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Abstract With a bottom-up assemble technology, heterogeneous magnetic nanobrushes, consisting of Co nanowire arrays and ferromagnetic Fe70Co30 nanofilm, have been fabricated using an anodic aluminum oxide template method combining with sputtering technology. Magnetic measurement suggests that the magnetic anisotropy of nanobrush depends on the thickness of Fe70Co30 layer, and its total anisotropy originates from the competition between the shape anisotropy of nanowire arrays and nanofilm. Micromagnetic simulation result indicates that the switching field of nanobrush is 1900 Oe, while that of nanowire array is 2700 Oe. These suggest that the nanobrush film can promote the magnetization reversal processes of nanowire arrays in nanobrush.

The development of cost-effective and highly sensitive short-wave infrared (SWIR) photodetectors is crucial for the expanding applications of SWIR imaging in civilian applications such as machine vision, autonomous driving, and augmented reality. Colloidal quantum dots (CQDs) have emerged as promising candidates for this purpose, offering distinct advantages over traditional III-V binary and ternary semiconductors. These advantages include the ability to precisely tune the bandgap through size modulation of CQDs and the ease of monolithic integration with Si readout integrated circuits (ROICs) via solution processing. Achieving a minimal reverse bias dark current density ( J d ) while maintaining high external quantum efficiency is essential for enhancing the light detection sensitivity of CQDs-based SWIR photodiodes to a level competitive with III-V semiconductors. This challenge has garnered increasing research attention in recent years. Herein, the latest advancements in understanding and mitigating J d in CQDs SWIR photodiodes are summarized. Starting with a brief overview of the material fundamentals of CQDs, the origins of J d in CQDs photodiodes, including reverse injection from electrode, diffusion/drift currents, Shockley-Read-Hall generation/recombination currents, trap-assisted tunneling, and shunt/leakage currents, are discussed together with their latest research progresses about strategies adopted to suppress J d . Finally, a brief conclusion and outlook on future research directions aimed at minimizing J d and retaining high photoresponse of CQDs SWIR photodiodes are provided.

Despite the corona-virus pandemic, Korean cosmetics maintain brand attachment in the Chinese market. This study identifies critical influencing and outcome factors of brand attachment within this consumer phenomenon. Specifically, it investigates the relationship between Chinese consumers' perceived brand authenticity and brand attachment, brand loyalty, willingness to pay a premium, and forgiveness. To this end, it uses AMOS 21.0 to analyze data collected through a questionnaire, testing the research model. The study reveals several key findings. Firstly, it assesses brand authenticity based on the following five sub-factors: consistency, naturalness, originality, advertisement truthfulness, and reliability. According to the assessment results, originality shows the most significant impact, followed by reliability, consistency, and naturalness. Furthermore, brand attachment significantly enhances brand loyalty, willingness to pay a premium, and forgiveness toward the brand. Higher levels of brand attachment lead to increased brand loyalty. In addition, greater brand attachment correlates with consumers' increased willingness to pay more for products and greater forgiveness towards the brand., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: You-Yu Dai reports administrative support was provided by 10.13039/501100009017Shandong Jiaotong University. You-Yu Dai reports statistical analysis was provided by China Society of Logistics and China Federation of Logistics & Purchasing. Honyun Wang reports investigation support was provided by Shandong Provincial Office of Philosophy and Social Science Work. Yan Wang reports data curation was provided by Shandong Provincial Bureau of Statistics. The corresponding author sometimes serves as a reviewer for Heliyon - YYD. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Tanshinones are bioactive ingredients derived from the herbal plant Salvia miltiorrhiza and are used for treating diseases of the heart and brain, thus ensuring quality of S. miltiorrhiza is paramount. Applying the endophytic fungus Trichoderma atroviride D16 can significantly increase the content of tanshinones in S. miltiorrhiza, but the potential mechanism remains unknown. In the present study, the colonization of D16 effectively enhanced the levels of Ca 2+ and H 2 O 2 in the roots of S. miltiorrhiza, which is positively correlated with increased tanshinones accumulation. Further experiments found that the treatment of plantlets with Ca 2+ channel blocker (LaCl 3 ) or H 2 O 2 scavenger (DMTU) blocked D16-promoted tanshinones production. LaCl 3 suppressed not only the D16-induced tanshinones accumulation but also the induced Ca 2+ and H 2 O 2 generation; nevertheless, DMTU did not significantly inhibit the induced Ca 2+ biosynthesis, implying that Ca 2+ acted upstream in H 2 O 2 production. These results were confirmed by observations that S. miltiorrhiza treated with D16, CaCl 2 , and D16+LaCl 3 exhibit H 2 O 2 accumulation and influx in the roots. Moreover, H 2 O 2 as a downstream signal of Ca 2+ is involved in D16 enhanced tanshinones synthesis by inducing the expression of genes related to the biosynthesis of tanshinones, such as DXR, HMGR, GGPPS, CPS, KSL and CYP76AH1 genes. Transcriptomic analysis further supported that D16 activated the transcriptional responses related to Ca 2+ and H 2 O 2 production and tanshinones synthesis in S. miltiorrhiza seedlings. This is the first report that Ca 2+ and H 2 O 2 play important roles in regulating fungal-plant interactions thus improving the quality in the D16-S. miltiorrhiza system., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects., 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 © 2024 Wu, Yang, Huang, Fan, Dai, Hu, Tang, Liu, Xu, Liu, Cai, Niu, Ren, Yao, Qin, Chen, Huang, Zhang, You, Wang, He, Hong, Sun, Zhan and Lin.)

Soil nutrients and inorganic elements affect not only the growth and development of medicinal plants but also the formation and accumulation of active ingredients in traditional Chinese medicines. The content of tanshinones and 28 inorganic elements in Salviae Miltiorrhizae Radix et Rhizoma samples from 18 producing areas in 6 provinces was determined, and 35 physical and chemical properties of the corresponding soil samples were determined. The enrichment characteristics of inorganic elements in Salviae Miltiorrhizae Radix et Rhizoma were analyzed. The correlation analysis and stepwise regression analysis were performed to screen out the main soil factors affecting the content of tanshinones in Salviae Miltiorrhizae Radix et Rhizoma. The results showed that the content of tanshinones in the samples from different areas varied significantly, being the highest in the samples from Shandong, the second in the samples from Henan, and low in the samples from Shanxi and Sichuan. K, Mg, Ca, and Na were rich in Salviae Miltiorrhizae Radix et Rhizoma samples, among which Na and K had the highest enrichment coefficients. The results of correlation and regression analyses showed that soil K, Na, Ti, and total nitrogen were the main soil factors affecting the tanshinones in Salviae Miltiorrhizae Radix et Rhizoma. Specifically, the content of tanshinones was positively correlated with Ti and negatively correlated with Na, K, and total nitrogen in the soil. Therefore, during the planting of Salvia miltiorrhiza, the land should be selected with full consideration to the salinity and saline land should be avoided. Secondly, the application of nitrogen and potassium fertilizers can be appropriately reduced, and water-soluble elemental fertilizers for S. miltiorrhiza should be developed.

Background: Liver fibrosis is a formidable global medical challenge, with no effective clinical treatment currently available. Yinhuang granule (YHG) is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos. It is frequently used for upper respiratory tract infections, pharyngitis, as well as acute and chronic tonsillitis., Aim: To investigate the potential of YHG in alleviating carbon tetrachloride (CCl 4 )-induced liver fibrosis in mice., Methods: To induce a hepatic fibrosis model in mice, this study involved intraperitoneal injections of 2 mL/kg of CCl 4 twice a week for 4 wk. Meanwhile, liver fibrosis mice in the low dose of YHG (0.4 g/kg) and high dose of YHG (0.8 g/kg) groups were orally administered YHG once a day for 4 wk. Serum alanine/aspartate aminotransferase (ALT/AST) activity and liver hydroxyproline content were detected. Sirius red and Masson's trichrome staining assay were conducted. Real-time polymerase chain reaction, western-blot and enzyme-linked immunosorbent assay were conducted. Liver glutathione content, superoxide dismutase activity level, reactive oxygen species and protein carbonylation amount were detected., Results: The administration of YHG ameliorated hepatocellular injury in CCl 4 -treated mice, as reflected by decreased serum ALT/AST activity and improved liver histological evaluation. YHG also attenuated liver fibrosis, evident through reduced liver hydroxyproline content, improvements in Sirius red and Masson's trichrome staining, and lowered serum hyaluronic acid levels. Furthermore, YHG hindered the activation of hepatic stellate cells (HSCs) and ameliorated oxidative stress injury and inflammation in liver from CCl 4 -treated mice. YHG prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of Nrf2-dependent downstream antioxidant genes. In addition, YHG promoted mitochondrial biogenesis in liver from CCl 4 -treated mice, as demonstrated by increased liver adenosine triphosphate content, mitochondrial DNA levels, and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and nuclear respiratory factor 1., Conclusion: YHG effectively attenuates CCl 4 -induced liver fibrosis in mice by inhibiting the activation of HSCs, reducing inflammation, alleviating liver oxidative stress damage through Nrf2 activation, and promoting liver mitochondrial biogenesis., Competing Interests: Conflict-of-interest statement: The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

PM 2.5 is extremely harmful to the atmospheric environment and human health, and a timely and accurate understanding of PM 2.5 with high spatial and temporal resolution plays an important role in the prevention and control of air pollution. Based on multi-angle implementation of atmospheric correction algorithm (MAIAC), 1 km AOD products, ERA5 meteorological data, and pollutant concentrations (CO, O 3 , NO 2 , SO 2 , PM 10 , and PM 2.5 ) in the Guangdong-Hong Kong-Macao Greater Bay Area during 2015-2020, a geographically and temporally weighted regression model (GTWR), BP neural network model (BPNN), support vector machine regression model (SVR), and random forest model (RF) were established, respectively, to estimate PM 2.5 concentration. The results showed that the estimation ability of the RF model was better than that of the BPNN, SVR, and GTWR models. The correlation coefficients of the BPNN, SVR, GTWR, and RF models were 0.922, 0.920, 0.934, and 0.981, respectively. The RMSE values were 7.192, 7.101, 6.385, and 3.670 μg·m -3 . The MAE values were 5.482, 5.450, 4.849, and 2.323 μg·m -3 , respectively. The RF model had the best effect during winter, followed by that during summer, and again during spring and autumn, with correlation coefficients above 0.976 in the prediction of different seasons. The RF model could be used to predict the PM 2.5 concentration in the Greater Bay Area. In terms of time, the daily ρ (PM 2.5 ) of cities in the Greater Bay Area showed a trend of "decreasing first and then increasing" in 2021, with the highest values ranging from 65.550 μg·m -3 to 112.780 μg·m -3 and the lowest values ranging from 5.000 μg·m -3 to 7.899 μg·m -3 . The monthly average concentration showed a U-shaped distribution, and the concentration began to decrease in January and gradually increased after reaching a trough in June. Seasonally, it was characterized by the highest concentration during winter, the lowest during summer, and the transition during spring and autumn. The annual average ρ (PM 2.5 ) of the Greater Bay Area was 28.868 μg·m -3 , which was lower than the secondary concentration limit. Spatially, there was a "northwest to southeast" decreasing distribution of PM 2.5 in 2021, and the high-pollution areas clustered in the central part of the Greater Bay Area, represented by Foshan. Low concentration areas were mainly distributed in the eastern part of Huizhou, Hong Kong, Macao, Zhuhai, and other coastal areas. The spatial distribution of PM 2.5 in different seasons also showed heterogeneity and regionality. The RF model estimated the PM 2.5 concentration with high accuracy, which provides a scientific basis for the health risk assessment associated with PM 2.5 pollution in the Greater Bay Area.

This study aims to investigate whether tetramethylpyrazine(TMP) can stimulate angiogenesis in cerebral microvascular endothelial cells and alleviate cerebral ischemic stroke(CIS) and to explore the underlying mechanisms. In the animal study, adult Sprague-Dawley rats(n=15) were assigned into sham surgery(sham), middle cerebral artery occlusion/reperfusion(MCAO/R), and MCAO/R+TMP(intraperitoneal injection of 20 mg·kg~(-1)) groups. The neurological function was evaluated by the Z-Longa method. The cerebral infarction volume was detected by TTC staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the expression of vascular endothelial growth factor(VEGF), angiopoietin(Ang), and platelet-derived growth factor(PDGF). Immunofluorescence staining was employed to detect Ki67 and the expression of vascular endothelial growth factor A(VEGFA) and slient information regulator 1(SIRT1). Western blot was employed to determine the expression levels of VEGFA, SIRT1, angiopoietin-2(Ang-2), and platelet-derived growth factor B(PDGFB). In the cell study, mouse brain-derived endothelial cells(Bend.3) were cultured, and the optimal concentration of TMP was determined. Then, VEGF, Ang, and PDGF were detected by ELISA after the addition of cabozantinib. Western blot was employed to measure the expression of VEGFA, Ang-2, and PDGFB. Immunofluorescence staining was used to detect CD31, CD34, and Ki67, and the proliferation, migration, and tube formation ability of Bend.3 cells were observed in vitro. Western blot and immunofluorescence staining were performed to measure the expression of SIRT1 and VEGFA after addition of the SIRT1-specific inhibitor selisistat(EX-527). The results showed that compared with the sham group, the MCAO/R group had severe neurological function damage, increased infarction volume, up-regulated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, and PDGFB, and down-regulated expression of Ki67 and SIRT1(P<0.01). Compared with the MCAO/R group, the MCAO/R+TMP group presented alleviated neurological function damage, reduced infarction volume, and activated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, Ki67, and SIRT1(P<0.01). The cell experiments showed that compared with the normal group, Bend.3 cells were activated by oxygen glucose deprivation/reoxygenation(OGD/R) treatment(P<0.05, P<0.01). Compared with the OGD/R group, the OGD/R+TMP group upregulated the expression levels of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, SIRT1, Ki67, CD31, and CD34, enhanced the angiogenic ability of Bend.3 cells without being inhibited by BMS or EX-527(P<0.05, P<0.01, P<0.001). The results suggest that TMP can activate the SIRT1/VEGFA signaling pathway to stimulate angiogenesis and alleviate CIS injury.

Background: Acute myeloid leukemia (AML) is characterized by a high recurrence and mortality rate. Cuproptosis is involved in cell death regulation in in a variety of solid tumors. Long non-coding RNAs that regulate cuproptosis genes in the pathogenesis of acute leukemia have yet to be explored., Methods: First, cuproptosis genes with distinct expression levels were discovered by contrasting AML with normal samples from the TCGA and GTEx cohorts. Pearson correlation and univariate Cox-regression analysis were performed to identify cuproptosis-associated lncRNAs with significant prognostic values. Then the least absolute shrinkage and selection operator (LASSO) Cox regression was utilized to establish a multi-gene signature to predict AML prognosis. Next, Kaplan-Meier estimator, receiver operating characteristic curve, and a nomogram were performed to evaluate the predictive capacity of the risk signature. Functional enrichment analyses were employed to assess their function. Moreover, qRT-PCR testing of lncRNA expression in AML samples was conducted. The competing endogenous RNA (ceRNA) network was constructed to find the target genes., Results: A risk model based on the signature of three cuproptosis-associated lncRNAs was developed. The results showed that the model possessed excellent prognostic potential. The nomogram raised the accuracy in predicting AML survival. In addition, functional enrichment analyses demonstrated an enrichment of inflammatory and immune-related pathways. Moreover, correlations between the risk signature and clinicopathological variables, tumor mutational burden, RNA stemness score, immune profile, and drug sensitivity were observed. Furthermore, we discovered that TRAF3IP2-AS1 may function as a ceRNA to regulate cuproptosis and ferroptosis gene expression., Conclusion: The risk signature established in this study could serve as a reliable biosignature for AML prognosis. And the findings presented here may facilitate research on cuproptosis in AML., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yan Shen reports financial support was provided by Chongqing Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: As the aging of the population continues to deepen, the pressure on social pensions is gradually increasing, and the issue of assistance has become a problem that must be solved. With the development of science and technology, people's living standard is constantly improving. The older-adult care services expected by the older-adult are wider than meeting the basic daily needs of individuals. The current industry should also consider combining modern science and technology with the older-adult care service industry to serve older-adult better and enable older-adult care service providers to move towards the service needs that make people happier and healthier. This research is about constructing and evaluating China's older-adult care services smart supply chain., Methods: Based on the research results of previous scholars, this paper divides the Sun construction of the smart supply chain of China endowment service into four aspects: policy aspect, economic aspect, social aspect, and technical aspect; the four significant elements are divided into the first-level indicators, and 16 second-level indicators are divided under the first-level indicators. The importance and satisfaction of each evaluation index were obtained by distributing questionnaires to the managers who study the supply chain and the employees who are related to the old-age service., Results and Discussion: After the reliability analysis, the importance-performance analysis (IPA) quadrant analysis chart of the evaluation index was constructed using importance-performance analysis. The index of creating a smart supply chain system for China's old-age service is given priority, the supply chain system of China's old-age care service is further improved, and the social security of China's old-age service is enlarged., 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 Dai, Liu and Sun.)

Background: Resistance to antibiotics is one the main factors constraining the treatment and control of Helicobacter pylori ( H. pylori ) infections. Therefore, there is an urgent need to develop new antimicrobial agents to replace antibiotics. Our previous study found that linolenic acid-metronidazole (Lla-Met) has a good antibacterial effect against H. pylori, both antibiotic-resistant and sensitive H. pylori . Also, H. pylori does not develop resistance to Lla-Met. Therefore, it could be used for preparing broad-spectrum antibacterial agents. However, since the antibacterial mechanism of Lla-Met is not well understood, we explored this phenomenon in the present study., Aim: To understand the antimicrobial effect of Lla-Met and how this could be applied in treating corresponding infections., Methods: H. pylori cells were treated with the Lla-Met compound, and the effect of the compound on the cell morphology, cell membrane permeability, and oxidation of the bacteria cell was assessed. Meanwhile, the differently expressed genes in H. pylori in response to Lla-Met treatment were identified., Results: Lla-Met treatment induced several changes in H. pylori cells, including roughening and swelling. In vivo experiments revealed that Lla-Met induced oxidation, DNA fragmentation, and phosphatidylserine ectropionation in H. pylori cells. Inhibiting Lla-Met with L-cysteine abrogated the above phenomena. Transcriptome analysis revealed that Lla-Met treatment up-regulated the expression of superoxide dismutase SodB and MdaB genes, both anti-oxidation-related genes., Conclusion: Lla-Met kills H. pylori mainly by inducing oxidative stress, DNA damage, phosphatidylserine ectropionation, and changes on cell morphology., 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.)

Aim: To evaluate the lateral geniculate nucleus (LGN) volume and height using magnetic resonance imaging (MRI) in glaucoma patients., Methods: Literatures retrieval was carried out through PubMed, Web of Science, Embase, and Cochrane Library. Studies that compared the volume and height of LGN in glaucoma patients with that in control subjects were included. The volume and height of LGN were extracted from the included studies. The Review Manager 5.4.1 software was used for the Meta-analysis., Results: This Meta-analysis included 10 cross-sectional studies, including the eyes of 223 glaucoma patients and 185 healthy controls. Compared with the control subjects, the volume and height of LGN in glaucoma patients measured by MRI were significantly reduced {-29.13 mm 3 , 95% [confidence interval (CI): -44.82 to -13.43, P =0.0003; -0.61 mm, 95%CI: -0.78 to -0.44, P <0.00001, respectively]}. Subgroup analysis demonstrated that the differences of LGN volume and height between glaucoma patients and control subjects in the older group were smaller than that in the younger group, and LGN volume decreased with the increase of glaucoma severity., Conclusion: The results demonstrate that the volume and height of LGN are decreased in glaucoma patients, and LGN volume can be considered a parameter of glaucoma severity., (International Journal of Ophthalmology Press.)

Numerous studies have demonstrated that multiple intrinsic and extrinsic factors shape the structure and composition of gut microbiota in a host. The disorder of the gut microbiota may trigger various host diseases. Here, we collected fecal samples from wild-caught Japanese geckos ( Gekko japonicus ) and captive conspecifics fed with mealworms (mealworm-fed geckos) and fruit flies (fly-fed geckos), aiming to examine the dietary and sexual correlates of the gut microbiota. We used 16S rRNA gene sequencing technology to determine the composition of the gut microbiota. The dominant phyla with a mean relative abundance higher than 10% were Verrucomicrobiota, Bacteroidota, and Firmicutes. Gut microbial community richness and diversity were higher in mealworm-fed geckos than in wild geckos. Neither community evenness nor beta diversity of gut microbiota differed among wild, mealworm-fed, and fly-fed geckos. The beta rather than alpha diversity of gut microbiota was sex dependent. Based on the relative abundance of gut bacteria and their gene functions, we concluded that gut microbiota contributed more significantly to the host's metabolic and immune functions. A higher diversity of gut microbiota in mealworm-fed geckos could result from higher chitin content in insects of the order Coleoptera. This study not only provides basic information about the gut microbiota of G. japonicus but also shows that gut microbiota correlates with dietary habits and sex in the species.

A series of 1,4-naphthoquinone derivatives containing were synthesized as anti-cancer agents and the crystal structure of compound 5a was confirmed by X-ray diffraction. In addition, the inhibitory activities against four cancer cell lines (HepG2, A549, K562, and PC-3) were tested, respectively, and compound 5i showed significant cytotoxicity on the A549 cell line with the IC 50 of 6.15 μM. Surprisingly, in the following preliminary biological experiments, we found that compound 5i induced autophagy by promoting the recycling of EGFR and signal transduction in the A549 cell, resulting in the activation of the EGFR signal pathway. The potential binding pattern between compound 5i and EGFR tyrosine kinase (PDB ID: 1M17) was also identified by molecular docking. Our research paves the way for further studies and the development of novel and powerful anti-cancer drugs.

Quaternary ammonium compounds (QACs) are a class of cationic surfactants that can be used as the main active ingredient of disinfectants. The increased use of QACs is concerning as exposure from inhalation or ingestion to these compounds that has been associated with adverse effects on the reproductive and respiratory systems. Humans are exposed to QACs primarily by food consumption and inhalation of air. QAC residues pose significant threats to public health. Given the importance of assessing potential residue levels for QACs in food, therefore, a method was developed for the simultaneous detection of six common QACs and one emerging QAC (Ephemora) in frozen food by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) coupled with the modified QuEChERS method. The main factors governing the response, recovery, and sensitivity of the method, including extraction solvents, types and dosages of adsorbents, apparatus conditions, and mobile phases, were optimized in the course of sample pretreatment and instrument analysis. QAC residues in frozen food were extracted using 20 mL methanol-water (90∶10, containing 0.5% formic acid) for 20 min by the vortex shock method. The mixture was ultrasonicated for 10 min and centrifuged at 10000 r/min for 10 min. A 1-mL aliquot of the supernatant was transferred to a new tube and purified using 100 mg of PSA adsorbents. After mixing and centrifugation at 10000 r/min for 5 min, the purified solution was analyzed. Target analytes were separated on an ACQUITY UPLC BEH C 8 chromatographic column (50 mm×2.1 mm, 1.7 μm) at a column temperature of 40 ℃ and a flow rate of 0.3 mL/min. The injection volume was 1 μL. Gradient elution was performed using methanol and 5 mmol/L ammonium acetate solution as the mobile phases. Multiple reaction monitoring (MRM) was conducted in the positive electrospray ionization (ESI + ) mode. The matrix-matched external standard method was used to quantify seven QACs. The optimized chromatography-based method completely separated the seven analytes. Good linear relationships were obtained for the seven QACs in the range of 0.1-100.0 ng/mL. The correlation coefficient ( r 2 ) ranged from 0.9971 to 0.9983. The limits of detection and limits of quantification ranged from 0.5 to 1.0 μg/kg and 1.5 to 3.0 μg/kg, respectively. Accuracy and precision were determined by spiking salmon and chicken samples with 3.0, 10.0, and 100.0 μg/kg of analytes, in compliance with the current legislation, with six replicates per determination. The average recoveries of the seven QACs ranged from 65.4% to 101%. The relative standard deviations (RSDs) were between 0.64% and 16.8%. Matrix effects of the analytes were between -27.5% and 33.4% in salmon and chicken samples after purifying using PSA. The developed method was applied to the determination of seven QACs in rural samples. QACs were detected in only one sample; the level did not exceed European Food Safety Authority specified residue limit standards. The detection method has high sensitivity, good selectivity and stability, and the results are accurate and reliable. It is suitable for the simultaneous rapid determination of seven QAC residues in frozen food. The results provide valuable information for future risk assessment studies targeting this class of compounds.

This study expects to provide a reference for the catering industry. The travel industry expands sales channels and turnover tends to choose a strategic alliance with the alliance objects mutually beneficial cooperation to improve their competitiveness. This study examines the effects of alliance conditions and person-organization fit (P-O-fit) on the performance of strategic alliances between travel industries. Furthermore, this study contained the intermediary performance as a moderator to examine the influences of alliance conditions and P-O-fit on the performance of strategic alliances. There were 406 usable questionnaires collected. We verified the hypotheses by the structural equation modeling method. The results suggest that the alliance conditions have positive and significant direct effects on the performance of strategic alliances. Moreover, the P-O-fit also has positive and significant effects on the performance of strategic alliances. Furthermore, the intermediary performance has substantial moderating effects on the influences of P-O-fit on the performance of strategic alliances. The conclusion provides a theoretical and practical basis between performance and the travel industry., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To confirm the therapeutic effect of recombinant human thrombopoietin (rhTPO) on rhesus monkeys irradiated with 5.0 Gy 60 Co γ-ray, and provide experimental basis for clinical treatment of similar patients., Methods: Fourteen adult rhesus monkeys were irradiated with 60 Co γ-ray on both sides at the dose of 5.0 Gy (dose rate 69.2 cGy/min) to establish the acute radiation sickness model. The monkeys were divided into irradiation group (n=5), rhTPO 5 μg/kg group (n=4) and rhTPO 10 μg/kg group (n=5). Two hours after irradiation, the three groups of monkeys were injected with saline 0.1 ml/kg, rhTPO 5 μg/kg（0.1 ml/kg） and rhTPO 10 μg/kg(0.2 ml/kg), respectively. The general signs, survival, peripheral hemogram and serum biochemistry of rhesus monkeys were observed before and after irradiation, and the differences between rhTPO group and irradiation control group were compared., Results: After total body irradiation with 5.0 Gy 60 Co γ-ray, rhesus monkeys successively showed fever, hemorrhage, sharp decrease of whole blood cell counts in peripheral blood and disorder of serum biochemical indexes. Compared with the irradiated control group, a single intramuscular injection of rhTPO 5 μg/kg or 10 μg/kg 2 hours after irradiation could improve the symptoms of fever and bleeding, increase the nadir of peripheral red blood cells and platelets counts, shorten the duration of hemocytopenia, and advance the time for blood cells to return to the pre-irradiation level. The serum biochemical results showed that rhTPO could improve the abnormality of serum biochemical indexes in rhesus monkeys induced by 5.0 Gy total body irradiation to some extent. Compared with the two administration groups, the therapeutic effect of rhTPO 10 μg/ kg was better., Conclusion: A single injection of rhTPO 5 μg/ kg or 10 μg/ kg 2 hours after irradiation can alleviate the injury of multilineage hematopoiesis and promote the recovery in monkeys irradiated by 5.0 Gy γ-ray. It also improves animal signs and has obvious therapeutic effect on acute radiation sickness.

Advanced exfoliation techniques are crucial for exploring the intrinsic properties and applications of 2D materials. Though the recently discovered Au-enhanced exfoliation technique provides an effective strategy for the preparation of large-scale 2D crystals, the high cost of gold hinders this method from being widely adopted in industrial applications. In addition, direct Au contact could significantly quench photoluminescence (PL) emission in 2D semiconductors. It is therefore crucial to find alternative metals that can replace gold to achieve efficient exfoliation of 2D materials. Here, the authors present a one-step Ag-assisted method that can efficiently exfoliate many large-area 2D monolayers, where the yield ratio is comparable to Au-enhanced exfoliation method. Differing from Au film, however, the surface roughness of as-prepared Ag films on SiO 2 /Si substrate is much higher, which facilitates the generation of surface plasmons resulting from the nanostructures formed on the rough Ag surface. More interestingly, the strong coupling between 2D semiconductor crystals (e.g., MoS 2 , MoSe 2 ) and Ag film leads to a unique PL enhancement that has not been observed in other mechanical exfoliation techniques, which can be mainly attributed to enhanced light-matter interaction as a result of extended propagation of surface plasmonic polariton (SPP). This work provides a lower-cost and universal Ag-assisted exfoliation method, while at the same time offering enhanced SPP-matter interactions., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Although excessive salt consumption appears to hasten intestinal aging and increases susceptibility to cardiovascular disease, the molecular mechanism is unknown. In this study, mutual validation of high salt (HS) and aging fecal microbiota transplantation (FMT) in C56BL/6 mice was used to clarify the molecular mechanism by which excessive salt consumption causes intestinal aging. Firstly, we observed HS causes vascular endothelial damage and can accelerate intestinal aging associated with decreased colon and serum expression of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and increased malondialdehyde (MDA); after transplantation with HS fecal microbiota in mice, vascular endothelial damage and intestinal aging can also occur. Secondly, we also found intestinal aging and vascular endothelial damage in older mice aged 14 months; and after transplantation of the older mice fecal microbiota, the same effect was observed in mice aged 6-8 weeks. Meanwhile, HS and aging significantly changed gut microbial diversity and composition, which was transferable by FMT. Eventually, based on the core genera both in HS and the aging gut microbiota network, a machine learning model was constructed which could predict HS susceptibility to intestinal aging. Further investigation revealed that the process of HS-related intestinal aging was highly linked to the signal transduction mediated by various bacteria. In conclusion, the present study provides an experimental basis of potential microbial evidence in the process of HS related intestinal aging. Even, avoiding excessive salt consumption and actively intervening in gut microbiota alteration may assist to delay the aging state that drives HS-related intestinal aging in clinical practice., 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 © 2022 Liu, Zhao, Zhang, Li, Wu, Dai, Sheng, Ren and Xue.)

Background: Hepatocellular carcinoma (HCC), which has high rates of recurrence and metastasis and is the main reason and the most common tumor for cancer mortality worldwide, has an unfavorable prognosis. N7-methylguanosine (m7G) modification can affect the formation and development of tumors by affecting gene expression and other biological processes. In addition, many previous studies have confirmed the unique function of long noncoding RNAs (lncRNAs) in tumor progression; however, studies exploring the functions of m7G-related lncRNAs in HCC patients has been limited. Methods: Relevant RNA expression information was acquired from The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov), and m7G-related lncRNAs were identified via gene coexpression analysis. Afterward, univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate regression analyses were implemented to construct an ideal risk model whose validity was verified using Kaplan-Meier survival, principal component, receiver operating characteristic (ROC) curve, and nomogram analyses. In addition, the potential functions of lncRNAs in the novel signature were explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes ( KEGG) analyses and gene set enrichment analysis (GSEA). At last, in both risk groups and subtypes classified based on the expression of the risk-related lncRNAs, we analyzed the immune characteristics and drug sensitivity of patients. Results: After rigorous screening processes, we built a model based on 11 m7G-related lncRNAs for predicting patient overall survival (OS). The results suggested that the survival status of patients with high-risk scores was lower than that of patients with low-risk scores, and a high-risk score was related to malignant clinical features. Cox regression analysis showed that the m7G risk score was an independent prognostic parameter. Moreover, immune cell infiltration and immunotherapy sensitivity differed between the risk groups. Conclusion: The m7G risk score model constructed based on 11 m7G-related lncRNAs can effectively assess the OS of HCC patients and may offer support for making individualized treatment and immunotherapy decisions for HCC patients., 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 © 2022 Dai, Gao, Chen, Liu, Zeng, Zhou and Wu.)

Objective: After subarachnoid hemorrhage, magnesium could reduce the incidence of delayed cerebral ischemia; however, it is still controversial. This study updated the results of recently published magnesium-related studies and conducted an exploratory analysis of the impact of application strategies and intervention factors on the results., Methods: Public databases were searched from the date of their inception to May 10, 2021. Randomized controlled trials on magnesium agent-related regimens for subarachnoid hemorrhage patients were included., Results: In total, 28 articles were included in the meta-analysis. For delayed cerebral ischemia, magnesium-related interventions significantly reduced the risk of delayed cerebral ischemia compared with nonmagnesium interventions (odds ratios: 0.40; 95% confidence interval: 0.28-0.56; p < 0.01). For cerebral vasospasm, a random effects model showed that magnesium significantly reduced the risk of cerebral vasospasm (odds ratios: 0.46; 95% confidence interval: 0.33-0.63; p < 0.01). In the subgroup analysis, intracranial magnesium (odds ratios: 6.67; 95% confidence interval: 1.14-38.83; p =0.03) and magnesium plus hydrogen (odds ratios: 10; 95% confidence interval: 1.59-62.73; p =0.01) produced significant results in improving the good recovery rate compared to the control. In the network meta-analysis, magnesium plus nimodipine and simvastatin even showed an effective trend in death/persistent vegetative status improvement., Conclusion: This study supports the beneficial effect of magnesium in reducing the risk of delayed cerebral ischemia. Based on a single randomized controlled trial, immediate intracranial magnesium therapy with intravenous hydrogen after subarachnoid hemorrhage can increase the good recovery rate. Therefore, more high-quality studies are needed to confirm this finding., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Xiao-Hong Ba et al.)

Objective: To study the effect of interleukin-6 (IL-6) gene deletion on radiation-induced hematopoietic injury in mice and relative mechanism., Methods: Before and after whole body 60 Co γ-ray irradiation, it was analyzed and compared that the difference of peripheral hemogram, bone marrow hematopoietic stem and progenitor cells conts in IL-6 gene knockout (IL-6 -/- ) and wild-type (IL-6 +/+ ) mice and serum IL-6 and G-CSF expression levels in above- mentioned mouse were detected. Moreover, 30 days survival rate of IL-6 -/- and IL-6 +/+ mice after 8.0 Gy γ-ray irradiation were analyzed., Results: IL-6 levels in serum of IL-6 +/+ and IL-6 -/- mice were respectively (98.95±3.85) pg/ml and (18.36±5.61) pg/ml, which showed a significant statistical differences (P<0.001). There were no significant differences of peripheral blood cell counts and G-CSF level in serum between IL-6 +/+ and IL-6 -/- mice before irradiation (P>0.05). However, the number of leukocytes, neutrophils, lymphocytes, monocytes, platelets in peripheral blood and G-CSF level in serum of IL-6 -/- mice were significantly decreased at 6 h after 8.0 Gy γ-ray irradiation compared with that of IL-6 +/+ mice. On days 30 after 8.0 Gy γ-ray irradiation, the survival rate of IL-6 +/+ and IL-6 -/- mice was 62.5% and 12.5%, and the mean survival time of dead mice was 16.0±1.0 and 10.6±5.3 days, respectively. On days 14 after 6.5 Gy γ-ray irradiation, bone marrow nucleated cells in IL-6 +/+ and IL-6 -/- mice were respectively (10.0±1.2)×10 6 and (8.3±2.2)×10 6 per femur. Compared with IL-6 +/+ mice, the proportion of Lin - Sca-1 - c-kit + (LK) in bone marrow of IL-6 -/- mice had no significant change (P>0.05), but the proportion of Lin - Sca-1 + c-kit + (LSK) was significantly decreased (P<0.05)., Conclusion: IL-6 plays an obvious role in regulating hematopoietic radiation injury, and IL-6 deficiency can inhibit the radiation-induced increase of endogenous G-CSF level in serum, aggravates the damage of mouse hematopoietic stem cells（HSC） and the reduction of mature blood cells in peripheral blood caused by ionizing irradiation, resulting in the shortening of the survival time and significant decrease of the survival rate of mice exposed to lethal dose radiation.

Metronidazole (Met) is the first choice for treating Helicobacter pylori ( Hp ). However, Hp is easy to resistant, making Met unable to be widely used. How to overcome Hp 's Met resistance is still an issue. In this study, Met was used as the primary raw material with linolenic acid to prepare a novel compound-linolenic acid-metronidazole (Lla-Met). The MIC, minimum bactericidal concentration (MBC), colonization amount of Hp in gastric mucosa, etc., were evaluated, respectively. Lla-Met was successfully prepared by the detection of nuclear magnetic resonance, etc., and its MIC and MBC to Hp were 2~4 μg/mL, 8~16 μg/mL. Moreover, in vivo experiments, Lla-Met significantly reduced the colonization of drug-resistant Hp in gastric mucosa. In the toxicity test, Lla-Met inhibited rate to GES-1 and BGC823 cells were 15% at 128 μg/mL; the mice were administered 10 times treatment Lla-Met treatment (240 mg/kg), have no difference significant injuries were found in their stomach, liver, spleen, kidney, and weight. In addition, Hp G27 continued for 18 days in vitro with sub-Lla-Met concentration, G27 did not show drug resistance to Lla-Met; Lla-Met did not exert an effect on non- Hp species with 128 μg/mL; Compared with a neutral environment, when the acid concentration is 3.0, Lla-Met is not decomposed and has better stability. Conclusion: Lla-Met, a newly prepared compound, has relatively well antibacterial of Met-resistant and sensitive Hp , with a capability of overcoming the metronidazole resistance of Hp.

Although consumers generally accept and care about environmental issues, consumers have not adjusted their behavior accordingly. Based on the diamond model theory, this study proposes and tests the direct impact of personal green commitments on low-carbon travel motivation and constraint, and the possibility of subsequent low-carbon travel intention. According to the results of 358 valid questionnaire surveys, this study shows that green commitments positively affect the low-carbon travel motivation and intention, while negatively affecting the low-carbon travel constraint. The low-carbon travel motivation has some mediating effects. The research results can be used as a reference by relevant managers of the tourism industry to make changes in the content of travel services that are more suitable for specific populations.

Background: At present, there is no ideal method to cure diabetes, and there are few reports on the treatment of diabetes with probiotics., Aim: To propose a method for preparing a new type of chromium- and zinc-rich Acetobacter aceti ( A. aceti ) and explore its ability to enhance the hypoglycemic effects of probiotics in the treatment of diabetes., Methods: A. aceti was cultured in a liquid medium that contained chromium trichloride and zinc chloride, both at a concentration of 64 mg/mL, with the initial concentration of the bacterial solution 1 × 10 4 CFU/mL. After the bacterial solution had been inducted for 48 h, the culture media was changed and the induction was repeated once. The levels of chromium and zinc in the bacteria were detected by inductively coupled plasma mass spectrometry, and the contents of NADH and glucose dehydrogenase were determined using an NAD/NADH kit and glucose dehydrogenase kit, respectively. Streptozotocin was used to establish a mouse model to evaluate the hypoglycemic effects of the proposed chromium- and zinc-rich A. aceti . Ten-times the therapeutic dose was administered to evaluate its biological safety. The effect on MIN6 islet cells was also assessed in vitro ., Results: The levels of chromium metal, metallic zinc, NADH coenzyme, and glucose dehydrogenase in A. aceti prepared by this method were 28.58-34.34 mg/kg, 5.35-7.52 mg/kg, 5.13-7.26 μM, and 446.812-567.138 U/g, respectively. The use of these bacteria resulted in a better hypoglycemic effect than metformin, promoting the repair of tissues and cells of pancreatic islets in vivo and facilitating the growth of MIN6 pancreatic islet cells and increasing insulin secretion in vitro . Ten-times the therapeutic dose of treatment was non-toxic to mice., Conclusion: Chromium trichloride and zinc chloride can be employed to induce the preparation of chromium- and zinc-rich A. aceti , which can then promote the hypoglycemic effect found in normal A. aceti . The bacteria biotransforms the chromium and zinc in a way that could increase their safety as a treatment for diabetes., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Based on the service encounter perspective, this study combines theoretical foundations for such factors as service quality and the characteristics of the hospital service industry to develop a research model scale to investigate whether the quality of hospital services affects patients' perceptions of health service encounters, trust, and loyalty. Nowadays, with the advancement of medical technology, patients pay more attention to the quality of medical services and good service encounters provided by healthcare professionals in order to establish positive patient relationships; hospitals need to improve their own service quality and establish good patient trust relationships so that doctor-patient satisfaction and loyalty can be improved. In a review of related literature, this study found that most past studies focused on issues related of quality of medical services and patient satisfaction, but ignored those related to the relationship between medical service encounters and patient trust and loyalty, as well as the lack of scientific measurement markers for service encounters in the Chinese medical service industry. Therefore, this study uses the Service Encounter Perspective and Service Quality Theory Development Research Scale to collect and analyze data for a typical case of a Chinese tertiary hospital. Finally, this study explores the relationship between the four variables of service quality, service encounter, trust, and loyalty by means of a questionnaire and statistical analysis of the data. Finally, it is concluded that the higher the service quality of the hospital, the higher the customer trust, the higher the service encounter, and in the greater the doctor-patient loyalty., Competing Interests: G-YL was employed by Shandong Holyscape Marketing Research & Consulting Co., Ltd. The remaining 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 © 2022 Shie, Huang, Li, Lyu, Yang, Dai, Su and Wu.)

Objective: In order to analyze the clinical characteristics of epileptic seizures in children with acute lymphoblastic leukemia (ALL) during treatment., Methods: The clinical and imaging data of children diagnosed as ALL with epilepsy seizures from January 2013 to December 2020 were retrospectively analyzed., Results: A total of 2217 children with ALL were admitted during the study, of whom 229 (10.33%) had epileptic seizures after ALL treatment. Among them, 45 (19.65%) were in the high-risk group and 184 (80.35%) were in the low-risk group. Epileptic seizures mainly occurred in the induction remission period (24.02%), maintenance treatment period (25.33%) and after bone marrow transplantation (21.40%). The common causes were MTX-related demyelinating encephalopathy (34.06%) and reversible posterior encephalopathy syndrome (PRES) (25.3%). The first symptom was mainly convulsion (34.50%). The first attack had a comprehensive attack and partial attack. Most patients stop themselves. 30 cases (13.10%) had acute recurrence of epilepsy (recurrence within 3 months after the first attack), and 49 cases (25.76%) had neurological dysfunction after follow-up. 36 cases developed symptomatic epilepsy. Among the 130 children who completed the follow-up, 78 (60.00%) had no obvious neurological sequelae, and 52 (40.0%) had neurological sequelae. Among the 52 cases, there were 34 cases of mild sequelae and 18 cases of severe sequelae, including 8 cases of epilepsy combined with cognitive impairment., Conclusion: Epileptic seizure is a common neurological complication during ALL treatment. The etiology and associated manifestations of the first epileptic seizure are diverse. Early neuroimaging and EEG examination are helpful for early diagnosis and treatment., 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 © 2022 Li, Tang, Zhang, Shi, Dai and Qu.)

Low-carbon travel has emerged as a topic of interest in tourism and academia. Studies have offered reasons tourists may engage in low-carbon travel; however, these explanations are scattered throughout the literature and have yet to be integrated into low-carbon travel motivation and constraint constructs. This study develops a low-carbon travel motivation scale (LCTMS) and a low-carbon travel constraint scale (LCTCS). It performs reliability and validity testing to measure the low-carbon travel motives and obstacles. Items were collected primarily by literature review, and, then, by surveys of 382 tourists from low-carbon travel destinations and 390 from non-low-carbon travel destinations. Through a rigorous scale development process, this study identifies six dimensions of the LCTMS (environmental protection, experience-seeking, escape or social connection, industry pleas and measures for environmental protection, low-carbon products, and green transportation) and four dimensions of the LCTCS (intrapersonal constraints, interpersonal constraints, structural constraints, and the not a travel option).

For a certain kind of decision event, the decision maker does not know the internal mechanism and knowledge information of the decision events.When this kind of decision events gives multiple selection branches, it is found that there is a decision psychological tendency to find the most common features by comparing the selection branches. Based on this, a zero-knowledge decision making (ZKDM) method is proposed. By defining the feature points and feature sets of the selection branches of the decision events, the characteristic moments of the system are constructed and the branch with the most common characteristics is obtained. It is observed that through the findings of investigation the probability of arriving at the correct choice based on the ZKDM method is high. The effectiveness of the ZKDM method may be related to the fact that the designers of decision events usually determine the correct selection branch first, before changing it to design other branches. A questionnaire survey of 279 respondents reveals that more than half of them actually adopt such a design idea. Furthermore, a separate questionnaire survey of 465 decision-makers reveal that 19.14% of the respondents clearly adopt ZKDM., (© 2022. The Author(s).)

Helicobacter pylori ( H. pylori ) has a high rate of infection and antibiotic resistance and poses a serious threat to human life. One of the main strategies to overcome drug resistance is to develop new treatment plans. Traditional Chinese medicine (TCM) that is commonly used to treat many diseases in China can reduce drug resistance and increase the eradication rate of H. pylori . In this paper, we review the research progress on TCM in the treatment of H. pylori infection. The mechanism of action of TCM is reviewed and research and applications of TCM in the treatment of H. pylori are demonstrated. Finally, we discuss problems confronting the use of TCM for the treatment of H. pylori infection and propose possible solutions. In addition, the plans of TCM in H. pylori treatment were also screened: Dampness-heat syndrome in the spleen and stomach, deficiency of spleen and stomach, and cold-heat complicated syndrome, and the effective components therein are studied. The antibacterial effect of TCM is relatively slow; for rapid improvement of the treatment effect of refractory H. pylori gastritis, we provide an appropriate treatment regime combining TCM and Western medicine with immune-regulatory and synergistic antibacterial effects., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The evaluation of clinical efficacy of traditional Chinese medicine (TCM) is the focus of the development of Chinese medicine, but at present there is no internationally recognized clinical efficacy evaluation system, which prevents TCM going abroad. Evidence-based medicine (EBM) research methods have achieved good results in the evaluation of TCM, but there are still some problems. How to use EBM methods in accordance with China's national conditions and develop evidence-based TCM that meets its own characteristics is the key to the current discussion., Methods: Search websites such as PubMed, China National Knowledge Infrastructure, Wanfang Data and VIP by computer, and search papers related to evidence-based clinical research of TCM., Results: A total of 15 high quality representative research papers published in internationally renowned journals were selected for example, including 4 randomized controlled trials (RCTs) related to Chinese medicine, 9 RCTs related to acupuncture, and 2 observational studies on the safety of TCM., Conclusions: EBM method is suitable for clinical research of TCM. There are differences between "disease" and "syndromes" in the use of TCM. Based on the further standardization of syndromes and classification of TCM, modern clinical research methods can be reasonably applied. However, the quality of clinical research related to TCM is not high, and there is a lack of research related to the safety of it, which should be paid attention to and improved in future research.

The study aims to investigate the role of microRNA-149-3p (miR-149-3p) in regulating osteogenic differentiation of human adipose-derived stem cells (hADSCs) by targeting v-akt murine thymoma viral oncogene homolog 1 (AKT1). Bioinformatics websites and a dual luciferase reporter assay were used to predict and verify the targeting relationship between miR-149-3p and AKT1. The hADSCs were divided into the blank, negative control (NC), mimic, control siRNA, AKT1 siRNA, and miR-149-3p inhibitors + AKT1 siRNA groups and then subjected to Alizarin Red staining, Alkaline phosphatase (ALP) staining, ALP activity detections, MTT assay, and EdU cell proliferation assay. Gene or protein expression was quantified using quantitative real-time PCR (qRT-PCR) or Western blotting, respectively. The miR-149-3p expression increased gradually and AKT1 expression decreased gradually during osteogenic differentiation of hADSCs. The prediction of bioinformatics websites miRTarBase and TargetScan and the dual luciferase reporter assay indicated that miR-149-3p can directly target AKT1. After hADSCs were transfected with miR-149-3p mimic, AKT1 expression was significantly downregulated. However, transfection with AKT1 siRNA did not have an impact on miR-149-3p in hADSCs. In comparison with the AKT1 siRNA group, the miR-149-3p inhibitors + AKT1 siRNA group showed decreased miR-149-3p expression but increased AKT1 expression. In addition, AKT1 siRNA enhanced the cell viability and proliferation of hADSCs and increased mineral calcium deposition and ALP activity, resulting in higher expression of osteogenic differentiation-related genes, which was reversed by miR-149-3p inhibition. The miR-149-3p can increase the expression of osteogenic differentiation-related genes by targeting AKT1 and thereby enhance the osteogenic differentiation of hADSCs., (© 2021 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Evidence suggests that histone modification disorders are involved in leukemia pathogenesis. We previously reported that LukS-PV, a component of Panton-Valentine leukocidin (PVL), has antileukemia activities that can induce differentiation, increase apoptosis, and inhibit proliferation of acute myeloid leukemia (AML) cells. Furthermore, LukS-PV inhibited hepatoma progression by regulating histone deacetylation, speculating that LukS-PV may exert antileukemia activity by targeting histone modification regulators. In this study, the results showed that LukS-PV induced apoptosis by downregulating the methyltransferase SET8 and its target histone H4 monomethylated at Lys 20 (H4K20me1). Furthermore, chromatin immunoprecipitation sequencing and polymerase chain reaction identified the kinase PIK3CB as a downstream target gene for apoptosis mediated by SET8/H4K20me1. Finally, our results indicated that LukS-PV induced apoptosis via the PIK3CB-AKT-FOXO1 signaling pathway by targeting SET8. This study indicates that SET8 downregulation is one of the mechanisms by which LukS-PV induces apoptosis in AML cells, suggesting that SET8 may be a potential therapeutic target for AML. Furthermore, LukS-PV may be a drug candidate for the treatment of AML that targets epigenetic modifications., 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 © 2021 Xu, Shi, Zhang, Ding, Ma, Song, Qiang, Chang, Dai, Mei and Ma.)

Near-infrared (NIR) in vivo fluorescence imaging has exhibited the distinct advantage of high optical resolution at deeper penetration into biological tissues. Ag 2 Te quantum dots (QDs), with a relatively narrow band gap, show great promise for fluorescence emission at long wavelengths in the second near-infrared (NIR-II) window for bioimaging. However, existing Ag 2 Te QDs have severely hindered the application of in vivo bioimaging due to their poor fluorescence brightness and stability, so it is important to prepare Ag 2 Te QDs with high quantum yield and stability as well as high biocompatibility in the NIR-II window. Herein, we designed an integrated method for the preparation of water-soluble Ag 2 Te QDs by mutual adaptation of QD synthesis and surface modification. We first synthesized high-quality Ag 2 Te QDs with different NIR-II emission wavelengths and the photoluminescence quantum yields (PLQYs) up to 6.51% by rapidly injecting the TBP-Te precursor into a hot solvent to form a highly fluorescent Ag 2 Te core. Then water-dispersible Ag 2 Te QDs were obtained by direct exchange of the hydrophobic Ag 2 Te QD surface ligands with thiol ligands. The PLQY of the water-soluble Ag 2 Te QDs obtained by this method can still be maintained at 4.94%. With these highly bright and stable Ag 2 Te QDs, the abdominal vessels, hindlimb arterial vessels, venous vessels, sacral lymph nodes, and tumor vessels were visualized non-invasively in vivo in the NIR-II window in mice. The results demonstrate that the integrated strategy of QD synthesis and modification provides valuable technical support for further in-depth applications of Ag 2 Te QDs.

The standardized diagnosis and treatment of tumor and the rational use of antineoplastic drugs are not only the central issue of the government and society, but also the difficulty of medical quality control. In order to implement "the Administrative Measures for the Clinical Application of Antineoplastic Drugs (Trial)" issued by the National Health Commission of the People's Republic of China, on the basis of extensive investigation and through Delphi method and several rounds of expert discussion, an expert consensus on the guiding road map and management points of drug classification was formed. Suggestions are provided to guide other medical institutions to do the related work in the graded management of antineoplastic drugs.

We observed the potential neuroprotective effect of exogenous vitamin D on cerebral ischemia in vitamin D deficiency rats and explored its mechanism. Sixty Sprague Dawley rats were randomly divided into three groups including control (CON) group, vitamin D deficiency (VDD) group and vitamin D deficiency combined with exogenous vitamin D (VDD + VD) group, with 20 rats in each group. The rats in the CON group were fed with normal diet, while the rats in the VDD and VDD + VD groups with vitamin D-deficient diet for 8 weeks, and then underwent middle cerebral artery occlusion (MCAO). Six hours later, exogenous 25-hydroxyvitaminD (25-VD 3 ) was intravenously injected into the rats of the VDD + VD group every 24 h for 4 times. Motor behaviors were significantly better and 25-VD 3 level in the left brain tissue was significantly higher in the CON group than in the VDD and VDD + VD groups 102 h after MCAO (all P < 0.05). Although the motor behaviors, infarct volume and 25-VD 3 level in brain tissue showed a good tendency in the VDD + VD group as compared with VDD group, the two groups were not significantly different (all P > 0.05). GPR78 was significantly higher, but apoptosis and CHOP significantly lower in the VDD + VD group than in the VDD group (all P < 0.05). The aggravation of cerebral ischemia caused by vitamin D deficiency is possibly due to up-regulating GRP78 and down-regulating CHOP in brain tissue., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Videos of animal behavior are used to quantify researcher-defined behaviors of interest to study neural function, gene mutations, and pharmacological therapies. Behaviors of interest are often scored manually, which is time-consuming, limited to few behaviors, and variable across researchers. We created DeepEthogram: software that uses supervised machine learning to convert raw video pixels into an ethogram, the behaviors of interest present in each video frame. DeepEthogram is designed to be general-purpose and applicable across species, behaviors, and video-recording hardware. It uses convolutional neural networks to compute motion, extract features from motion and images, and classify features into behaviors. Behaviors are classified with above 90% accuracy on single frames in videos of mice and flies, matching expert-level human performance. DeepEthogram accurately predicts rare behaviors, requires little training data, and generalizes across subjects. A graphical interface allows beginning-to-end analysis without end-user programming. DeepEthogram's rapid, automatic, and reproducible labeling of researcher-defined behaviors of interest may accelerate and enhance supervised behavior analysis. Code is available at: https://github.com/jbohnslav/deepethogram., Competing Interests: JB, NW, KC, YD, DY, AK, MC, LO, CW, CH none, TC None, (© 2021, Bohnslav et al.)

Background: The drug resistance rate of clinical Helicobacter pylori ( H. pylori ) isolates has increased. However, the mechanism of drug resistance remains unclear. In this study, drug-resistant H. pylori strains were isolated from different areas and different populations of Chinese for genomic analysis., Aim: To investigate drug-resistant genes in H. pylori and find the genes for the early diagnosis of clarithromycin resistance., Methods: Three drug-resistant H. pylori strains were isolated from patients with gastritis in Bama County, China. Minimal inhibitory concentrations of clarithromycin, metronidazole, and levofloxacin were determined and complete genome sequencing was performed with annotation. Hp1181 and hp1184 genes were found in these strains and then detected by reverse transcription polymerase chain reaction. The relationships between hp1181 or hp1184 and clarithromycin resistance were ascertained with gene mutant and drug-resistant strains. The homology of the strains with hp26695 was assessed through complete genome detection and identification. Differences in genome sequences, gene quantity, and gene characteristics were detected amongst the three strains. Prediction and analysis of the function of drug-resistant genes indicated that the RNA expression of hp1181 and hp1184 increased in the three strains, which was the same in the artificially induced clarithromycin-resistant bacteria. After gene knockout, the drug sensitivity of the strains was assessed., Results: The strains showing a high degree of homology with hp26695 , hp1181 , and hp1184 genes were found in these strains; the expression of the genes hp1184 and hp1181 was associated with clarithromycin resistance., Conclusion: Hp1181 and hp1184 mutations may be the earliest and most persistent response to clarithromycin resistance, and they may be the potential target genes for the diagnosis, prevention, and treatment of clarithromycin resistance., Competing Interests: Conflict-of-interest statement: Li XH, Huang YY, Zhao LJ, Li RJ, Dai YY, Qin C, and Huang YQ are employed by Youjiang Medical University for Nationalities; Lu LM and Chen H are employed by Wannan Medical College; Luo XK is employed by National Hospital of Guangxi Zhuang Autonomous Region; all other authors have nothing to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

In this paper, emotions are classified into four types, namely, respect for the strong, envying the strong, sympathy for the weak, and bullying the weak. The corresponding relationship between the four emotion types and the two behaviors of competition and cooperation is then defined. The payoff matrices of the game based on emotions are obtained and the evolutionary dynamics of the four emotion types in a finite population based on the Moran process are studied. Next, we derive the absorption probabilities of a 4×4 symmetric evolutionary game of the population. The influence of the payoff parameters and the natural selection intensity on the result of the group evolution are then analyzed. The calculations indicate that there are differences in the absorption probabilities of the four absorption states of the system. At a steady state, individuals of the types envying the strong and bullying the weak have the highest probability of occupying the entire population, and individuals of the type respect for the strong and sympathy for the weak have the lowest one. By comparing the level of cooperation and average payoffs at a steady state, we observe that the level of cooperation and average payoffs based on the proposed model are better than those of the prisoner's dilemma game with two behaviors. Therefore, emotional evolution can promote cooperation and achieve better group fitness.

Objective: To observe the expressions of complement 3 (C3) and endothelial cell injury-associated proteins before and after cathepsin L (CTSL) blockade in renal injury of trichloroethylene (TCE) -sensitized mice. Methods: In June 2018, 41 SPF female BALB/c mice were divided respectively into blank control group ( n =5) , vehicle control group ( n =5) , TCE group ( n =15) and TCE+CTSLi group ( n =16) to establish trichloroethylene-sensitized mice model by pretreating the mice with intraperitoneal injection of CTSL inhibitor (CTSLi) and using TCE for the first and last challenge. According to the skin sensitization score, the mice were divided into positive group and negative group. 72 hours after the last challenge, the renal function indexes of the mice were detected, the pathological changes of mice kidneys were observed, and the glomerular C3 and endothelial cell damage-related proteins [vascular cell adhesion molecule 1 (VCAM-1) , tight junction protein 5 (Claudin-5) and Syndecan-1] expression levels were detected. Results: The sensitization rates of mice in TCE group and TCE+CTSLi group were 53.3% (8/15) and 50.0% (8/16) , respectively, and there was no significant difference between the two groups ( P >0.05) . Compared with vehicle control group and the corresponding TCE negative group, the serum creatinine (CRE) and blood urea nitrogen (BUN) levels of mice in the TCE positive group was increased, while the TCE positive group were higher than the TCE+CTSLi positive group ( P <0.05) . Pathological examination showed obvious vacuolar degeneration and cellular edema in the mice kidney of the TCE positive group. In the TCE+CTSLi positive group, the above pathological damage was significantly improved. Immunohistochemical results showed that the expression of glomerular C3 fragment and VCAM-1 in TCE positive group were significantly higher than that of the vehicle control and TCE negative group ( P <0.05) , while TCE+CTSLi positive group was significantly lower than that of TCE positive group ( P <0.05) . Western blot test results showed that the relative expression levels of Claudin-5 and Syndecan-1 protein in the mice glomeruli of TCE positive group were significantly lower than those in the vehicle control group and TCE negative group ( P <0.05) . Compared with the TCE positive group, the Claudin-5 protein was increased in the kidney of the TCE+CTSLi positive group, but the difference was not statistically significant ( P >0.05) , while the Syndecan-1 protein was significantly increased in the TCE+CTSLi positive group ( P <0.05) . Conclusion: CTSL may mediate the glomerular structural damage by cutting complement C3, activating the complement system, damaging endothelial cell structural protein Syndecan-1 and overexpressing adhesion molecule VCAM-1 in TCE-sensitized mice. Inhibiting the expression of CTSL may be an effective way to protect the glomerular integrity of structure and function in pharmacology.

Context: Clinically, Pinellia ternata (Thunb.) Breit. (Araceae) ( PT ) has been widely used in the treatment of atherosclerosis and hyperlipidaemia, but the underlying mechanisms are still not clearly understood., Objective: This research was conducted to confirm the mechanism by which PT affects carotid artery intimal hyperplasia., Materials and Methods: An intestinal hyperplasia Sprague-Dawley rat model was established by carotid artery injury. The rats were randomly divided into five groups ( n  = 8): sham, model, PT (with daily intragastric administration of 10 g/mL/kg PT tubers water extract), PT +LY294002 (with intraperitoneal injection of 50 mg/kg LY294002 + 10 g/mL/kg PT ) and endothelial progenitor cells (EPCs) (with injection of 5 × 10 5 /cells), and treated for 4 or 8 weeks., Results: HE staining showed that PT attenuated intimal hyperplasia. RT-PCR, Western blotting and immunohistochemistry showed that PT increased the expression of vascular endothelial growth factor (VEGF) and eNOS in the atherosclerotic carotid artery. PT increased the Dil-acLDL + /FITC-UEA-1 + population (from 0.41 ± 0.085% to 0.60 ± 0.092%) in the blood, decreased TCHO, TG, LDL-C, IL-6 and TNF-α levels, and increased HDL-C and IL-10 levels in the blood. However, these changes were reversed by the PI3K/Akt pathway inhibitor LY294002., Discussion and Conclusions: PT can be developed as an atherosclerosis and carotid intimal hyperplasia treatment drug. Therefore, further study will focus on the effects of PT on intimal hyperplasia in wire-injured atherosclerosis patients and explore in depth some other relevant molecular mechanisms.

Early neurologic deterioration (END) in the acute phase of ischemic stroke is a serious clinical event, which is closely related to poor prognosis. Therefore, it is important to identify presentation features that predict END and take relevant treatment measures, as they could help to prevent the deterioration of high-risk patients. The prospective intervention study was carried out from January 2018 to December 2019. We included consecutive patients hospitalized for acute ischemic stroke (AIS) within 6 hours of onset. Patients were randomly assigned (1 : 1) to recanalization therapy plus Huoxiang Zhengqi Pill (HXZQ) (intervention group) or standard recanalization therapy alone (control group). The primary outcome was the development of END according to predefined criteria within the first 1 week of stroke onset. Poisson regression was used to identify predictors for END. Of the 155 patients enrolled in the study (age, 63 ± 11 years; 28.4% female), 20 (12.9%) developed END. Univariate analysis showed that the use of HXZQ and Essen stroke risk score (ESRS) (low risk group) were protective factors for END, while advanced age was a risk factor for END. However, in multivariate analysis, only ESRS (OR, 0.232; 95%CI, 0.058-0.928; P =0.039) and the use of HXZQ (OR, 0.297; 95%CI, 0.096-0.917; P =0.035) were statistically significant. ESRS can be used as the prediction factor of END. HXZQ has small side effects and wide indication. It could be used in the treatment of AIS., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Zhi-Xin Huang et al.)

Animals in captivity undergo a range of environmental changes from wild animals. An increasing number of studies show that captivity significantly affects the abundance and community structure of gut microbiota. The northern grass lizard (Takydromus septentrionalis) is an extensively studied lacertid lizard and has a distributional range covering the central and southeastern parts of China. Nonetheless, little is known about the gut microbiota of this species, which may play a certain role in nutrient and energy metabolism as well as immune homeostasis. Here, we examined the differences in the gut microbiota between two groups (wild and captive) of lizards through 16S rRNA sequencing using the Illumina HiSeq platform. The results demonstrated that the dominant microbial components in both groups consisted of Proteobacteria, Firmicutes, and Tenericutes. The two groups did not differ in the abundance of these three phyla. Citrobacter was the most dominant genus in wild lizards, while Morganella was the most dominant genus in captive lizards. Moreover, gene function predictions showed that genes at the KEGG pathway levels2 were more abundant in wild lizards than in captive lizards but, at the KEGG pathway levels1, the differences in gene abundances between wild and captive lizards were not significant. In summary, captivity exerted a significant impact on the gut microbial community structure and diversity in T. septentrionalis, and future work could usefully investigate the causes of these changes using a comparative approach., (© 2020 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Three new carbazole alkaloids, zanthoaustrones A-C (1-3), as well as nine known compounds 4-12, were isolated and characterized from the roots of Zanthoxylum austrosinense Huang (Rutaceae). Their chemical structures were elucidated on the basis of extensive and comprehensive spectroscopic methods, while the known alkaloids were identified by the comparison of their observed spectroscopic data including NMR data, MS data and optical rotation values with the data described in the literature. Furthermore, the antiproliferative activities as well as the anti-inflammatory effects of all isolated alkaloids in vitro were evaluated. All obtained alkaloids 1-12 displayed notable antiproliferative activities against diverse human cancer cell lines exhibiting IC 50 values in range of 0.85 ± 0.06 to 29.56 ± 0.17 µM, which is equivalent to the positive control (cisplatin) showing IC 50 values ranging from 1.58 ± 0.09 to 28.69 ± 0.21 µM. Moreover, compounds 1-12 exhibited pronounced inhibitory activities on nitric oxide (NO) production with IC 50 values displaying IC 50 values in range of 0.89 ± 0.05 to 9.62 ± 0.15 µM, which is comparable to the positive control (hydrocortisone) holding an IC 50 value of 4.06 ± 0.11 µM. These findings indicate that the separation and characterization of these alkaloids displaying significant antiproliferative activities together with anti-inflammatory effects from the roots of Z. austrosinense could be meaningful to the research and development of new anti-cancer drugs as well as anti-inflammatory agents., 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 © 2020 Elsevier Inc. All rights reserved.)

Objective: To explore the possible role of C5a in the pathogenesis of renal injury in TCE- sensitized mice, to analyze the impact of expression of neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemotactic protein-1 (MCP-1) in the presence or absence of C5a receptor antagonist (C5aRA) pretreatment. Methods: A total of 50 female specific pathogens free(SPF) BALB/c mice were randomly divided into blank control group ( n =5) , solvent control group ( n =5) , TCE group ( n =20) , and TCE+C5aRA group ( n = 20) . After one week for adaptive feeding, a mouse model of TCE-induced skin sensitization was established by treating with 50% TCE and 30% TCE in turn. The mice in solvent control group accept same reagents without TCE and the mice in blank control group underwent nothing. In TCE +C5aRA group, except for the TCE solution treatment, mice were intraperitoneally injected with 0.5 mg/kg C5aRA solution at the time of challenge. And the skin erythema and edema reaction were scored 24 h after the last challenge. The mice were divided into sensitization positive group and sensitization negative group according to the scoring result. The mice were aseptically sacrificed 72 h after the last challenge to obtain the kidneys. The structural damage of kidney was observed after histopathological staining. The levels of NGAL and MCP-1 mRNA and proteins were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) , respectively. Results: The sensitization rate of mice in TCE group and TCE+C5aRA group was 45.0% (9/20) and 40.0% (8/20) , respectively. No skin lesions was found in the mice of blank control group and solvent control group. The results of histopathological staining showed that the TCE sensitization positive mice showed renal tubular dilatation, vacuolar degeneration of renal tubular epithelial cells, and infiltration of interstitial cells. The pathological damage of the kidney in TCE sensitization positive group was mild, and no inflammatory cell infiltration was seen. The data of qRT-PCR showed that the expression levels of NGAL and MCP-1 mRNA in the TCE sensitization positive group were significantly increased than in solvent control group and TCE sensitization negative group ( P <0.05) , while the levels of NGAL and MCP-1 mRNA in TCE+C5aRA sensitization positive group were decreased than TCE sensitization positive group ( P <0.05) . The results of IHC showed that the expression levels of NGAL and MCP-1 in TCE protein sensitization positive group were significantly higher than those in solvent control group and TCE sensitization negative group ( P <0.05) . After C5aRA pretreatment, the expression levels of NGAL and MCP-1 protein were decreased than the mice in TCE sensitization positive group ( P <0.05) . Conclusion: The regulation of C5a on the expression of MCP-1 and NGAL may participate in TCE- induced mice kidney damage, and pharmacological inhibition of C5a seems to be an effective way to protect the kidney injury in TCE-sensitized mice.

With the continuous improvement of modern medical technology, medical practice has become more and more procedural. The medical process is often dominated by doctors, while the value orientation of patients is often ignored, lacking effective communication between doctors and patients. In response to this phenomenon, Charon R proposed the concept of narrative medicine, which has been recognized by all walks of life. In recent years, the value of medical humanism has attracted more attention, and the research on narrative medicine at home and abroad is increasing gradually. But at present, most of the research on narrative medicine is in terms of theory, lacking clinical research. How to make narrative medicine applied in the real world is the focus of current research. Following the concept of narrative medicine, and taking the study on doctor-patient parallel medical record to evaluate the real clinical efficacy of traditional Chinese medicine(TCM) and Western medicine(WM) in the treatment of digestive diseases as an example, this study is to explore the design contents and key points of the clinical trial scheme of doctor-patient co-construction of TCM and WM under narrative medicine, and discuss the activity form and clinical efficacy evaluation method under narrative medicine. Clinical trial design includes four aspects: medicine, ethics, statistics and trial management. This study explored the design of the doctor-patient co-construction clinical trial scheme under narrative medicine from both theoretical and practical aspects, providing reference for the design and research of future doctor-patient co-construction scheme, and expecting to establish a better efficacy evaluation method of TCM and WM.