Journal articles on the topic 'Sheng huo bao'

Samchulkunbi-tang (SCT, Shen Zhu Jian pi tang in Chinese) is said to have been first recorded by Zheng Zhi Zhun Sheng during the Ming Dynasty in China. Records of SCT in Korea are known to have been cited in Donguibogam (Dong Yi Bao Jian in Chinese), Uibang Hwaltu (Yi Fang Huo Tao in Chinese), and Bang Yak Hapyeon (Fang Yao He Bian in China). Although SCT is widely used in treating chronic gastritis and gastric ulcers, the beneficial effect on renal vascular function is unknown. Hypertension is a risk factor for cardiovascular disease and endothelial dysfunction in humans and experimental animal models of arterial hypertension. In addition, kidney dysfunction is characterized by hypertension diseases. This study was conducted to evaluate the effect of SCT on the vascular function in vitro (human umbilical cord endothelial cells, HUVECs) and in vivo (NG‐nitro‐L‐arginine methyl ester, L-NAME-induced hypertensive rats). The phosphorylation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) is closely related to nitric oxide (NO) production in HUVECs, and SCT in this study significantly increased these. For three weeks, hypertensive rat models were induced by L-NAME administration (40 mg/kg/day) with portable water. It was followed by oral administration with 100 and 200 mg/kg/day for two weeks to confirm the effectiveness of SCT. As a result, systolic blood pressure decreased in the SCT-treated groups, compared with that in the L-NAME-induced hypertensive group. SCT treatment restored vasorelaxation by stimulating acetylcholine and cGMP production in the thoracic aorta. In addition, SCT treatment decreased intima-media thickness, attenuated the reduction of eNOS expression, and increased endothelin-1 expression. It also increased p-Akt and p-eNOS expression in hypertensive rat aorta. Furthermore, regarding renal function parameters, SCT ameliorated urine osmolality, urine albumin level, serum creatinine, and blood urea nitrogen levels. These results demonstrate that the oriental medicine SCT exerts potent vascular and renal protective effects on nitric oxide-deficient hypertensive rats and HUVECs

Traditional Chinese medicine (TCM) divides fracture treatment into three stages. Many TCM herbs and formulas have been used to treat fractures for thousands of years. However, research regarding the Chinese herbal products (CHPs) that should be used at different periods of treatment is still lacking. This study aims to identify the CHPs that should be used at different periods of treatment as well as confirm the TCM theory of fracture periods medicine. We used prescriptions of TCM outpatients with fracture diagnoses analyzed using the Chang Gung Research Database (CGRD) from 2000 to 2015. According to the number of days between the date of the fracture and the clinic visit date, all patients were assigned to one of three groups. Patients with a date gap of 0-13 days were assigned to the early period group; those with a date gap of 14-82 days were assigned to the middle period group; and those with a date gap of 83-182 days were assigned to the late period group. We observed the average number of herbal formulas prescribed by the TCM doctor at each visit was 2.78, and the average number of single herbs prescribed was 6.47. The top three prescriptions in the early fracture period were Zheng-gu-zi-jin-dang, Shu-jing-huo-xue-tang, and Wu-ling-san. In the middle fracture period, the top three formulas were Zheng-gu-zi-jin-dang, Shu-jing-huo-xue-tang, and Zhi-bai-di-huang-wan. In the late fracture period, the top three formulas were Shu-jing-huo-xue-tang, Gui-lu-er-xian-jiao, and Du-huo-ji-sheng-tang. The main single herbs used in the early fracture period were Yan-hu-suo, Gu-sui-bu, and Dan-shen. From the middle to the late period, the most prescribed single herbs were Xu-duan, Gu-sui-bu, and Yan-hu-suo. We concluded that the results showed that the CGRD utilization pattern roughly meets the TCM theory at different fracture periods.

Semilinear stochastic dynamic systems in a separable Hilbert space often model some evolution phenomena arising in physics and engineering. In this paper, we study the existence and uniqueness of mild solutions to neutral semilinear stochastic functional dynamic systems under local non-Lipschitz conditions on the coefficients by means of the stopping time technique. We especially generalize and improve the results that appeared in Govinadan (2005), Bao and Hou (2010), and Jiang and Shen (2011).

Abstract Background: T-1101, a novel small molecule, is the first-in-class oral agent that specifically disrupts the interaction between two commonly overexpressed, critical mitotic regulators, Hec1 and Nek2, within cancer cells. Such disruption leads to abnormal mitosis followed by apoptosis of cancer cells and provides a potential therapeutic strategy for cancer treatment. T-1101, with growth inhibition concentrations (IC50) ranging from14 to 74 nM across various human cancer cell lines, exhibited potent anti-liver and breastcancer activities in vivo, and highly active (IC50 7-19 nM) in MDR (multiple drugresistance) expressing cell lines. The effective inhibitory dose of T-1101 was determined to be between 10 and 25 mg/kg twice a day in xenograft animal models. Moreover, T-1101 has synergistic activity when combined with other anticancer drugs such as doxorubicin, topotecan and paclitaxel etc. Clinically, oral powder for constitution (OPC) form was first used in the initial study. To improve better patient compliance, the capsule (CAP) form is then deployed in current T-1101’s phase 1 study. Methods: Two T-1101 oral formulations (OPC and CAP) have been designed for the first-in-human, multi-center, open-label, dose-escalation studies to evaluate the safety, tolerability and establish the Recommended Phase 2 Dose (RP2D) in subjects with advanced refractory solid tumors. The secondary objectives are to assess the pharmacokinetics (PK) and therapeutic response after receiving treatment. DLT was determined within the first treatment cycle. Patients showing clinical benefit after first 2cycles of T-1101may enter extension cohort to continue the treatment. In OPC 3+3 escalation study (NCT03195764, NCT03349073), T-1101 was administered orally once daily, days 1 to 14 every 21 days per cycle with 8 planned dose levels at dose of 9, 18, 36, 54, 72, 90, 108 to 126 mg/m2. The OPC study was terminated at 36 mg/m2 before the primary endpoint (determination of maximum tolerated dose; MTD) was reached and subsequent dosing level will be evaluated with the CAP formulation. Based on the 52% of relative oral bioavailability (%F) of CAP versus OPC in preclinical Beagle dogs’ PK study, the starting dose of CAP form of T-1101 was determined at 100 mg daily forconsecutive 28-day per cycle for 2 cycles with dose levels of 100, 200, 225, 250, 300 and 350 mg/day. The accelerated titration and Bayesian Optimal Interval (BOIN) designs are used for the T-1101 capsule dose escalation study (NCT04685473), in which one subject will be enrolled per dose level until one subject have DLT or two subjects experience ≥ Grade 2 drug-related AE during Cycle 1 at any dose level, then the dose escalation will follow the BOIN design. Cohorts 1 (100 mg/day) 2 (200 mg/day) and 3 (225 mg/day) have been completed without DLT. As of November 2023, the trial remains open to enrollment. Citation Format: Wu-Chou Su, Li-Yuan Bai, Hui-Hua Hsiao, Her-Shyong Shiah, Yu-Min Yeh, Shang-Hung Chen, Shang-Yin Wu, Hui-Ching Wang, Hui-Jen Tsai, Kwang-Yu Chang, Jui-Hung Tsai, Chun-Hui Lee, Chieh Hua Lee, Yu-Sheng Chao, Li-Tzong Chen. Trial in progress: Phase 1 dose escalation study of T-1101, a first-in-class oral Hec1/Nek2 inhibitor, in patients with advanced refractory solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT167.

Abstract Background: The implementation of the multi-cancer early detection (MCED) test offers a valuable adjunct to existing screening methods, enabling more efficient detection of cancer and potentially leading to improved treatment outcomes and prognoses for patients. Here, we report on the performance of an MCED test, which utilizes plasma cfDNA and leverages genome-wide fragmentomics-based characteristics to identify cancer signals and predict the signal origin across a diverse range of cancer types. Methods: Plasma cfDNA from evaluable blood samples was analyzed using an MCED blood test called MERCURY, a robust machine learning classifier leveraging the low-coverage whole-genome sequencing and a comprehensive set of genome-wide features derived from cfDNA fragmentomics. A carefully selected cohort of 3076 cancer patients representing 13 cancer types, in addition to 3477 healthy controls, were pre-specified into the training and internal validation sets to train and internally validate the models to assess cancer and tissue of origin (TOO). The classifier was trained to a target specificity of 99% and locked before analysis of the independent validation set. The independent validation was enrolled prospectively and consists of 1465 participants (cancer: n= 732; non-cancer: n= 733). Results: The performance metrics in the internal validation set demonstrated that the sensitivity and specificity for cancer detection were 0.865 (95% CI [0.840, 0.887]) and 0.989 (95% CI [0.980, 0.994]), respectively. These impressive results were further substantiated in the independent validation set, where the overall sensitivity and specificity were found to be 0.874 (95% CI [0.848, 0.897]) and 0.978 (95% CI [0.965, 0.987]) respectively. Notably, the sensitivity showed an incremental increase with the stage of cancer (Stage I: 0.769, 95% CI [0.708, 0.821]; Stage II: 0.840, 95% CI [0.784, 0.886]; Stage III: 0.923, 95% CI [0.874, 0.954]; Stage IV: 0.971, 95% CI [0.901, 0.995]. Regarding the TOO model, a total of 10 cancer types with more than 100 patients in the model construction cohort were considered. The TOO model achieved a prediction accuracy of 83.5% (95% CI [80.7%, 86.6%]) and 91.8% (95% CI [89.6%, 94.1%]) for the top predicted origin and the top two predicted origins, respectively, amongst the true positive cases in the independent validation set. Conclusions: In this pre-specified, large-scale study, the MCED test, utilizing cfDNA fragmentomics, demonstrates its remarkable ability to assess cancer signal with an elevated level of sensitivity and specificity across 13 distinct types of cancer. Moreover, it displays noteworthy accuracy in predicting the tissue of origin. The performances are to be further validated in a prospective cohort study (NCT06011694). Citation Format: Hua Bao, Xiaoxi Chen, Min Wu, Shiting Tang, Xuxiaochen Wu, Wanxiangfu Tang, Dongqin Zhu, Shanshan Yang, Shuang Chang, Peng He, Xiuxiu Xu, JinPeng Zhang, Yi Shen, Shuyu Wu, Ya Jiang, Sisi Liu, Xian Zhang, Xue Wu, Yang Shao. Development and performance of a multi-cancer early detection test utilizing plasma cfDNA fragmentomics: A large-scale, prospective, multicenter study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1266.

Abstract Background: MET gene amplification is associated with poor prognosis in gastric cancer (GC) and gastroesophageal junction adenocarcinomas (GEJ). Savolitinib is a potent and highly selective oral MET tyrosine-kinase inhibitor. Here we reported the preliminary efficacy and safety from a phase 2 trial of savolitinib monotherapy in patients (pts) with MET-amplified advanced or metastatic GC/GEJ. (NCT04923932). Methods: Eligible pts had 2L+ GEJ or GC, with MET amplification and measurable lesions. Pts received savolitinib at 600 mg QD for body weight (BW) ≥50 kg, while 400 mg QD for BW <50 kg in 21-day cycles until disease progression or meeting other criteria for end of treatment. Savolitinib BID regimen has also been additionally explored. The primary endpoint was objective overall response rate (ORR) evaluated by Independent Review Committee (IRC). One interim analysis (IA) was pre-defined at the first 20 QD pts who had at least 2 tumor assessments. Results: As of IA, 20 pts were enrolled for QD regimen. Demographics and clinical outcomes are shown in table 1. The mean relative dose intensity of 93.07%. Median duration of exposure was 2.09 months. Confirmed ORR by IRC was 45%, and reached 50% in 16 patients with MET GCN (high) while only 1 PR was observed in 4 patients with MET GCN (low). Duration of response rate at 4-month was 85.7% with median follow up time of 5.5 months. The most common Gr≥3 TRAE (≥5%) were platelet count decreased, hypersensitivity, anemia, neutropenia and hepatic function abnormal. In all pts, only 1 patient discontinued treatment due to grade 4 liver function abnormal (TRAE) and no patient died due to TRAE. Conclusion: Savolitinib monotherapy had manageable safety and showed promising efficacy in pts with MET-amplified GEJ or GC, particularly in pts with MET high GCN. BID regimen is being investigated to further evaluate the efficacy and safety of savolitinib in pts with MET high GCN. Table 1. Pts baseline characteristics and clinical efficacy Baseline Characteristics ITT in IA (n=20) Median age (min, max), yearsSex (male/female), nECOG (0/1/2)Median BMI (min, max), (kg/m2)Primary location of tumor (GC/GEJ)Tumor stage (IV)Prior line of therapy (1/2/≥3)MET GCN (high/low) 57.00 (39.5, 76.8)17/33/15/220.8 (14.9, 25.8)16/4205/10/516/4 Clinical Efficacy By IRC By Investigator Confirmed objective response rateDisease control rate4m-DoR rate,% (95% CI) 45%65%85.7 (33.4, 97.9) 40%55%71.4 (25.8, 92.0) Citation Format: Zhi Peng, Hua Wang, Baorui Liu, Huiting Xu, Zhenyang Liu, Tianshu Liu, Jun Zhang, Yuxian Bai, Ying Yuan, Tao Wu, Feng Ye, Qinghua Pan, Jufeng Wang, Enxiao Li, Diansheng Zhong, Yueyin Pan, Yanru Qin, Yan Yang, Yusheng Wang, Aiping Zhou, Yongshun Chen, Dianbao Zhang, Hongli Liu, Xiujuan Qu, Shubin Wang, Ning Liu, Jinsheng Wu, Wei Li, Kejun Nan, Hongming Pan, Jianming Xu, Chunmei Bai, Heling Liu, Jia Wei, Runzhi Chen, Rongrong Li, Wei Li, Jinghong Zhou, Hongyan Yin, Qian Xu, Songhua Fan, Yongxin Ren, Weiguo Su, Lin Shen. A multicenter Phase II study of savolitinib in patients with MET-amplified gastroesophogeal junction adenocarcinomas or gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT152.

Abstract Background: The mammalian target of rapamycin (mTOR) is a serine/threonine kinase related to the lipid kinases of the phosphoinositide 3-kinase (PI3K) family, which has been confirmed to be closely related to the development of a variety of human cancers. Onatasertib (ATG-008) is a 2nd generation mTOR inhibitor which inactivates both mTORC1 and mTORC2. Our previous clinical investigation (NCT01177397) has demonstrated preliminary evidence of antitumor activity of onatasertib across multiple solid and hematologic malignancies, with encouraging signals of activity in subjects with hepatitis B virus (HBV)+ unresectable, refractory HCC. Methods: Asian patients with advanced HBV+ HCC who had experienced progressive disease after at least 1 line of systemic therapy were enrolled in this study. Onatasertib was administered orally once a day (QD) at 3 dose levels (15 mg, 30 mg and 45 mg) or 20 mg twice daily (BID). The primary endpoints were pharmacokinetics (PK), safety and efficacy (NCT03591965). Results: As of July 11, 2022, 73 patients were enrolled and evaluated. The median age was 52.0 years and the median follow up duration was 26.5 months. The mean number of prior lines was 1.8. 63 patients (86.3%) had at least one Grade 3-4 treatment emergent adverse event (TEAE), and 25 (34.2%) had at least one serious adverse event (SAE). Among the 73 subjects, 3 achieved confirmed partial response (PR), all in the 45 mg QD cohort. 18 pts were enrolled in the 45 mg QD cohort, in which 11 (61.1%) pts had received at least 2 prior lines of systemic therapy and 15 (83.3%) pts had been exposed to an anti-PD-1/PD-L1 antibody. The overall response rate (ORR) in the 45 mg QD cohort was 16.7%. The median progression-free survival (mPFS) was 3.0 months (95% CI 1.9, 4.6) in the intention to treat (ITT) population and was 5.3 months (95% CI 1.9, 7.6) in the 45mg QD cohort. Median overall survival time (mOS) was not evaluable in the 45 mg QD cohort and the mOS was 13.4 months (95% CI 7.4, 19.8) in the ITT population. Onatasertib demonstrated linear pharmacokinetics between 15 mg QD and 45 mg QD in this Asian population and there was no significant exposure accumulation after multiple dosing, as previously seen in the US population. Conclusion: Onatasertib (ATG-008) showed encouraging single agent antitumor activity in patients with HBV+ advanced HCC after at least 1 prior systemic therapy, notably in the 45 mg QD dose level, in which most patients had been previously exposed to anti-PD-L1/PD-1 therapy. The results indicates that onatasertib has potential efficacy in HBV+ HCC patients who failed prior CPI treatment. Further study may be warranted, particularly in HBV+ HCC patients who have failed prior anti-VEGFR and anti-PDL1/PD-1 therapy. Citation Format: Shukui Qin, Xiaoyan Lin, Zhiqaing Meng, Zhenggang Ren, Yuxian Bai, Shanzhi Gu, Li Zheng, Qiu Li, Sun-Yong Oh, Yabing Guo, Yoong-Koo Kang, Wei-Yu Kao, Wei Li, Jung-Hwan Yoon, Helong Zhang, Pei-Jer Chen, Tsai-Sheng Yang, Jeong Heo, Zhendong Zheng, Hui Xie, Zhinuan Yu. Result of an open-label phase 2 trial of dual TORC1/TORC2 inhibitor onatasertib (ATG-008) in HBV+ advanced hepatocellular carcinoma (HCC) subjects who have received at least one prior line of systemic therapy (TORCH) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT150.

New generation of electrochemical energy storage devices is needed to face the continuous increase in energy stored capacity demand at lower costs from human society. Moreover, due to the constant increase in number of batteries produced, the development of more sustainable devices without the consumption of limited resources at affordable costs is an actual research challenge. The conventional lithium batteries, the most widespread kind of electrochemical energy storage devices, made by an intercalation cathode (e.g., LiCoO2, LiFePO4) and a graphite anode suffer of limited capacity for high-performance application (such as in electric vehicles) and use limited mineral resources with adverse environmental consequences. Iron fluoride is a promising conversion cathode for positive electrodes in next-gen lithium batteries due to its low cost, great abundance, and ease of extraction1,2. The main problems of metal fluoride-based cathodes are the low conductivity and the structural changes during charge/discharge cycles that limit device capacity and lifespan. To effectively increase the storage capacity, several attempts to use metal lithium anodes have been made. However, this solution is now limited to primary batteries because of dendrites growth during metal plating that causes capacity fading and safety concerns. In the last decade, batteries based on fluoride-ion shuttling are drawing attention3,4 due to the possibility to use a high-capacity conversion cathode, exploiting a multi-electron transfer, and a metal anode without dendrites formation. This kind of devices, in the early stage of development, rely on electrochemical fluorination of an electropositive metal anode and the defluorination of a more “noble” metal fluoride without a metal plating-stripping process. Nowadays, electrolyte limitation is the main challenge for the development of a fluoride-ion battery that can compete with state-of-the-art lithium-ion batteries. In this work, a surfactant-assisted solvothermal route to obtain iron fluoride hydrate (FeF3 0.33 H2O) is presented. A hierarchical grape-like structure was obtained and it was tested as cathode active material in a 2025 coin-cell working in a metal-lithium battery configuration. In these tests it showed improved performance, compared to the same synthesis without surfactant. The synthetized material was also characterized by morphological and electrochemical point of view by means of Electrochemical Impedance Spectroscopy (EIS), galvanostatic charge discharge (GCD) and cyclic voltammetry (CV). The possibility to use the same cathodic material in a room-temperature fluoride-ion battery with a metal anode was assessed by using fluoride conducting liquid electrolytes5: encouraging results about the feasibility were achieved; however, further research in the field of liquid electrolytes resulted fundamental for bringing performances of this technology to the level of actual lithium batteries. References: [1] Bai, Y.; Zhou, X.; Zhan, C.; Ma, L.; Yuan, Y.; Wu, C.; Chen, M.; Chen, G.; Ni, Q.; Wu, F.; Shahbazian-Yassar, R.; Wu, T.; Lu, J.; Amine, K. Nano Energy 2017, 32, 10–18. [2] Wei, S.; Wang, X.; Jiang, M.; Zhang, R.; Shen, Y.; Hu, H. J. Alloys Compd. 2016, 689, 945–951. [3] Reddy, M. A.; Fichtner, M. Journal of Materials Chemistry 2011, 21 (43), 17059–17062. [4] Xiao, A. W.; Galatolo, G.; Pasta, M. Joule 2021, 5 (11), 2823–2844. [5] Davis, V. K.; Bates, C. M.; Omichi, K.; Savoie, B. M.; Momčilović, N.; Xu, Q.; Wolf, W. J.; Webb, M. A.; Billings, K. J.; Chou, N. H.; others. Science 2018, 362 (6419), 1144–1148.

BackgroundAnti-MDA5 antibody-positive dermatomyositis (anti-MDA5+DM) is a rare autoimmune disease associated with a high mortality rate due to rapid-progressive interstitial lung disease (RP-ILD), particularly in East Asia[1]. MDA5, acts as a cytoplasmic sensor of viral RNA, thus activating antiviral responses including the type I interferon (IFN) signaling pathway[2]. The involvement of type 1 IFN in the pathogenesis of MDA5+DM has been proposed based on the significantly elevated expression of its downstream stimulated genes(ISG) in muscle, skin, lung, and peripheral blood[3; 4]. Janus kinase inhibitor, which targets the IFN pathway, combined with glucocorticoid could improve the survival of early-stage MDA5+DM-ILD patients[5]. In clinical practice, there is still an urgent demand for sensitive biomarkers to facilitate clinical risk assessment and precise treatment.ObjectivesThis study aimed to investigate the clinical significance of interferon score, especially IFN-I score, in patients with anti-MDA5+DM.MethodsDifferent subtypes of idiopathic inflammatory myopathy, including anti-MDA5+DM(n=61), anti-MDA5-DM(n=20), antisynthetase syndrome(ASS,n=22),polymyositis(PM,n=6) and immune-mediated necrotizing myopathy(IMNM,n=9), and 58 healthy controls were enrolled.. A multiplex quantitative real-time PCR(RT-qPCR) assay using four TaqMan probes was utilized to evaluate two type I ISGs (IFI44, MX1, which are used for IFN-I score), one type II ISG (IRF1), and one housekeeping gene (HRPT1). Clinical features and disease activity index were compared between high and low IFN-I score groups in 61 anti-MDA5+DM patients. The association between laboratory findings and the predictive value of baseline IFN-I score level for mortality was analyzed.ResultsThe IFN scores were significantly higher in patients with anti-MDA5+DM than in HC (Figure 1A). The IFN-I score correlated positively with serum IFN α(r = 0.335, P =0.008), ferritin (r = 0.302, P = 0.018), and Myositis Disease Activity Assessment Visual Analogue Scale (MYOACT) score(r=0.426, P=0.001). Compared with patients with low IFN-I scores, patients with high IFN-I scores showed increased MYOACT score, CRP, AST, ferritin, and the percentages of plasma cells (PC%) but decreased lymphocyte count, natural killer cell count, and monocyte count. The 3-month survival rate was significantly lower in patients with IFN-I score > 4.9 than in those with IFN-I score ≤ 4.9(72.9% vs. 100%, P=0.044)(Figure 1B).ConclusionIFN score, especially IFN-I score, detected by multiplex RT-qPCR, can be a valuable biomarker for monitoring disease activity and predicting mortality in anti-MDA5+DM patients.References[1]I.E. Lundberg, M. Fujimoto, J. Vencovsky, R. Aggarwal, M. Holmqvist, L. Christopher-Stine, A.L. Mammen, and F.W. Miller, Idiopathic inflammatory myopathies. Nat Rev Dis Primers 7 (2021) 86.[2]G. Liu, J.H. Lee, Z.M. Parker, D. Acharya, J.J. Chiang, M. van Gent, W. Riedl, M.E. Davis-Gardner, E. Wies, C. Chiang, and M.U. Gack, ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity. Nat Microbiol 6 (2021) 467-478.[3]G.M. Moneta, D. Pires Marafon, E. Marasco, S. Rosina, M. Verardo, C. Fiorillo, C. Minetti, L. Bracci-Laudiero, A. Ravelli, F. De Benedetti, and R. Nicolai, Muscle Expression of Type I and Type II Interferons Is Increased in Juvenile Dermatomyositis and Related to Clinical and Histologic Features. Arthritis Rheumatol 71 (2019) 1011-1021.[4]Y. Ye, Z. Chen, S. Jiang, F. Jia, T. Li, X. Lu, J. Xue, X. Lian, J. Ma, P. Hao, L. Lu, S. Ye, N. Shen, C. Bao, Q. Fu, and X. Zhang, Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications. Nat Commun 13 (2022) 6458.[5]Z. Chen, X. Wang, and S. Ye, Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease. New England Journal of Medicine 381 (2019) 291-293.AcknowledgementsThis work was supported by the National Natural Science Foundation of China [81974251], and Shanghai Hospital Development Center, Joint Research of New Advanced Technology Project [SHDC12018106]Disclosure of InterestsNone Declared.

Objetivo: Esse estudo objetivou investigar percepções de estudantes de Odontologia quanto ao medo e à ansiedade em relação ao manejo de pacientes e ao risco de infecção por COVID-19. Materiais e métodos: Esse estudo transversal envolveu todos os alunos regularmente matriculados em Odontologia, no primeiro semestre de 2020, da Universidade Federal de Pelotas. Um questionário foi aplicado, coletando dados demográficos, nível de formação e perguntas relacionadas ao medo e ansiedade frente à pandemia de COVID-19. Quatro comparações de acordo com a fase da graduação (fase pré-clínica ou clínica), nível de graduação e pós-graduação e de acordo com os sexos foram feitas. Análises independentes para as comparações entre os sexos foram realizadas para os alunos de graduação e de pós-graduação (α<5%). Resultados: Foram incluídos 408 estudantes. Na graduação, mulheres relataram sentirem-se mais ansiosas ao realizar tratamento em pacientes com suspeita de COVID-19 (54%) e sentem mais medo ao ouvir que a infecção tem causado mortes (92,4%), na pós-graduação, responderam ser mais nervosas para conversar com pacientes em ambientes fechados em comparações com homens (P<0,05). Alunos em fase pré-clínica possuem significativamente menor receio (65,5%), ansiedade (32,3%) e nervosismo (28,3%) do contágio do COVID-19 quando comparados com aqueles na fase clínica. Conclusões: Mulheres e alunos na fase clínica apresentam maior ansiedade e nervosismo. Descritores: Ansiedade; Estudantes de Odontologia; Medo; Infecções por Coronavírus. Referências Chang J, Yuan Y, Wang D. [Mental health status and its influencing factors among college students during the epidemic of COVID-19]. Nan Fang Yi Ke Da Xue Xue Bao. 2020;40(2):171-176. World Health Organization. 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Ahmed MA, Jouhar R, Ahmed N, Adnan S, Aftab M, Zafar MS, Khurshid Z. Fear and Practice Modifications among Dentists to Combat Novel Coronavirus Disease (COVID-19) Outbreak. Int J Environ Res Public Health. 2020;17(8):2821. Talevi D, Socci V, Carai M, Carnaghi G, Faleri S, Trebbi E, di Bernardo A, Capelli F, Pacitti F. Mental health outcomes of the CoViD-19 pandemic. Riv Psichiatr. 2020;55(3):137-44. Mijiritsky E, Hamama-Raz Y, Liu F, Datarkar AN, Mangani L, Caplan J, Shacham A, Kolerman R, Mijiritsky O, Ben-Ezra M, Shacham M. Subjective Overload and Psychological Distress among Dentists during COVID-19. Int J Environ Res Public Health. 2020;17:5074. Rymarowicz J, Stefura T, Major P, Szeliga J, Wallner G, Nowakowski M, Pędziwiatr M. General surgeons' attitudes towards COVID-19: A national survey during the SARS-CoV-2 virus outbreak. Eur Surg. 2020;1-6. Adams JG, Walls RM. Supporting the Health Care Workforce During the COVID-19 Global Epidemic. JAMA. 2020;323(15):1439-40. Naz N, Iqbal S, Mahmood A. Stress, anxiety and depression among the dental students of university college of medicine and dentistry Lahore; Pakistan. Pak J Med Health Sci. 2017;11(4):1277-81. Waqas A, Iftikhar A, Malik Z, Aedma KK, Meraj H, Naveed S. Association of severity of depressive symptoms with sleep quality, social support and stress among Pakistani medical and dental students: A cross-sectional study. Global Psychiatry. 2019;2(2):211-20. Wang Y, Di Y, Ye J, Wei W. Study on the public psychological states and its related factors during the outbreak of coronavirus disease 2019 (COVID-19) in some regions of China. Psychol Health Med. 2020;1-10. Xiong J, Lipsitz O, Nasri F, Lui LMW, Gill H, Phan L, Chen-Li D, Iacobucci M, Ho R, Majeed A, McIntyre RS. Impact of COVID-19 pandemic on mental health in the general population: A systematic review. J Affect Disord. 2020;277:55-64. Liu N, Zhang F, Wei C, Jia Y, Shang Z, Sun L, Wu L, Sun Z, Zhou Y, Wang Y, Liu W. 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Heavy metals contamination is a serious threat to all life forms. Long term exposure of heavy metals can lead to different life-threatening medical conditions including cancers of different body parts. Phytoremediation and bioremediation offer a potential eco-friendly solution to such problems. Different microbes can interact with heavy metals in a variety of ways such as biotransformation, oxidation/reduction, and biosorption. Phytoremediation of the heavy metals using plants mostly involves rhizofilteration, phytoextraction, phytovolatization, and Phyto stabilization. A synergistic approach using both plants and microbes has proven much more efficient as compared to the individual applications of microbes or plants. This article aims to highlight the synergistic methods used in bioremediation, emphasizing the potent collaboration between bacteria and plants for environmental cleaning, along with the discussion of the importance of site-specific variables and potential constraints. 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Background: Treatment effect of current pharmacotherapies for migraine is unsatisfying. Discovering new anti-migraine natural products and nutraceuticals from large collections of Chinese medicine classical literature may assist to address this gap.Methods: We conducted a comprehensive search in the Encyclopedia of Traditional Chinese Medicine (version 5.0) to obtain migraine-related citations, then screened and scored these citations to identify clinical management of migraine using oral herbal medicine in history. Information of formulae, herbs and symptoms were further extracted. After standardisation, these data were analysed using frequency analysis and the Apriori algorithm. Anti-migraine effects and mechanisms of actions of the main herbs and formula were summarised.Results: Among 614 eligible citations, the most frequently used formula was chuan xiong cha tiao san (CXCTS), and the most frequently used herb was chuan xiong. Dietary medicinal herbs including gan cao, bai zhi, bo he, tian ma and sheng jiang were identified. Strong associations were constructed among the herb ingredients of CXCTS formula. Symptoms of chronic duration and unilateral headache were closely related with herbs of chuan xiong, gan cao, fang feng, qiang huo and cha. Symptoms of vomiting and nausea were specifically related to herbs of sheng jiang and ban xia.Conclusion: The herb ingredients of CXCTS which presented anti-migraine effects with reliable evidence of anti-migraine actions can be selected as potential drug discovery candidates, while dietary medicinal herbs including sheng jiang, bo he, cha, bai zhi, tian ma, and gan cao can be further explored as nutraceuticals for migraine.

Traditional Chinese Medicine (TCM) has been shown to be efficacious in treating leukemia for thousands of years. It has been shown that Shen Qi Sha Bai Decoction (SQSBD) has been extensively used in the treatment of acute myeloid leukemia (AML). However, the mechanism of SQSBD in treating AML remains unclear. In this study, we employed network pharmacology to analyze the potential active components and elucidate molecular mechanism of SQSBD in treating AML. A total of 268 active components were identified from SQSBD, among which 9 key components (Quercetin, luteolin, kaempferol, licochalcone A, formononetin, wogonin, β-sitosterol, oroxylin A, naringenin, and baicalein) were hit by the 6 hub targets (CDK1, MAPK1, JUN, PCNA, HSB1, STAT3) associated with leukemia. Molecular docking showed that two core active components, quercetin and licochalcone A, exhibited the highest component-like properties (DL), and could bind well to CDK1 and MAPK1 protein. The experimental validation of these two components showed that quercetin inhibited cell growth through CDK1 dephosphorylation-mediated cell cycle arrest at G2/M phase in human AML U937 and HL60 cells, and licochalcone A induced cell differentiation in these leukemia cells via activation of MAPK1 and upregulation of CD11b. All these results indicate that SQSBD is effective in the treatment of AML, and quercetin and licochalcone A are the major candidate compounds for AML treatment.

Aplastic Anemia (AA) is a rare but fatal hematologic disease that may occur at any age and especially higher in Asia. We investigated whether Chinese herbal medicine (CHM) is beneficial to AA patients as a complementary therapy using a nationwide population-based database in Taiwan between 2000–2016. Patient survival was estimated by Kaplan‒Meier survival analyses and Cox proportional-hazard model. CHM-users presented lower risks of overall and anemia-related mortalities when compared to non-users. The risk of overall mortality for CHM-users in AA patients was 0.70-fold [adjusted hazard ratio (aHR): 0.70, 95% confidence interval (CI): 0.66-0.74, p &lt; 0.001). The risk of anemia-related mortality was lower in CHM-users when compared to non-users (aHR: 0.46, 95% CI: 0.32-0.67, p &lt; 0.001). The association rule analysis revealed that CHM pairs were Ban-Zhi-Lian (BZL; Scutellaria barbata D. Don)→Bai-Hua-She-She-Cao (BHSSC; Oldenlandia diffusa (Willd.) Roxb.), followed by Dang-Gui (DG; Angelica sinensis (Oliv.) Diels)→Huang-Qi (HQi; Astragalus membranaceus (Fisch.) Bunge), and Xian-He-Cao (XHC; Agrimonia pilosa f. borealis (Kitag.) Chu)→Gui-Pi-Tang (GPT). Network analysis showed that BZL, BHSSC, DG, HQi, XHC, GPT, and Dan-Shen (DanS; Salvia miltiorrhiza var. charbonnelii (H.Lév.) C.Y.Wu) were commonly used CHMs for AA patients. Therefore, further studies for these commonly prescribed herbs are needed in functional investigations in hematopoiesis-stimulating effect and large-scale randomized controlled trials (RCT) in bone marrow failure related diseases.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer involving epithelial squamous-cell carcinoma of the nasopharynx that mainly occurs in individuals from East and Southeast Asia. We investigated whether Chinese herbal medicine (CHM) as a complementary therapy offers benefits to these patients. We retrospectively evaluated the Taiwan Cancer Registry (Long Form) database for patients with advanced NPC, using or not using CHM, between 2007–2013. Cox proportional-hazard model and Kaplan‒Meier survival analyses were applied for patient survival. CHM-users showed a lower overall and cancer-related mortality risk than non-users. For advanced NPC patients, the overall mortality risk was 0.799-fold for CHM-users, after controlling for age, gender, and Charlson comorbidity index (CCI) score (Cancer stages 3 + 4: adjusted hazard ratio [aHR]: 0.799, 95% confidence interval [CI]: 0.676–0.943, p = 0.008). CHM-users also showed a lower cancer-related mortality risk than non-users (aHR: 0.71, 95% CI: 0.53–0.96, p = 0.0273). Association rule analysis showed that CHM pairs were Ban-Zhi-Lian (BZL; Scutellaria barbata D.Don) and For single herbs, Bai-Hua-She-She-Cao (Herba Hedyotis Diffusae; Scleromitrion diffusum (Willd.) R.J.Wang (syn. Hedyotis diffusa Willd.) and Mai-Men-Dong (MMD; Ophiopogon japonicus (Thunb.) Ker Gawl.), and Gan-Lu-Yin (GLY) and BHSSC. Network analysis revealed that BHSSC was the core CHM, and BZL, GLY, and Xin-Yi-Qing-Fei-Tang (XYQFT) were important CHMs in cluster 1. In cluster 2, ShengDH, MMD, Xuan-Shen (XS; Scrophularia ningpoensis Hensl.), and Gua-Lou-Gen (GLG; Trichosanthes kirilowii Maxim.) were important CHMs. Thus, as a complementary therapy, CHM, and particularly the 8 CHMs identified, are important for the treatment of advanced NPC patients.

In this study, acidic hydrolysis to release the aglycone quercetin from plant extracts under ultrasound-assisted conditions was investigated. Based on the stability of quercetin, the suitable conditions were as follows: methanol/H2O (50:20, v/v) was added to the powder plants (ratio 50:1, ml/g), these mixtures were placed in ultrasonic bath of 37 kHz/550W; kept at 70°C within 30 min and then filtered. The filtrate was acidified with HCl (70:8, ml/ml). Lastly, the ultrasonication was carried out for hydrolysis for 1 hour (the second ultrasound) to obtain quercetin. We have obtained quercetin containing hydrolyzed extract from 10 plants to determine quercetin concentrations (using the HPLC optimized conditions) and evaluate the antioxidant activity (the capability to scavenge the DPPH radical). In 10 samples of plants that were obtained, both quercetin concentrations and antioxidant activity in the plant extract of the flower buds of Sophora japonica L have the highest value, then to the plant extract of Nelumbo nucifera Gaertn. In the Sophora flower-bud and the lotus leaf, quercetin content is calculated on dry material (mg/100g), 15423.04 and 5190.82 respectively; the average percentage inhibition of DPPH 100 µM (%) 55.26% and 32.23%., respectively. Keywords: Quercetin, HPLC, acid hydrolysis, ultrasound-assisted, antioxidant activity. References [1] S.G. Dmitrienko, V.A. Kudrinskaya, V.V. Apyari, Methods of extraction, preconcentration, and determination of quercetin, Journal of Analytical Chemistry 67 (4) (2012) 299-311. https://doi.org/ 101134/S106193481204003X.[2] H. Nishimuro, H. Ohnishi, M. Sato, M. Ohnishi-Kameyama, I. Matsunaga, S. Naito, K. Ippoushi, H. Oike, T. Nagata, H. Akasaka, S. Saitoh, K. Shimamoto, M. Konori, Estimated daily intake and seasonal food sources of quercetin in Japan, Nutrients 7 (4) (2015) 2345-2355. https://doi.org/ 10.3390/nu7042345.[3] C. Zhao, X. Ren, C. Li, H. Jiang, J. Guan, W. Su, Y. Li, Y. Tian, T. Wang, S. Li, Coupling ultrasound with heat-reflux to improve the extraction of quercetin, kaempferol, ginkgetin and sciadopitysin from Mairei Yew leaves, Applied Sciences 9 (4) (2019) 795-810. https://doi.org/10.3390/app9040795.[4] J. Azmir, M.S.I. Zaidul, M.M. Rahman, K.M. Sharif, A. Mohamed., F. Sahena, A.H.M. Jahurul, K. Ghafoor, N.A.N. Norulain, K.A.M. Omar, Techniques for extraction of bioactive compounds from plant materials : A review, Journal of Food Engineering 117 (4) (2013) 426-434. https://doi. org/10.1016/j.jfoodeng.2013.01.014.[5] L.H. Hoang, D.T.H. Anh, D.T. Hue, T.T.K. Oanh, N.Q. Huy, Determination of Quercetin Aglycone in Flos Sophorae japonicae Extract by High Performance Liquid Chromatography, VNU Journal of Science: Natural Sciences and Technology 33 (1S) (2017) 214-223 (in Vietnamese). https://doi.org/10.25073/2588-1140/ vnunst.4534. [6] A.M. Nuutila, K. Kammiovirta, M. Oksman-Caldentay, Comparison of methods for the hydrolysis of flavonoids and phenolic acids from onion and spinach for HPLC analysis, Food Chemistry 76 (4) (2002) 519-525. https://doi.org/ 10.1016/S0308-8146(01)00305-3.[7] L. Qiao, Y. Sun, R. Chen, Y. Fu, W. Zhang, X. Li, J. Chen, Y. Shen, X. Ye, Sonochemical effects on 14 flavonoids common in citrus : Relation to stability, Plos One 9 (2) (2014) e87766. https://doi. org/10.1371/journal.pone.0087766.[8] W. Brand-Williams, M.E. Cuvelier, C. Berset, Use of a free radical method to evaluate antioxidant activity, LWT - Food Science and Technology 28 (1995) 25-30. https://doi.org/10.1016/S0023-6438 (95)80008-5. [9] M. Biesaga, Influence of extraction methods on stability of flavonoids, Journal of Chromatography A 1218 (2011) 2505-2512. https://doi.org/10.1016/ j.chroma.2011.02.059.[10] L. Paniwnyk, E. Beaufoy, J.P. Lorimer, T.J. Manson, The extraction of rutin from flower buds of Sophora japonica, Ultrasonics Sonochemistry 8 (3) (2001) 299-301. https://doi.org/10.1016/S1350 -4177(00)00075-4.[11] X. He, Y. Bai, Z. Zhao, X. Wang, J. Fang, L. Huang, M. Zeng, Q. Zhang, Y. Zhang, Z. Zheng, Local and traditional uses, phytochemistry, and pharmacology of Sophora japonica L.: A review, Journal of Ethnopharmacology 187 (2016) 160-182. https://doi.org/10.1016/j.jep.2016.04.014.[12] I.Y. Bae, B.Y. Kwak, H.G. Lee, Synergistic antiradical action of natural antioxidants and herbal mixture for preventing dioxin toxicity, Food Science and Biotechnology 21 (2) (2012) 491-496. https://doi.org/10.1007/s10068-012-0062-9.

The above article, published online 15 Feb 2020 on Wiley Online Library (https://onlinelibrary.wiley.com/doi/10.1002/ijc.32911), has been retracted by agreement between the journal Editor‐in‐Chief (Prof. Christoph Plass), the authors, and Wiley Periodicals LLC. The retraction has been agreed following an investigation that began with a third party allegation of inappropriate image duplication in Figure 3b and 3h. After requesting original data from the authors also for the Western Blot figures in the entire manuscript, a detailed analysis revealed additional irregularities in the original data. As the concerns relate to several figure panels, the editors no longer have confidence in the data reported in this article.