摘要：
A549 cells were treated with different concentrations of anlotinib to create anlotinib‐resistant A549 cells (A549/anlotinib cells). miR‐181a‐3p mimics were transfected into A549/anlotinib cells. Meanwhile, A549 and A549/anlotinib cells were treated with β‐sitosterol at different concentrations. Cell Counting Kit‐8 (CCK‐8) was used to measure cell proliferation. The apoptosis level was detected by flow cytometry. Real‐time fluorescence quantitative PCR was used to detect the expression of miR‐181a‐3p. miR‐181a‐3p interaction with H/ACA ribonucleoprotein assembly factor (SHQ1) was predicted by miRDB and TargetScan Human databases and verified by luciferase reporter assay. The expressions of SHQ1, activating transcription factor 6 (ATF6) and glucose regulated protein 78 (GRP78) were detected by western blot. Our results show that β‐Sitosterol markedly promoted anlotinib‐resistant A549 cells apoptosis and inhibited the cell proliferation via activating SHQ1/UPR signaling via inhibiting miR‐181a‐3p. Abstract Anlotinib is used for the treatment of advanced non‐small cell lung cancer; however, the emergence of drug resistance limits its clinical application. β‐sitosterol may also be used to treat lung cancer, but there have been no studies evaluating β‐sitosterol against anlotinib‐resistant lung cancer. The purpose of this study was to determine the mechanism by which β‐sitosterol enhances the sensitivity of lung cancer cells to anlotinib. A549 cells were treated with different concentrations of anlotinib to generate anlotinib‐resistant cells (A549/anlotinib cells). miR‐181a‐3p mimics were transfected into A549/anlotinib cells. A549 and A549/anlotinib cells were treated with β‐sitosterol at various concentrations. The Cell Counting Kit‐8 (CCK‐8) assay was used to measure cell proliferation. Apoptosis was assessed by flow cytometry. Real‐time quantitative PCR was used to measure the expression of miR‐181a‐3p. The interaction of miR‐181a‐3p with the H/ACA ribonucleoprotein assembly factor (SHQ1) was predicted using the miRDB and TargetScan Human databases and verified with a luciferase reporter assay. The expression of SHQ1, activating transcription factor 6 (ATF6), and glucose‐regulated protein 78 (GRP78) were measured by western blot analysis. β‐Sitosterol effectively suppressed A549/anlotinib cell proliferation and promoted apoptosis. SHQ1 is a downstream target of miR‐181a‐3p. The expression of miR‐181a‐3p was inhibited; however, SHQ1 expression was increased by β‐sitosterol treatment of A549/anlotinib cells. The inhibition of SHQ1, ATF6, and GRP78 protein expression by β‐sitosterol in A549/anlotinib cells was rescued by increased miR‐181a‐3p. β‐Sitosterol markedly promotes anlotinib‐resistant A549 cell apoptosis and inhibits cell proliferation by activating SHQ1/UPR signaling through miR‐181a‐3p inhibition.
期刊：
Journal of Ethnopharmacology,2024年320:117417 ISSN：0378-8741
通讯作者：
Jin, J
作者机构：
[Zhang, Shuihan; Jin, Jian; Liu, Tingting; Jin, J; Shen, Bingbing; Zeng, Hongliang; Qin, You; Xie, Zhenni] Hunan Acad Chinese Med, Inst Chinese Med Resources, Changsha 410013, Hunan, Peoples R China.;[Zhang, Shuihan; He, Dan; Zeng, Hongliang; Xie, Zhenni] Hunan Univ Chinese Med, Grad Sch, Changsha 410036, Hunan, Peoples R China.;[Luo, Ji] Hunan Acad Chinese Med, Affiliated Hosp, Changsha 410013, Hunan, Peoples R China.
通讯机构：
[Jin, J ] H;Hunan Acad Chinese Med, Inst Chinese Med Resources, Changsha 410013, Hunan, Peoples R China.
关键词：
Anti-proliferation;MAPK3;PIK3R3;Poria cocos triterpenoids component fraction;Stomach cancer
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos F.A. Wolf is an edible fungus with forming sclerotia, which has the effects of promoting diuresis, exuding dampness, invigorating the spleen, and regulating the stomach. P. cocos has a high application in the clinic of traditional Chinese medicine, and some studies have indicated that P. cocos has a good effect on tumor diseases. According to ancient records and modern studies, P. cocos wine offers beneficial effects in terms of strengthening tendons and bones and anti-tumor effects. AIM OF THE STUDY: To understand the substance composition of P. cocos ethanol-soluble extract (PESE) and then further study the effect and potential mechanism of PESE components on gastric cancer. MATERIALS AND METHODS: In vitro and in vivo experiments were performed to detect the cell activity and apoptotic condition. Differential expression analysis and pathway enrichment were performed based on transcriptomics and were verified by real-time polymerase chain reaction and western blotting. The mice of the stomach cancer tumor model were randomly categorized into three groups. The weight and tumor volume of the mice were measured, and the pathological characteristics of tumor tissue and immunohistochemical changes were determined. Then, the main active components of PESE were detected by MKN45cell fishing. RESULTS: In vitro experiments showed that PESE inhibited the proliferation of MKN45cells, but it did not induce apoptosis. Based on the transcriptome and western blotting results, the inhibition of MKN45 proliferation by PESE may be influenced by mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase-protein kinase B (PI3K-Akt) signaling pathways. In vivo experiments showed that PESE inhibited tumor growth in mice and caused partial necrosis of tumor cells but had no toxic effect on mice. Cell fishing identified nine triterpenoids of P. cocos as the major active components of PESE. CONCLUSIONS: The results indicated that PESE has a significant inhibitory effect on stomach cancer, and its mechanism probably commonly affects the MAPK and PI3K-Akt signaling pathways, which could be due to the triterpenoid components.
作者机构：
[林旭鑫] Graduate School, Hunan University of Chinese Medicine, Changsha Hunan, 410208, P. R. China;[尚利杰; 付豪; 林旭鑫; 周鹭凡; 常青; 赵刚; 王怡帆] First Department of Minimally Invasive Spine, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang Henan, 471000, P. R. China;[沈素红; 付卓] Department of Functional Examination, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang Henan, 471000, P. R. China
作者机构：
[Hu, Fan; Li, Mei; Wang, Wei; Xu, Chongsi; Xiao, You] Hunan Univ Tradit Chinese Med, Affiliated Hosp 2, Dept Anorectal 5, Changsha, Peoples R China.;[He, Yuanyuan] Hunan Univ, Hunan Univ Chinese Med, Grad Sch, Changsha, Peoples R China.;[Wang, Zhenquan] Hunan Univ Tradit Chinese Med, Affiliated Hosp 2, Dept Anorectal 3, Changsha 410005, Peoples R China.;[Cao, Yi] Univ South China, Hengyang Med Sch, Sch Publ Hlth, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang, Peoples R China.
通讯机构：
[Zhenquan Wang] T;Third Department of Anorectal, The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, China
关键词：
3D Caco-2 spheroids;Kruppel-like factor 4 (KLF4);MoS2 nanosheets (NSs);Oral exposure;RNA-sequencing
摘要：
MoS(2) nanosheets (NSs) are novel 2D nanomaterials (NMs) being used in many important fields. Recently, we proposed the need to evaluate the influences of NMs on Kruppel-like factors (KLFs) even if these materials are relatively biocompatible. In this study, we investigated the influences of MoS(2) NSs or bulk on KLF4 signaling pathway in 3D Caco-2 spheroids in vitro and mouse intestines in vivo. Through the analysis of our previous RNA-sequencing data, we found that exposure to MoS(2) NSs or bulk activated KLF4 expression in 3D Caco-2 spheroids. Consistently, these materials also activated KLF4-related gene ontology (GO) terms and down-regulated a panel of KLF4-downstream genes. To verify these findings, we repeatedly exposed mice to MoS(2) NSs or bulk materials via intragastrical administration (1 mg/kg bodyweight, once a day, for 4 days). It was shown that oral exposure to these materials decreased bodyweight, leading to relatively higher organ coefficients. As expected, exposure to both types of materials increased Mo elements as well as other trace elements, such as Zn, Fe, and Mn in mouse intestines. The exposure also induced morphological changes of intestines, such as shortening of intestinal villi and decreased crypt depth, which may result in decreased intestinal lipid staining. Consistent with RNA-sequencing data, we found that material exposure increased KLF4 protein staining in mouse intestines and decreased two KLF4 downstream proteins, namely extracellular signal-regulated kinase (ERK) and serine/threonine kinase (AKT). We concluded that MoS(2) materials were capable to activate KLF4-signaling pathway in intestines both in vivo and in vitro.
摘要：
Circadian rhythms are internal 24-h intrinsic oscillations that are present in essentially all mammalian cells and can influence numerous biological processes. Cardiac function is known to exhibit a circadian rhythm and is strongly affected by the day/night cycle. Many cardiovascular variables, including heart rate, heart rate variability (HRV), electrocardiogram (ECG) waveforms, endothelial cell function, and blood pressure, demonstrate robust circadian rhythms. Many experiential and clinical studies have highlighted that disruptions in circadian rhythms can ultimately lead to maladaptive cardiac function. Factors that disrupt the circadian rhythm, including shift work, global travel, and sleep disorders, may consequently enhance the risk of cardiovascular diseases. Some cardiac diseases appear to occur at particular times of the day or night; therefore, targeting the disease at particular times of day may improve the clinical outcome. The objective of this review is to unravel the relationship between circadian rhythms and cardiovascular health. By understanding this intricate interplay, we aim to reveal the potential risks of circadian disruption and discuss the emerging therapeutic strategies, specifically those targeting circadian rhythms. In this review, we explore the important role of circadian rhythms in cardiovascular physiology and highlight the role they play in cardiac dysfunction such as ventricular hypertrophy, arrhythmia, diabetes, and myocardial infarction. Finally, we review potential translational treatments aimed at circadian rhythms. These treatments offer an innovative approach to enhancing the existing approaches for managing and treating heart-related conditions, while also opening new avenues for therapeutic development.
作者机构：
[林旭鑫] Graduate School, Hunan University of Chinese Medicine, Changsha Hunan, 410208, P. R. China;[尚利杰; 沈素红; 林旭鑫; 王庆丰; 付晓燕; 赵刚] First Department of Minimally Invasive Spine, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang Henan, 471000, P. R. China
期刊：
Journal of Antimicrobial Chemotherapy,2023年78(1):141-149 ISSN：0305-7453
通讯作者：
Xin Li
作者机构：
[Tian, Miaomei; Tong, Huan; Guo, Siwei; Xu, Bing; Li, You; Li, Xin; Yan, Bingqian] Third Hosp Changsha, Changsha, Hunan, Peoples R China.;[Tong, Huan; Guo, Siwei; Xu, Bing; Li, Xin] Inst Clin Applicat Antibiot, Changsha, Hunan, Peoples R China.;[Tian, Miaomei; Li, You; Yan, Bingqian] Hunan Univ Chinese Med, Grad Sch, Changsha, Hunan, Peoples R China.;[Wei, Minji] Peking Univ, Hosp 1, Inst Clin Pharmacol, Beijing, Peoples R China.;[Shao, Jing] Nanjing Yoko Pharmaceut Co Ltd, Nanjing, Peoples R China.
通讯机构：
[Xin Li] T;The Third Hospital of Changsha , Changsha, Hunan , China<&wdkj&>Institute of Clinical Application of Antibiotics , Changsha, Hunan , China
摘要：
OBJECTIVES: Sitafloxacin is one of the newer generation fluoroquinolones with highly active against multidrug-resistant (MDR) bacteria. Our objectives were to identify the sitafloxacin pharmacokinetic/pharmacodynamic (PK/PD) index and breakpoints against MDR isolate in the urinary tract infection model. METHODS: Forty-eight MDR isolates underwent sitafloxacin and levofloxacin microdilution susceptibility testing. A 24 h in vitro model was established that simulated the healthy subjects urodynamics of sitafloxacin fumarate injection. Ten MDR isolates (four carbapenem-resistant Escherichia coli, three carbapenem-resistant P. aeruginosa and three vancomycin-resistant E. faecium) were selected. The drug efficacy was quantified by the change in log colony counts within 24 h. A sigmoid Emax model was fitted to the killing effect data. Monte Carlo simulations were performed to assess target attainment for the sitafloxacin fumarate doses of 100 and 200 mg q24h. RESULTS: Analysis indicated that the MICs of sitafloxacin were all significantly lower than that of levofloxacin (P < 0.01). The UAUC0-24h/MIC targets required to achieve stasis, 1-log10 killing and 2-log10 killing were 63.60, 79.49 and 99.45 (carbapenem-resistant E. coli), 60.85, 90.31 and 128.95 (carbapenem-resistant P. aeruginosa), 65.91, 77.81 and 103.11 (vancomycin-resistant E. faecium). Monte Carlo simulation showed the infusion of sitafloxacin fumarate 100 mg q24h was able to achieve 90% probability of target attainment against bacteria with MIC of 8 mg/L for the common complicated urinary tract infections. CONCLUSIONS: Sitafloxacin fumarate injection is an alternative therapeutic agent for the treatment of UTIs caused by MDR isolates.
期刊：
British Journal of Clinical Pharmacology,2023年89(10):3067-3078 ISSN：0306-5251
通讯作者：
Xu, Bing;Li, X
作者机构：
[Tian, Miaomei; Li, You; Yan, Bingqian] Hunan Univ Chinese Med, Grad Sch, Changsha, Hunan, Peoples R China.;[Tian, Miaomei; Tong, Huan; Guo, Siwei; Xu, Bing; Li, You; Li, Xin; Li, Yuan; Yan, Bingqian] Third Hosp Changsha, Changsha, Hunan, Peoples R China.;[Tong, Huan; Guo, Siwei; Xu, Bing; Li, Xin; Li, Yuan] Inst Clin Applicat Antibiot, Changsha, Hunan, Peoples R China.;[Yu, Yunsong] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Infect Dis, Sch Med, Hangzhou, Peoples R China.;[Shao, Jing; Xin, Yuxia] Nanjing YOKO Pharmaceut Co Ltd, Nanjing, Peoples R China.
通讯机构：
[Li, X ; Xu, B] T;Third Hosp Changsha, 176 Western Laodong Rd, Changsha 410015, Hunan, Peoples R China.
关键词：
Monte Carlo simulation;YK-1169;carbapenem-resistant Klebsiella pneumoniae;pharmacokinetic;pharmacokinetic/pharmacodynamic
摘要：
ObjectiveThis study (NCT05588531) aimed to evaluate the safety and pharmacokinetics of cefepime-avibactam (YK-1169) in healthy Chinese subjects and explore the optimal regimen for treating carbapenem-resistant Klebsiella pneumoniae (CRKP) based on the pharmacokinetic/pharmacodynamic evaluation. MethodsYK-1169 single-ascending doses (0.5, 1.25, 2.5 or 3.75 g, 2-h infusion) and multiple doses (2.5 or 3.75 g every 8 h [q8h], 2-h infusion) given for 7 days were evaluated in pharmacokinetic studies. Subjects were randomized to receive cefepime (2 g), avibactam (0.5 g) or YK-1169 (2.5 g) to assess drug-drug interactions. The minimum inhibitory concentrations (MICs) of YK-1169 were determined by the broth microdilution method. Monte Carlo simulation was used to evaluate 10 different dose regimens. ResultsCefepime and avibactam both showed a linear pharmacokinetic profile. No accumulation was found after multiple doses. The cefepime C-max,C-ss and AUC(0-infinity,ss) were 9.20 and 16.0 mu g/mL, 407.2 and 659.45 mu g center dot h/mL in the 2.5 and 3.75 g multiple-dose groups, respectively. The avibactam C-max,C-ss and AUC(0-infinity,ss) were 0.545 and 0.837 mu g/mL, 53.31 and 79.55 mu g center dot h/mL in the 2.5 and 3.75 g multiple-dose groups, respectively. Cefepime and avibactam did not affect each other's pharmacokinetics. No serious adverse events occurred. All regimens achieved 90% probability of target attainment (PTA) goals when the MIC was <= 8 mg/L. The regimens of 2.5 (q8h, 2-h infusion), 3.75 (q8h, 2-, 3- and 4-h infusions) and 7.5 g (24-h continuous infusion) reached a 90% cumulative fraction of response. ConclusionYK-1169 had good antibacterial activity against CRKP and could be an option for CRKP infections. The regimen of 2.5 g q8h intravenously guttae (ivgtt) 2 h should be considered in future clinical trials.
摘要：
Improving hepatic glucose and lipid metabolisms is an important strategy to treat type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease (T2DM-NAFLD). Silybin (SLB) has the potential hepatoprotection, while its oral bioavailability is poor. This study aims to investigate the functional role and mechanism of liposomal SLB in modulating glucose/lipid metabolism in T2DM-NAFLD. SLB was prepared by thin film dispersion method and characterized using dynamic light scattering, scanning electron microscope, high performance liquid chromatography and zeta potential analyzer. A rat model of T2DM-NAFLD was used to determine the role of liposomal SLB in regulating glycolipid metabolism and hepatic damage. Rat primary hepatocytes were used to demonstrate the hepatoprotection mechanism of liposomal SLB. The encapsulation efficiency was more than 80%, which showed the average particle size of 119.76 nm. Also, the average Zeta potential was -4.76 mV. These liposomes were spherical. In rats with T2DM-NAFLD, liposomal SLB alleviated insulin resistance and lipid metabolism, thereby improving hepatic lipid accumulation, inflammation and fibrosis. Besides, liposomal SLB elevated AMPK phosphorylation, and decreased collagen I/III, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and the phosphorylation of Smad2/3. In hepatocyte model, compound C partially reversed the effects of liposomal SLB on cell viability, glycolipid metabolism and AMPK/TGF-β1/Smad pathway activation. Liposomal SLB ameliorates hepatic glucose and lipid metabolisms in T2DM-NAFLD via activating AMPK/TGF-β1/Smad pathway, providing an efficient strategy for treating T2DM-NAFLD.
作者机构：
[赖碧玉] School of Graduate, Hunan University of CM, Changsha 410208, China. 1494029288@qq.com;[李兴; 洪梦颖; 何永嘉; 陈瑶] School of Graduate, Hunan University of CM, Changsha 410208, China;[王双双; Li, Xing; 刘丹] Department of Rehabilitation, Changsha Chinese Medicine Hospital/Eighth Hospital of Changsha City, Changsha 410100, Hunan Province;[聂晶] Central South University;[佘畅] Department of Rehabilitation, Changsha Chinese Medicine Hospital/Eighth Hospital of Changsha City, Changsha 410100, Hunan Province. shechang159@163.com. LA - eng
作者机构：
[Hu, Zhuoyu; Hu, Qi; Chen, Xiangdong] Hunan Univ Chinese Med, Dept ophthalmol, Hosp 1, Changsha, Peoples R China.;[Wang, Xuan] Hunan Univ Chinese Med, Grad Sch, Changsha, Peoples R China.;[Chen, Xiangdong] Hunan Univ Chinese Med, Hosp 1, 95 Shaoshan Middle Rd, Changsha, Hunan, Peoples R China.
通讯机构：
[Chen, XD ] H;Hunan Univ Chinese Med, Hosp 1, 95 Shaoshan Middle Rd, Changsha, Hunan, Peoples R China.
关键词：
apoptosis;autophagy;diabetes retinopathy;traditional Chinese medicine monomer
摘要：
Diabetic retinopathy (DR) has become one of the top 3 blinding eye diseases in the world. In spite of recent therapeutic breakthroughs, it is not yet possible to cure DR through pharmacotherapy. Cell death is thought to play a key role in the pathogenesis of DR. Moderate modulation of cellular autophagy and inhibition of apoptosis have been identified as effective targets for the treatment of DR. Numerous phytochemicals have emerged as potential new drugs for the treatment of DR. We collected basic DR research on herbal monomers through keywords such as autophagy and apoptosis, and conducted a systematic search for relevant research articles published in the PubMed database. This review provides the effects and reports of herbal monomers on various DR cellular and animal models in vivo and in vitro in the available literature, and emphasizes the importance of cellular autophagy and apoptosis as current DR therapeutic targets. Based on our review, we believe that herbal monomers that modulate autophagy and inhibit apoptosis may be potentially effective candidates for the development of new drugs in the treatment of DR. It provides a strategy for further development and application of herbal medicines for DR treatment.
作者机构：
[Huang, Pan; Li, Ying; Peng, Youhua; Zeng, Bijun; Zhang, Yujin; Wang, Haizhen; Yang, Zhibo; Luo, Meijunzi] Hunan Univ Chinese Med, Hosp 2, Dept Dermatol, Domest Class Discipline Construct Project Chinese, Changsha 410005, Hunan, Peoples R China.;[Tang, Qing; Gao, Jie] Hunan Univ Chinese Med, Grad Sch, Changsha 410005, Hunan, Peoples R China.;[Gao, Jie] Ninth Hosp Changsha, Dept Dermatol, Changsha 410004, Hunan, Peoples R China.
通讯机构：
[Bijun Zeng; Zhibo Yang] D;Department of Dermatology, The Second Hospital of Hunan University of Chinese Medicine, The Domestic First-class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Department of Dermatology, The Second Hospital of Hunan University of Chinese Medicine, The Domestic First-class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine, Changsha, China
摘要：
BACKGROUND: Androgenetic alopecia can affect up to 70% of males and 40% of females; however, certain therapeutic medications offer partial and transitory improvement but with major side effects. Dendrobium officinale polysaccharide (DOP) has been reported to improve androgen-related hair loss in mice, but the molecular mechanism remains unclear. OBJECTIVES: To explore the effects of DOP on androgenetic alopecia. METHODS: In this study, testosterone was subcutaneously administered to shave dorsa skin of mice to establish androgenetic alopecia; the effects of DOP in androgenetic alopecia were explored by DOP administration. RESULTS: Testosterone treatment extended the time of skin growing dark and hair growing, decreased the mean numbers of follicles in skin tissues, decreased β-catenin and cyclin D1 levels, and elevated testosterone, DHT (dihydrotestosterone), and 5α-reductase levels. In contrast, DOP administration shortened skin growing dark and hair growing times, promoted follicle cell proliferation, increased follicle numbers, increased β-catenin and cyclin D1 levels, and decreased testosterone, DHT, and 5α-reductase levels. CONCLUSION: DOP application significantly improved testosterone-induced hair follicle miniaturization and hair loss, possibly through affecting the Wnt signaling and hair follicle stem cell functions. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
摘要：
Background: Psoralidin (PL) could affect the differentiation of bone marrow mesenchymal stem cells (BMSCs). The role of PL is still unclear in adipose-derived stem cells (ADSCs). Aims: This study aimed to investigate the effects of PL on ADSCs differentiation into nucleus pulposus-like cells and the TGF-beta/Smad signaling pathway. Methods: The proliferation and apoptosis of ADSCs were detected. The nucleus pulposus cell-related markers (CD24, BASP1, KRT19, and Aggrecan) and TGF-beta/Smad signaling pathway indexes were analyzed. Results: The results showed that compared to the control group, the cell activity was increased in the PL group, and the apoptosis rate was decreased. The mRNA and protein levels of nucleus pulposus cells markers (CD24, BASP1, KRT19, Aggrecan, and Collagen Type II) and TGF-beta/Smad signaling pathway-related indexes (TGF-beta, SMAD2, and SMAD3) were increased in PL group. After treatment with PL and TGF-beta silencing, the TGF- beta/Smad signaling pathway-related indicators (TGF-beta, SMAD2, and SMAD3) and nucleus pulposus cells markers (CD24, BASP1, KRT19, Aggrecan, and Collagen Type II) were found to be higher in the sh-TGF-beta +PL group than in the sh-TGF-beta group. Conclusion: In conclusion, our study showed that PL might induce the differentiation of ADSCs to nucleus pulposus cells through the TGF-beta/Smad signaling pathway. It might have the potential application value in the treatment of intervertebral disc degeneration.
摘要：
BACKGROUND: Many epidemiological studies have shown that idiopathic pulmonary fibrosis (IPF) is a risk factor for lung cancer (LC), but these studies do not provide direct evidence of a causal association between the two diseases. We investigated the causal association between IPF and different pathological types of LC based on the Mendelian randomization (MR) study. METHODS: The genome-wide association study (GWAS) data of IPF and LC were obtained from the latest published articles, and instrumental variables (IVs) for analysis were obtained after screening and eliminating the confounders. MR Analysis was carried out with the help of random effects inverse variance weighting (re-IVW), MR-egger, and weighted median method, and a comprehensive sensitivity test was conducted. RESULTS: The results of re-IVW analysis showed that IPF may increase the risk of lung squamous cell carcinoma (LUSC) (OR = 1.045, 95% CI 1.011 to 1.080, P = 0.008). In addition, no causal relationship was found between IPF and overall LC (OR = 0.977, 95% CI 0.933 to 1.023, P = 0.32), lung adenocarcinoma (LUAD) (OR = 0.967, 95% CI 0.903 to 1.036, P = 0.345) and small cell lung carcinoma (SCLC) (OR = 1.081, 95% CI 0.992 to 1.177, P = 0.074). A comprehensive sensitivity analysis ensured the reliability of the study. CONCLUSION: In conclusion, from the perspective of genetic association, we found that IPF is an independent risk factor for LUSC and may increase the risk of LUSC, but no such causal relationship was found in LUAD and SCLC.
作者机构：
[方闯; 匡泓俊; 曹洋; 夏叶婉] Postgraduate School of Hunan University of Chinese Medicine, Changsha 410208, China;[钟峰; 章薇; 罗容] Department of Acupuncture and Tuina Rehabilitation, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410007;[文钱] Department of Traditional Chinese Medicine, Huaihua Hospital of Traditional Chinese Medicine, Huaihua 418099, Hunan Province
作者：
Nie, Duorui;Liu, Siyu;Cai, Si;Xing, Xiaoqi;Xu, Fei
期刊：
Advances in Therapy,2022年39(11):5043-5057 ISSN：0741-238X
通讯作者：
Fei Xu
作者机构：
[Nie, Duorui; Liu, Siyu] Hunan Univ Chinese Med, Grad Sch, Changsha, Peoples R China.;[Cai, Si] China Pharmaceut Univ, Inst Technol, Nanjing, Peoples R China.;[Xing, Xiaoqi; Xu, Fei] Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Peoples R China.;[Xu, Fei] Hunan Engn Technol Res Ctr Bioact Subst Discovery, Changsha, Peoples R China.;[Xu, Fei] Hunan Prov Sino US Int Joint Res Ctr Therapeut Dr, Changsha, Peoples R China.
通讯机构：
[Fei Xu] C;College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, Changsha, China<&wdkj&>Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, China
摘要：
INTRODUCTION: Chemotherapy (CT) is the main treatment for patients with unresected pancreatic cancer (PC). Whether the addition of radiotherapy to chemotherapy improves the prognosis of elderly patients with unresected PC is unclear. The aim of our study was to compare the efficacy of chemoradiotherapy (CRT) with chemotherapy alone in elderly patients with unresected PC. METHODS: The clinical data of elderly patients with unresected PC who received chemotherapy between 2004 and 2017 were determined from the Surveillance, Epidemiology, and End Results (SEER) database, and the patients were divided into CT and CRT groups. The primary outcome was overall survival (OS), and secondary endpoints were cancer-specific survival (CSS) and cancer-specific mortality (CSM). Propensity matching analysis (PSM) was used to balance the differences between the two groups. OS and CSS were assessed using Kaplan-Meier analysis, while CSM was assessed using a competing risk model. Subgroup analyses were also performed, and Cox regression was used to adjust for confounding factors. RESULTS: A total of 17,814 patients were diagnosed with PC including 14,222 who received CT alone and 3592 who received CRT. The 1-year OS of the CT and CRT groups after PSM was 30.1% and 40.8%, and the 1-year CSS was 31.4% and 42.1%, respectively. Overall, the CRT group had better OS, CSS, and CSM rates than the CT group before and after PSM (P < 0.05). After adjustment for age, sex, race, histological grade, stage, and other factors, the CRT group still had a lower risk of death than the CT group, and subgroup analysis further revealed the survival benefit of CRT in each population. CONCLUSIONS: CRT improves the outcome of patients with non-surgical PC over 65years of age. But prospective studies are needed to validate our results.
作者机构：
[田瑶] Graduate School, Hunan University of Chinese Medicine, Changsha 410000, China;[傅满姣; 贝承丽] Tuberculosis Intensive-care Unit, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410000, China
期刊：
Complementary Therapies in Medicine,2022年67:102831 ISSN：0965-2299
作者机构：
[Zhao, Jie] Hunan Univ Chinese Med, Grad Sch, Changsha 410208, Hunan, Peoples R China.;[Ai, Jun] Guangxi Univ Chinese Med, Basic Med Sch, Nanning 530200, Guangxi, Peoples R China.;[Shi, Wei; Meng, LiFeng; Mo, Chao] Guangxi Univ Chinese Med, Affiliated Hosp 1, Dept Nephrol, 327 Xian Hu Rd, Nanning 530023, Guangxi, Peoples R China.;[Mo, Chao] Guangxi Univ Chinese Med, Grad Sch, Nanning 530200, Guangxi, Peoples R China.;[Meng, LiFeng] Southwest Med Univ, Tradit Chinese & Western Med Lab Controlling Orga, Luzhou 646000, Sichuan, Peoples R China.
摘要：
BACKGROUND: Bailing Capsule (BLC), Jinshuibao (JSB), Huangkui Capsule (HKC), Uremic Clearance Granule (UCG), Tripterygium glycosides (TG), Compound Xueshuantong Capsule (CXC), and Shenyan Kangfu Tablet (SYKFT) as classic Chinese patent medicines (CPMs), have been widely used and shown beneficial effects on the treatment of early diabetic kidney disease (DKD). However, the comparative efficacy of seven CPMs in the treatment of early DKD remains unknown. OBJECTIVE: To evaluate and compare the efficacy of seven CPMs (BLC, JSB, HKC, UCG, TG, CXC, SYKFT) combined with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) on early DKD by a Bayesian network meta-analysis (NMA) of randomized controlled trials (RCTs). METHODS: A comprehensive and systematic literature search was performed in PubMed, Embase, Cochrane Library, Web of Science, Clinical Trials.gov, China Biology Medicine, Chinese National Knowledge Infrastructure, Chinese Scientific Journal, and Wanfang databases from inception to March 14, 2021, for full-text RCTs that evaluated the efficacy of seven CPMs combined with ACEI/ARB on patients with early DKD. Two reviewers independently screened studies for eligibility, extracted data, and assessed the risk of bias. Agreement between reviewers was measured using kappa statistics. Mean difference (MD) and odds ratio (OR) were calculated to evaluate continuous variables and dichotomous, respectively. The random effect modeling NMA was performed and the ranking probability of interventions in various outcomes was also conducted based on the surface under the cumulative ranking curve (SUCRA). Begg's and Egger's tests were used to evaluate publication bias. The certainty of the evidence for outcomes was evaluated according to the GRADE system. RESULTS: A total of 62 RCTs with 5362 patients with early DKD were identified. The value of Kappa calculated for the various parameters extracted by the two investigators was 0.821 (P<0.001). Among these CPMs, UCG+ACEI/ARB showed the best effectiveness for urinary albumin excretion rate (UAER) (MD 32.25, 95% CrI 19.11-45.67, low certainty) with SUCRA 92%. JSB+ACEI/ARB showed the highest effectiveness for 24-h urinary total protein (24-h UTP) (MD 76.92, 95% CrI 53.54-100.58, low certainty) with SUCRA 97%. CXC+ACEI/ARB showed the highest effectiveness for serum creatinine (SCr) (MD 26.02, 95% CrI 6.10-45.95, low certainty) with SUCRA 96%. HKC+ACEI/ARB showed the highest effectiveness for blood urea nitrogen (BUN) (MD 1.46, 95% CrI 0.42-2.54, very low certainty) with SUCRA 86%. BLC+ACEI/ARB showed significant differences in triglyceride (TRIG) (MD -1.17, 95% CrI -1.93 to -0.43, low certainty) with SUCRA 90%, total cholesterol (TC) (MD -1.17, 95% CrI -1.97 to -0.39, very low certainty) with SUCRA 90%, and C-reaction protein (CRP) (MD -0.90, 95% CrI -1.51 to -0.32, very low certainty) with SUCRA 76%. CONCLUSIONS: CPMs+ACEI/ARB might be positive efficacious interventions from which patients with DKD will derive benefit. UCG+ACEI/ARB, JSB+ACEI/ARB, CXC+ACEI/ARB, and HKC+ACEI/ARB might be potentially the preferred intervention for reducing UAER, 24-h UTP, SCr, and BUN levels, respectively. BLC+ACEI/ARB has a better impact on lowing TRIG, TC, and CRP levels in patients with early DKD. However, more high-quality, large-scale, multi-center RCTs and stronger head-to-head trials are required to confirm these findings.
作者机构：
[来奕恬; 周竞颖; 丁攀婷] Graduate School of Hunan University of Chinese Medicine, Changsha 410208, China;[刘密; 李南; 张国山] College of Acupuncture-moxibustion-Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208;[邱冉冉] The First Hospital of Hunan University of Chinese Medicine, Changsha 410007
作者机构：
[何兰] College of Integration of Traditional Chinese and Western Medicine, Hunan University of Traditional Chinese Medicine, Changsha 410208, China;[罗晶婧; 范婧莹; 周芳亮; 史红健] Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine, Changsha 410208, China;[何迎春] Hunan Provincial Ophthalmology and Otolaryngology Diseases Prevention and Treatment with Traditional Chinese Medicine and Visual Function Protection Engineering and Technological Research Center, Changsha 410208, China;[蒋益兰] Department of Oncology, Hunan Academy of Traditional Chinese Medicine Affiliated Hospital, Changsha 410006, China
通讯机构：
[Lan, H.] C;[Yilan, J.] D;Department of Oncology, China;College of Integration of Traditional Chinese and Western Medicine, China
