}$ ratio, responsivity, specific detectivity and DUV/visible (265 nm/450 nm) rejection ratio reach as high as 106, 168.5 mA/W, $5.3 \times 10^{12}$ Jones, and 104, respectively, at zero bias. The responsivity can be further enhanced to 254.6 mA/W by applying a small reverse bias of −1.0 V. In addition, the photodetector can function as a DUV light image sensor to reliably record an “H” pattern with a decent resolution. The present study paves a way for designing high-performance cost-effective DUV photodetectors towards practical optoelectronic applications.

Postoperative cognitive dysfunction (POCD; cognitive change associated with anesthesia and surgery) is one of the most serious long-term postoperative complications that occur in elderly patients. Dexmedetomidine (DEX) has been shown to be beneficial for improving outcomes of postoperative cognitive function. However, the exact mechanism underlying this role requires is yet to be found. The present study aims to determine the pathways involved in the protective effects of DEX against POCD in C57BL/6 J aged mice. DEX was administered after POCD modeling in C57BL/6 J aged mice. The cognitive function was evaluated after DEX treatment using novel object recognition, open field, and Y-maze tests. We also assessed its effects on neuron apoptosis and production of TNF-α and IL-1β in mouse brain tissues as well as expression levels of DNA damage-related proteins p53, p21, and γH2AX. Interactions between early growth response 1 (EGR1) and p53, microRNA (miR)-381, and EGR1 were identified by ChIP and luciferase reporter assays, and gain- and loss-of-function experiments were performed to confirm the involvement of their interaction in POCD. DEX administration attenuated hippocampal neuron apoptosis, neuroinflammation, DNA damage, and cognitive impairment in aged mice. miR-381 targeted EGR1 and disrupted its interaction with p53, leading to a decline in hippocampal neuron apoptosis, DNA damage, neuroinflammation, and cognitive impairment. Furthermore, DEX administration resulted in the enhancement of miR-381 expression and the subsequent inhibition of EGR1/p53 to protect against cognitive impairment in aged mice. Overall, these results indicate that DEX may have a potential neuroprotective effect against POCD via the miR-381/EGR1/p53 signaling, shedding light on the mechanisms involved in neuroprotection in POCD.

Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment and may progress to dementia. However, the brain functional mechanism of T2DM‐related dementia is still less understood. Recent resting‐state functional magnetic resonance imaging functional connectivity (FC) studies have proved its potential value in the study of T2DM with cognitive impairment (T2DM‐CI). However, they mainly used a mass‐univariate statistical analysis that was not suitable to reveal the altered FC “pattern” in T2DM‐CI, due to lower sensitivity. In this study, we proposed to use high‐order FC to reveal the abnormal connectomics pattern in T2DM‐CI with a multivariate, machine learning‐based strategy. We also investigated whether such patterns were different between T2DM‐CI and T2DM without cognitive impairment (T2DM‐noCI) to better understand T2DM‐induced cognitive impairment, on 23 T2DM‐CI and 27 T2DM‐noCI patients, as well as 50 healthy controls (HCs). We first built the large‐scale high‐order brain networks based on temporal synchronization of the dynamic FC time series among multiple brain region pairs and then used this information to classify the T2DM‐CI (as well as T2DM‐noCI) from the matched HC based on support vector machine. Our model achieved an accuracy of 79.17% in T2DM‐CI versus HC differentiation, but only 59.62% in T2DM‐noCI versus HC classification. We found abnormal high‐order FC patterns in T2DM‐CI compared to HC, which was different from that in T2DM‐noCI. Our study indicates that there could be widespread connectivity alterations underlying the T2DM‐induced cognitive impairment. The results help to better understand the changes in the central neural system due to T2DM., We used high‐order functional connectivity to reveal the abnormal connectomics pattern in T2DM with cognitive impairment with a multivariate, machine learning‐based strategy. We also investigated whether such patterns were different between T2DM with cognitive impairment and T2DM without cognitive impairment to better understand T2DM‐induced cognitive impairment. Our study is well suited for publication in Human Brain Mapping as we used this method is highly advanced and desirable for extensive applications in the future. Meanwhile, it is of great help for standardizing the methodology and boosting clinical applications of the functional imaging‐based machine learning with improved reproducibility, generalizability, and interpretability.

Post-traumatic stress disorder (PTSD) is a psychiatric disease that seriously affects brain function. Currently, selective serotonin reuptake inhibitors (SSRIs) are used to treat PTSD clinically but have decreased efficiency and increased side effects. In this study, nasal cannabidiol inclusion complex temperature-sensitive hydrogels (CBD TSGs) were prepared and evaluated to treat PTSD. Mice model of PTSD was established with conditional fear box. CBD TSGs could significantly improve the spontaneous behavior, exploratory spirit and alleviate tension in open field box, relieve anxiety and tension in elevated plus maze, and reduce the freezing time. Hematoxylin and eosin and c-FOS immunohistochemistry slides showed that the main injured brain areas in PTSD were the prefrontal cortex, amygdala, and hippocampus CA1. CBD TSGs could reduce the level of tumor necrosis factor-α caused by PTSD. Western blot analysis showed that CBD TSGs increased the expression of the 5-HT1A receptor. Intranasal administration of CBD TSGs was more efficient and had more obvious brain targeting effects than oral administration, as evidenced by the pharmacokinetics and brain tissue distribution of CBD TSGs. Overall, nasal CBD TSGs are safe and effective and have controlled release. There are a novel promising option for the clinical treatment of PTSD., Graphical abstract Nasal delivery of cannabidiol inclusion complex temperature-sensitive hydrogels could effectively target to brains for the treatment of mice with post-traumatic stress disorder (PTSD), which is a novel promising option for the clinical treatment of PTSD.Image 1

Introduction Metastasis is the primary cause of lung cancer-related death. Nevertheless, the underlying molecular mechanisms and evolutionary patterns of lung cancer metastases are still elusive. Methods We performed whole-exome sequencing for 40 primary tumors (PTs) and 61 metastases from 47 patients with lung cancer, of which 40 patients had paired PTs and metastases. The PT-metastasis genomic divergence, metastatic drivers, timing of metastatic dissemination, and evolutionary origins were analyzed using appropriate statistical tools and mathematical models. Results There were various degrees of genomic heterogeneity when comparing the paired primary and metastatic lesions or comparing metastases of different sites. Multiple metastasis-selected/enriched genetic alterations were found, such as MYC amplification, NKX2-1 amplification, RICTOR amplification, arm 20p gain, and arm 11p loss, and these results were were also featured in a meta-analysis cross-validated using an independent cohort from Memorial Sloan-Kettering Cancer Center database. To elucidate the metastatic seeding time, we applied a metastatic model and found 61.1% of the tumors were late dissemination, in which the metastatic seeding happened approximately 2.74 years before clinical detection. One exception was lymph node metastases whose dissemination time was relatively early. By analyzing the evolutionary origins, we reported that nonlymph node metastases were mainly seeded by the PT (87.5%) rather than the earlier colonized lymph node metastases. Conclusions Our results shed light on the molecular features that potentially drive lung cancer metastases. The distinct temporospatial pattern of disease progression revealed that lung cancer was susceptible to either late dissemination or indolent early lymph node metastases, leaving a potential time window to minimize metastases by early cancer detection.

To estimate the prevalence of primary immune thrombocytopenia (ITP) and describe ITP-associated healthcare resource utilization (HRU) among Texas Medicaid beneficiaries.A retrospective analysis using 2012-2015 Texas Medicaid claims data was conducted to estimate the annual prevalence of ITP. HRU was summarized for the 12-month period following initial ITP diagnosis. Logistic regression and generalized linear model were used to investigate predictors for all-cause and ITP-related HRU.The average annual prevalence of ITP was 17.0 per 100,000 persons; higher among females vs males (17.4 vs 13.6 per 100,000) and highest among adults aged ≥ 65 years (36.7 per 100,000). Among 325 patients included in the HRU analyses, 49.2% received ITP therapies. More than half of patients had at least one all-cause emergency department (ED) visit (70.5%) and/or hospitalization (56.0%). One-third (32.6%) experienced at least one ITP-related ED visit and 40.3% had at least one ITP-related hospitalization. Compared to adults aged 18-49 with ITP, children aged 0-4 (odds ratio [OR] = 3.65,There are 17 patients diagnosed with ITP for every 100,000 Texas Medicaid enrollees annually, with higher prevalence in females and the elderly. Children are more likely to experience hospitalizations and ED visits associated with ITP. ITP patients in Texas Medicaid utilize more healthcare resources compared to the general Medicaid population.

Background Coronary artery calcification (CAC) is an independent risk factor of major adverse cardiovascular events; however, the impact of CAC on in-hospital death and adverse clinical outcomes in patients with coronavirus disease 2019 (COVID-19) remains unclear. Objective To explore the association between CAC and in-hospital mortality and adverse events in patients with COVID-19. Methods This multicenter retrospective cohort study enrolled 2067 laboratory-confirmed COVID-19 patients with definitive clinical outcomes (death or discharge) admitted from 22 tertiary hospitals in China between January 3, 2020 and April 2, 2020. Demographic, clinical, laboratory results, chest CT findings, and CAC on admission were collected. The primary outcome was in-hospital death and the secondary outcome was composed of in-hospital death, admission to intensive care unit (ICU), and requiring mechanical ventilation. Multivariable Cox regression analysis and Kaplan–Meier plots were used to explore the association between CAC and in-hospital death and adverse clinical outcomes. Results The mean age was 50 years (SD,16) and 1097 (53.1%) were male. A total of 177 patients showed high CAC level, and compared with patients with low CAC, these patients were older (mean age: 49 vs. 69 years, P

Summary Background & aims To date, the prevalence of Gestational diabetes mellitus (GDM) in China was 17.5%. Given the substantial relevance of GDM for medium- and long-term health of both mother and offspring and the paucity of existing data on the link between maternal diet and glucose homeostasis during pregnancy in Asian population, additional studies are needed. To examine the relevance of dietary glycemic index (GI), glycemic load (GL) and fiber intake before and during pregnancy for the development of GDM and glucose homeostasis over the course of pregnancy. Methods Cox proportional hazards analysis and linear mixed effects regressions were performed on data from 9317 women for whom three food frequency questionnaires (pre-pregnancy, 1st and 2nd trimesters) and biochemical measures during pregnancy were available. Investigated outcome variables included GDM risk, fasting plasma glucose (FPG), glycated hemoglobin (HbA1C), and homeostasis model assessment insulin resistance (HOMA-IR) in the 1st, 2nd and 3rd trimesters. Results Women in the highest tertile of dietary GI (or GL) before pregnancy, in the 1st, or the 2nd trimester respectively had a 12% (15%), 25% (23%) or 29% (25%) higher risk of developing GDM than those in the lowest tertile (all p for trend ≤ 0.02). Women with the highest dietary fiber intake before pregnancy, in the 1st or 2nd trimester had a 11%, 17% or 18% lower GDM risk (all p for trend ≤ 0.03). Moreover, increases in GI or GL and decreases in fiber intake over the course of pregnancy (1st to 3rd trimesters) were independently associated with adverse concurrent developments in FPG, HbA1C and HOMA-IR (p ≤ 0.03). Conclusions Our study indicates that dietary GI, GL and fiber intake before and during pregnancy affects glucose homeostasis of pregnant Chinese women.

Solar-blind deep-ultraviolet (DUV) photodetectors based on Ga2O3 have attracted great attention due to their potential applications for many military and civil purposes. However, the development of device integration for optoelectronic system applications remains a huge challenge. Herein, we report a facile method for patterned-growth of high-quality β-Ga2O3 thin films, which are assembled into a photodetectors array comprising 8 × 8 device units. A representative detector exhibits outstanding photoresponse performance, in terms of an ultra-low dark current of ∼0.62 pA, a large Ilight/Idark ratio exceeding 104, a high responsivity of ∼0.72 A W−1 and a decent specific detectivity of ∼4.18 × 1011 Jones, upon 265 nm DUV illumination. What is more, the DUV/visible (250/400 nm) rejection ratio is as high as 103 with a sharp response cut-off wavelength at ∼280 nm. Further optoelectronic analysis reveals that the photodetectors array has good uniformity and repeatability, endowing it the capability to serve as a reliable DUV light image sensor with a decent spatial resolution. These results suggest that the proposed technique offers an effective avenue for patterned growth of β-Ga2O3 thin films for multifunctional DUV optoelectronic applications.

Yang Liu,1,* Feng-Jiao Zhang,2,* Xi-Xi Zhao,3,* Yuan Yang,4 Chun-Yi Liang,3 Li-Li Feng,5 Xiang-Bo Wan,5 Yi Ding,1 Yao-Wei Zhang1 1Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 2Shanghai Concord Medical Cancer Center, Shanghai, 200001, People’s Republic of China; 3Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Medical Image Processing, School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 5Department of Radiation Oncology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Ding; Yao-Wei Zhang Tel +86 20-62786616Email dingyi197980@126.com; weiyaozhang2@163.comPurpose: Neoadjuvant chemoradiotherapy (nCRT) has become the standard treatment for locally advanced rectal cancer (LARC). However, the accuracy of traditional clinical indicators in predicting tumor response is poor. Recently, radiomics based on magnetic resonance imaging (MRI) has been regarded as a promising noninvasive assessment method. The present study was conducted to develop a model to predict the pathological response by analyzing the quantitative features of MRI and clinical risk factors, which might predict the therapeutic effects in patients with LARC as accurately as possible before treatment.Patients and Methods: A total of 82 patients with LARC were enrolled as the training cohort and internal validation cohort. The pre-CRT MRI after pretreatment was acquired to extract texture features, which was finally selected through the minimum redundancy maximum relevance (mRMR) algorithm. A support vector machine (SVM) was used as a classifier to classify different tumor responses. A joint radiomics model combined with clinical risk factors was then developed and evaluated by receiver operating characteristic (ROC) curves. External validation was performed with 107 patients from another center to evaluate the applicability of the model.Results: Twenty top image texture features were extracted from 6192 extracted-radiomic features. The radiomics model based on high-spatial-resolution T2-weighted imaging (HR-T2WI) and contrast-enhanced T1-weighted imaging (T1+C) demonstrated an area under the curve (AUC) of 0.8910 (0.8114– 0.9706) and 0.8938 (0.8084– 0.9792), respectively. The AUC value rose to 0.9371 (0.8751– 0.9997) and 0.9113 (0.8449– 0.9776), respectively, when the circumferential resection margin (CRM) and carbohydrate antigen 19-9 (CA19-9) levels were incorporated. Clinical usefulness was confirmed in an external validation cohort as well (AUC, 0.6413 and 0.6818).Conclusion: Our study indicated that the joint radiomics prediction model combined with clinical risk factors showed good predictive ability regarding the treatment response of tumors as accurately as possible before treatment.Keywords: rectal cancer, neoadjuvant chemoradiotherapy, magnetic resonance imaging, tumor response

A 60‐year‐old man was hospitalized because of numbness and weakness in the right upper limb. Magnetic resonance imaging revealed a large mass in the right upper lobe invading the right eighth cervical and first thoracic nerve root. Biopsy pathology confirmed primary lung adenocarcinoma with a clinical stage of cT4N0M0 IIIA, negative for anaplastic lymphoma kinase fusion gene and epidermal growth factor receptor mutations but positive for programmed death ligand 1 (3%). Neoadjuvant tislelizumab and chemotherapy were offered to this patient with Pancoast tumor, and tumor shrinkage of 71% was achieved. After the operation, surgical pathology indicated pathologic complete response (pCR). Circulating tumor cells testing was negative after the first adjuvant treatment. In this case, we provide real‐world evidence of encouraging pCR with neoadjuvant tislelizumab and chemotherapy for a patient with Pancoast tumor., • Neoadjuvant tislelizumab and chemotherapy was offered for a patient with Pancoast tumor (TNM stage, cT4N0M0 IIIA). • Surgical resection was successfully performed and a pCR was achieved.

Purpose Studies regarding the association between dietary fat intake and gestational diabetes mellitus (GDM) are limited and provide conflicting findings. Thus, the study aims to examine the association of dietary fat intake in the year preceding pregnancy and during pregnancy with the risk of GDM, taking the relevance of dietary protein intake on GDM into consideration. Methods A prospective study was conducted in 6299 singleton pregnancies, using the data from the Nutrition in Pregnancy and Growth in Southwest China (NPGSC). A validated food frequency questionnaire was used to assess dietary fat intake in the year preceding pregnancy and during the first and second trimesters of pregnancy. Logistic regression analysis was used to assess the prospective associations of dietary fat intake and the type and source of dietary fats in different time windows with GDM risk. Results Higher intake of total fat [OR (95% CI): 2.21 (1.19–4.20), P = 0.02] during 12–22 weeks of gestation was associated with higher GDM risk. However, adjustment for animal protein intake greatly attenuated this association [OR (95% CI): 1.81 (0.93, 3.64), P = 0.11]. Total fat intake neither in the year preceding pregnancy nor during the early pregnancy was associated with GDM risk. Moreover, insignificant associations were observed between intakes of vegetable fat, animal fat, cholesterol, saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid one year before pregnancy and during the first and second trimesters and GDM risk. Conclusion Our study indicated that dietary fat intake one year before pregnancy and across the two pregnancy trimesters preceding the diagnosis of GDM has no relevance on GDM risk among Chinese women, particularly those with normal BMI, low, or normal calorie intake.

Interleukin (IL)-17 and its related cytokines have been shown to be involved in myocardial fibrosis and irreversible ventricular remodelling, which have predictive values in the development of left ventricular diastolic dysfunction (LVDD). This study aimed to assess the correlation between IL-17 and LVDD, and investigate the prognostic value of IL-17 among patients with normal left ventricular ejection fraction (LVEF).A total of 120 patients with normal LVEF underwent left ventricular (LV) catheterisation for LV end-diastolic pressure (LVEDP) measurement and routine echocardiography. The follow-up period was 30 (18, 35) months.The levels of IL-17 and IL-6 from the systemic blood were significantly increased in non-heart failure (HF) patients with LVDD (p0.001). Receiver operating characteristic (ROC) revealed that the combination of IL-17 and IL-6 showed the highest diagnostic accuracy in predicting LVDD (AUC, 0.890; 95% CI, 0.835-0.945; p0.001), and the cut-off value was 41.5 pg/mL. On logistic regression analysis, the increment of the combination of IL-17 and IL-6 was an independent predictor for the prognosis of LVDD (odds ratio, 1.25; 95% CI, 1.01-1.12; p0.05). According to the cut-off value of the combination of IL-17 and IL-6, the patients with lower levels of IL-17 and IL-6 (41.5 pg/mL group) had a better prognosis. The increased levels of IL17 and IL-6 were significantly correlated with the levels of fibrotic parameters.Assessment of LVDD by measuring the combination of IL-17 and IL-6 might provide valuable prognostic significance for non-HF patients with LVDD.

Purpose: Although enzalutamide (ENZ) has been widely used to treat de novo or castration-resistant metastatic prostate cancer, resistance develops and disease progression is ultimately inevitable. There are currently no approved targeted drugs to specifically delay or overcome ENZ resistance. Experimental Design: We selected several ENZ-resistant cell lines that replicated clinical characteristics of the majority of patients with ENZ-resistant disease. A high-throughput pharmacologic screen was utilized to identify compounds with greater cytotoxic effect for ENZ-resistant cell lines, compared with parental ENZ-sensitive cells. We validated the potential hits in vitro and in vivo, and used knockdown and overexpression assays to study the dependencies in ENZ-resistant prostate cancer. Results: ABT199 (BCL-2 inhibitor) and IMD0354 (IKKB inhibitor) were identified as potent and selective inhibitors of cell viability in ENZ-resistant cell lines in vitro and in vivo which were further validated using loss-of-function assays of BCL-2 and IKKB. Notably, we observed that overexpression of BCL-2 and IKKB in ENZ-sensitive cell lines was sufficient for the emergence of ENZ resistance. In addition, we confirmed that BCL-2 or IKKB inhibitors suppressed the development of ENZ resistance in xenografts. However, validation of both BCL-2 and IKKB in matched castration-sensitive/resistant clinical samples showed that, concurrent with the development of ENZ/abiraterone resistance in patients, only the protein levels of IKKB were increased. Conclusions: Our findings identify BCL-2 and IKKB dependencies in clinically relevant ENZ-resistant prostate cancer cells in vitro and in vivo, but indicate that IKKB upregulation appears to have greater relevance to the progression of human castrate-resistant prostate cancer.

The faithful execution of molecular programme underlying oocyte maturation and meiosis is vital to generate competent haploid gametes for efficient mammalian reproduction. However, the organization and principle of molecular circuits and modules for oocyte meiosis remain obscure. Here, we employed the recently developed single-cell RNA-seq technique to profile the transcriptomes of germinal vesicle (GV) and metaphase II (MII) oocytes, aiming to discover the dynamic changes of mRNAs and long non-coding RNAs (lncRNAs) during oocyte in vitro meiotic maturation. During the transition from GV to MII, total number of detected RNAs (mRNAs and lncRNAs) in oocytes decreased. Moreover, 1,807 (602 up- and 1,205 down-regulated) mRNAs and 313 (177 up- and 136 down-regulated) lncRNAs were significantly differentially expressed (DE), i.e., more mRNAs down-regulated, but more lncRNAs up-regulated. During maturation of pig oocytes, mitochondrial mRNAs were actively transcribed, eight of which (ND6, ND5, CYTB, ND1, ND2, COX1, COX2 and COX3) were significantly up-regulated. Both DE mRNAs and targets of DE lncRNAs were enriched in multiple biological and signal pathways potentially associated with oocyte meiosis. Highly abundantly expressed mRNAs (including DNMT1, UHRF2, PCNA, ARMC1, BTG4, ASNS and SEP11) and lncRNAs were also discovered. Weighted gene co-expression network analysis (WGCNA) revealed 20 hub mRNAs in three modules to be important for oocyte meiosis and maturation. Taken together, our findings provide insights and resources for further functional investigation of mRNAs/lncRNAs in in vitro meiotic maturation of pig oocytes.

The diagnosis and treatment of massive hemoptysis remain challenging. We report a 28-year-old woman with refractory massive hemoptysis caused by a mediastinal hemangioma. Despite multiple bronchial artery embolizations and fiberoptic bronchoscopy treatments, effective control of the bleeding and clearing of the airway was not possible. Finally, with the support of venovenous extracorporeal membrane oxygenation, mediastinal hemangioma resection and right upper lobe sleeve resection were simultaneously performed. During the operation, many blood clots in the airway were removed. The airway bleeding was effectively controlled, and the patient recovered.

Little research has examined burn injury in the pediatric population with autism spectrum disorder (ASD). We used data from Taiwan’s National Health Insurance Research Database to identify 15,844 participants aged

Peripheral inflammation and nerve injury usually accompany each other. However, whether inflammatory and neuropathic pain share similar mechanisms at all stages is unknown. TRPV1 and P2X3 are two major ion channels in dorsal root ganglia (DRGs) and are involved in chronic pain. Here, their function and expression in DRGs at different phases of the two types of pain were investigated. Both the paw withdrawal threshold (PWT) and paw withdrawal latency were decreased in rats injected with complete Freud's adjuvant (CFA). However, only the PWT was decreased in rats with spared nerve injury (SNI). CFA increased the magnitude of the TRPV1-mediated Ca2+ response but not the P2X3-mediated Ca2+ response 14 days after injection. Consistent with this result, the P2X3 expression level in CFA rats was increased only at 3 days after injection. SNI surgery increased the magnitudes of the TRPV1- and P2X3-mediated Ca2+ responses and upregulated both TRPV1 and P2X3 expression in lumbar DRGs. The distributions of TRPV1 and P2X3 in DRGs after modeling were observed, and TRPV1 was found to be highly expressed mainly in the L4-L5 DRGs in CFA rats and in the L5-L6 DRGs in SNI rats. P2X3 was highly expressed in the L4-L6 DRGs in CFA rats 3 days after injection but was only highly expressed in the L4 DRG 14 days after modeling. On the other hand, SNI promoted the P2X3 expression L4-L5 DRGs 3 days after surgery, but only L6 DRG 14 days after modeling. All the results indicate that P2X3 and TPRV1 are involved in inflammatory and neuropathic pain by different expression levels and distributions in the lumbar DRG in the chronic stage.

This study reveals an uncovered mechanism for the regulation of polyamine homeostasis through protein arginyl citrullination of antizyme (AZ), a natural inhibitor of ornithine decarboxylase (ODC). ODC is critical for the cellular production of polyamines. AZ binds to ODC dimers and promotes the degradation of ODC via the 26S proteasome. This study demonstrates the protein citrullination of AZ catalyzed by peptidylarginine deiminase type 4 (PAD4) both in vitro and in cells. Upon PAD4 activation, the AZ protein was citrullinated and accumulated, leading to higher levels of ODC proteins in the cell. In the PAD4-overexpressing and activating cells, the levels of ODC enzyme activity and the product putrescine increased with the level of citrullinated AZ proteins and PAD4 activity. Suppressing cellular PAD4 activity reduces the cellular levels of ODC and downregulates cellular polyamines. Furthermore, citrullination of AZ in the C-terminus attenuates AZ function in the inhibition, binding, and degradation of ODC. This paper provides evidence to illustrate that PAD4-mediated AZ citrullination upregulates cellular ODC and polyamines by retarding ODC degradation, thus interfering with the homeostasis of cellular polyamines, which may be an important pathway regulating AZ functions that is relevant to cancer biology.