Allostatic load in rat model: An efficient tool for evaluating and understanding aging.

AIM: Aging and age-related diseases are an ever-increasing social and public health problem. Allostatic load (AL) shows great potential as an interdisciplinary tool for assessing the aging of human beings but as yet lacks investigation in animal models which is our study focus at. METHODS: Here a continuous study of AL was conducted on naturally aging rats. Blood samples were collected from the rats at ages of 5, 8, 14, 18, and 21 months. Dozens of blood biochemical indicators, including serum corticosterone, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, interleukin-6, 25-hydroxyvitamin D, free fatty acid, CD3+ T cell count, CD4+/CD3+ T cell ratio, CD8+/CD3+ T cell ratio, and CD3/4/8+ T cell apoptosis, were determined. RESULTS: AL was scored from those indicators, and we found that AL score gradually increased with age. CONCLUSIONS: AL can reliably reveal the cumulative and systemic changes in aging. Geriatr Gerontol Int 2024; 24: 1077-1084.

The superior allele LEA12OR in wild rice enhances salt tolerance and yield.

Soil salinity has negative impacts on food security and sustainable agriculture. Ion homeostasis, osmotic adjustment and reactive oxygen species scavenging are the main approaches utilized by rice to resist salt stress. Breeding rice cultivars with high salt tolerance (ST) and yield is a significant challenge due to the lack of elite alleles conferring ST. Here, we report that the elite allele LEA12OR, which encodes a late embryogenesis abundant (LEA) protein from the wild rice Oryza rufipogon Griff., improves osmotic adjustment and increases yield under salt stress. Mechanistically, LEA12OR, as the early regulator of the LEA12OR-OsSAPK10-OsbZIP86-OsNCED3 functional module, maintains the kinase stability of OsSAPK10 under salt stress, thereby conferring ST by promoting abscisic acid biosynthesis and accumulation in rice. The superior allele LEA12OR provides a new avenue for improving ST and yield via the application of LEA12OR in current rice through molecular breeding and genome editing.

Haplotype-resolved gapless genome and chromosome segment substitution lines facilitate gene identification in wild rice.

The abundant genetic variation harbored by wild rice (Oryza rufipogon) has provided a reservoir of useful genes for rice breeding. However, the genome of wild rice has not yet been comprehensively assessed. Here, we report the haplotype-resolved gapless genome assembly and annotation of wild rice Y476. In addition, we develop two sets of chromosome segment substitution lines (CSSLs) using Y476 as the donor parent and cultivated rice as the recurrent parents. By analyzing the gapless reference genome and CSSL population, we identify 254 QTLs associated with agronomic traits, biotic and abiotic stresses. We clone a receptor-like kinase gene associated with rice blast resistance and confirm its wild rice allele improves rice blast resistance. Collectively, our study provides a haplotype-resolved gapless reference genome and demonstrates a highly efficient platform for gene identification from wild rice.

Noncystoscopic Removal of Double-J Stent in Women: Feasibility and Safety.

OBJECTIVE: To evaluate the feasibility and safety of a simple noncystoscopic method previously applied in children for removing double-J stents applied in women by comparing the hospitalization time, operation time, costs, complications, and success rate. METHODS: One hundred eighty women who underwent either cystoscopic or noncystoscopic double-J stent removal in a randomized manner. They were randomly assigned 1:1 to groups of cystoscopic double-J stent removal (n = 90) or noncystoscopic double-J stent removal (n = 90). The age ranged from 19 to 72years. After the removal of the double-J stent, the operation time, costs, complications, and success rate were compared between the two groups. RESULTS: The operation time of the noncystoscopic group was lower than that of the cystoscopic group (6.0(5.0,7.0) minutes vs 2.0(2.0,3.0) minutes, P < .001). The hospitalization costs of the noncystoscopic group were significantly shorter than that of the cystoscopic group (1361.2(1331.4,1379.2) Yuan vs 873.9(868.5,896.1) Yuan, P < .001). There were no complications such as infection and massive bleeding in the two groups during and after the operation. Most noncystoscopic double-J stent removal can succeed in less than three attempts (88/90). All patients in the noncystoscopic group used this technique to remove the double-J stent. CONCLUSION: Noncystoscopic removal of double-J stent has the advantages of short operation time and low hospitalization costs. It is a safe and feasible minimally invasive method to replace cystoscopic removal of the double-J stent.

Multispectral transparent electromagnetic-wave-absorbing optical window technology based on a random grid.

A multimode detection system has stringent requirements in terms of electromagnetic characteristic control and electromagnetic compatibility. To meet these requirements, we designed and manufactured a type of transparent electromagnetic-wave-absorbing optical window based on a random grid (EAOWRG) in this study. Owing to the design and regulation of the materials of the random grid and the structures of the metasurface, the optical window has excellent multispectral transparency, electromagnetic wave absorption, and electromagnetic shielding performance. The experimental results showed that the transmissivity of the EAOWRG in the optical spectral ranges of 460-800 nm and 8-12 µm is above 89.77%, the electromagnetic reflectivity in the frequency ranges of 3.6-7.2 GHz and 14.3-17.7 GHz is not more than - 5 dB, the bandwidth at which the electromagnetic reflectivity is not more than -10 dB is 4.4 GHz, the electromagnetic shielding effectiveness in the frequency range of 2-18 GHz is above 31 dB. The average radar cross section of the detection system using the EAOWRG in the ± 60° angle domain at 6 GHz is 8.79 dB lower than that before processing. The detection system has a good imaging effect in the visible and infrared bands, meeting the requirements of the electromagnetic characteristic control and electromagnetic compatibility, and has good application prospects.

S14G-Humanin ameliorates ovalbumin-induced airway inflammation in asthma mediated by inhibition of toll-like receptor 4 (TLR4) expression and the nuclear factor κ-B (NF-κB)/early growth response protein-1 (Egr-1) pathway.

Asthma is a chronic inflammatory disease with a high morbidity rate in children and significantly impacts their healthy growth. It is reported that Th2 cell-mediated airway inflammation and activated oxidative stress are involved in the pathogenesis of asthma. S14G-humanin (HNG) is a derivative of Humanin with higher activity. The present study proposes to explore the potential treating property of HNG on asthma. An asthma model was constructed in mice using ovalbumin (OVA), the mice were treated with 2.5 mg/kg and 5 mg/kg HNG for 16 days. Dramatically increased lung weight index, elevated number of monocytes, eosinophils, and neutrophils, promoted production of Th2 cytokines including interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13), and severe histological pathology were observed in OVA-challenged mice, all of which were extremely alleviated by 2.5 mg/kg and 5 mg/kg HNG. Furthermore, the increased malondialdehyde (MDA) level and declined superoxide dismutase (SOD) activity in OVA-challenged mice were abolished by 2.5 mg/kg and 5 mg/kg HNG. Lastly, the upregulated TLR4, p-NF-κB p65, and early growth response 1 (Egr-1) in lung tissues of OVA-challenged mice were pronouncedly downregulated by 2.5 mg/kg and 5 mg/kg HNG. Collectively, our data suggested that HNG ameliorated airway inflammation in asthma partially due to NF-κB and Egr-1-mediated responses.

Intratumoral Heterogeneity in Lung Cancer.

The diagnosis and treatment of lung cancer (LC) is always a challenge. The difficulty in the decision of therapeutic schedule and diagnosis is directly related to intratumoral heterogeneity (ITH) in the progression of LC. It has been proven that most tumors emerge and evolve under the pressure of their living microenvironment, which involves genetic, immunological, metabolic, and therapeutic components. While most research on ITH revealed multiple mechanisms and characteristic, a systemic exposition of ITH in LC is still hard to find. In this review, we describe how ITH in LC develops from the perspective of space and time. We discuss elaborate details and affection of every aspect of ITH in LC and the relationship between them. Based on ITH in LC, we describe a more accurate multidisciplinary therapeutic strategy on LC and provide the newest opinion on the potential approach of LC therapy.

Overexpression of lncRNA77580 Regulates Drought and Salinity Stress Responses in Soybean.

Emerging evidence indicates that long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. However, the biological functions of most plant lncRNAs are still unknown. We previously discovered a soybean abiotic-stress-related lncRNA, lncRNA77580, and cloned the entire full-length sequence. Here, in order to fully identify the function of lncRNA77580 in soybean stress response, we created transgenic soybean lines overexpressing lncRNA77580. Compared with the wild type, overexpression of lncRNA77580 enhances the drought tolerance of soybean. However, the transgenic plants exhibit increased sensitivity to high salinity at the seedling stage. We found that lncRNA77580 modulates the transcription of different gene sets during salt and drought stress response. Under water deficit at the reproductive stage, lncRNA77580 overexpression increases the seed yield by increasing the seed number per plant. These results provide insight into the role of lncRNA77580 in soybean stress response.

Foxtail millet MYB-like transcription factor SiMYB16 confers salt tolerance in transgenic rice by regulating phenylpropane pathway.

R2R3-MYB transcription factors play an important role in the synthesis of phenylpropanoid-derived compounds, which in turn provide salt tolerance in plant. In this study, we found that the expression of foxtail millet R2R3-MYB factor SiMYB16 can be induced by salt and drought. SiMYB16 is localized in the nucleus and acts as a transcriptional activator. Phylogenetic analysis indicates that SiMYB16 belongs to the R2R3-MYB transcription factor family subgroup 24. Transgenic rice expressing SiMYB16 (OX16) had a higher survival rate, lower malondialdehyde content, and heavier fresh weight compared with type (WT) under salt stress conditions. The transgenic plants also had a higher germination rate in salt treatment conditions and higher yield in the field compared with wild-type plants. Transcriptome analysis revealed that the up-regulated differential expression genes in the transgenic rice were mainly involved in phenylpropanoid biosynthesis, fatty acid elongation, phenylalanine metabolism, and flavonoid biosynthesis pathways. Quantitative real-time PCR analysis also showed that the genes encoding the major enzymes in the lignin and suberin biosynthesis pathways had higher expression level in SiMYB16 transgenic plants. Correspondingly, the content of flavonoid and lignin, and the activity of fatty acid synthase increased in SiMYB16 transgenic rice compared with wild-type plants under salt stress treatment. These results indicate that SiMYB16 gene can enhance plant salt tolerance by regulating the biosynthesis of lignin and suberin.

Influence of discrimination perception on career exploration of higher vocational students: Chain mediating effect test.

Explore the influence mechanism of discrimination perception on higher vocational Students' career exploration, it provides empirical evidence for promoting vocational college Students' career exploration and career development. Using the questionnaire survey method, 893 higher vocational students from four higher vocational colleges in Jiangsu Province were investigated by using the Discrimination Perception Scale, the Core Self-Evaluation Scale (CSES), the Chinese version of the Acceptance and Action Questionnaire, the Chinese version of the Cognitive Fusion Questionnaire (CFQ) and the Career Exploration Scale (CES). The data were analyzed using SPSS26.0 and Amos23.0, and the results showed that discrimination perception was significantly negatively correlated with core self-evaluation, psychological flexibility and career exploration (r = -0.487, -0.497, -0.326, p < 0.01), core self-evaluation was significantly positively correlated with psychological flexibility and career exploration (r = 0.518, 0.352, p < 0.01), and psychological flexibility was significantly positively correlated with career exploration (r = 0.386, p < 0.01); Core self-evaluation and psychological flexibility mediated the effect between discrimination perception and career exploration with effect sizes of -0.054 and -0.061, respectively; Core self-evaluation and psychological flexibility mediated the chain effect between discrimination perception and career exploration of higher vocational students with effect sizes of -0.030. Therefore, discrimination perception not only directly influences career exploration of higher vocational students, but also indirectly influences career exploration of higher vocational students through the separate mediating effects of core self-evaluation and psychological flexibility and the chain mediating effects of core self-evaluation and psychological flexibility. Accordingly, the following suggestions are put forward, which should pay attention to the cultivation of core self-evaluation and psychological flexibility of higher vocational students, strengthen the teaching quality and improve the image of vocational colleges.

Effects of ginger extract and its major component 6-gingerol on anti-tumor property through mitochondrial biogenesis in CD8+ T cells.

Ginger extract (GE) and its major component 6-gingerol (6G) have been reported to exert anti-tumor effects in various cancers. The underlying mechanism, however, has not been well demonstrated. Here, we have focused on the relationship between promotion of mitochondrial biogenesis in tumor infiltrating CD8+ T cells induced by GE and 6G and their cytotoxic effect. The results showed that GE induced 56% inhibition of tumor growth in Lewis lung carcinoma (LLC) xenograft mouse model and 6G induced 33% (25 mg/kg) and 37% (50 mg/kg) inhibition. GE increased mitochondrial mass of CD8+ T cells in tumor and draining lymph nodes (DLNs) significantly, while 6G had no significant effect. GE and 6G both had no significant influence on histopathological changes of liver and kidney in mice. In the co-culture system of CTLL-2 cells and LLC cells, GE enhanced the cytotoxicity of CTLL-2 cells against LLC cells by 14% and 19% at concentrations of 2.5 and 5 mg/ml, respectively. 6G did not promote cytotoxicity of CTLL-2 cells. GE increased mitochondrial mass at 5 and 10 mg/ml and mtDNA copy number and ATP production at 2.5, 5, 10 mg/ml in CTLL-2 cells. 6G promoted mtDNA copy number at 50, 100, 150 µM and mitochondrial mass and ATP production at 25, 50, 100, 150 µM in CTLL-2 cells. These results suggest that promotion of mitochondrial biogenesis and function in tumor infiltrating CD8+ T cells may play an essential role in GE-induced inhibition of tumor growth. The current results perfect the mechanism of anti-tumor effect of ginger, which is beneficial for further application in cancer management. PRACTICAL APPLICATION: Ginger, as a worldwide food seasoning and herbal medicine in traditional Chinese medicine, has been reported to possess anti-tumor efficacy. To our knowledge, it is the first time to focus on ginger's ability of promoting mitochondrial biogenesis in tumor infiltrating CD8+ T cells to explore the mechanism of its anti-tumor effect. Our observations demonstrate that ginger inhibits tumor growth via promoting mitochondrial biogenesis and function of T cells. The present study links food to anti-tumor immunity and provides impetus to investigate and design dietary supplements for cancer management.

Icariside II enhances cisplatin-induced apoptosis by promoting endoplasmic reticulum stress signalling in non-small cell lung cancer cells.

Although cisplatin is the most effective first-line drug in the management of advanced non-small cell lung cancer (NSCLC), drug resistance remains a major clinical challenge. There is increasing evidence that icariside II (IS) exhibits antitumour activity in a variety of cancers. In the current study, we investigated the anticancer effects of icariside II combined with cisplatin and elucidated the underlying mechanism in NSCLC. Here, we showed that cotreatment with IS and cisplatin inhibited cell proliferation and induced cellular apoptosis. Using mRNA sequencing (mRNA-seq), we identified differentially expressed genes (DEGs) in which there was an enrichment in PERK-mediated unfolded protein response (UPR) signalling. The western blot results revealed that IS activated endoplasmic reticulum (ER) stress, including three branches of UPR signalling, PERK, IRE1 and ATF6, and the downstream PERK-eIF2α-ATF4-CHOP pathway, thus potentiating the apoptosis induced by cisplatin. In addition, the combination of IS with cisplatin significantly reduced xenograft tumour growth in C57BL/6 and BALB/c nude mice in vivo. Notably, the combination therapy displayed no evident toxicity. Taken together, IS enhances cisplatin-induced apoptosis partially by promoting ER stress signalling in NSCLC, suggesting that combination treatment with IS and cisplatin is a novel potential therapeutic strategy for NSCLC.

SiMYB19 from Foxtail Millet (Setaria italica) Confers Transgenic Rice Tolerance to High Salt Stress in the Field.

Salt stress is a major threat to crop quality and yield. Most experiments on salt stress-related genes have been conducted at the laboratory or greenhouse scale. Consequently, there is a lack of research demonstrating the merit of exploring these genes in field crops. Here, we found that the R2R3-MYB transcription factor SiMYB19 from foxtail millet is expressed mainly in the roots and is induced by various abiotic stressors such as salt, drought, low nitrogen, and abscisic acid. SiMYB19 is tentatively localized to the nucleus and activates transcription. It enhances salt tolerance in transgenic rice at the germination and seedling stages. SiMYB19 overexpression increased shoot height, grain yield, and salt tolerance in field- and salt pond-grown transgenic rice. SiMYB19 overexpression promotes abscisic acid (ABA) accumulation in transgenic rice and upregulates the ABA synthesis gene OsNCED3 and the ABA signal transduction pathway-related genes OsPK1 and OsABF2. Thus, SiMYB19 improves salt tolerance in transgenic rice by regulating ABA synthesis and signal transduction. Using rice heterologous expression analysis, the present study introduced a novel candidate gene for improving salt tolerance and increasing yield in crops grown in saline-alkali soil.

Large DNA fragment deletion in lncRNA77580 regulates neighboring gene expression in soybean (Glycine max).

Long non-coding RNAs (lncRNAs) affect gene expressions via a wide range of mechanisms and are considered important regulators of numerous essential biological processes, including abiotic stress responses. However, the biological functions of most lncRNAs are yet to be determined. Moreover, to date, no effective methods have been developed to study the function of plant lncRNAs. We previously discovered a salt stress-related lncRNA, lncRNA77580 in soybean (Glycine max L.). In this study, we cloned the full-length lncRNA77580 and found that it shows nuclear-specific localisation. Furthermore, we employed CRISPR/Cas9 technology to induce large DNA fragment deletions in lncRNA77580 in soybean using a dual-single guide RNA/Cas9 design. As a result, we obtained deletion mutant soybean roots with targeted genomic fragment deletion in lncRNA77580. Deletion and overexpression of lncRNA77580 were found to alter the expression of several neighboring protein-coding genes associated with the response to salt stress. The longer the deleted DNA fragment in lncRNA77580, the greater the influence on the expression of lncRNA77580 itself and neighboring genes. Collectively, the findings of this study revealed that large DNA fragment deletion in lncRNAs using the CRISPR/Cas9 system is a powerful method to obtain functional mutations of soybean lncRNAs that could benefit future research on lncRNA function in soybean.

GmNAC06, a NAC domain transcription factor enhances salt stress tolerance in soybean.

KEY MESSAGE: We found GmNAC06 plays an important role in salt stress responses through the phenotypic, physiological and molecular analyses of OE, VC, and Mutant composite soybean. Salinization affects 20% of all cultivated land worldwide because of the high salinity of irrigation water and the excessive use of water, and this amount is increasing daily. NAC (NAM, ATAF, and CUC) have been found to be involved in salt stress. In this study, a soybean NAC gene, GmNAC06 (Glyma06g21020.1), was cloned and functionally characterized. The results of expression analysis suggested that salt stress could influence the expression level of GmNAC06. The subcellular localization analysis results suggested that GmNAC06 may function as a transcription factor. Under salt stress, the overexpression technology combined with CRISPR-Cas9 system found that GmNAC06 could cause the accumulation of proline and glycine betaine to alleviate or avoid the negative effects of ROS; similarly, it could control the Na+/K+ ratios in hairy roots to maintain ionic homeostasis. The fresh weight of the transgenic hairy roots and the histochemical ROS staining of wild leaves suggested that transgenic hairy roots influence the function of wild leaves under salt stress conditions. Moreover, the expression levels of GmUBC2 and GmHKT1 were higher in the GmNAC06 hairy roots than in the control. Thus, the overexpression of GmNAC06 in hairy roots notably causes an entire composite plant to exhibit salt tolerance. The phenotype of composite soybean plants and transgenic Arabidopsis plants suggest that GmNAC06 plays a role in response to salt stress and could be useful in generating salt tolerant transgenic crops.

Silencing of lncRNA MIAT alleviates LPS-induced pneumonia via regulating miR-147a/NKAP/NF-κB axis.

PURPOSE: Pneumonia is a respiratory disease with an increasing incidence in recent years. More and more studies have revealed that lncRNAs can regulate the transcriptional expression of target genes at different stage. Herein, we aimed to explore the effect of lncRNA MIAT in LPS-induced pneumonia, and further illuminate the possible underlying mechanisms. METHOD AND RESULTS: Mice were intraperitoneally injected with LPS, and the lung inflammation was evaluated. Microarray showed lncRNA MIAT was up-regulated in LPS-induced pulmonary inflammation. And qRT-PCR and FISH assay indicated that MIAT was increased in mice with LPS injection. Functional analysis showed sh-MIAT inhibited LPS-induced inflammation response, inhibited apoptosis level and protected lung function. As well, si-MIAT removed the injury of LPS on mouse lung epithelial TC-1 cells, and inhibited the activation of NF-κB signaling. Furthermore, MIAT acted as a sponge of miR-147a, and miR-147a directly targeted NKAP. Functionally, AMO-147a or NKAP remitted the beneficial effects of si-MIAT on LPS-induced inflammation response of TC-1 cells. CONCLUSION: Deletion of MIAT protected against LPS-induced lung inflammation via regulating miR-147a/NKAP, which might provide new insight for pneumonia treatment.

Targeting REV7 effectively reverses 5-FU and oxaliplatin resistance in colorectal cancer.

BACKGROUND: Despite an enormous research effort, patients diagnosed with advanced colorectal cancer (CRC) still have low prognosis after surgical resection and chemotherapy. The major obstacle for CRC treatment is chemoresistance to front line anti-cancer drugs, such as 5-fluorouracil (5-FU) and oxaliplatin. However, the mechanism of chemoresistance to these drugs remains unclear. METHODS: Cell viability to 5-FU and oxaliplatin was measured by the CellTiter-Glo® 2.0 Cell Viability Assay. The endogenous REV7 protein in CRC cells was detected by western blotting. The translesion synthesis (TLS) events were measured by plasmid-based TLS efficiency assay. Cell apoptosis was evaluated by caspase3/7 activity assay. The in vivo tumor progression was analyzed by HT29 xenograft mice model. RESULTS: In this study, we found that expression of REV7, which is a key component of translesion synthesis (TLS) polymerase ζ (POL ζ), is significantly increased in both 5-FU and oxaliplatin resistant CRC cells. TLS efficiency analysis revealed that upregulated REV7 protein level results in enhanced TLS in response to 5-FU and oxaliplatin. Importantly, inhibition of REV7 by CRISPR/Cas9 knockout exhibited significant synergy with 5-FU and oxaliplatin in cell culture and murine xenograft model. CONCLUSION: These results suggest that combination of REV7 deficiency and 5-FU or oxaliplatin has strong inhibitory effects on CRC cells and identified REV7 as a promising target for chemoresistant CRC treatment.

Genome-wide identification of microRNAs and phased siRNAs in soybean roots under long-term salt stress.

BACKGROUND: Salinity stress, as the key limiting factor for agricultural productivity, can activate a series of molecular responses and alter gene expression in plants. Endogenous regulatory small RNAs, such as microRNAs (miRNAs) and phased siRNAs (phasiRNAs), play crucial roles during stress adaptation and prevent the injury from environmental circumstances. OBJECTIVE: To identify long-term salt stress responsive miRNAs and phasiRNAs as well as their associated genes and pathways in soybean roots. METHODS: Small RNA and degradome sequencing strategies were applied to genome widely investigate miRNAs and phasiRNAs in soybean roots under control and long-term salt stress conditions. RESULTS: In this study, stringent bioinformatic analysis led to the identification of 253 conserved and 38 novel miRNA candidates. Results of expression profiling, target and endogenous target mimics predictions provided valuable clues to their functional roles. Furthermore, 156 genes were identified to be capable of generating 21 nt and 24 nt phasiRNAs, in which 37 candidates were confirmed by degradome data for miRNA-directed cleavage. Approximately 90% of these phasiRNA loci were protein coding genes. And GO enrichment analysis pointed to "signal transduction" and "ADP binding" entries and reflected the functional roles of identified phasiRNA genes. CONCLUSION: Taken together, our findings extended the knowledge of salt responsive miRNAs and phasiRNAs in soybean roots, and provided valuable information for a better understanding of the regulatory events caused by small RNAs underlying plant adaptations to long-term salt stress.

The effectiveness and safety of extracorporeal shock wave lithotripsy for the management of kidney stones: A protocol of systematic review and meta-analysis.

BACKGROUND: Extracorporeal shockwave lithotripsy (ESWL) has gained worldwide popularity as one of the most commonly used minimally invasive management of urinary tract stones. The objective of this study was to evaluate the efficacy and safety of ESWL for patients with kidney stones (KS). MATERIALS AND METHODS: This protocol established in this study has been reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Web of Science, PubMed, Embase, Cochrane Library, China Biomedical Literature Database (CBM), China Knowledge Network Database (CNKI), Chinese Scientific Journal Database (VIP), and Wan Fang Database were searched for case-control studies in ESWL treating patients with KS until July 1, 2020. We will use a combination of Medical Subject Heading and free-text terms with various synonyms to search based on the Eligibility criteria. Two investigators independently reviewed the included studies and extracted relevant data. The relative risk (RR) and 95% confidence intervals (CIs) were used as effect estimate. I test, substantial heterogeneity, sensitivity analysis, and publication bias assessment will be performed accordingly. Stata 14.0 and Review Manger 5.3 are used for a meta-analysis. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: The results of this review will be widely disseminated through peer-reviewed publications and conference presentations. This evidence may also provide helpful evidence of the efficacy and safety of ESWL treating patients with KS. PROSPERO REGISTRATION NUMBER: CRD42019157243.

Inhibition of autophagy enhances timosaponin AIII-induced lung cancer cell apoptosis and anti-tumor effect in vitro and in vivo.

AIMS: Timosaponin AIII (TAIII), an active component with anti-tumor activity from Anemarrhena asphodeloides Bunge, can induce both autophagy and apoptosis of cancer cells. The present study aimed to reveal the promoting or inhibiting role of TAIII-induced autophagy on TAIII-induced apoptosis, to determine the respective upstream signaling pathways for TAIII-induced autophagy and apoptosis; and to observe the therapeutic potential of TAIII in human non-small cell lung cancer in vivo. METHODS AND MATERIALS: WST-1 assay was used to determine the effect of TAIII on cell growth and proliferation. Apoptosis was detected by DAPI staining and flow cytometry. Autophagy was verified by immunofluorescence and transmission electron microscopy. Western blot was used to determine the levels of protein expression. Furthermore, the anti-tumor activity of TAIII was observed in nude mice. KEY FINDINGS: TAIII at high concentrations from 10 µM to 30 µM induced both autophagy and apoptosis in human non-small cell lung cancer cells in a time- and concentration-dependent manner. TAIII at low concentration (1 µM) only induced autophagy. The AMP-activated protein kinase (AMPK) signaling pathway was identified to be responsible for TAIII-induced autophagy both at high or low concentrations. The MAPK/Erk1/2 signaling pathway was identified to be responsible for TAIII-induced apoptosis at the high concentration (20 µM). TAIII-induced autophagy protected cancer cells from apoptosis, and combination of TAIII and autophagy inhibitor showed higher anti-cancer activity.