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Ming-ming Li,1,* Chen-xi Yue,1,* Shuang Fu,1 Xin Zhang,1 Chang-Jiu Zhao,2 Rui-tao Wang1 1Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, People’s Republic of China; 2Department of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chang-Jiu ZhaoDepartment of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical University, No. 23 Post Street, Nangang District, Harbin, Heilongjiang 150001, People’s Republic of ChinaTel/fax +86 451 5360 3622Email changjiu_zhao@126.comRui-tao WangDepartment of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, No. 150 Haping Street, Nangang District, Harbin, Heilongjiang 150081, People’s Republic of ChinaTel +86 451 8629 8353Fax +86 451 8629 8352Email ruitaowang@126.comBackground: Platelets play a crucial role in breast cancer (BC) progression and metastases. Mean platelet volume (MPV) is an indicator of platelet activation. The aim of the present study was to assess whether there is a difference in MPV between patients with metastatic BC with liver metastases and those with BC without liver metastases.Methods: Between January 2014 and December 2017, 211 metastatic BC patients with synchronous liver metastases and 215 BC patients without metastases were retrospectively analyzed. Patients’ clinicopathological characteristics data were collected.Results: MPV levels were reduced in patients with liver metastases compared with those in patients without liver metastases. There were significant differences in MPV levels according to liver metastases status both in premenopausal and in postmenopausal non-TNBC or non-HER2+ patients. Moreover, in postmenopausal HER2+ or TNBC patients, MPV levels were lower in patients with liver metastases compared with those in patients without liver metastases. In the group with non-liver metastasis, platelet distribution width was significantly associated with tumor N stage. In addition, the prevalence of BC liver metastases decreased as MPV quartiles increased. After adjusting for other risk factors, the odds ratios for liver metastases according to MPV quartiles were 1.000, 0.267 (0.134–0.530), 0.072 (0.034–0.152), and 0.137 (0.066–0.281), respectively.Conclusion: MPV is reduced in BC patients with liver metastases compared with that in BC patients without metastases. Moreover, MPV is independently associated with the presence of liver metastases.Keywords: breast cancer, liver metastases, mean platelet volume, patient stratification, blood profiling

Qun-You Tan,1,* Jing-Qing Zhang,2,* Na Wang,3,* Hong Yang,4 Xiaoling Li,5 Hua-Rong Xiong,2 Jian-Yong Wu,2 Chun-Jing Zhao,3 Hong Wang,2 Hua-Feng Yin2 1Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 2Medicine Engineering Research Center, Chongqing Key Laboratory of Biochemical & Molecular Pharmacology, Chongqing Medical University, Chongqing, 3School of Pharmacy, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 4School of Pharmacy, Medical College of Soochow University, Soochow, People's Republic of China; 5TJ Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA, USA*These authors contributed equally to this workObjective: Previous studies on various enzymosomes (functional lipid vesicles encapsulating an enzyme) have been mostly carried out in vitro and have focused on preserving catalytic activity and improving the stability of the enzyme. Until now, few studies have focused on their in vivo fate. Similarly, although we have previously reported the increased in vitro uricolytic activity (about 2.2 times higher than that of free uricase, or three times higher than that of PEGylated uricase, Puricase®, under physiological pH and temperature) and improved stability of the novel alkaline enzymosomes (functional lipid vesicles encapsulating uricase from Candida utilis: uricase-containing lipid vesicles, UOXLVs), it is still necessary to study the biological properties and hypouricemic effects of UOXLVs in vivo.Methods: The enzyme kinetics, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary safety of UOXLVs were evaluated.Results: The Michaelis constant (Km) value of the UOXLVs was slightly lower than that of the free enzyme. The enzyme release from the UOXLVs lasted over 12 hours and their circulation half-life was about sevenfold longer than that of the free uricase. Meanwhile, the UOXLVs had a 22-fold increase in the area under the curve compared with the free uricase. Furthermore, it took less than 3 hours for the UOXLVs to lower the plasma uric acid concentration from a high to a normal level, compared with 6 hours for the free uricase. In addition, the UOXLVs had much less immunogenicity than free uricase and were well tolerated by all animals throughout the observation period.Conclusion: The UOXLVs markedly improved the biological properties and enhanced the hypouricemic effects of uricase in vivo.Keywords: biological properties, hypouricemic effect, uricase, alkaline enzymosomes, in vivo

Abstract: The neuronal Ca2+-sensor protein VILIP-1, known to affect clathrin-dependent receptor trafficking, has been shown to interact with the cytoplasmic loop of the α4-subunit of the α4β2 nicotinic acetylcholine receptor (nAChR), which is the most abundant nAChR subtype with high-affinity for nicotine in the brain. The α4β2 nAChR is crucial for nicotine addiction and the beneficial effects of nicotine on cognition. Its dysfunction has been implicated in frontal lobe epilepsy, Alzheimer''s disease and schizophrenia. Here we report that overexpression of VILIP-1 enhances ACh responsiveness, whereas siRNA against VILIP-1 reduces α4β2 nAChR currents of hippocampal neurons. The underlying molecular mechanism likely involves enhanced constitutive exocytosis of α4β2 nAChRs mediated by VILIP-1. The two interaction partners co-localize in a Ca2+-dependent manner with syntaxin-6, a Golgi-SNARE protein involved in trans-Golgi membrane trafficking. Thus, we speculate that regulation of VILIP-1-expression might modulate surface expression of ligand-gated ion channels, such as the α4β2 nAChRs, possibly comprising a novel form of physiological up-regulation of ligand-gated ion channels. [Copyright &y& Elsevier]

Background: Portal shunt and immune status related to the spleen are related to the occurrence of hepatic encephalopathy (HE). It is unknown whether spleen volume before transjugular intrahepatic portosystemic shunt (TIPS) is related to postoperative HE., Aim: To investigate the relationship between spleen volume and the occurrence of HE., Methods: This study included 135 patients with liver cirrhosis who underwent TIPS, and liver and spleen volumes were elevated upon computed tomography imaging. The Kaplan-Meier curve was used to compare the difference in the incidence rate of HE among patients with different spleen volumes. Univariate and multivariate Cox regression analyses were performed to identify the factors affecting overt HE (OHE). Restricted cubic spline was used to examine the shapes of the dose-response association between spleen volumes and OHE risk., Results: The results showed that 37 (27.2%) of 135 patients experienced OHE during a 1-year follow-up period. Compared with preoperative spleen volume (901.30 ± 471.90 cm 3 ), there was a significant decrease in spleen volume after TIPS (697.60 ± 281.0 cm 3 ) in OHE patients. As the severity of OHE increased, the spleen volume significantly decreased ( P < 0.05). Compared with patients with a spleen volume ≥ 782.4 cm 3 , those with a spleen volume < 782.4 cm 3 had a higher incidence of HE ( P < 0.05). Cox regression analysis showed that spleen volume was an independent risk factor for post-TIPS OHE (hazard ratio = 0.494, P < 0.05). Restricted cubic spline model showed that with an increasing spleen volume, OHE risk showed an initial increase and then decrease ( P < 0.05)., Conclusion: Spleen volume is related to the occurrence of OHE after TIPS. Preoperative spleen volume is an independent risk factor for post-TIPS OHE., 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.)

Objective: To investigate the regulatory effect and mechanism of interleukin-22 (IL-22) on the gingival epithelial barrier in the context of periodontal inflammation. Methods: IL-22 knockout (IL-22 KO) mice were constructed, and periodontitis mice models were established through oral gavage with polymicrobial inoculation. DNAs were extracted from the oral plaques of IL-22 KO periodontitis mice group ( n= 7) and their wild-type littermates periodontitis group ( n= 7) to establish a periodontitis-related oral microbiota database"PD-RiskMicroDB", determining the relationship between changes in oral microbiota and microbial function in two groups using 16S rRNA sequencing results. Gingival epithelial cells (GEC) were cultured by modified trypsinization method, and were stimulated with 100 μg/L IL-22, Porphyromonas gingivalis (Pg) (multiplicity of infection:100), separately or together for 3 and 12 hours. The experimental groups were as follows: control group (no stimulation), IL-22 group, Pg group and Pg+IL-22 group. The expression of barrier protein E-cadherin in each group at 3 h was detected by immunofluorescence, real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting. Fluorescein isothiocyanate-dextran-mediated epithelial cell permeability experiment was conducted to clarify the changes in permeability of GEC in each group at 3 and 12 h. The mRNA expressions of E-cadherin in the gingival epithelium of wild-type littermates periodontitis group and IL-22 KO periodontitis group were detected by RT-qPCR. Fifteen C57BL/6 wild-type mice were randomly divided into control group ( n= 5), periodontitis group ( n= 5) and periodontitis+IL-22 treatment group ( n= 5). RT-qPCR and immunohistochemistry (IHC) staining were used to detect the expression level of E-cadherin in the gingival epithelium of each group. Results: 16S rRNA sequencing results showed that the composition of oral microbiota changed in IL-22 KO periodontitis group, of which the abundance of bacterial genera related to periodontal tissue invasion was significantly increased (linear discriminant analysis score: 2.22, P= 0.009), compared with wild-type littermates periodontitis group. In vitro cell experiments showed that after Pg infection for 3 hours, the cell connections of GEC in Pg group were interrupted, and the fluorescence intensity of E-cadherin was reduced in Pg group compared with the control group. Meanwhile, the mRNA and protein expression levels of E-cadherin (mRNA: 0.69±0.12; protein: 0.60±0.12) were downregulated compared with the control group [mRNA: 1.00±0.00 ( P= 0.043); protein: 1.04±0.08 ( P= 0.003)], respectively. The fluorescence intensity of E-cadherin in the Pg+IL-22 group was enhanced compared with Pg group, and expression levels of E-cadherin mRNA (1.16±0.10) and protein (0.98±0.07) in Pg+IL-22 group showed a significant increase compared with Pg group [mRNA: 0.69±0.12 ( P= 0.005); protein: 0.60±0.12 ( P= 0.007)]. The result of epithelial permeability test showed that there was no statistical difference in epithelial permeability among control group, Pg group, IL-22 group and Pg+IL-22 group with treatment for 3 hours ( F= 0.20, P= 0.893). While when the treatment time turned to be 12 hours, the epithelial barrier permeability showed a significant increase in Pg group (1.39±0.15) compared with control group (1.00±0.00, P= 0.027), and a decrease in Pg+IL-22 group (1.02±0.18) compared with Pg group (1.39±0.15, P= 0.034). In vivo , the mRNA expression of E-cadherin in the gingival epithelium of IL-22 KO periodontitis group decreased significantly (0.32±0.21) compared with wild-type littermates periodontitis group (1.01±0.01) ( t= 5.70, P= 0.005). Moreover, RT-qPCR and IHC staining results showed that the mRNA expression level of E-cadherin (0.40±0.07) and absorbance value of E-cadherin positive expression (0.02±0.00) in gingival epithelial tissue of periodontitis group were both significantly down-regulated compared with control group [mRNA: 1.00±0.00 ( P= 0.005); absorbance value of E-cadherin positive expression: 0.04±0.01 ( P= 0.006)]. Meanwhile, the mRNA expression level of E-cadherin (1.06±0.24) and the absorbance value of E-cadherin positive expression (0.03±0.01) were both observed increase in periodontitis+IL-22 treatment group compared with periodontitis group ( P= 0.003, P= 0.039). Conclusions: IL-22 may exert a protective effect on the gingival epithelial barrier in an inflammatory environment by regulating the invasiveness of oral microbiota and the expression of host barrier protein.

Viburnum luzonicum Rolfe is widely used in China as folk medicine. The bioactivity evaluation indicated that the n -BuOH fraction of V. luzonicum leaves (VLLB) could significantly inhibit α ‑amylase and α -glucosidase. In order to clarify its active constituents, the phytochemical analysis on VLLB was first performed using HPLC-QTOF-MS/MS, and three new phenolic compounds, viburosides A-C ( 1 - 3 ), along with seven known analogues ( 4 - 10 ) were isolated through preparative HPLC. The undescribed compounds were determined by extensive spectroscopic analyses ( 1 H and 13 C NMR, HSQC, HMBC, HRESIMS, and ORD) and enzymatic hydrolysis. In the in vitro enzyme assays, compounds 1 - 8 showed potent α ‑amylase and α -glucosidase inhibitory activities. The enzymatic kinetics and molecular docking of the strongest inhibitors 2 and 3 against the corresponding target enzyme were also performed.

The extraction of active ingredients from traditional Chinese medicine has received considerable attentions. In this study, 16 kinds of natural deep eutectic solvent (NADES) with ultrasonic were selected to extract saponins from purple yam root and the extraction mechanism was investigated. The results showed that chloride/acrylic acid (1:2; n/n) had the highest extraction yield for saponins. The optimal extraction process parameters were 24% water content, 20 mL/g liquid-solid ratio, and ultrasonic extraction for 85 min (81 °C, 600 W). The extraction rate (ER) of purple yam saponins was 0.935%, close to the fitted result of 96.5 mg/g. Molecular dynamics simulations and FT-IR results showed that the NADES may extract the saponin constituents from purple yam through hydrogen bonding. Compared with traditional extraction methods and molecularly imprinted polymer methods, NADES has a higher ER and lower cost (1.53 $/g), which provides a reference for subsequent industrial quantitative production., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

The macrophage to myofibroblasts transition (MMT) has been reported as a newly key target in renal fibrosis. Lycium barbarum L. is a traditional Chinese medicine for improving renal function, in which its polysaccharides (LBPs) are the mainly active components. However, whether the role of LBPs in treating renal fibrosis is related to MMT process remain unclear. The purpose of this study was to explore the relationship between the regulating effect on MMT process and the anti-fibrotic effect of LBPs. Initially, small molecular weight LBPs fractions (LBP-S) were firstly isolated via Sephadex G-100 column. Then, the potent inhibitory effect of LBP-S on MMT process was revealed on bone marrow-derived macrophages (BMDM) model induced by TGF-β. Subsequently, the chemical structure of LBP-S was elucidated through monosaccharide, methylation and NMR spectrum analysis. In vivo biodistribution characteristics studies demonstrated that LBP-S exhibited effectively accumulation in kidney via intraperitoneal administration. Finally, LBP-S showed a satisfactory anti-renal fibrotic effect on unilateral ureteral obstruction operation (UUO) mice, which was significantly reduced following macrophage depletion. Overall, our findings indicated that LPB-S could alleviate renal fibrosis through regulating MMT process and providing new candidate agents for chronic kidney disease (CKD) related fibrosis treatment., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Saponin is an essential natural compound in purple yams with high nutritional and medicinal value. In this work, a multitemplate molecule-imprinted polymer (MMIP) was synthesized with dioscin, protodioscin, and diosgenin templates. The MMIPs were characterized with scanning electron microscopy, thermogravimetric analysis, Brunauer-Emmett-Teller (BET) adsorption, and Fourier transform infrared spectroscopy. The efficacy of the MMIPs was assessed with static, dynamic, selective adsorption, desorption, and reusability experiments. The three saponins were selectively extracted and determined by MMIP-high-performance liquid chromatography. The polymer morphology was regular and spherical. The amount of the MMIP adsorbed was 74.825 mg/g, and the imprinting factor was 2.1. The MMIP adsorbed the three saponins from purple yam extract, with recovery rates of 95.5-103.43 % and desorption rates of 85 %-98 %. In addition, the MMIPs were reused at least six times. These results demonstrated that the MMIPs efficiently and selectively extracted dioscin, protodioscin, and diosgenin from food matrices at high rates., 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 © 2024 Elsevier Ltd. All rights reserved.)

Two new phenolic allopyranosides, named viburluzosides A and B ( 1 , 2 ), together with eight known phenolic glycosides ( 3  -  10 ) were discovered from the stems of Viburnum luzonicum Rolfe under the guidance of LC-MS analyses coupled with bioactivity evaluation. They were purified through various chromatography methods and identified by extensive spectroscopic analyses ( 1 H and 13 C NMR, HSQC, HMBC, and HRESIMS) and chemical methods. The in vitro evaluation on α -glucosidase and aldose reductase (AR) inhibitory activities of isolated compounds were conducted. Compounds 1  -  4 and 6  -  9 exhibited α -glucosidase inhibitory activities with IC 50 values of 5.35 - 21.34 μM and AR inhibitory activities with IC 50 values of 6.21 - 40.06 μM. Moreover, the inhibitory kinetics analyses of compounds 1 and 2 were also performed.

Integral imaging is a kind of true three-dimensional (3D) display technology that uses a lens array to reconstruct vivid 3D images with full parallax and true color. In order to present a high-quality 3D image, it's vital to correct the axial position error caused by the misalignment and deformation of the lens array which makes the reconstructed lights deviate from the correct directions, resulting in severe voxel drifting and image blurring. We proposed a sub-pixel marking method to measure the axial position error of the lenses with great accuracy by addressing the sub-pixels under each lens and forming a homologous sub-pixel pair. The proposed measurement method relies on the geometric center alignment of image points, which is specifically expressed as the overlap between the test 3D voxel and the reference 3D voxel. Hence, measurement accuracy could be higher. Additionally, a depth-based sub-pixel correction method was proposed to eliminate the voxel drifting. The proposed correction method takes the voxel depth into consideration in the correction coefficient, and achieves accurate error correction for 3D images with different depths. The experimental results well confirmed that the proposed measuring and correction methods can greatly suppress the voxel drifting caused by the axial position error of the lenses, and greatly improve the 3D image quality.

Objective: This study aims to explore the relationships between serum indoxyl sulfate (IS) and Klotho protein levels with vascular calcification in patients with chronic kidney disease (CKD) stages 3-5., Methods: From December 2021 to January 2023, a total of 108 CKD patients in stages 3-5 were enrolled in this cross-sectional investigation. Demographic information and routine clinical biochemistry test results were gathered. Serum levels of IS and Klotho were quantified through enzyme-linked immunosorbent assays. Furthermore, multislice spiral computed tomography was employed to evaluate vascular calcification. The association between serum IS or Klotho levels and abdominal aorta calcification was assessed using univariate analysis and logistic regression analyses., Results: With the progression of CKD stages, serum creatinine, phosphorus, intact parathyroid hormone (iPTH), serum IS, and abdominal aortic calcification exhibited incremental trends, while serum calcium and Klotho protein levels showed a diminishing trend, with statistically significant differences ( P < 0.05). Significant differences were observed in age, blood phosphorus, calcium, total parathyroid hormone, serum IS, and Klotho protein levels between patients with and without aortic calcification ( P < 0.05). Logistic regression analysis demonstrated that advanced age, high IS level, and low Klotho protein level were independent risk factors for abdominal aortic calcification in CKD patients ( P < 0.05)., Conclusion: This study indicates elevated serum IS levels and decreased Klotho protein levels in CKD patients. High IS level and low Klotho level were independent risk factors for abdominal aortic calcification., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Yan Gao et al.)

Gliomas are one of the most common primary malignant tumours of the central nervous system (CNS), of which glioblastomas (GBMs) are the most common and destructive type. The glioma tumour microenvironment (TME) has unique characteristics, such as hypoxia, the blood-brain barrier (BBB), reactive oxygen species (ROS) and tumour neovascularization. Therefore, the traditional treatment effect is limited. As cellular oxidative metabolites, ROS not only promote the occurrence and development of gliomas but also affect immune cells in the immune microenvironment. In contrast, either too high or too low ROS levels are detrimental to the survival of glioma cells, which indicates the threshold of ROS. Therefore, an in-depth understanding of the mechanisms of ROS production and scavenging, the threshold of ROS, and the role of ROS in the glioma TME can provide new methods and strategies for glioma treatment. Current methods to increase ROS include photodynamic therapy (PDT), sonodynamic therapy (SDT), and chemodynamic therapy (CDT), etc., and methods to eliminate ROS include the ingestion of antioxidants. Increasing/scavenging ROS is potentially applicable treatment, and further studies will help to provide more effective strategies for glioma 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 © 2023 Yang, Zhu, Sun, Zhao, Bai, Wang and Ma.)

To explore the effect of Internet+diet self-management intervention technology on the blood pressure control of hypertension high-risk population through the intervention of hypertension high-risk population in Haikou City community, so as to provide scientific evidence for the prevention and treatment of cardiovascular diseases (CVD). The multi-stage cluster sampling method was used, and 295 hypertension high-risk participants were recruited from 15 communities in Haikou City from July to December 2021. The 15 communities were randomly divided into three groups: blank group, traditional group and Internet plus group by random number table method. The blank group referred to the group (99 participants) that did not take special intervention measures but the routine interventions in accordance with the "National Basic Public Health Service Standards (the Third Edition) Health Education Service Standards". On the basis of the blank group, the traditional group (95 participants) was intervened by giving additional traditional methods such as holding lectures and distributing popular science books. The Internet plus group (101 participants) was given additional Internet measures on the basis of the intervention of the traditional group. After 6 months, questionnaires, laboratory biochemical tests, and physical measurements were conducted. SPSS 25.0 software was applied for data analysis. Measurement data that followed normal distribution were statistically described by using mean±standard deviation, analysis of variance was used for inter group comparisons before intervention, analysis of covariance was used for inter group comparisons after intervention, and Bonferroni adjustment was used for pairwise comparisons between groups. Measurement data that did not follow the Normal distribution were represented by M ( Q 1 , Q 3 ). The rank sum test was used for inter group comparison. The k sample Kruskal Wallis single factor ANOVA was used to compare the distribution between different groups. Counting data were described by composition ratio or rate. Under the premise of balanced comparison between groups before intervention, Chi-squared test was used for inter group comparison after intervention, and Bonferroni adjustment method was used for pairwise comparison between groups. The results showed that a total of 295 participants were included, with males accounting for 35.6% (105) and females accounting for 64.4% (190). The age ranged from 55 to 74 years old, with an average age of (64.69±5.73) years. The number of married accounted for 95.6% (282 participants). There were no statistically significant differences in gender, age, family history, education level, occupation, marital status, drinking habits, regular exercise, dietary status, SBP (systolic blood pressure), DBP (diastolic blood pressure), pulse pressure difference, BMI (body mass index), folic acid, and 24-hour urine sodium among the three groups upon enrollment ( P values>0.05). After the intervention, the drinking rate was as follows: Internet plus group (29, 28.7%)2 =28.948, P <0.001); Regular exercise rate was higher in the Internet plus group (37, 36.6%) than in the traditional group (18, 18.9%) and the blank group (16, 16.2%) (χ 2 =13.476, P =0.001). After the intervention, compared with the participants in the blank group, the intake of energy, carbohydrate, dietary fiber, sodium and folic acid in the Internet plus group were significantly different (all P <0.05); Compared with the participants in the traditional group, the energy, carbohydrate and dietary fiber intake of the participants in the Internet plus group were significantly different (all P <0.05). After the intervention, the blood pressure levels in the Internet plus group [ SBP: (128.95±6.55) mmHg, DBP: (79.88±5.75) mmHg ] and the traditional group [ SBP: (129.63±8.41) mmHg, DBP: (79.77±7.73) mmHg ] were lower than those in the blank group [ SBP: (132.93±8.41) mmHg, DBP: (82.42±7.76) mmHg ] (SBP: F =9.417, P <0.001; DBP: F =6.967, P =0.001), the 24-hour urinary sodium level in the Internet plus group (143.63±38.58) mmol/24 h was lower than that in the traditional group (163.31±35.67) mmol/24 h and the blank group (154.14±35.52) mmol/24 h ( F =11.509, P <0.001). In conclusion, compared with the traditional intervention mode, the "Internet plus diet self-management intervention" mode is more likely to promote the development of a healthy lifestyle for people at high risk of hypertension, effectively improve blood pressure and 24-hour urine sodium level, and facilitate CVD prevention.

Objective: To estimate the prevalence and risk factors associated with tuberculosis (TB) among people living with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) in China., Methods: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. After the literature was screened based on the inclusion and exclusion criteria, STATA ® version 17.0 software was used for the meta-analysis. The heterogeneity among study data was assessed using I 2 statistics. Subgroup analysis and meta-regressions were performed to further explore the source of heterogeneity., Results: A total of 5241 studies were retrieved. Of these, 44 studies were found to be eligible. The pooled prevalence of HIV/TB co-infection was 6.0%. The risk factors for HIV/TB co-infection included a low CD4 + T cell count, smoking, intravenous drug use and several other sociodemographic and clinical factors. Bacillus Calmette-Guérin (BCG) vaccination history was a protective factor., Conclusion: A high prevalence of TB was observed among people living with HIV/AIDS in China. Low CD4 + T cell count, smoking, and intravenous drug use were the primary risk factors for HIV/TB co-infection, whereas BCG vaccination history was a protective factor. Checking for TB should be prioritized in HIV screening and healthcare access., Systematic Review Registration: Registered on PROSPERO, Identifier: CRD42022297754., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Compared with conventional scattered backlight systems, integral imaging (InIm) display system with collimated backlight can reduce the voxel size, but apparent voxel separation and severe graininess still exist in reconstructed 3D images. In this paper, an InIm 3D display system with anisotropic backlight control of sub-pixels was proposed to resolve both voxel aliasing and voxel separation simultaneously. It consists of an anisotropic backlight unit (ABU), a transmissive liquid crystal panel (LCP), and a lens array. The ABU with specific horizontal and vertical divergence angles was proposed and designed. Within the depth of field, the light rays emitted from sub-pixels are controlled precisely by the ABU to minimize the voxel size as well as stitch adjacent voxels seamlessly, thus improving the 3D image quality effectively. In the experiment, the prototype of our proposed ABU-type InIm system was developed, and the spatial frequency was nearly two times of conventional scattered backlight InIm system. Additionally, the proposed system eliminated the voxel separation which usually occurs in collimated backlight InIm system. As a result, voxels reconstructed by our proposed system were stitched in space without aliasing and separation, thereby greatly enhancing the 3D resolution and image quality.

Wound is a common surgical disease characterized by skin defect or functional limitation. Studies have found that acupuncture-moxibustion plays an important role in wound healing. In this paper, we reviewed the mechanisms of acupuncture-moxibustion in promoting wound repair. Outcomes display that acupuncture-moxibustion has an action in promoting wound restoration by improving wound flow perfusion, promoting angiogenesis, increasing the number of fibroblasts and regulating collagen synthesis. In addition, acupuncture can effectively promote wound healing by controlling the release of inflammatory cytokines, up-regulating the expression of growth factors such as vascular endothelial growth factor and transforming growth factor-β1, and affecting phosphatidylinositol-3-kinase/protein kinase B, mitogen-activated protein kinase and advanced glycation end products/receptor for AGEs signaling pathways. Based on the above studies, it is highly recommended that future studies should pay more attention to the multi-mechanism coordinated regulation target center, and the therapeutic means and dose-effect relationship of acupuncture-moxibustion in tissue repair.

Danyikangtai powder has a definite therapeutic effect on pancreatitis. However, the internal mechanism is unclear. The purpose of this experiment is to quickly identify the blood components of danyikangtai powder and evaluate its efficacy. 25 blood components were identified by comparing the components with the same mass spectrometry information from in vivo and in vitro samples. The AR42J cells of the pancreatitis model were treated with drug-containing plasma, and the drug efficacy was evaluated by investigating the amylase release rate. This study provides a scientific reference for its pharmacological research and rational clinical application.

Motivation: Transcriptional dynamics are governed by the action of regulatory proteins and are fundamental to systems ranging from normal development to disease. RNA velocity methods for tracking phenotypic dynamics ignore information on the regulatory drivers of gene expression variability through time., Results: We introduce scKINETICS (Key regulatory Interaction NETwork for Inferring Cell Speed), a dynamical model of gene expression change which is fit with the simultaneous learning of per-cell transcriptional velocities and a governing gene regulatory network. Fitting is accomplished through an expectation-maximization approach designed to learn the impact of each regulator on its target genes, leveraging biologically motivated priors from epigenetic data, gene-gene coexpression, and constraints on cells' future states imposed by the phenotypic manifold. Applying this approach to an acute pancreatitis dataset recapitulates a well-studied axis of acinar-to-ductal transdifferentiation whilst proposing novel regulators of this process, including factors with previously appreciated roles in driving pancreatic tumorigenesis. In benchmarking experiments, we show that scKINETICS successfully extends and improves existing velocity approaches to generate interpretable, mechanistic models of gene regulatory dynamics., Availability and Implementation: All python code and an accompanying Jupyter notebook with demonstrations are available at http://github.com/dpeerlab/scKINETICS., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: To observe the effect of moxibustion at "Zusanli"(ST36) on the silent information regulator 1 (SIRT1) /p53 signaling pathway in subacute aging model rats, so as to reveal its mechanisms in delaying aortic aging., Methods: Male SD rats were divided into blank group, model group, prevention group and treatment group, with 20 rats in each group. Subacute aging model was established by intraperitoneal injection of D-galactose(500 mg·kg -1 ·d -1 ). In the morning, rats in the prevention group received moxibustion at ST36 with 3 moxa cones after modeling operation, once every day for 42 d. From the day after the 42-day modeling, rats in the treatment group received the same moxibustion treatment as the prevent group for 28 d. Rats in the blank and model group were fixed in the similar way as the other two groups, for 5 min. Contents of serum SIRT1, p53, endothelial nitric oxide synthase(eNOS) and vascular endothelial growth factor(VEGF) were detected by ELISA. Histopathological changes of aortic tissue were observed after HE staining. Expressions of SIRT1 and p53 mRNAs and proteins in aortic tissue were detected by qPCR and Western blot., Results: Compared with the blank group, the model group showed aging symptoms, the prevention group was similar to the blank group, and the treatment group was slightly better than the model group. Compared with the blank group, content of serum p53, expressions of p53 mRNA and protein in aortic tissues were significantly increased ( P <0.05, P <0.01), while contents of serum SIRT1, VEGF, eNOS, and expressions of SIRT1 mRNA and protein in aortic tissues were significantly decreased ( P <0.05, P <0.01) in the model group. Compared with the model group, content of serum p53, and expression of p53 mRNA and protein in aortic tissues were significantly decreased ( P <0.05, P <0.01) in the prevention and treatment groups, while the contents of serum SIRT1, VEGF, eNOS, and the expressions of SIRT1 mRNA and protein in aortic tissues were significantly increased ( P <0.05, P <0.01). Compared with the treatment group, rats in the prevention group displayed significant improvement of the above indexes ( P <0.05). Compared with the blank group, the endothelial cells were disordered, the vessel wall was significantly thickened, and the senescent cells were increased in the model group; the blood vessel walls were thinner to varying degrees, and the senescent cells were reduced and unevenly distributed in the prevention and treatment groups. The histopathological lesion was improved more obviously in the prevention group than the treatment group., Conclusion: Moxibustion at ST36 can alleviate vascular endothelial injury and oxidative stress in subacute aging rats, which may be related to its effect in regulating the SIRT1/p53 signaling pathway.

Malignant liver tumors have a high incidence and mortality rate. Therefore, it is of great significance to promptly learn about tumor advancement status through relevant examinations for patients' follow-up, diagnosis, and therapy as well as the improvement of the five-year survival rate. The primary lesions and intrahepatic metastases of malignant liver tumors have been better demonstrated in the clinical study with the use of various isotope-labeled fibroblast activating protein inhibitors because of their low uptake in liver tissues and high tumor/background ratio, which provides a new method for early diagnosis, precise staging, and radionuclide therapy. In light of this context, a review of the research progress of fibroblast-activating protein inhibitors for the diagnosis of liver malignant tumors is presented.

Drought is one of the most significant abiotic stress threatening to crop production worldwide. Soybean is a major legume crop with immense economic significance, but its production is highly dependent on optimum rainfall or abundant irrigation. As the global climate changes, it is more important to find solutions to make plants more resilient to drought. The prime aimed of the study is to investigate the effect of melatonin on drought tolerance in soybean and its potential mechanisms. Soybean seedlings were treated with 20% polyethylene glycol 6000 (PEG 6000) and subjected to osmotic stress (14 days) with or without 100 μM melatonin treatment. Our results revealed that melatonin supplementation significantly mitigated PEG-induced growth retardation and increased water absorption ability. Foliar application of melatonin also increased gas exchange and the chlorophyll fluorescence attributes by the mitigation of the osmotic-induced reduction of the reaction activity of photosystems I and II, net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), electron transport activity, and photosynthetic efficiency. In addition, PEG-induced elevated production of reactive oxygen species (ROS) and malondialdehyde (MDA) content were significantly reversed by melatonin treatment. Equally important, melatonin boosted the antioxidant activities of soybean plants. Moreover, osmotic stress substantially increased abscisic acid (ABA) accumulation in roots and leaves, while melatonin-received plant leaves accumulated less ABA but roots content higher ABA. Similarly, melatonin significantly suppressed ABA biosynthesis and signaling gene expression in soybean exposed to drought stress. Furthermore, osmotic stress significantly suppressed plasmalemma ( GmPIPs ) and tonoplast aquaporin ( GmTIPs ) genes expression, and their transcript abundance was up-regulated by melatonin co-addition. Taken together, our results indicated that melatonin potentially improves drought tolerance of soybean through the regulation of ABA and aquaporin gene expression, increasing photosynthetic efficiency as well as enhancing water uptake efficiency., 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 Jahan, Zhao, Shi, Liang, Jabborova, Nasar and Zhou.)

The response to tumor-initiating inflammatory and genetic insults can vary among morphologically indistinguishable cells, suggesting as yet uncharacterized roles for epigenetic plasticity during early neoplasia. To investigate the origins and impact of such plasticity, we performed single-cell analyses on normal, inflamed, premalignant, and malignant tissues in autochthonous models of pancreatic cancer. We reproducibly identified heterogeneous cell states that are primed for diverse, late-emerging neoplastic fates and linked these to chromatin remodeling at cell-cell communication loci. Using an inference approach, we revealed signaling gene modules and tissue-level cross-talk, including a neoplasia-driving feedback loop between discrete epithelial and immune cell populations that was functionally validated in mice. Our results uncover a neoplasia-specific tissue-remodeling program that may be exploited for pancreatic cancer interception.

Lung cancer is one of the most common malignant tumours worldwide, with the highest mortality rate. Approximately 1.6 million deaths owing to lung cancer are reported annually; of which, 85% of deaths occur owing to non-small-cell lung cancer (NSCLC). At present, the conventional treatment methods for NSCLC include radiotherapy, chemotherapy, targeted therapy and surgery. However, drug resistance and tumour invasion or metastasis often lead to treatment failure. The ubiquitin-proteasome pathway (UPP) plays an important role in the occurrence and development of tumours. Upregulation or inhibition of proteins or enzymes involved in UPP can promote or inhibit the occurrence and development of tumours, respectively. As regulators of UPP, ubiquitin-specific proteases (USPs) primarily inhibit the degradation of target proteins by proteasomes through deubiquitination and hence play a carcinogenic or anticancer role. This review focuses on the role of USPs in the occurrence and development of NSCLC and the potential of corresponding targeted drugs, PROTACs and small-molecule inhibitors in the treatment of NSCLC., 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 Yang, Zhao, Jin, Zheng and Ma.)

Sepsis-associated encephalopathy (SAE) is commonly defined as diffuse brain dysfunction and can manifest as delirium to coma. Accumulating evidence has suggested that perineuronal net (PNN) plays an important role in the modulation of the synaptic plasticity of central nervous system. We here investigated the role of PNN in SAE induced by lipopolysaccharide (LPS) injection. Behavioral tests were performed by open field, Y-maze, and fear conditioning tests at the indicated time points. The densities of vesicular γ-aminobutyric acid transporter, vesicular glutamate transporter 1, PNN, and parvalbumin (PV) in the hippocampus were evaluated by immunofluorescence. Matrix metalloproteinases-9 (MMP-9) expression and its activity were detected by Western blot and gel zymography, respectively. Local field potential was recorded by in vivo electrophysiology. LPS-treated mice displayed significant cognitive impairments, coincided with activated MMP-9, decreased PNN and PV densities, reduced inhibitory and excitatory input onto PV interneurons enwrapped by PNN, and decreased gamma oscillations in hippocampal CA1. Notably, MMP-9 inhibitor SB-3CT treatment rescued most of these abnormalities. Taken together, our study demonstrates that active MMP-9 mediated PNN remodeling, leading to reduced inhibitory and excitatory input onto PV interneurons and abnormal gamma oscillations in hippocampal CA1, which consequently contributed to cognitive impairments after LPS injection., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To observe the effect of "lingguibafa" moxibustion at "opening" time on the level of superoxide dismutase(SOD), malondialdehyde(MDA), the protein expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in aging model rats., Methods: SD rats were randomly divided into blank control, model and lingguibafa groups, with 8 rats in each group. The aging model was established by daily intraperitoneal injection of D-galactose (500 mg/kg) for 42 consecutive days. After successful modeling, moxibustion intervention was applied at"lingguibafa" acupoints, 3 moxa-cone for each acupoint, once a day for 28 consecutive days. The contents of SOD and MDA in serum were detected by ELISA. Morphological changes of testicular tissue and the number of Leydig cells were observed after HE staining. Apoptosis rate of testicular cells was detected by TUNEL staining. The protein expression levels of Bcl-2 and Bax in testis were detected by Western blot., Results: Compared with the blank control group, the SOD content in the serum, the number of testicular Leydig cells, the expression level of Bcl-2 protein in testis were significantly decreased ( P <0.01) in the model group, while the MDA content in the serum, the apoptosis rate of testicular cells and the expression level of Bax protein in testis were significantly increased ( P <0.01). Compared with the model group, the SOD content in serum, the number of testicular Leydig cells, the Bcl-2 protein expression in testis were significantly increased ( P <0.01), while the MDA content in serum, the apoptosis rate of testicular cells, the expression level of Bax protein in testis were significantly decreased( P <0.01) in the lingguibafa group., Conclusion: Moxibustion on acupoints at "opening" time can delay testicular aging, and the mechanism may be related to balancing the metabolism of free radicals, reducing oxidative damage, and inhibiting the apoptosis of testicular cells.

Introduction: Surplus use of chemical nitrogen (N) fertilizers to increase agricultural Q9 production causes severe problems to the agricultural ecosystem and environment. This is contrary to N use efficiency and sustainable agricultural production., Methods: Hence, this study was designed to investigate the effect of maizesoybean intercropping on N uptake, N yield, N utilization use efficiency, and the associated nitrogen assimilatory enzymes of maize crops under different N fertilization for two consecutive years 2021-2022., Results: The findings of the study showed that intercropping at the optimal N rate (N1) (250 kg N ha-1) increased significantly maize grain yield by 30 and 34%, residue yield by 30 and 37%, and 100-grain weight by 33 and 39% in the year 2021 and 2022, respectively. As compared with mono-cropping, at this optimal N rate, the respective increase (of maize's crop N yield indices) for 2021 and 2022 were 53 and 64% for grain N yield, and 53 and 68% for residue N yield. Moreover, intercropping at N1 resulted in higher grain N content by 28 and 31%, residue N content by 18 and 22%, and total N uptake by 65 and 75% in 2021 and 2022, respectively. The values for the land equivalent ratio for nitrogen yield (LERN) were greater than 1 in intercropping, indicating better utilization of N under the intercropping over mono-cropping. Similarly, intercropping increased the N assimilatory enzymes of maize crops such as nitrate reductase (NR) activity by 19 and 25%, nitrite reductase (NiR) activity by 20 and 23%, and glutamate synthase activity (GOGAT) by 23 and 27% in 2021 and 2022, respectively. Consequently, such increases resulted in improved nitrogen use efficiency indices such as N use efficiency (NUE), partial factor nitrogen use efficiency (PFNUE), nitrogen uptake efficiency (NUpE), and nitrogen agronomic efficiency (NAE) under intercropping than mono-cropping., Conclusion: Thus, this suggests that maize-soybean intercropping under optimal N fertilization can improve the nitrogen status and nitrogen use efficiency of maize crops by regulating the nitrogen assimilatory enzymes, thereby enhancing its growth and yield. Therefore, prioritizing intercropping over an intensive mono-cropping system could be a better option for sustainable agricultural production., 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 Nasar, Zhao, Khan, Gul, Gitari, Shao, Abbas, Haider, Iqbal, Ahmed, Rehman, Liang, Zhou and Yang.)

This study used the zebrafish model to explore the hepatotoxicity of Rhododendri Mollis Flos(RMF). The mortality was calculated according to the number of the survival of zebrafish larvae 4 days after fertilization under different concentration of RMF, and the dose-toxicity curve was fitted to preliminarily evaluate the toxicity of RMF. The liver phenotypes under the sublethal concentration of RMF in the treatment group and the blank control group were observed by hematoxylin-eosin(HE) staining and acridine orange(AO) staining. Meanwhile, the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined to confirm the hepatotoxicity of RMF. Real-time quantitative polymerase chain reaction(real-time PCR) and Western blot were used to determine the expressions of genes and proteins in zebrafish larvae. Gas chromatography time-of-flight mass spectrometry(GC-TOF-MS) was used to conduct untargeted metabolomics testing to explore the mechanism. The results showed that the toxicity of RMF to zebrafish larvae was dose-dependent, with 1 100 μg·mL~(-1) of the absolute lethal concentration and 448 μg·mL~(-1) of sublethal concentration. The hepatocyte apoptosis and degeneration appeared in the zebrafish larvae under the sublethal concentration of RMF. The content of ALT and AST in zebrafish larvae at the end of the experiment was significantly increased in a dose-dependent manner. Under the sublethal concentration, the expressions of genes and proteins related to apoptosis in zebrafish larvae were significantly increased as compared with the blank control group. The results of untargeted metabolomics showed that the important metabolites related to the he-patotoxicity of RMF were mainly enriched in alanine, aspartic acid, glutamic acid, and other pathways. In conclusion, it is inferred that RMF has certain hepatotoxicity to zebrafish larvae, and its mechanism may be related to apoptosis.

Background: Complex carcinogenic mechanisms and the existence of tumour heterogeneity in multiple myeloma (MM) prevent the most commonly used staging system from effectively interpreting the prognosis of patients. Since the microenvironment plays an important role in driving tumour development and MM occurs most often in middle-aged and elderly patients, we hypothesize that ageing of bone marrow mesenchymal stem cells (BM-MSCs) may be associated with the progression of MM., Methods: In this study, we collected the transcriptome data on MM from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Differentially expressed genes in both senescent MSCs and MM tumour cells were considered relevant damaged genes. GO and KEGG analyses were applied for functional evaluation. A PPI network was constructed to identify hub genes. Subsequently, we studied the damaged genes that affected the prognosis of MM. Least absolute shrinkage and selection operator (lasso) regression was used to identify the most important features, and a risk model was created. The reliability of the risk model was evaluated with the other 3 GEO validation cohorts. In addition, ROC analysis was used to evaluate the novel risk model. An analysis of immune checkpoint-related genes, tumour immune dysfunction and exclusion (TIDE), and immunophenotypic scoring (IPS) were performed to assess the immune status of risk groups. pRRophetic was utilized to predict the sensitivity to administration of chemotherapeutic agents., Results: We identified that MAPK, PI3K, and p53 signalling pathways were activated in both senescent MSCs and tumour cells, and we also located hub genes. In addition, we constructed a 14-gene prognostic risk model, which was analysed with the ROC and validated in different datasets. Further analysis revealed significant differences in predicted risk values across the International Staging System (ISS) stage, sex, and 1q21 copy number. A high-risk group with higher immunogenicity was predicted to have low proteasome inhibitor sensitivity and respond poorly to immunotherapy. Lipid metabolism pathways were found to be significantly different between high-risk and low-risk groups. A nomogram was created by combining clinical data, and the optimization model was further improved. Finally, real-time qPCR was used to validate two bortezomib-resistant myeloma cell lines, and the test confirmed that 10 genes were detected to be expressed in resistant cell lines with the same trend as in the high-risk cohort compared to nonresistant cells., Conclusion: Fourteen genes related to ageing in BM-MSCs were associated with the prognosis of MM, and by combining this genotypic information with clinical factors, a promising clinical prognostic model was established., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Yang-Jia Cao et al.)

The oriental armyworm Mythimna separata (Walker) is a devastating pest of cereal crops mainly in Asia and Oceania and recently become resistant to beta-cypermethrin (beta-CP). However, molecular biological studies of its response to beta-CP are scarce, and related genomic information is not available. In this study, we sequenced and de novo assembled the transcriptome of beta-CP susceptible M. separata (MsS-whole, abbr. MsS-W). A total of 30,486 unigenes were obtained, with an N50 length of 506 bp. A number of 21,051 unigenes were matched to public databases, of which 10,107 were classified into 59 gene ontology subcategories, 5792 were assigned into 25 clusters of orthologous groups of proteins subgroups and 12,123 were assigned to 257 Kyoto Encyclopedia of Genes and Genomes pathways. A total of 729 simple sequence repeats were detected. In addition, a total of 323 cytochrome P450-associated sequences from nine lepidopterous species, of which 130 were from M. separata, were analyzed using the maximum likelihood method and Bayesian inference. Among the 130 cytochrome P450-associated sequences from M. separata, 60 were dropped into CYP3 clan, which is associated with metabolizing xenobiotics and plant natural compounds. Furthermore, the beta-CP susceptible (MsS-2) and resistant (MsR-2) M. separata population transcriptomes were sequenced. Certain critical genes involved in beta-CP detoxification were detected and verified by quantitative real-time polymerase chain reaction. Collectively, our results provided a basis for further studies of the molecular mechanism of insecticide resistance in M. separata., (© 2022 Wiley Periodicals LLC.)

Objective: To analyze the level and influence factors of inflammatory factors among electrical workers in Hainan Province. Methods: A total of 509 electrical workers were selected as the research subjects with random cluster sampling in September 2020. Basic information was collected by questionnaire, the serum IL-6, IL-8 and TNF-α levels of the subjects were detected by Luminex.Mann-Whitney U test and Kruskal-wallis H test were used for univariate analysis. Ordinal logistic regression analysis was used for potential influencing factors of the level of inflammatory factors. Results: The median concentrations of IL-6, IL-8 and TNF-α in serum were 2.78, 9.77 and 8.18 pg/ml. Compared with women, male was a risk factor for the increase of IL-6 levels ( OR =1.80, 95% CI : 1.08~3.00, P =0.024) . Compared with 51-60 years old, 21-31 years old ( OR =0.27, 95% CI : 0.18~0.42, P <0.001) , 31-41 years old ( OR =0.27, 95% CI : 0.17~0.43, P <0.001) and 41-51 years old ( OR =0.64, 95% CI : 0.41~0.99, P =0.043) were protective factors for the increase of IL-8 level. Compared with day shift workers, shift work was a risk factor for the increase of IL-8 level ( OR =1.73, 95% CI : 1.21~2.48, P =0.003) . Compared with women, male was a risk factor for the increase of TNF-α levels ( OR =2.87, 95% CI : 1.70~4.86, P <0.001) . Compared with workers who exposed to 7 or more occupational hazard factors, exposed to 1~3 ( OR =0.53, 95% CI : 0.30~0.92, P =0.024) occupational hazard factors were protective factors for the increase of TNF-α levels. Conclusion: The level of inflammatory factors was related to sex, age, work system and occupational environment, which can provide basic data for follow-up research on occupational population.

This study aims to evaluate the anti-tumor and analgesic activities of Compound Kushen Injection(CKI) based on zebrafish model in vivo and investigate the anti-tumor mechanism. To be specific, zebrafish tumor xenotransplantation model was established by microinjection of murine LPC H12 cells into yolk sac. Then the high-dose CKI(H-CKI), medium-dose CKI(M-CKI), low-dose CKI(L-CKI) groups, and the model group were set. The anti-tumor activity of CKI was evaluated with the tumor area growth fold and integral absorbance(IA) growth fold 72 h after administration. The peripheral pain and central pain in zebrafish were respectively induced with acetic acid(AA) and phorbol myristate acetate(PMA). Zebralab ViewPoint system was employed to monitor behavioral trajectory of zebrafish, and movement times, movement time, movement distance, and movement velocity were used to evaluate the analgesic activity of CKI. Finally, real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) was performed to detect the expression levels of apoptosis-related B lymphocyte tumor-2(Bcl-2) and phosphatidylinositol-3-kinase(PI3 K)/protein kinase B(Akt or PKB) pathway-related genes, for the verification of the anti-tumor mechanism. Compared with the model group, M-CKI and H-CKI significantly reduced the growth folds of tumor area and IA, relief the peripheral pain and central pain. The mechanism was that CKI can up-regulate the expression of cysteine aspartic acid specific protease-3(caspase-3, Casp3) and caspase-9(Casp9), down-regulate the expression of phosphoinositide 3-kinase(PI3 K) and Akt, and significantly reduce the expression of Bcl-2, hypoxia-inducible factor-1α(HIF-1α), and vascular endothelial growth factor(VEGF). In conclusion, CKI has significant inhibitory effect on tumor growth and pain, which is related to the PI3 K/Akt signaling pathway. The pathway mediates cell apoptosis, suppresses tumor growth, and alleviates tumor pain.

Background: Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis and hepatocyte injury, is an obesity-induced metabolic dysregulation with few available therapeutic options. Enhancement of the mitochondrial function was considered as an effective treatment for NALFD. Unsaturated fatty acids (UFAs) have been shown to have beneficial effects on metabolic syndrome disease such as hyperlipidemia, coronary artery disease and cardiovascular diseases. The seed oil of Rosa roxburghii Tratt (ORRT) was of high quality in terms of its high amount of unsaturated fatty acids. However, the effects of ORRT on NALFD have not been reported so far., Purpose: The study aimed to evaluate the protective effects and molecular mechanism of ORRT for the treatment of NAFLD in vivo and in vitro., Methods: The beneficial effects, especially improving the mitochondrial function, and the potential mechanism of ORRT on NAFLD were studied both in vivo and in vitro. Lipid levels were determined by triglyceride (TG), total cholesterol (TC), and Oil Red O staining. Oxidative stress and inflammation were assessed by detecting antioxidant enzyme activity, MDA content, and ELISA assay. Blood TG, TC, HDL-c and LDL-c levels were measured in HFD mice. Western blot analyses were used to determine the levels of the protein involved in fatty acid oxidation, oxidative metabolism, and mitochondria biogenesis and function. The mitochondrial membrane potential level was measured by JC-1 staining to teste the effect of ORRT on mitochondrial function in vitro. GW6471 (inhibitor of PPARα) was used to confirm the relationship between PPARα and PGC-1α., Results: ORRT significantly restrained NAFLD progression by attenuating lipid accumulation, oxidative stress and inflammatory response. Furthermore, ORRT upregulated thermogenesis-related gene expressions, such as uncoupling protein 1 (UCP1) and p38 mitogen-activated protein kinase (p38 MAPK). The results showed that the expression of key genes involved in fatty acid oxidation (e.g., CPT-1α, ACADL, PPARα) and in mitochondrial biogenesis and function (e.g., TFAM, NRF1, PGC-1α, and COX IV) was significantly increased. Together with the observed MMP improvement, these findings suggested that ORRT activated the mitochondrial oxidative pathway. Additionally, GW6471 inhibited the ORRT on promoting the expression of PGC-1α, CPT-1α, and ACADL. In conclusion, ORRT possessed the potential to prevent lipid accumulation via the PPARα/PGC-1α signaling pathway, which could be developed as a natural health-promoting oil against NAFLD., (Copyright © 2021. Published by Elsevier GmbH.)

Objective: To observe the effect of herbal-cake-separated moxibustion on changes of vascular endothelial growth factor (VEGF)/VEGF receptor(VEGFR) in endometriosis (EMs) model rats, so as to analyze the regulatory mechanism of herbal-cake-separated moxibustion on EMs., Methods: SD rats were randomly divided into sham operation, model, herbal-cake-separated moxibustion, and medication groups, with 30 rats in each group. The EMs rats model was established by removing the endometrium. Herbal-cake-separated moxibustion was applied to "Dazhui"(GV14) and "Mingmen"(GV4) for 6 moxa-cones every time. Rats of the medication group was treated by gavage of gestrinone (60 mg/kg). All the treatments were conducted once daily for 7 days. The ectopic endometrial volume was calculated and the pathological condition was observed by HE staining. The levels of vascular endothelial growth factor A (VEGFA), soluble VEGFR (sVEGFR) and tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-2 and IL-6 in peritoneal fluid were measured by ELISA. The morphology of macrophages in peritoneal fluid was observed under microscope. The phagocytic capacity and activity of macrophages were detected by colorless malachite green colo-rimetry and MTT colorimetry, respectively., Results: Compared with the sham operation group, the volume of endometriosis increased significantly and showed obvious angiogenesis; the expression levels of VEGFA, sVEGFR, TNF-α, IL-1, IL-2 and IL-6 in rats peritoneal fluid were significantly increased ( P <0.05). The number and volume of macrophages, and the phagocytic function and activity of macrophages ( P <0.05) were all decreased. After the treatment, all the indexes mentioned above were all significantly reversed in the herbal-cake-separated moxibustion and medication groups ( P <0.05), and the effects of herbal-cake-separated moxibustion were superior to the gestrinone ( P <0.05)., Conclusion: Herbal-cake-separated moxibustion can inhibit the activation of VEGF/VEGFR, reduce the inflammatory response of EMs rats and enhance the phagocytosis of macrophages.

Background: Several recent findings have revealed that targeting of cell cycle reentry and (or) progression may provide an opportunity for the therapeutic intervention of Alzheimer's disease (AD). FOXG1 has been shown to play important roles in pattern formation, cell proliferation, and cell specification. Thus far, the roles of FoxG1 and its involvement in AD are largely unknown., Objective: Our study aimed to explore the intervention effect of FOXG1 on AD pathology and its potential mechanism with a particular focus on cell cycle regulation., Methods: We investigated the association of Foxg1 gene variants with AD-like behavioral deficits, p21 expression, neuronal apoptosis, and amyloid-β (Aβ) aggregate formation; we further determined whether targeting FOXG1-regulated cell cycle has therapeutic potential in AD., Results: Paralleling AD-like behavioral abnormalities, neuronal apoptosis, and Aβ deposits, a significant reduction in the expression of FOXG1 was observed in APP/PS1 mice at 6 months of age. Using the APP/PS1;Foxg1fl/fl-CreAAV mouse line, we found that FOXG1 potentially antagonized cell cycle reentry by negatively regulating the levels of p21-activated kinase (PAK3). By reducing p21cip1-mediated arrest at the G2 stage and regulating cyclin A1- and cyclin B-dependent progression patterns of the cell cycle, FOXG1 blocked neuronal apoptosis and Aβ deposition., Conclusion: These results indicate that FOXG1 contributes to the regulation of the neuronal cell cycle, thereby affecting brain abnormalities in AD. An elevation of the FOXG1 level, either pharmacologically or through other means, could present a therapeutic strategy for AD.

Background: The relationship between allergies and sinusitis, though extensively studied, remains poorly defined. While several studies proposed a cause-and-effect relationship between allergy and chronic sinusitis, several others reported the lack of any existing association. This study aimed to investigate the relationship between allergy and sinusitis., Methods: We conducted a cross-sectional study using a representative sample of the US population from the National Health and Nutrition Examination Survey 2005‒2006 (n  = 7244). A self-reported allergy questionnaire and total and allergen-specific IgE levels were used for analysis. Participants were divided into positive and negative allergy symptoms groups (PAS, NAS, respectively) to eliminate the influence of allergy symptoms on the apparent incidence of sinusitis. Pearson's chi-square test and the linear regression analysis using Durbin Watson test were used for statistical analysis., Results: Sinusitis incidence in the PAS group (22.4%; 521/2327) was significantly higher than that in the NAS group (7.1%; 348/4917) [odds ratios (OR)  = 3.788, 95% confidence interval (CI) 3.272‒4.384, P  < 0.001]. sinusitis incidence in non-sensitized and sensitized groups was not statistically different. After controlling for allergy symptoms, there was a negative correlation between sensitization status and the occurrence of sinusitis in the PAS group (OR  = 1.407, 95% CI 1.156‒1.711, P  < 0.01). Increase in serum total IgE levels correlated with decrease in incidence of sinusitis in both PAS and NAS groups. sinusitis incidence was significantly reduced in the PAS group in participants sensitized to allergens such as cockroaches, ragweed, ryegrass, Bermuda grass, oak, birch, and thistle., Conclusion: Allergy is related to sinusitis incidence. It is likely that sensitization status could reduce the incidence of sinusitis, albeit in an antigen-specific manner., (© 2021. The Author(s).)

Stem cell transplantation shows enormous potential for treatment of incurable retinal degeneration (RD). To determine if and how grafts connect with the neural circuits of the advanced degenerative retina (ADR) and improve vision, we perform calcium imaging of GCaMP5-positive grafts in retinal slices. The organoid-derived C-Kit + /SSEA1 - (C-Kit + ) retinal progenitor cells (RPCs) become synaptically organized and build spontaneously active synaptic networks in three major layers of ADR. Light stimulation of the host photoreceptors elicits distinct neuronal responses throughout the graft RPCs. The graft RPCs and their differentiated offspring cells in inner nuclear layer synchronize their activities with the host cells and exhibit presynaptic calcium flux patterns that resemble intact retinal neurons. Once graft-to-host network is established, progressive vision loss is stabilized while control eyes continually lose vision. Therefore, transplantation of organoid-derived C-Kit + RPCs can form functional synaptic networks within ADR and it holds promising avenue for advanced RD treatment., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To observe the effect of Zhulian needle insertion by slow twirling technique on the contents of hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) and apoptosis rate in kidney tissue of aging model rats and explore the potential mechanism of such needling technique., Methods: A total of 40 adult male SD rats were randomized into a blank control group, a model control group, a Zhulian needling technique group and a routine acupuncture group, 10 rats in each one. Except the blank control group, the sub-acute aging rat models were established by intraperitoneal injection with 10% D-galactose solution, 5 mL/kg in the rats of the other groups. In the Zhulian needling technique group and the routine acupuncture group, Zhulian needle insertion by slow twirling technique and the routine acupuncture technique were exerted at "Guanyuan" (CV 4) and "Zusanli" (ST 36) respectively. The needles were retained for 30 min, once a day, for 28 days totally. After intervention, the content of H 2 O 2 in kidney tissue was detected by colorimetry, the content of MDA in kidney tissue was detected by thiobarbituric acid method and the apoptosis rate of kidney cells was detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling., Results: Compared with the blank control group, the contents of H 2 O 2 and MDA in kidney tissue and kidney cell apoptosis rate were all increased in the model control group ( P <0.05). Compared with the model control group, the contents of H 2 O 2 and MDA in kidney tissue and kidney cell apoptosis rate were all reduced in the Zhulian needling technique group and the routine acupuncture group ( P <0.05), and these indexes in the Zhulian needling technique group were all lower than the routine acupuncture group ( P <0.05)., Conclusion: Zhulian needle insertion by slow twirling technique delays aging probably by regulating peroxidation and apoptosis.

Ethnopharmacological Relevance: Ranunculus japonicus Thunb. (short for R. japonicus) is a topically applied herb with the activities of removing jaundice, nebula and edema, preventing malaria, stopping asthma, promoting diuresis and relieving pain. It was firstly recorded in Zhouhou Beiji Fang and has been used for the treatment of malaria, ulcers, carbuncle, jaundice, migraine, stomachache, toothache and arthritis for over 1800 years., Aim of the Study: This study aimed to uncover the potentially effective components of R. japonicus and the pharmacological mechanisms against rheumatoid arthritis (RA) by combing LC-MS and network pharmacology., Materials and Methods: Firstly, the chemical constituents of R. japonicus were qualitatively identified by UPLC-ESI-LTQ-Orbitrap MS. Then we performed target prediction by PharmMapper, protein-protein interaction (PPI) analysis via String, GO and KEGG pathway enrichment analysis by DAVID and constructed the compound-target-pathway network using Cytoscape. Thirdly, crucial compounds in the network were quantitatively analyzed to achieve quality control of R. japonicus. Finally, the pharmacological activities of R. japonicus and two potentially bioactive ingredients were validated in RA-FLSs (Rheumatoid Arthritis Fibroblast-like Synoviocytes) in vitro., Results: Overall fifty-four ingredients of R. japonicus were identified and forty-five components were firstly discovered in R. japonicus. Among them, twenty-seven validated compounds were predicted to act on twenty-five RA-related targets and they might exhibit therapeutic effects against RA via positive regulation of cell migration, etc. Nine potentially bioactive components of R. japonicus which played important roles in the compound-target-pathway network were simultaneously quantified by an optimized UPLC-ESI-Triple Quad method. In vitro, compared to control group, R. japonicus extract, berberine and yangonin significantly inhibited the migration capacity of RA-FLSs after 24 h treatment., Conclusion: This study clarified that R. japonicus and the bioactive ingredients berberine and yangonin might exert therapeutic actions for RA via suppressing the aggressive phenotypes of RA-FLSs through combined LC-MS technology and network pharmacology tools for the first time. The present research provided deeper understanding into the chemical profiling, pharmacological activities and quality control of R. japonicus and offered reference for further scientific research and clinical use of R. japonicus in treating RA., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)