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Jiang-Peng Cao,1– 3 Yuan-Hao Du,1,2,4 Lan-Yu Jia,5 Xiu-Mei Yin,1– 3 Li-Hong Yang,1,2 Lin-Ling Chen,6 Tao Jiang,1,2 Man Zhang,4 Tian Qiu1– 3 1Department of Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China; 3Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 4School of acupuncture & moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 5Department of Geriatric medicine, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, People’s Republic of China; 6Department of Traditional Chinese Medicine, Huzhou Central Hospital, Huzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Yuan-Hao Du, Email jpjs_cn@sina.comBackground: Cerebral blood flow and vascular structures serve as the fundamental components of brain metabolism and circulation. Acupuncture, an alternative and complementary medical approach, has demonstrated efficacy in treating cerebral ischemic stroke (CIS). Nevertheless, the mechanisms underlying the impact of acupuncture on vascular smooth muscle cell (VSMC) function remain uncertain. The objective of this systematic review and meta-analysis is to assess the alterations in VSMC function following acupuncture stimulation in CIS models.Methods: The databases PubMed, Web of Science, SCOPUS, and EMBASE were queried until November 2022 using a predetermined search strategy. The FORMAT BY SYRCLE guidelines were adhered to, and the risk of bias of the included studies was evaluated using the Risk of Bias tool developed by the Systematic Review Centre for Laboratory Animal Experimentation. The random-effects model was employed to estimate the standardized mean difference (SMD).Results: Eighteen articles are included in this review. Acupuncture showed significant positive effects on the region cerebral blood flow (SMD=8.15 [95% CI, 4.52 to 11.78]) and neurological deficiency (SMD=− 3.75 [95% CI, − 5.54 to − 1.97]). Descriptive analysis showed a probable mechanism of acupuncture stimulation in CIS rats related to VSMC function. Limitations and publication bias were presented in the studies.Conclusion: In this systematic review and meta-analysis, our findings indicate that acupuncture stimulation has the potential to improve regional cerebral blood flow and alleviate neurological deficits, possibly by regulating VSMC function. However, it is important to exercise caution when interpreting these results due to the limitations of animal experimental design and methodological quality.Keywords: acupuncture therapy, vascular smooth muscle cell, vasomotor, cerebral ischemic stroke, systematic review

Li-Fang Zhang,1,2 Zhi-Wei Zhou,2 Zhen-Hai Wang,1 Yan-Hui Du,1 Zhi-Xu He,3 Chuanhai Cao,2 Shu-Feng Zhou2,31Department of Neurology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, Guizhou, People’s Republic of ChinaAbstract: There is an increasing prevalence of Alzheimer’s disease (AD), which has become a public health issue. However, the underlying mechanisms for the pathogenesis of AD are not fully understood, and the current therapeutic drugs cannot produce acceptable efficacy in AD patients. Previous animal studies have shown that coffee (Coff), caffeine (Caff), and melatonin (Mel) have beneficial effects on AD. Disturbed circadian rhythms are observed in AD, and chronotherapy has shown promising effects on AD. In this study, we examined whether a combination of Coff or Caff plus Mel produced a synergistic/additive effect on amyloid-ß (Aß) generation in Neuro-2a (N2a)/amyloid precursor protein (APP) cells and the possible mechanisms involved. Cells were treated with Coff or Caff, with or without combined Mel, with three different chronological regimens. In regimen 1, cells were treated with Coff or Caff for 12 hours in the day, followed by Mel for 12 hours in the night. For regimen 2, cells were treated with Coff or Caff plus Mel for 24 hours, from 7 am to 7 am the next day. In regimen 3, cells were treated with Coff or Caff plus Mel with regimen 1 or 2 for 5 consecutive days. The extracellular Aβ40/42 and Aβ oligomer levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. The expression and/or phosphorylation levels of glycogen synthase kinase 3β (GSK3β), Erk1/2, PI3K, Akt, Tau, Wnt3α, β-catenin, and Nrf2 were detected by Western blot assay. The results showed that regimen 1 produced an additive antiamyloidogenic effect with significantly reduced extracellular levels of Aβ40/42 and Aβ42 oligomers. Regimen 2 did not result in remarkable effects, and regimen 3 showed a less antiamyloidogenic effect compared to regimen 1. Coff or Caff, plus Mel reduced oxidative stress in N2a/APP cells via the Nrf2 pathway. Coff or Caff, plus Mel inhibited GSK3β, Akt, PI3K p55, and Tau phosphorylation but enhanced PI3K p85 and Erk1/2 phosphorylation in N2a/APP cells. Coff or Caff, plus Mel downregulated Wnt3α expression but upregulated β-catenin. However, Coff or Caff plus Mel did not significantly alter the production of T helper cell (Th)1-related interleukin (IL)-12 and interferon (IFN)-γ and Th2-related IL-4 and IL-10 in N2a/APP cells. The autophagy of cells was not affected by the combinations. Taken together, combination of Caff or Coff, before treatment with Mel elicits an additive antiamyloidogenic effects in N2a/APP cells, probably through inhibition of Aβ oligomerization and modulation of the Akt/GSK3β/Tau signaling pathway.Keywords: Alzheimer’s disease, Aβ oligomer, coffee, caffeine, melatonin, Tau, Nrf2, chronotherapy, Akt

There is an urgent need to develop phototherapeutic agents with imaging capabilities to assess the treatment process and efficacy in real-time during cancer phototherapy for precision cancer therapy. The safe near-infrared (NIR) fluorescent dyes have garnered significant attention and are desirable for theranostics agents. However, until now, achieving excellent photostability and fluorescence (FL) imaging capability in aggregation-caused quenching (ACQ) dyes remains a big challenge. Here, for the only FDA-approved NIR dye, indocyanine green (ICG), we developed a dual-ferrocene (Fc) chimeric nanonetwork ICG@HFFC based on the rigid-flexible strategy through one-step self-assembly, which uses rigid Fc-modified hyaluronic acid (HA) copolymer (HA-Fc) and flexible octadecylamine (ODA) bonded Fc (Fc-C 18 ) as the delivery system. HA-Fc reserved the ability of HA to target the CD44 receptor of the tumor cell surface, and the dual-Fc region provided a rigid space for securely binding ICG through metal-ligand interaction and π-π conjugation, ensuring excellent photostability. Additionally, the alkyl chain provided flexible confinement for the remaining ICG through hydrophobic forces, preserving its FL. Thereby, a balance is achieved between outstanding photostability and FL imaging capability. In vitro studies showed improved photobleaching resistance, enhanced FL stability, and increased singlet oxygen ( 1 O 2 ) production efficiency in ICG@HFFC. Further in vivo results display that ICG@HFFC had good tumor tracing ability and significant tumor inhibition which also exhibited good biocompatibility.. Therefore, ICG@HFFC provides an encouraging strategy to realize simultaneous enhanced tumor tracing and photothermal/photodynamic therapy (PTT/PDT) and offers a novel approach to address the limitations of ACQ dyes.

Background: Yigong San (YGS) is a representative prescription for the treatment of digestive disorders, which has been used in clinic for more than 1000 years. However, the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear., Aim: To explore the mechanism of YGS anti-gastric cancer and immune regulation., Methods: Firstly, collect the active ingredients and targets of YGS, and the differentially expressed genes of gastric cancer. Secondly, constructed a protein-protein interaction network between the targets of drugs and diseases, and screened hub genes. Then the clinical relevance, mutation and repair, tumor microenvironment and drug sensitivity of the hub gene were analyzed. Finally, molecular docking was used to verify the binding ability of YGS active ingredient and hub genes., Results: Firstly, obtained 55 common targets of gastric cancer and YGS. The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6, EGFR, MMP2, MMP9 and TGFB1 as the hub genes. The 5 hub genes were involved in gastric carcinogenesis, staging, typing and prognosis, and their mutations promote gastric cancer progression. Finally, molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets., Conclusion: YGS has the effect of anti-gastric cancer and immune regulation., Competing Interests: Conflict-of-interest statement: All authors declare no financial or commercial conflict of interest for this manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The underlying mechanism of fluorosis has not been fully elucidated. The purpose of this study was to explore the mechanism of fluorosis induced by sodium fluoride (NaF) using proteomics. Six offspring rats exposed to fluoride without dental fluorosis were defined as group A, 8 offspring rats without fluoride exposure were defined as control group B, and 6 offspring rats exposed to fluoride with dental fluorosis were defined as group C. Total proteins from the peripheral blood were extracted and then separated using liquid chromatography-tandem mass spectrometry. The identified criteria for differentially expressed proteins were fold change > 1.2 or < 0.83 and P < 0.05. Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the oeCloud tool. The 177 upregulated and 22 downregulated proteins were identified in the A + C vs. B group. KEGG pathway enrichment analysis revealed that transforming growth factor-β (TGF-β) signaling pathway significantly enriched. PPI network constructed using Cytoscape confirmed RhoA may play a crucial role. The KEGG results of genes associated with fluoride and genes associated with both fluoride and inflammation in the GeneCards database also showed that TGF-β signaling pathway was significantly enriched. The immunofluorescence in HPA database showed that the main expression sites of RhoA are plasma membrane and cytosol, while the main expression site of Fbn1 is the Golgi apparatus. In conclusion, long-term NaF intake may cause inflammatory response in the peripheral blood of rats by upregulating TGF-β signaling pathway, in which RhoA may play a key role., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Late-onset capsule block syndrome (CBS) is a rare complication of cataract phacoemulsification and the implantation of a posterior chamber intraocular lens (PCIOL), which manifests six months to years after surgery. The hallmark of CBS is the formation of an opaque liquid substance between the implanted intraocular lens (IOL) and the posterior capsule. However, its pathogenesis remains unclear., Case Presentation: A 64-year-old female patient with chronic angle-closure glaucoma (axis length < 21 mm) underwent trabeculectomy surgery combined with phacoemulsification and PCIOL. After a 4-year follow-up, a decline in visual acuity occurred in her right eye due to the location of opaque fluid in the visual axis and distension of the capsular bag. The initial course of action was to release the trapped fluid. Neodymium: yttrium-aluminum-garnet (Nd: YAG) laser capsulotomy could not be employed due to her non-dilating pupil and high extension of the posterior capsule. Subsequently, anterior capsule peeling and anterior segment vitrectomy surgery were performed. The depth of the anterior chamber (ACD), the distance between the face of the retro-IOL and the posterior capsule, the best-corrected visual acuity (BCVA), and the visual quality (VQ) were measured both before and after surgery. Inflammatory cytokine levels in the opaque substances (OS) trapped between the PCIOL and the posterior capsule were assessed using a flow cytometer and compared to normal statistical data in aqueous humor. After surgery, the patient experienced a significant improvement in BCVA and VQ. The distance between the face of the retro-IOL and the posterior capsule was on the verge of disappearing. However, ACD did not differ between pre- and post-operatively. Interleukin-8 (IL-8) and basic fibroblast growth factor (BFGF) concentrations were higher in the OS than in aqueous humor, especially in the former. However, the concentration of vascular cell adhesion molecule (VCAM) in the OS was lower than in aqueous humor., Conclusions: Anterior segment vitrectomy surgery proved to be a successful treatment for late-onset CBS, presenting a challenging case. In the human lens, inflammatory cytokines originating from the opaque substances may contribute to abnormal metabolism in the sealed area, a consequence of late-onset CBS., (© 2024. The Author(s).)

Background: Pachymic acid (PA) is derived from Poria cocos. PA has a variety of pharmacological and inhibitory effects on various tumors. However, the mechanism of action of PA in gastric cancer (GC) remains unclear., Aim: To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification., Methods: The GeneCards and OMIM databases were used to derive the GC targets, while the Pharm Mapper database provided the PA targets. Utilizing the STRING database, a protein-protein interaction network was constructed and core targets were screened. The analyses of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis were conducted, and molecular docking and clinical correlation analyses were performed on the core targets. Ultimately, the network pharmacology findings were validated through in vitro cell assays, encompassing assessments of cell viability, apoptosis, cell cycle, cloning, and western blot analysis., Results: According to network pharmacology analysis, the core targets were screened, and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC, according to KEGG enrichment analysis. The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation, induce apoptosis, and pause the cell cycle., Conclusion: Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets. This has also been supported by in vitro cell studies, which serve as benchmarks for further research., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Recent studies suggest machine learning represents a promising predictive option for patients in intensive care units (ICU). However, the machine learning performance regarding its actual predictive value for early detection in acute kidney injury (AKI) patients remains uncertain., Objective: This study represents the inaugural meta-analysis aiming to investigate the predictive value of machine learning for assessing the risk of AKI among ICU patients., Methods: PubMed, Web of Science, Embase, and the Cochrane Library were all thoroughly searched from inception to June 25, 2022. Eligible studies for inclusion were those concentrating on the predictive value and the development, validation, or enhancement of a prediction model for AKI patients in the ICU. Measures of effects, including c-index, sensitivity, specificity, and their corresponding 95% confidence intervals (CIs), were employed for analysis. The risk of bias in the included original studies was assessed using Probst. The meta-analysis in our study was carried out using R version 4.2.0., Results: The systematic search yielded 29 articles describing 13 machine-learning models, including 86 models in the training set and 57 in the validation set. The overall c-index was 0.767 (95% CI [0.746, 0.788]) in the training set and 0.773 (95% CI [0.741, 0.804]) in the validation set. The sensitivity and specificity of included studies are as follows: sensitivity [train: 0.66 (95% CI [0.59, 0.73]), validation: 0.73 (95% CI [0.68, 0.77])]; and specificity [train: 0.83 (95% CI [0.78, 0.87])], validation: 0.75 (95% CI [0.71, 0.79])]., Conclusion: The machine learning-based method for predicting the risk of AKI in hospital ICU patients has excellent predictive value and could potentially serve as a prospective application strategy for early identification. PROSPERO Registration number ID: CRD42022362838., Competing Interests: The authors declare there are no competing interests., (©2023 Du et al.)

Cancer seriously endangers human health. Gastrointestinal cancer is the most common and major malignant tumor, and its morbidity and mortality are gradually increasing. Although there are effective treatments such as radiotherapy and chemotherapy for gastrointestinal tumors, they are often accompanied by serious side effects. According to the traditional Chinese medicine and food homology theory, many materials are both food and medicine. Moreover, food is just as capable of preventing and treating diseases as medicine. Medicine and food homologous herbs not only have excellent pharmacological effects and activities but also have few side effects. As a typical medicinal herb with both medicinal and edible uses, some components of ginger have been shown to have good efficacy and safety against cancer. A mass of evidence has also shown that ginger has anti-tumor effects on digestive tract cancers (such as gastric cancer, colorectal cancer, liver cancer, laryngeal cancer, and pancreatic cancer) through a variety of pathways. The aim of this study is to investigate the mechanisms of action of the main components of ginger and their potential clinical applications in treating gastrointestinal tumors., Competing Interests: Conflict-of-interest statement: The authors declare having no conflict of interests for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Microtiter plates are suitable for screening and process development of most microorganisms. They are currently the container of choice for high-throughput and small-scale microbial culture, but require optimization for specific work. In this research, a novel type of microtiter plate was developed using computational fluid dynamics (CFD) technology. The new plate provided high oxygen supply and optimal mixing effects for the fermentation culture of docosahexaenoic acid (DHA) producing strains, surpassing the conventional method of strain screening with shake flasks, which was insufficient. The shape of the microtiter plate was modified, and baffles were introduced to improve mass transfer and oxygen supply effects in the vibrating bioreactor. CFD technology was used to model the new plate's characteristics, establishing the superiority of hexagonal microtiter plates with six baffles. Parameters in the incubation process, such as vibration frequency and liquid load, were optimized, and the final result achieved an oxygen transfer coefficient (K L a) of 0.61 s -1 and a volume power input of 2364 w m -3 , which was four to five times better than the original 96-well plate. The culture results optimized by the model were also verified. Therefore, this new microtiter plate provides a powerful tool for future high-throughput screening of strains., (© 2023 Wiley-VCH GmbH.)

Acute kidney injury (AKI) is associated with high morbidity and mortality. Our previous study has demonstrated that TMEM16A, a Ca 2+ -activated chloride channel, contributes to renal fibrosis progression in chronic kidney disease. However, whether TMEM16A is involved in AKI is still unknown. In this study, we established cisplatin AKI mice model and found that TMEM16A expression was upregulated in the injured kidney. In vivo knockdown of TMEM16A effectively prevented cisplatin-induced tubular cell apoptosis, inflammation and kidney function loss. Western blot and transmission electron microscopy (TEM) revealed that TMEM16A knockdown inhibited Drp1 translocation from the cytoplasm to mitochondria and prevented mitochondrial fission in tubular cells. Consistently, in cultured HK2 cells, knockdown or inhibition of TMEM16A by shRNA or its specific inhibitor suppressed cisplatin-induced mitochondrial fission and its associated energy dysfunction, ROS accumulation, and cell apoptosis via inhibiting Drp1 activation. Further investigation showed that genetic knockdown or pharmacological inhibition of TMEM16A inhibited cisplatin-induced Drp1 Ser-616 site phosphorylation through ERK1/2 signaling pathway, whereas overexpression of TMEM16A promoted this effect. Treatment with Drp1 or ERK1/2 inhibitor could efficiently prevent cisplatin-induced mitochondrial fission. Collectively, our data suggest that TMEM16A inhibition alleviated cisplatin-induced AKI by preventing tubular cell mitochondrial fission through the ERK1/2 / Drp1 pathway. Inhibition of TMEM16A may be a novel therapeutic strategy for AKI., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Aging is associated with an increased risk of cardiovascular disease. Previous studies have demonstrated that compound 3 (C3), a derivative of marine compound xyloallenoide A isolated from the mangrove fungus Xylaria sp. (no. 2508), exhibited strong angiogenic activities in zebrafish. In this study, we examined the effects of C3 on the senescence of endothelial progenitor cells isolated from human peripheral blood (hEPCs). The results showed that treatment with angiotensin II (AngII) for 24 h induced hEPC senescence, as demonstrated by increased SA-β-galactosidase staining. Moreover, there is a significant decrease in telomerase activity and cellular viability in AngII-treated hEPCs. These changes in aging hEPCs were greatly recovered by C3 in a dose-dependent manner. Furthermore, C3 significantly restored the AngII-induced decrease of sirtuin type 1 (SIRT1) expression, a well-known antiaging protein. In addition, AngII increased AMP-activated protein kinase (AMPK) phosphorylation and reduced Akt phosphorylation in aging hEPCs, which were also reversed by C3. Importantly, the inhibition of C3 on hEPC senescence and AMPK/Akt dysregulation was significantly attenuated by the SIRT1-specific inhibitor nicotinoyl. These results indicated that C3 protects hEPC against AngII-induced senescence by increasing SIRT1 expression levels and balancing the AMPK/Akt signaling pathway. The inhibition of hEPCs senescence by C3 might protect EPCs against dysfunction induced by pathological factors in the elderly population. C3 may provide a novel drug candidate for the treatment of aging-related disorders., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

The fermentation production of docosahexaenoic acid (DHA) is an industrial process with huge consumption of freshwater resource and nutrient, such as carbon sources and nitrogen sources. In this study, seawater and fermentation wastewater were introduced into the fermentation production of DHA, which could solve the problem of fermentation industry competing with humans for freshwater. In addition, a green fermentation strategy with pH control using waste ammonia, NaOH and citric acid as well as FW recycling was proposed. It could provide a stable external environment for cell growth and lipid synthesis while alleviating the dependence on organic nitrogen sources of Schizochytrium sp. It was proved that this strategy has good industrialization potential for DHA production, and the biomass, lipid and DHA yield reached to 195.8 g/L, 74.4 g/L and 46.4 g/L in 50 L bioreactor, respectively. This study provides a green and economic bioprocess technology for DHA production by Schizochytrium sp., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Known for its species abundance and evolutionary status complexity, family Roseobacteraceae is an important subject of many studies on the discovery, identification, taxonomic status, and ecological properties of marine bacteria. This study compared and analyzed the phylogenetic, genomic, biochemical, and chemo taxonomical properties of seven species from three genera (Psychromarinibacter, Lutimaribacter, and Maritimibacter) of the family Roseobacteraceae. Moreover, a novel strain, named C21-152 T was isolated from solar saltern sediment in Weihai, China. The values of 16S rRNA gene sequence similarity, the average nucleotide identity (ANI), the average amino acid identity (AAI), and the digital DNA-DNA hybridization (dDDH) between genomes of the novel strain and Psychromarinibacter halotolerans MCCC 1K03203 T were 97.19, 78.49, 73.45, and 21.90%, respectively. Genome sequencing of strain C21-152 T revealed a complete Sox enzyme system related to thiosulfate oxidization as well as a complete pathway for the final conversion of hydroxyproline to α-ketoglutarate. In addition, strain C21-152 T was resistant to many antibiotics and had the ability to survive below 13% salinity. This strain had versatile survival strategies in saline environments including salt-in, compatible solute production and compatible solute transport. Some of its physiological features enriched and complemented the knowledge of the characteristics of the genus Psychromarinibacter. Optimum growth of strain C21-152 T occurred at 37 ℃, with 5-6% (w/v) NaCl and at pH 7.5. According to the results of the phenotypic, chemotaxonomic characterization, phylogenetic properties and genome analysis, strain C21-152 T should represent a novel specie of the genus Psychromarinibacter, for which the name Psychromarinibacter sediminicola sp. nov. is proposed. The type strain is C21-152 T (= MCCC 1H00808 T  = KCTC 92746 T  = SDUM1063002 T )., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Gastric cancer (GC) is the most aggressive malignant tumor of the digestive tract. However, there is still a lack of effective treatment methods in clinical practice. Studies have shown that dehydroandrographolide (DA) has been shown to have anti-cancer activity in a variety of cancers, but it has not been reported in GC. Firstly, we obtained data on DA target genes, GC-related genes, and differentially expressed genes (DEGs) from the PharmMapper, GeneCards, and GEO databases, respectively. Then, the STRING database was used to construct the protein-protein interaction network of intersection genes, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of intersection genes were performed. Finally, 8 hub target genes were identified by analyzing their expression and prognostic survival, and molecular docking between the hub genes and DA was performed. In this study, 293 DA drug target genes, 11,366 GC-related genes, and 3184 DEGs were identified. Gene Ontology and KEGG analysis showed that the intersection genes of DA targets and GC-related genes were mainly related to cancer pathways involving apoptosis and cell adhesion. The intersection genes of DEGs, DA targets, and GC-related genes were also mainly related to cancer pathways involving chemical carcinogenesis, and drug metabolism. The molecular docking results showed that the 8 hub target genes had an apparent affinity for DA, which could be used as potential targets for DA treatment of GC. The results of this study show that the molecular mechanism by which DA inhibits GC metastasis involves multiple target genes. It may play an essential role in inhibiting the invasion and metastasis of GC by regulating the expression and polymorphism of hub target genes, such as MMP9, MMP12, CTSB, ESRRG, GSTA1, ADHIC, CA2, and AKR1C2., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Gastric cancer (GC) is one of the most common cancer types worldwide, and its prevention and treatment methods have garnered much attention. As the active ingredient of licorice, 18β-glycyrrhetinic acid (18β-GRA) has a variety of pharmacological effects. The aim of this study was to explore the effective target of 18β-GRA in the treatment of GC, in order to provide effective ideas for the clinical prevention and treatment of GC., Aim: To investigate the mechanism of 18β-GRA in inhibiting cell proliferation and promoting autophagy flux in GC cells., Methods: Whole transcriptomic analyses were used to analyze and screen differentially expressed microRNAs (miRNAs) in GC cells after 18β-GRA intervention. Lentivirus-transfected GC cells and the Cell Counting Kit-8 were used to detect cell proliferation ability, cell colony formation ability was detected by the clone formation assay, and flow cytometry was used to detect the cell cycle and apoptosis. A nude mouse transplantation tumor model of GC cells was constructed to verify the effect of miR-328-3p overexpression on the tumorigenicity of GC cells. Tumor tissue morphology was observed by hematoxylin and eosin staining, and microtubule-associated protein light chain 3 (LC3) expression was detected by immunohistochemistry. TransmiR, STRING, and miRWalk databases were used to predict the relationship between miR-328-3p and signal transducer and activator of transcription 3 (STAT3)-related information. Expression of STAT3 mRNA and miR-328-3p was detected by quantitative polymerase chain reaction (qPCR) and the expression levels of STAT3, phosphorylated STAT3 (p-STAT3), and LC3 were detected by western blot analysis. The targeted relationship between miR-328-3p and STAT3 was detected using the dual-luciferase reporter gene system. AGS cells were infected with monomeric red fluorescent protein-green fluorescent protein-LC3 adenovirus double label. LC3 was labeled and autophagy flow was observed under a confocal laser microscope., Results: The expression of miR-328-3p was significantly upregulated after 18β-GRA intervention in AGS cells ( P = 4.51E-06). Overexpression of miR-328-3p inhibited GC cell proliferation and colony formation ability, arrested the cell cycle in the G0/G1 phase, promoted cell apoptosis, and inhibited the growth of subcutaneous tumors in BALB/c nude mice ( P < 0.01). No obvious necrosis was observed in the tumor tissue in the negative control group (no drug intervention or lentivirus transfection) and vector group (the blank vector for lentivirus transfection), and more cells were loose and necrotic in the miR-328-3p group. Bioinformatics tools predicted that miR-328-3p has a targeting relationship with STAT3, and STAT3 was closely related to autophagy markers such as p62. After overexpressing miR-328-3p, the expression level of STAT3 mRNA was significantly decreased ( P < 0.01) and p-STAT3 was downregulated ( P < 0.05). The dual-luciferase reporter gene assay showed that the luciferase activity of miR-328-3p and STAT3 3' untranslated regions of the wild-type reporter vector group was significantly decreased ( P < 0.001). Overexpressed miR-328-3p combined with bafilomycin A 1 (Baf A 1 ) was used to detect the expression of LC3 II. Compared with the vector group, the expression level of LC3 II in the overexpressed miR-328-3p group was downregulated ( P < 0.05), and compared with the Baf A 1 group, the expression level of LC3 II in the overexpressed miR-328-3p + Baf A 1 group was upregulated ( P < 0.01). The expression of LC3 II was detected after intervention of 18β-GRA in GC cells, and the results were consistent with the results of miR-328-3p overexpression ( P < 0.05). Additional studies showed that 18β-GRA promoted autophagy flow by promoting autophagosome synthesis ( P < 0.001). qPCR showed that the expression of STAT3 mRNA was downregulated after drug intervention ( P < 0.05). Western blot analysis showed that the expression levels of STAT3 and p-STAT3 were significantly downregulated after drug intervention ( P < 0.05)., Conclusion: 18β-GRA promotes the synthesis of autophagosomes and inhibits GC cell proliferation by regulating the miR-328-3p/STAT3 signaling pathway., Competing Interests: Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Objective: Parkinson's disease is one of the most common neurodegenerative diseases in the world, which seriously damages motor and balance ability. Dual-task training is discussed as an appropriate intervention. The aim of this review was to synthesize the existing research findings on the efficacy of dual-task training for people with Parkinson's disease., Data Resources: A systematic search on PubMed, CENTRAL, Embase, Web of Science, and PEDro, randomized-controlled trials (RCTs) of dual-task training for individuals with Parkinson's disease., Methods: Articles published until 1 November 2022 were included. Our search identified 7 RCTs with a total of 406 subjects. Review Manager 5.4 software was used for bias evaluation and to process the results of the outcome measures collected from the investigations., Results: Dual-task training was associated with significant improvement in most motor and balance outcomes including gait velocity (standard mean difference (SMD) = 0.62; 95% CI, 0.37-0.87; I 2  = 31%; P  = 0.21), cadence (SMD = 0.29; 95% CI, 0.05-0.53; I 2  = 0%; P  = 0.71), timed-up-and-go test (mean difference (MD) = -2.38; 95% CI, -3.93 to -0.84; I 2  = 32%; P  = 0.22) and mini-balance evaluation systems test (MD = 2.04; 95% CI, 1.05-3.03; I 2  = 0%; P  = 0.92)., Conclusion: Evidence from meta-analyses suggests that dual-task training may improve motor and balance abilities in Parkinson's disease patients. Future research should focus on finding the most appropriate dual-task treatment model for patients with different degrees, in order to further improve the rehabilitation treatment of Parkinson's disease.

Utilizing mycoremediation is an important direction for managing heavy metal pollution. Zn 2+ pollution has gradually become apparent, but there are few reports about its pollution remediation. Here, the Zn 2+ remediation potential of Paraisaria dubia , an anamorph of the entomopathogenic fungus Ophiocordyceps gracilis , was explored. There was 60% Zn 2+ removed by Paraisaria dubia mycelia from a Zn 2+ -contaminated medium. To reveal the Zn 2+ tolerance mechanism of Paraisaria dubia , transcriptomic and metabolomic were executed. Results showed that Zn 2+ caused a series of stress responses, such as energy metabolism inhibition, oxidative stress, antioxidant defense system disruption, autophagy obstruction, and DNA damage. Moreover, metabolomic analyses showed that the biosynthesis of some metabolites was affected against Zn 2+ stress. In order to improve the tolerance to Zn 2+ stress, the metabolic mechanism of metal ion transport, extracellular polysaccharides (EPS) synthesis, and microcycle conidiation were activated in P. dubia . Remarkably, the formation of microcycle conidiation may be triggered by reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) signaling pathways. This study supplemented the gap of the Zn 2+ resistance mechanism of Paraisaria dubia and provided a reference for the application of Paraisaria dubia in the bioremediation of heavy metals pollution.

Background: Gastric cancer (GC) is a common gastrointestinal malignancy worldwide. Based on cancer-related mortality, the current prevention and treatment strategies for GC still show poor clinical results. Therefore, it is important to find effective drug treatment targets., Aim: To explore the molecular mechanism of 18β-glycyrrhetinic acid (18β-GRA) regulating the miR-345-5p/TGM2 signaling pathway to inhibit the proliferation of GC cells., Methods: CCK-8 assay was used to determine the effect of 18β-GRA on the survival rate of GES-1 cells and AGS and HGC-27 cells. Cell cycle and apoptosis were detected by flow cytometry, cell migration was detected by a wound healing assay, the effect of 18β-GRA on subcutaneous tumor growth in BALB/c nude mice was investigated, and the cell autophagy level was determined by MDC staining. TMT proteomic analysis was used to detect the differentially expressed autophagy-related proteins in GC cells after 18β-GRA intervention, and then the protein-protein interaction was predicted using STRING (https://string-db.org/). MicroRNAs (miRNAs) transcriptome analysis was used to detect the miRNA differential expression profile, and use miRBase (https://www.mirbase/) and TargetScan (https://www.targetscan.org/) to predict the miRNA and complementary binding sites. Quantitative real-time polymerase chain reaction was used to detect the expression level of miRNA in 18β-GRA treated cells, and western blot was used to detect the expression of autophagy related proteins. Finally, the effect of miR-345-5p on GC cells was verified by mir-345-5p overexpression., Results: 18β-GRA could inhibit GC cells viability, promote cell apoptosis, block cell cycle, reduce cell wound healing ability, and inhibit the GC cells growth in vivo . MDC staining results showed that 18β-GRA could promote autophagy in GC cells. By TMT proteomic analysis and miRNAs transcriptome analysis, it was concluded that 18β-GRA could down-regulate TGM2 expression and up-regulate miR-345-5p expression in GC cells. Subsequently, we verified that TGM2 is the target of miR-345-5p, and that overexpression of miR-345-5p significantly inhibited the protein expression level of TGM2. Western blot showed that the expression of autophagy-related proteins of TGM2 and p62 was significantly reduced, and LC3II, ULK1 and AMPK expression was significantly increased in GC cells treated with 18β-GRA. Overexpression of miR-345-5p not only inhibited the expression of TGM2, but also inhibited the proliferation of GC cells by promoting cell apoptosis and arresting cell cycle., Conclusion: 18β-GRA inhibits the proliferation of GC cells and promotes autophagy by regulating the miR-345-5p/TGM2 signaling pathway., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study aims to construct the core outcome set for the clinical trials of adhesive capsulitis treated with acupuncture and moxibustion. Using systematic review, semi-structured interview, Delphi questionnaire survey, analytic hierarchy process and expert consensus meeting, the primary outcomes are obtained, i.e. local tenderness, pain degree during movement, range of motion, changes in range of motion, function score, and score of local symptoms of shoulder joint. The secondary outcomes are myofascial thickness, thickness of the inferior wall of the joint capsule, health status, activity of daily living, incidence of adverse events, laboratory indexes, vital signs, cost-effectiveness, total effective rate, and patient satisfaction. It is expected to provide a reference for the outcome selection in clinical trials and the generation of medical evidences in the treatment of adhesive capsulitis with acupuncture and moxibustion.

Background: Accumulating evidence indicates that circular RNAs (circRNAs) play important roles in various cancers. Hsa&#95;circ&#95;0008832 (circFBXO7) is a circRNA generated from the second exon of the human F-box only protein 7 (FBXO7). Mouse circFbxo7 is a circRNA generated from the second exon of mouse F-box only protein 7 (Fbxo7). The role of human circFBXO7 and mouse circFbxo7 in non-small cell lung cancer (NSCLC) has not been reported., Methods: The expression of circFBXO7 was measured by quantitative real-time PCR. Survival analysis was performed to explore the association between the expression of circFBXO7 and the prognosis of patients with NSCLC. Lung cancer cell lines were transfected with plasmids. Cell proliferation, cell cycle, and tumorigenesis were evaluated to assess the effects of circFBXO7. Fluorescence in situ hybridization assay was used to identify the location of circFBXO7 and circFbxo7 in human and mouse lung cancer cells. Luciferase reporter assay was conducted to confirm the relationship between circFBXO7 and microRNA., Results: In this study, we found that circFBXO7 was downregulated in NSCLC tissues and cell lines. NSCLC patients with high circFBXO7 expression had prolonged overall survival. Overexpression of circFBXO7 inhibited cell proliferation both in vitro and in vivo. Mechanistically, we demonstrated that circFBXO7 upregulated the expression of miR-296-3p target gene Krüppel-like factor 15 (KLF15) and KLF15 transactivated the expression of CDKN1A., Conclusions: CircFBXO7 acts as a tumor suppressor by a novel circFBXO7/miR-296-3p/KLF15/CDKN1A axis, which may serve as a potential biomarker and therapeutic target for NSCLC., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: The decomposition of plant litter mass is responsible for substantial carbon fluxes and remains a key process regulating nutrient cycling in natural and managed ecosystems. Litter decomposition has been addressed in agricultural monoculture systems, but not in intercropping systems, which produce species-diverse litter mass mixtures. The aim here is to quantify how straw type, the soil environment and their combined effects may influence straw decomposition in widely practiced maize/legume intercropping systems., Methods: Three decomposition experiments were conducted over 341 days within a long-term intercropping field experiment which included two nitrogen (N) addition levels (i.e. no-N and N-addition) and five cropping systems (maize, soybean and peanut monocultures and maize/soybean and maize/peanut intercropping). Experiment I was used to quantify litter quality effects on decomposition; five types of straw (maize, soybean, peanut, maize-soybean and maize-peanut) from two N treatments decomposed in the same maize plot. Experiment II addressed soil environment effects on root decomposition; soybean straw decomposed in different plots (five cropping systems and two N levels). Experiment III addressed 'home' decomposition effects whereby litter mass (straw) was remained to decompose in the plot of origin. The contribution of litter and soil effects to the home-field advantages was compared between experiment III ('home' plot) and I-II ('away' plot)., Results and Discussions: Straw type affected litter mass loss in the same soil environment (experiment I) and the mass loss values of maize, soybean, peanut, maize-soybean, and maize-peanut straw were 59, 77, 87, 76, and 78%, respectively. Straw type also affected decomposition in the 'home' plot environment (experiment III), with mass loss values of maize, soybean, peanut, maize-soybean and maize-peanut straw of 66, 74, 80, 72, and 76%, respectively. Cropping system did not affect the mass loss of soybean straw (experiment II). Nitrogen-addition significantly increased straw mass loss in experiment III. Decomposition of maize-peanut straw mixtures was enhanced more by 'home-field advantage' effects than that of maize-soybean straw mixtures. There was a synergistic mixing effect of maize-peanut and maize-soybean straw mixture decomposition in both 'home' (experiment III) and 'away' plots (experiment I). Maize-peanut showed greater synergistic effects than maize-soybean in straw mixture decomposition in their 'home' plot (experiment III). These findings are discussed in terms of their important implications for the management of species-diverse straw in food-production intercropping systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Surigaoge, Yang, Su, Du, Ren, Fornara, Christie, Zhang and Li.)

Aim: To determine whether an antisense RNA corresponding to the human Alu transposable element (Aluas RNA) can protect human lens epithelial cells (HLECs) from methylglyoxal-induced apoptosis., Methods: Cell counting kit-8 (CCK-8) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to assess HLEC viability. HLEC viability/death was detected using a Calcein-AM/PI double staining kit; the annexin V-FITC method was used to detect HLEC apoptosis. The cytosolic reactive oxygen species (ROS) levels in HLECs were determined using a reactive species assay kit. The levels of malondialdehyde (MDA) and the antioxidant activities of total-superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) were assessed in HLECs using their respective kits. RT-qPCR and Western blotting were used to measure mRNA and protein expression levels of the genes., Results: Aluas RNA rescued methylglyoxal-induced apoptosis in HLECs and ameliorated both the methylglyoxal-induced decrease in Bcl-2 mRNA and the methylglyoxal-induced increase in Bax mRNA. In addition, Aluas RNA inhibited the methylglyoxal-induced increase in Alu sense RNA expression. Aluas RNA inhibited the production of ROS induced by methylglyoxal, restored T-SOD and GSH-Px activity, and moderated the increase in MDA content after treatment with methylglyoxal. Aluas RNA significantly restored the methylglyoxal-induced down-regulation of Nrf2 gene and antioxidant defense genes, including glutathione peroxidase, heme oxygenase 1, γ-glutamylcysteine synthetase and quinone oxidoreductase 1. Aluas RNA ameliorated methylglyoxal-induced increases of the mRNA and protein expression of Keap1 that is the negative regulator of Nrf2., Conclusion: Aluas RNA reduces apoptosis induced by methylglyoxal by enhancing antioxidant defense., (International Journal of Ophthalmology Press.)

Objective: Mucosal immunization was an effective defender against pathogens. Nasal vaccines could activate both systemic and mucosal immunity to trigger protective immune responses. However, due to the weak immunogenicity of nasal vaccines and the lack of appropriate antigen carriers, very few nasal vaccines have been clinically approved for human use, which was a major barrier to the development of nasal vaccines. Plant-derived adjuvants are promising candidates for vaccine delivery systems due to their relatively safe immunogenic properties. In particular, the distinctive structure of pollen was beneficial to the stability and retention of antigen in the nasal mucosa., Methods: Herein, a novel wild-type chrysanthemum sporopollenin vaccine delivery system loaded with a w/o/w emulsion containing squalane and protein antigen was fabricated. The unique internal cavities and the rigid external walls within the sporopollenin skeleton construction could preserve and stabilize the inner proteins. The external morphological characteristics were suitable for nasal mucosal administration with high adhesion and retention., Results: Secretory IgA antibodies in the nasal mucosa can be induced by the w/o/w emulsion with the chrysanthemum sporopollenin vaccine delivery system. Moreover, the nasal adjuvants produce a stronger humoral response (IgA and IgG) compared to squalene emulsion adjuvant. Mucosal adjuvant benefited primarily from prolongation of antigens in the nasal cavity, improvement of antigen penetration in the submucosa and promotion of CD8+ T cells in spleen., Disccusion: Based on effective delivering both the adjuvant and the antigen, the increase of protein antigen stability and the realization of mucosal retention, the chrysanthemum sporopollenin vaccine delivery system has the potential to be a promising adjuvant platform. This work provide a novel idea for the fabrication of protein-mucosal delivery vaccine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer YX declared a shared affiliation, with with several of the authors, JL, ZYC, JWC, XZY, to the handling editor at the time of the review., (Copyright © 2023 Liu, Yan, Li, Du, Zhu, Ye, Cao, Dong, Li, Xu, Bai, Li, Zhang, Wang, Li, Sun and Yin.)

Context and Results: 6-Azido-8-nitrotetrazolo[1,5-b]pyridazine-7-amine (3at) is a promising green energetic material, which meets the development requirements of environment-friendly explosives. By discussing the relationship between lattice parameters and pressure, it is found that the compression ratio indicates anisotropy of compressibility. And bond lengths get shorter under pressure, resulting in stronger intermolecular bonds. The N 3 group rotates under pressure. And then, the optical properties basically change regularly with the change of pressure. As the pressure increases, the absorption range widens. In the low energy interval, it shows transparency, and then with the increase of energy and pressure, it shows better optical activity. With the increase of pressure and energy, the absorption coefficient increases, representing that the optical activity becomes high. Finally, according to the analysis of mechanical properties, 3at exhibited brittle behavior at 0 GPa and 100 GPa, while at 10 to 90 GPa, the values of ν and B/G are malleable., Computational and Theoretical Techniques: Based on density functional theory, the crystal parameters, electronic properties, optical properties, and elastic and mechanical properties of 3at under different pressures were studied theoretically. The GGA-PW91+OBS method was used to calculate the physical parameters under pressure, such as lattice parameters, energy band structures, dielectric function, refractive index, absorption coefficient, and elastic constants. Physical properties under (3at) pressure are predicted., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To explore the effect of electroacupuncture (EA) intervention on the vasoconstriction of cerebral artery smooth muscle cells after cerebral infarction., Methods: Male Wistar rats were randomly divided into 3 groups by a random number table: the model group (n=24), the EA group (n=24), and the normal group (n=6). The model and the EA groups were divided into different time subgroups at 0.5, 1, 3, and 6 h after middle cerebral artery occlusion (MCAO), with 6 rats in each subgroup. MCAO model was established using intraluminal suture occlusion method. The EA group was given EA treatment at acupoint Shuigou (GV 26) instantly after MCAO for 20 min. The contents of cerebrovascular smooth muscle MLCK, the 3 subunits of myosin light chain phosphatase (MLCP) MYPT1, PP1c-δ and M20, as well as myosin-ATPase activity were detected using immunohistochemistry and Western blotting., Results: The overall expression level of the MYPT1 and PP1c-δ in the model group was significantly higher (P<0.01). After EA intervention, the 0.5 h group expression level was close to that of the normal group (P>0.05), and the other subgroups were still significantly higher than the normal group (P<0.01). After EA intervention, the expression level of each subgroup was significantly lower than the corresponding model group. There was a significant difference between the 0.5 and 1 h subgroups (P<0.01), while a difference was also observed between the 3 and 6 h subgroups (P<0.05). The dynamic change rule gradually increased with the prolongation of infarction time within 6 h after infarction., Conclusion: EA intervention can inhibit contraction of cerebral vascular smooth muscle cells and regulate smooth muscle relaxation by regulating MLCK pathway., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The aim of this study was to examine the association between serum complement 1q (C1q) and the associated factors of acute ischemic stroke in patients with type 2 diabetes (T2DM)., Methods: The baseline clinical variables of the participants were collected, and the levels of blood lipids, blood sugar, inflammatory cytokines, and C1q in the three groups were then compared. The variables which affected the associated factors of acute ischemic stroke in T2DM cases were determined., Results: The levels of C1q in the DAIS group were increased significantly compared with those in the T2DM group. Receiver operating characteristic curve analyses showed that the AUC for C1q and the combined diagnosis of acute ischemic stroke were 0.830 (95%CI 0.747-0.914), with a sensitivity of 0.854 and specificity of 0.780. The results of Pearson's correlation analyses demonstrated that C1q was associated positively with low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (PBG), 2-h postprandial blood glucose (2h PG), and high-sensitive C reaction protein (hs-CRP) (all p < .05). Stratified analysis showed that there was a positive relationship between C1q and the associated factors of acute ischemic stroke for partial LDL-C, and hs-CRP strata. Logistic model analysis suggested that C1q was an independent risk factor for acute ischemic stroke in patients with T2DM. After adjusting for potential confounders, a one-standard deviation (SD) increase in C1q level was strongly related to an approximately 1.5-fold increased risk of acute ischemic stroke in cases with a hs-CRP ≥1.78 mg/L., Conclusion: In DAIS patients, the levels of C1q were increased significantly and were an independent associated factor which affected the occurrence of acute ischemic stroke.

Objective: To evaluate the reporting quality of randomized controlled trials (RCTs) of acupuncture for labor pain, and to explore relevant factors for facilitating reporting transparency and integrity for future RCTs., Method: Eight Chinese and English databases were systematically searched from their inception until August 31, 2021. General characteristics and methodological quality of the included reports were evaluated based on the CONSORT statement and the STRICTA guidelines. Descriptive statistical analysis was performed. Cohen's κ -statistics were calculated to assess the agreement of all items between two reviewers., Results: A total of 84 RCTs were included. Based on the CONSORT statement, a positive reporting rate (greater than 80%) was evident for the items "trial design" "participants" "intervention" "outcomes" "numbers analyzed" and "generalizability". The quality of reporting for the items "randomized in the title or abstract" "sample size" "allocation concealment" "implementation" "blinding" "recruitment" "ancillary analyses" "harms" "interpretation" "registration" and "protocol" was poor with positive rates less than 10%. Based on the STRICTA guidelines, the items "extent to which treatment varied" "number of needle insertions per subject per session" and "control or comparator interventions" had poor reporting quality with positive rates of less than 10%. Substantial agreement was observed for most items and excellent agreement for some items., Conclusion: The reporting quality of RCTs of acupuncture for labor pain is suboptimal generally. Rigorous adherence to the CONSORT statement and the STRICTA guidelines should be emphasized in future studies to improve the quality of acupuncture RCT reports., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Jiang, Jiang, Cui, Yang, Du, Li, Pang and Li.)

Background: Twenty-four-hour oscillations of circadian rhythms control comprehensive biological processes in the human body. In lung adenocarcinoma (LUAD), chronic circadian rhythm disruption is positively associated with tumorigenesis. However, few studies focus on circadian clock gene signatures (CGSs) for prognosis evaluation of patients with early-stage LUAD., Methods: In this study, we aimed to construct a robust prognostic circadian rhythm-related biomarker from multiple public databases, including the Gene Expression Omnibus database and The Cancer Genome Atlas database. The least absolute shrinkage and selection operator (LASSO)-penalized Cox regression model was performed to select optimal circadian clock gene pairs. Bioinformatic analyses were performed to estimate the abundance of different immune cells and immunohistochemical analyses were conducted to validate the differential proportion of tumor-infiltrating lymphocytes in different groups., Results: Results demonstrated that the CGS could accurately identify patients with early-stage LUAD at a high risk in the training dataset [hazard ratio (HR) =3.06; 95% confidence interval (CI): 2.47-3.78; P<0.001], testing dataset (HR =2.44; 95% CI: 1.74-3.43; P<0.001), and validation dataset (HR =2.09, 95% CI: 1.09-4.00; P=0.023). Bioinformatic and immunohistochemical analyses demonstrated that the abundance of tumor-infiltrating CD4 + T cells was higher in the low-CGS groups. Integration of the CGS and clinical characteristics improved the accuracy of the CGS in predicting overall survival (OS) of patients with early-stage LUAD., Conclusions: In conclusion, the CGS was an independent immune-related circadian biomarker that could identify early-stage LUAD patients with different OS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-570/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Liquid submerged fermentation is an effective strategy to achieve large-scale production of active ingredients by macrofungi, and controlling mycelium morphology is a key factor restricting the development of this technology. Mining for superior morphological regulatory factors and elucidation of their regulatory mechanisms are vital for the further development of macrofungal fermentation technology. In this study, microparticles were used to control the morphology of Paraisaria dubia (P. dubia) in submerged fermentation, and the underlying regulatory mechanisms were revealed by transcriptomic. The relative frequency of S-type pellet diameter increased significantly from 7.14 to 88.31%, and biomass increased 1.54 times when 15 g/L talc was added. Transcriptome analysis showed that the morphological regulation of filamentous fungi was a complex biological process, which involved signal transduction, mycelium polar growth, cell wall synthesis and cell division, etc. It also showed a positive impact on the basic and secondary metabolism of P. dubia. We provided a theoretical basis for controlling the mycelium morphology of P. dubia in submerged fermentation, which will promote the development of macrofungal fermentation technology., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the era of sustainable development, the use of cell factories to produce various compounds by fermentation has attracted extensive attention; however, industrial fermentation requires not only efficient production strains, but also suitable extracellular conditions and medium components, as well as scaling-up. In this regard, the use of biological models has received much attention, and this review will provide guidance for the rapid selection of biological models. This paper first introduces two mechanistic modeling methods, kinetic modeling and constraint-based modeling (CBM), and generalizes their applications in practice. Next, we review data-driven modeling based on machine learning (ML), and highlight the application scope of different learning algorithms. The combined use of ML and CBM for constructing hybrid models is further discussed. At the end, we also discuss the recent strategies for predicting bioreactor scale-up and culture behavior through a combination of biological models and computational fluid dynamics (CFD) models.

Background: Gastric carcinoma (GC) is a common gastrointestinal malignancy worldwide. Based on the cancer-related mortality, the current prevention and treatment strategies for GC still show poor clinical results. Therefore, it is important to find effective drug treatment targets., Aim: To explore the mechanism by which 18β-glycyrrhetinic acid (18β-GRA) regulates mitochondrial ribosomal protein L35 (MRPL35) related signal proteins to inhibit the proliferation of GC cells., Methods: Cell counting kit-8 assay was used to detect the effects of 18β-GRA on the survival rate of human normal gastric mucosal cell line GES-1 and the proliferation of GC cell lines MGC80-3 and BGC-823. The apoptosis and cell cycle were assessed by flow cytometry. Cell invasion and migration were evaluated by Transwell assay, and cell scratch test was used to detect cell migration. Furthermore, a tumor model was established by hypodermic injection of 2.5 × 10 6 BGC-823 cells at the selected positions of BALB/c nude mice to determine the effect of 18β-GRA on GC cell proliferation, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect MRPL35 expression in the engrafted tumors in mice. We used the term tandem mass tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry to screen for differentially expressed proteins (DEPs) extracted from GC cells and control cells after 18β-GRA intervention. A detailed bioinformatics analysis of these DEPs was performed, including Gene Ontology annotation and enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and so on. Moreover, STRING database (https://string-db.org/) was used to predict protein-protein interaction (PPI) relationships and Western blot was used to detect the expression of proteins of interest in GC cells., Results: The results indicated that 18β-GRA could inhibit the proliferation of GC cells in a dose- and time-dependent manner. It could induce GC cell apoptosis and arrest the cell cycle at G0/G1 phase. The proportion of cells arrested at S phase decreased with the increase of 18-GRA dose, and the migration and invasiveness of GC cells were inhibited. The results of animal experiments showed that 18β-GRA could inhibit tumor formation in BALB/c nude mice, and qRT-PCR results showed that MRPL35 expression level was significantly reduced in the engrafted tumors in mice. Using TMT technology, 609 DEPs, among which 335 were up-regulated and 274 were down-regulated, were identified in 18β-GRA intervention compared with control. We found that the intervention of 18β-GRA in GC cells involved many important biological processes and signaling pathways, such as cellular processes, biological regulation, and TP53 signaling pathway. Notably, after the drug intervention, MRPL35 expression was significantly down-regulated ( P = 0.000247), TP53 expression was up-regulated ( P = 0.02676), and BCL2L1 was down-regulated ( P = 0.01699). Combined with the Retrieval of Interacting Genes/Proteins database, we analyzed the relationship between MRPL35, TP53, and BCL2L1 signaling proteins, and we found that COPS5, BAX, and BAD proteins can form a PPI network with MRPL35, TP53, and BCL2L1. Western blot analysis confirmed the intervention effect of 18β-GRA on GC cells, MRPL35, TP53, and BCL2L1 showed dose-dependent up/down-regulation, and the expression of COPS5, BAX, and BAD also increased/decreased with the change of 18β-GRA concentration., Conclusion: 18β-GRA can inhibit the proliferation of GC cells by regulating MRPL35, COPS5, TP53, BCL2L1, BAX, and BAD., Competing Interests: Conflict-of-interest statement: All authors declare no financial or commercial conflict of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Purpose: Renal fibrosis is the final common outcome in most forms of chronic kidney disease (CKD). However, the underlying causal mechanisms remain obscure. The present study examined whether transmembrane member 16A (TMEM16A), a Ca 2+ -activated chloride channel, contributes to the progression of renal fibrosis., Experimental Approach: Masson staining, western blot and immunohistochemistry were used to measure renal fibrosis and related proteins expression. MQAE was used to evaluate the intracellular Cl - concentration., Key Results: TMEM16A expression was significantly up-regulated in fibrotic kidneys of unilateral ureteral obstruction (UUO) and high-fat diet murine models and in renal samples of IgA nephropathy patients. In vivo knockdown of TMEM16A with adenovirus harbouring TMEM16A-shRNA or inhibition of TMEM16A channel activity with inhibitors CaCCinh-A01 or T16Ainh-A01 effectively prevented UUO-induced renal fibrosis and decreased protein expression of fibronectin, α-SMA and collagen in the obstructed kidneys. In cultured HK2 cells, knockdown or inhibition of TMEM16A suppressed TGF-β1-induced epithelial-mesenchymal transition, reduced snail1 expression and phosphorylation of Smad2/3 and ERK1/2, whereas overexpression of TMEM16A showed the opposite effects. TGF-β1 increased [Cl - ]i in HK2 cells, which was inhibited by knockdown or inhibition of TMEM16A. Reducing [Cl - ]i significantly blunted TGF-β1-induced Smad2/3 phosphorylation and profibrotic factors expression. The profibrotic effects of TGF-β1 were also reduced by inhibition of serum- and glucocorticoid-inducible protein kinase 1 (SGK1). SGK1 was also suppressed by reducing [Cl - ]i., Conclusion and Implications: Blockade of TMEM16A prevented the progression of kidney fibrosis, likely by suppressing [Cl - ]i/SGK1/TGF-β1 signalling pathway. TMEM16A may be a potential new therapeutic target against renal fibrosis., (© 2021 The British Pharmacological Society.)

Background: Diabetic nephropathy (DN) is one of the most typical microangiopathies caused by diabetes. It often leads enormous physiological and psychological burdens for patients and seriously affects their quality of life. Therefore, effective combination therapy is necessary for these patients. In this study, we performed a meta-analysis to systematically evaluate and discuss the efficacy and safety of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in the treatment of DN., Methods: The PubMed, Embase, Web of Science, and Medline databases were selected as the sources of the literature search, and the search was limited to studies published in English. Studies related to ACEIs and ARBs in the treatment of DN published from January 2001 to January 2021 were included in this analysis. Meta-analysis was performed to calculate the reinforcement mean difference., Results: In total, eight articles involving 1,893 cases with DN were included in this study. The results of this systematic review and meta-analysis showed that for patients with diabetic nephropathy，there were significant differences in 24-hour proteinuria [mean difference (MD) =-78.46, 95% confidence interval (95% CI): -80.25 to -76.66, P<0.00001], systolic blood pressure (MD =-9.11, 95% CI: -13.44 to -4.78, P<0.0001), and diastolic blood pressure (MD =-3.39, 95% CI: -5.68 to -1.11, P=0.004) between the combined ACEI and ARB group and the single ACEI or ARB group (P<0.05). In terms of safety, in addition to the significant difference in serum potassium (MD =0.1, 95% CI: 0.05 to 0.15, P=0.0001) between the combined ACEI and ARB group and the single drug group (P<0.1), there were no notable differences in serum creatinine (MD =0.66, 95% CI: -8.0 to 2.12, P=0.37), creatinine clearance (MD =-0.25, 95% CI: -0.62, 0.11, P=0.17), or the incidence of adverse reactions [odds ratio (OR) =1.19, 95% CI: 0.81 to 1.75, P=0.37]., Discussion: A total of eight studies were included in this meta-analysis. The results showed that for patients with diabetic nephropathy, the combination of ACEI and ARB was more effective than ACEI or ARB alone, and also had higher safety.

Objective: To explore the clinical effect of Pinggan Jiangya decoction combined with penetrating needling at Baihui (GV20) in a period of day from 7 am to 9 am in the treatment of grade 1 and 2 essential hypertension (EH)., Methods: A total of 150 cases of grade 1 and 2 EH patients were randomized into an observation group and a control group, 75 cases in each group. In the control group, Pinggan Jiangya decoction was prescribed for oral administration one dose a day, while in the observation group, on the basis of the treatment as the control group, penetrating needling was exerted at GV20 once daily. The treatment duration was 8 weeks. Before and after treatment, the TCM syndrome score, 24 h average systolic blood pressure (24 h ASBP), 24 h average diastolic blood pressure (24 h ADBP), 24 h average pulse pressure difference (24 h PP), morning blood pressure surge (MBPS), 24 h SBP variability (24 h SBPV), 24 h DBP variability (24 h DBPV), serum levels of 5-hydroxytryptamine (5-HT) and melatonin (MT) were compared in the patients of the two groups. The clinical therapeutic effect was observed in the two groups., Results: After the treatment, in the self-comparison of each group, the scores of headache, vertigo, backache, soft knees, tinnitus, 24 h ASBP， 24 h ADBP, 24 h PP, MBPS, 24 h SBPV and 24 h DBPV in the two groups were lower than those before treatment ( P <0.01), and the above indexes in the observation group were lower than those in the control group ( P <0.01). The level of serum 5-HT after the treatment was lower than that of before the treatment ( P <0.01), while the level of MT was higher than that of before the treatment ( P <0.01) in both two groups, and the level of 5-HT in the observation group was lower than that of the control group, while the level of MT was higher than that of the control group ( P <0.01). The total effective rate of the observation group was 93.3% (70/75), better than 76.0% (57/75) of the control group ( P <0.01)., Conclusion: Pinggan Jiangya decoction combined with penetrating needling at GV20 in a period of day from 7 am to 9 am can regulate the levels of serum MT and 5-HT, effectively reduce blood pressure, improve blood pressure variability, control morning peak blood pressure, and has a remarkable effect in the treatment of grade 1 and 2 EH.

Objective: To investigate the effect of electro-acupuncture (EA) on vasomotor symptoms in rats with acute cerebral infarction, by observing the changes in the expression of factors related to the phosphatidylinositol (PI) system., Methods: Forty-two Wistar rats were randomly divided into 3 groups by a random number table: the control group (n=6), the model group (n=18) and the EA group (n=18). The EA group was given EA treatment at Shuigou (GV 26) instantly after modeling with middle cerebral artery occlusion (MCAO) method, while the model and control groups were not given any treatment. The degrees of neurological deficiency were evaluated using neurological severity scores (NSS) and the brain blood flow was evaluated by a laser scanning confocal microscope. Western blot analysis was conducted to detect the expression levels of G-protein subtype (Gq) and calmodulin (CaM). Competition for protein binding was conducted to detect the expression level of inositol triphosphate (IP3). Thin layer quantitative analysis was conducted to detect the expression level of diacylglycerol (DAG). The expression level of intracellular concentration of free calcium ion ([Ca 2+ ] i ) was detected by flow cytometry., Results: The NSS of the model group was significantly higher than the control group at 3 and 6 h after MCAO (P<0.01), while the EA group was significantly lower than the model group at 6 h (P<0.01). The cerebral blood flow in the model group was significantly lower than the control group at 1, 3 and 6 h after MCAO (P<0.01), while for the EA group it was remarkably higher than the model group at the same time points (P<0.01). The expressions of Gq, CaM, IP3, DAG and [Ca 2+ ] i in the model group were significantly higher than the control group (P<0.05 or P<0.01), and those in the EA group were significantly lower than the model group at the same time points (P<0.05 or P<0.01)., Conclusion: EA treatment at GV 26 can effectively decrease the over-expression of related factors of PI system in rats with acute cerebral infarction, improve cerebral autonomy movement, and alleviate cerebral vascular spasm., (© 2021. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Medical treatment is a less invasive alternative to surgical management of missed miscarriage. Studies have shown that pretreatment with mifepristone can increase the complete abortion rate in management of first-trimester missed miscarriage compared with misoprostol alone. Two studies have also shown that pretreatment with letrozole could increase the efficacy compared with misoprostol alone. So far, there is no trial comparing letrozole and mifepristone pretreatment for missed miscarriage. We designed this randomised controlled trial to test the hypothesis that for first-trimester missed miscarriage, letrozole pretreatment is non-inferior to mifepristone pretreatment followed by misoprostol in terms of complete abortion rate., Methods and Analysis: This is a prospective open-label non-inferiority randomised controlled trial conducted in a single centre. In total, 294 women diagnosed with first-trimester missed miscarriage opting for medical treatment is recruited with informed consent. They are randomly assigned to receive mifepristone or letrozole pretreatment. In the mifepristone group, each woman takes 200 mg mifepristone orally followed 24-48 hours later by 800 µg misoprostol vaginally. In the letrozole group, each woman takes 10 mg letrozole orally per day for 3 days, followed by 800 µg misoprostol vaginally on the third day of letrozole administration. Follow-up is conducted on days 15 and 42 after misoprostol administration. The primary outcome is the overall complete abortion rate. Secondary outcomes include side effects and complications during the study period. Data will be analysed with both intention-to-treat and per protocol approaches. A p<0.05 will be considered as indicating statistical significance., Ethics and Dissemination: Ethics approval has been obtained from the Institutional Review Board of the University of Hong Kong-Shenzhen Hospital with approval number: (2020)166. Findings will be disseminated in a peer-reviewed journal and in national and/or international meetings to guide future practice., Trial Registration Number: ChiCTR2000041480., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Polysaccharides are important active ingredients in Ophiocordyceps gracilis with many physiological functions. It can be obtained from the submerged fermentation by the anamorph (Paraisaria dubia) of Ophiocordyceps gracilis. However, it was found that the mycelial pellets of Paraisaria dubia were dense and increased in volume in the process of fermentation, and the center of the pellets was autolysis due to the lack of nutrient delivery, which extremely reduced the yield of polysaccharides. Therefore, it is necessary to excavate a fermentation strategy based on morphological regulation for Paraisaria dubia to promote polysaccharides accumulation., Results: In this study, we developed a method for enhancing polysaccharides production by Paraisaria dubia using microparticle enhanced technology, talc microparticle as morphological inducer, and investigated the enhancement mechanisms by transcriptomics. The optimal size and dose of talc were found to be 2000 mesh and 15 g/L, which resulted in a high polysaccharides yield. It was found that the efficient synthesis of polysaccharides requires an appropriate mycelial morphology through morphological analysis of mycelial pellets. And, the polysaccharides synthesis was found to mainly rely on the ABC transporter-dependent pathway revealed by transcriptomics. This method was also showed excellent robustness in 5-L bioreactor, the maximum yields of intracellular polysaccharide and exopolysaccharides were 83.23 ± 1.4 and 518.50 ± 4.1 mg/L, respectively. And, the fermented polysaccharides were stable and showed excellent biological activity., Conclusions: This study provides a feasible strategy for the efficient preparation of cordyceps polysaccharides via submerged fermentation with talc microparticles, which may also be applicable to similar macrofungi., (© 2021. The Author(s).)

Three kinds of nano-concrete, i.e., 2.0% nano-SiO 2 doped, 2.0% nano-CaCO 3 doped and 1.0% nano-SiO 2 -1.0% nano-CaCO 3 co-doped concretes (NS, NC, NSC) were prepared for a study on static property and dynamic property under different strain rates (50-130 s -1 ) using HYY series hydraulic servo test system and Φ100 mm split Hopkinson pressure bar test system, and a comparison with plain concrete (PC) as well. The results have shown that under static load, as compared with PC, NC has both strength and elastic modulus increased obviously, while NS has strength decreased and elastic modulus increased, and under dynamic load, there is an obvious strain rate effect for the dynamic compressive strength, impact toughness, energy dissipation and impact failure mode of concrete. Under the same strain rate, the dynamic compressive strength, peak strain, impact toughness and energy dissipation of NC are significantly increased, while its dynamic elastic modulus is decreased. Compared with PC, NS has dynamic compressive strength, peak strain, impact toughness and energy dissipation decreased, and dynamic elastic modulus increased, NC has static and dynamic mechanical properties improved, NS has static and dynamic mechanical properties weakened, and NSC is between PC and NC in static and dynamic mechanical properties, but generally improved. Doped with nano-CaCO 3 , NC has compactness improved, weak areas reduced, and pore size distribution optimized, while doped with nano-SiO 2 , NS has obvious internal weak areas, with pore structure degraded., (© 2022. The Author(s).)

Endothelial tight junctions (TJs) serve as an important barrier in vascular endothelial structure and maintain vascular function homeostasis. Occludin, the most representative tight junction protein, is involved in sealing cell connections and maintaining the integrity and permeability of vascular endothelium. Recent studies have shown that alterations in the expression, distribution, and structure of endothelial TJs may lead to many related vascular diseases and pathologies (such as stroke, atherosclerosis, and pulmonary hypertension etc.). Here, we reviewed the research advances on the relationship between occludin and vascular endothelial injury, including the biological information of occludin, the signal pathways that occludin exerts the protective effect of vascular endothelium, and the relationship between occludin and vascular endothelial injury-related diseases.

Single-crystalline Ni-rich cathodes are promising candidates for the next-generation high-energy Li-ion batteries. However, they still suffer from poor rate capability and low specific capacity due to the severe kinetic hindrance at the nondilute state during Li + intercalation. Herein, combining experiments with density functional theory (DFT) calculations, we demonstrate that this obstacle can be tackled by regulating the oxidation state of nickel via injecting high-valence foreign Ta 5+ . The as-obtained single-crystalline LiNi 0.8 Co 0.1 Mn 0.1 O 2 delivers a high specific capacity (211.2 mAh g -1 at 0.1 C), high initial Coulombic efficiency (93.8 %), excellent rate capability (157 mAh g -1 at 4 C), and good durability (90.4 % after 100 cycles under 0.5 C). This work provides a strategy to mitigate the Li + kinetic hindrance of the appealing single-crystalline Ni-rich cathodes and will inspire peers to conduct an intensive study., (© 2021 Wiley-VCH GmbH.)

Objective: To explore the effect of scalp acupuncture combined with suspension training on balance ability and motor function in stroke patients with balance dysfunction., Methods: A total of 105 stroke patients with balance dysfunction were randomly divided into a combined group (35 cases, 2 cases dropped off), a scalp acupuncture group (35 cases, 3 cases dropped off) and a suspension training group (35 cases, 2 cases dropped off). The scalp acupuncture group was treated with scalp acupuncture at bilateral suboccipital lateral line, parietal midline, upper 1/5 line of anterior oblique line of parietal and temporal and line 1 of the parietal lateral line on the opposite side of hemiplegia. The suspension training group was treated with suspension training. The combined group was treated with suspension training at the same time of scalp acupuncture. All the treatment was given once a day, 30 min each time, 5 days a week, for a total of 6 weeks. The Berg balance scale (BBS) score, balance tester and Fugl-Meyer assessment (FMA) score were used to evaluate the motor function and balance ability before treatment, 3 and 6 weeks into treatment. The clinical efficacy was evaluated in the 3 groups., Results: The scores of BBS and FMA in each group at 3 and 6 weeks into treatment were higher than those before treatment ( P <0.05); the scores of BBS and FMA in the combined group were higher than those in the scalp acupuncture group and the suspension training group ( P <0.05). At 3 and 6 weeks into treatment, the length and area of centroid locus of balance tester in each group were lower than those before treatment ( P <0.05); the length and area of centroid locus of balance tester in the combined group were lower than those in the scalp acupuncture group and the suspension training group ( P <0.05). The total effective rate of the combined group was 97.0% (32/33), which was higher than 87.5% (28/32) in the scalp acupuncture group and 90.9% (30/33) in the suspension training group ( P <0.05)., Conclusion: Scalp acupuncture combined with suspension training could improve the balance ability and motor function in stroke patients with balance dysfunction, and the curative effect is better than simple scalp acupuncture and simple suspension training.

The knowledge, attitude, and practice of nurses in intensive care units (ICUs) are determinants for the efficacy of preventing the medical device-related pressure injury (MDRPI). The aim of this study was to determine the level and factors of knowledge, attitude, and practice of nurses' ICUs on preventing medical MDRPI in western China. An annual cross-sectional study was conducted in hospitals of western China from May 2020 to September 2020. Nurses' knowledge and attitudes were assessed using Clinical Nurses Prevention MDRPI of Critically Ill Patients for the Knowledge, Attitude, Practice Assessment Scale. SPSS software version 25.0 and independent t-test, Chi-square, Fisher exact, one-way analysis of variance, and multiple linear regression tests were used for data analysis. A total of 1002 nurses in ICUs from 37 hospitals in Gansu Province, China, participated in this study. The scores of overall KAP, knowledge, attitudes, and practice were 149.17 ± 24.62, 53.83 ± 12.23, 37.24 ± 6.35 and 58.10 ± 9.83, respectively. There was a positive and significant relationship between three variables. Findings revealed that nurses' knowledge score in the Tertiary hospital was higher than scores of other hospitals as 3.840 units. Moreover, the knowledge score and practice score of nurses with bachelor's degree or above were higher than other nurses and are 0.978 and 1.106 units, respectively. Based on the findings, practice of nurses increased by 0.992 units, with a 1-year increase in work experience of nurses in the ICU. The levels of knowledge, attitude, and practice of nurse in ICUs on preventing MDRPI were acceptable. The findings of the study highlight that a comprehensive approach should be conducted for raising the level of knowledge, attitude, and practice of nurses' ICUs on preventing medical MDRPI, as well as improving the quality of care for critically ill patients., (© 2021 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Objective: To observe the effect of electroacupuncture (EA) of "Shuigou" (GV26) on the activities of sonic hedgehog(Shh) signaling molecules (Shh, Ptch, Smo，Gli and Gli2) in ischemic brain tissues in rats with cerebral ischemia (CI), so as to explore its mechanisms underlying improvement of CI., Methods: Male Wistar rats were randomly divided into blank control group( n =10), sham operation group ( n =90), model group( n =90) and EA group ( n =90). The CI model was established by occlusion of the right middle cerebral artery (MCAO). According to the postoperative time points of MCAO, the later three groups were further divided into 1, 3, 6, 9, 12 and 24 h, and 3, 7 and 12 d subgroups, with 10 rats in each subgroup. EA (15 Hz, 2 mA) was applied to GV26 for 20 min. The 1 h to 24 h subgroups were treated immediately after modeling, the 3-12 d subgroups treated one time a day. The neurological severity score (NSS, 0 to 18 points) was used to evaluate the rats' neurological function, and TTC staining was employed to assess the cerebral ischemic volume (percentage of cerebral infarct volume, CIV). Western blot was employed to detect the expression of Shh, Ptch, Smo, Gli1 and Gli2 proteins in the ischemic cerebral tissue., Results: Compared with the sham operation group, the NSS scores of the model group increased at all time points ( P <0.01). The percentages of CIV of the model group from 3 h to 12 d were obviously higher than those of the sham operation group ( P <0.01). The NSS scores at 3, 7 and 12 d and the percentages of CIV at 1, 3, 7 and 12 d after MCAO were significant lower in the EA group than in the model group ( P <0.05). The protein expression levels of Shh from 12 h to 12 d (i.e. 12 h, 24 h, 3, 7 and 12 d), Ptch from 6 h to 12 d, Smo from 9 h to 12 d, Gli1 at 9 h, 12 h, and from 3 d to 12 d, Gli2 at 6, 9 and 12 h, and 3 d were significantly higher in the model group than in the sham operation group ( P <0.05, P <0.01), while those of Shh at 3, 7 and 12 d, Ptch from 24 h to 7 d, Smo from 12 h to 7 d, Gli1 from 24 h to 7 d, Gli2 at 12 h, 3 and 7 d were significantly higher in the EA group than in the model group ( P <0.05, P <0.01). No statistical significances were found between the sham operation and the blank control groups in all the indexes mentioned above ( P >0.05)., Conclusion: EA of GV26 can improve neurological function and reduce infarct volume in MCAO rats, which may be related to its function in up-regulating the activities of Shh signaling pathway in the ischemic cerebral tissues.

Objective: To analyze the epidemiological and etiological characteristics of sever fever with thrombocytopenia syndrome (SFTS) cases in Henan province during 2017-2020. Methods: Descriptive epidemiology method was used to analyze the characteristics of SFTS cases in Henan during 2017-2020. Patients' sera in acute phase were collected and tested using real-time fluorescence RT-PCR. The S segment complete sequences of the isolated sever fever with thrombocytopenia syndrome virus (SFTSV) strains were amplified and homology analysis was performed to construct the phylogenetic tree. Results: A total of 1 767 SFTS cases, including 1 000 suspected cases and 767 confirmed cases, were reported in Henan during this period, and 11 cases, including 3 suspected cases and 8 confirmed cases died, the case fatality rate was 0.62% (11/1 767). The incidence decreased year by year. The cases were distributed in 28 counties of 6 cities, and 1 681 cases were reported in Xinyang, accounting for 95.13% (1 681/1 767) of the total. The cases mainly occurred from April to October, accounting for 96.10% (1 698/1 767) of the total. The incidence in males (0.38/100 000) was significantly lower than that in females (0.54/100 000) ( χ 2 =54.855, P <0.001). Up to 93.44% (1 651/1 767) of the cases were aged between 40 and 84 years. Farmers accounted for 96.10% (1 698/1 767) of the total cases. One family cluster outbreak occurred in 4 years. A total of 1 110 samples were detected by Henan CDC, in which 435 were SFTS virus positive with an average positive rate of 39.19% (435/1 110). The differences in positive rates of SFTS virus among different years were significant (χ2=25.405, P <0.001). The sequence homology of complete S segment of the 39 SFTS virus strains ranged from 94.76% to 99.82%. The genetic evolution analysis on the complete S segment of the 39 SFTS virus strains showed that 34 strains belonged to genotype A, 2 strains belonged to genotype B, and 3 strains belonged to genotype D. Conclusions: The incidence of SFTS in Henan was sporadic, and decreased year by year. SFTS had obvious regional and seasonal characteristics, and the area affected by SFTS expanded. The incidence of SFTS was high in elderly female farmers, and the positive rate of SFTS virus varied greatly in different years. The main type of SFTS virus in Henan was genotype A, but the etiological surveillance is still needed.

The instability of slope has already threatened life and property safety of the people, and improving the monitoring method of slope stability has important theoretical and practical significance for disaster prevention and reduction. According to the idea of "Newton force sudden drop and catastrophic occurrence" proposed by M.C. He in the landslide monitoring, a numerical model with constant resistance bolt has been established. Through numerical simulation research, it is found that the maximum principal stress, minimum principal stress and shear stress of the intersection point P of landslide surface and constant resistance bolt are sudden growth and sudden decrease, the vertical displacement and lateral displacement of this point P appear rise and fall before three kinds of stress. When loading to the next step of the step where three stress have reduced to a minimum value the slope is unstable and destroyed. At this time, the constant resistance bolt has undergone larger plastic deformation and damaged. Finally, comparing the stress curves and the acoustic emission (AE) curves, it can be seen that stress decreases from the maximum value and the AE curves begin to show a significant rise, the two curves display opposite law. It can be seen from the AE diagram that the failure mode of the slope is a combined tension and shear failure. The numerical test results provide a new idea for real-time monitoring and forecasting of slope., (© 2021. The Author(s).)

Background: Coronary heart disease (CHD) causes many adverse cardiovascular events and poses a threat to the patient's health and quality of life., Aim: To evaluate ultrasonography for evaluation of cardiac function and lesion degree in patients with CHD., Methods: A total of 106 patients with CHD (study group) and 106 healthy individuals (control group) in our hospital from March 2019 to September 2020 were selected for this study. All subjects were examined by ultrasound, and the mitral orifice's early-to-late diastolic blood flow velocity ratio (E/A), left ventricular end-diastolic volume (LVDd), and left atrial diameter (LAD) were measured. Values were compared between the study group and healthy group, and the correlation between the ultrasonic parameters of patients with different cardiac function grades and the degree of CHD were assessed. In addition, the ultrasonic parameters of patients with different prognoses were compared after a follow-up for 6 mo., Results: E/A (1.46 ± 0.34) of the study group was smaller than that of the control group (1.88 ± 0.44), while LVDd (58.24 ± 5.05 mm) and LAD (43.31 ± 4.38 mm) were larger (48.15 ± 3.93 and 34.94 ± 2.81, respectively; P < 0.05). E/A for patients with grade III disease (1.41 ± 0.43) was smaller and their LVDd (60.04 ± 4.21 mm) and LA (44.16 ± 2.79 mm) were larger than those in patients with grade II disease (1.71 ± 0.48, 52.18 ± 3.67 mm, and 39.68 ± 2.37, respectively; P < 0.05). Patients with grade IV disease had smaller E/A (1.08 ± 0.39) and larger LVDd (66.81 ± 5.39 mm) and LAD (48.81 ± 3.95 mm) than patients with grade II and III disease ( P < 0.05). In patients with moderate disease, E/A (1.44 ± 0.41) was smaller and LVDd (59.95 ± 4.14 mm) and LAD (45.15 ± 2.97 mm) were larger than in patients with mild disease (1.69 ± 0.50, 51.97 ± 3.88 and 38.81 ± 2.56 mm, respectively; P < 0.05). In patients with severe disease, E/A (1.13 ± 0.36) was smaller and LVDd (67.70 ± 6.11 mm) and LAD (49.09 ± 4.05 mm) were larger than in patients with moderate disease ( P < 0.05). E/A was negatively correlated with cardiac function classification and disease severity, while LVDd and LAD were positively correlated with cardiac function classification and disease severity ( P < 0.05). E/A (1.83 ± 0.51) for patients with good prognosis was higher than that for those with poor prognosis (1.39 ± 0.32), while LVDd (49.60 ± 4.39 mm) and LAD (36.13 ± 3.05 mm) were lower ( P < 0.05)., Conclusion: The ultrasonic parameters of patients with CHD are abnormal, and differ significantly in patients with different cardiac function grades, lesion degree, and prognosis., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest between them., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)