Objective To prepare a multifunctional mesoporous silica-based nanocarrier system(MMSN@Gem)with gemcitabine and investigate its effect on bladder cancer cells BIU-87.Methods The multifunctional meso-porous silica-based nano drug-carrying system was prepared by a modified method.Transmission electron microsco-py,high-performance liquid chromatography,and thermal imaging were used to characterize the morphology,drug-carrying and photothermal properties of MMSN@Gem.The effect of MMSN@Gem on BIU-87 bladder cancer cells was detected by in vitro experiments.Results MMSN@Gem exhibited a well-defined spherical morphology with an average particle size of(102.48±1.03)nm with a drug loading capacity of 25.04％±0.17％,and an average zeta potential of(-24.84±0.07)mV.The photothermal conversion efficiency was 40.7％which significantly enhanced the release of Gem under near-infrared irradiation.In vitro studies showed that MMSN@Gem significantly inhibited BIU-87 cell activity,induced apoptosis of BIU-87 cells,reduced migration and invasion ability,and enhanced its uptake by BIU-87 cells.Conclusions MMSN@Gem exhibits excellent photothermal properties,enhances cellular uptake efficiency,inhibits the proliferation and migration of BIU-87 cells,and promotes apoptosis,providing a promising drug delivery system for the clinical treatment of bladder cancer.

Sj?gren's syndrome(SS)is one of the common rheumatic diseases in clinical practice.Modern medicine commonly uses drugs such as artificial tears,saliva,glucocorticoids,immunosuppressants,and biologics to control the condition.Clinical practice has shown that in addition to modern medical basic treatment,the use of traditional Chinese medicine(TCM)can help improve the clinical efficacy of SS.According to the symptoms and signs of Sj?gren's syndrome in TCM,it is classified as"dryness and obstruction",and the core pathogenesis of the disease is spleen deficiency and deficiency of body fluids.Subsequently,toxic and pathogenic factors gather,leading to the decline of internal organs.The initial causes are spleen damage,unstable barrier,and invasion of pathogenic factors.The core link is spleen dysfunction,insufficient body fluid,and dryness arising from it.Spleen deficiency generates evil,obstruction of qi,and lack of body fluids are the root causes of illness.The main treatment method is the"spleen strengthening method",which treats spleen deficiency,dampness and stagnation,and the body fluid is not distributed.The treatment focuses on strengthening the spleen and qi,supplementing the lungs and generating fluids.Spleen deficiency leads to loss of vitality,blood stasis obstructs blood vessels,and the treatment is to strengthen the spleen,soothe the liver,remove blood stasis,and unblock the orifices.The spleen yang is not vigorous,and qi transformation is impaired.The treatment is to invigorate the spleen and warm the stomach,promote yang circulation,and promote diuresis.

Sj?gren's syndrome(SS)is one of the common rheumatic diseases in clinical practice.Modern medicine commonly uses drugs such as artificial tears,saliva,glucocorticoids,immunosuppressants,and biologics to control the condition.Clinical practice has shown that in addition to modern medical basic treatment,the use of traditional Chinese medicine(TCM)can help improve the clinical efficacy of SS.According to the symptoms and signs of Sj?gren's syndrome in TCM,it is classified as"dryness and obstruction",and the core pathogenesis of the disease is spleen deficiency and deficiency of body fluids.Subsequently,toxic and pathogenic factors gather,leading to the decline of internal organs.The initial causes are spleen damage,unstable barrier,and invasion of pathogenic factors.The core link is spleen dysfunction,insufficient body fluid,and dryness arising from it.Spleen deficiency generates evil,obstruction of qi,and lack of body fluids are the root causes of illness.The main treatment method is the"spleen strengthening method",which treats spleen deficiency,dampness and stagnation,and the body fluid is not distributed.The treatment focuses on strengthening the spleen and qi,supplementing the lungs and generating fluids.Spleen deficiency leads to loss of vitality,blood stasis obstructs blood vessels,and the treatment is to strengthen the spleen,soothe the liver,remove blood stasis,and unblock the orifices.The spleen yang is not vigorous,and qi transformation is impaired.The treatment is to invigorate the spleen and warm the stomach,promote yang circulation,and promote diuresis.

OBJECTIVE To compare the anti-oxidative effects of "three decoctions for COVID-19" (Qingfei Paidu decoction, Huashi Baidu decoction, Xuanfei Baidu decoction) in parallel experimental models. METHODS In the cell-free system, the total antioxidant capacity was investigated by FRAP method. The scavenging effects of DPPH radicals and superoxide anions were evaluated by DPPH and NBT reduction method, respectively. The scavenging effect of hydroxyl radicals was determined by a fluorescence method based on the end-product MDA. The anti-lipid peroxidation activity was investigated using the FeSO4-induced rat liver homogenate MDA method. Based on these five antioxidant indicators, the antioxidant capabilities of the extracts of three decoctions were parallelly compared in the cell-free system. Furthermore, in lipopolysaccharide-activated RAW264.7 cells, the productions of intracellular and mitochondrial reactive oxygen species(ROS) were detected using the L-012 probe and the MitoSOX mitochondrial superoxide red fluorescence probe, respectively; and intracellular NADPH oxidase activity was measured using the lucigenin probe. These three indicators were used to parallelly compare the antioxidant capabilities of the extracts of three decoctions. RESULTS In the cell-free system, three decoctions for COVID-19 could concentration-dependently scavenge DPPH radicals, superoxide anions and hydroxyl radicals, and potently inhibit the lipid peroxidation. At the equal extract concentration, their scavenging effects on DPPH radicals and superoxide anions and the total antioxidant capacity were comparable; while Huashi Baidu decoction exhibited the strongest ability to scavenge hydroxyl radicals and inhibit lipid peroxidation. In the cell system, three decoctions could reduce lipopolysaccharide-elevated intracellular ROS level by weakening NADPH oxidase activity; meanwhile, they could decrease mitochondrial ROS productions, among which Qingfei Paidu decoction possessed the most comprehensive effection. CONCLUSION Collectively, three decoctions for COVID-19 exert diverse antioxidant effects in both cell-free and cell systems, and each of them possesses the distinct advantages. Given that oxidative stress is pivotal during the pathological process of COVID-19, the results may suggest that the antioxidant ability of three decoctions is one of the pharmacodynamic basis for their clinical use.

Objective To explore the effect and possible pharmacological mechanism of Bufei Tongbi Decoction in the treatment of systemic lupus erythematosus interstitial lung disease (SLE-ILD).Methods The effective components and related targets of Bufei Tongbi Decoction were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Uniprot database. Key genes for SLE-ILD were screened based on DrugBank,DisGeNET,GeneCards,PharmGKB,OMIM,and GEO databases. Using Cytoscape software,a drug active ingredient-target-disease relationship network diagram was constructed to obtain the effective active ingredients and possible mechanisms of action of Bufei Tongbi Decoction in the treatment of SLE-ILD. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to reveal related target genes and pathway functions. Taking C57BL/6 mice as normal group,MRL/lpr mice were injected with bleomycin 5mg/kg in the nasal cavity. According to the random number table method,the mice were divided into model group,Bufei Tongbi Decoction low-dose group (10.4 g/(kg·d)),Bufei Tongbi Decoction medium-dose group (20.8 g/(kg·d)),Bufei Tongbi Decoction high-dose group (41.6 g/(kg·d)) and prednisone group (3 mg/(kg·d)). The intervention lasted for 28 days. Hematein eosin and Masson staining were used to observe the pathological changes of mouse lung tissue,the expressions of transforming growth factor-β1 (TGF-β1) and collagen type Ⅲ (Col-Ⅲ) in lung tissue were detected by immunohistochemistry,and the expressions of interleukin-1β(IL-1β),interleukin-10 (IL-10) and interleukin-17 (IL-17) in serum were detected by ELISA. The mRNA expressions of matrix metallopeptidase 1(MMP-1),hypoxia inducible factor-1α(HIF-1α),retinoid-related orphan receptor γt (RORγt ) and forkhead box P3 (FOXP3) in lung tissue were analyzed by RT-PCR,the protein expressions of HIF-1α and MMP-1 in lung tissue were detected by Western blotting,and the expressions of T helper 17 cells (Th17) and regulatory T cells (Treg cells) in blood were detected by cytometry.Results A total of 163 effective ingredients,259 targets,1729 SLE-ILD disease targets,958 SLE-ILD differential genes and 40 drug-disease interaction targets were obtained by screening. GO functional enrichment and KEGG pathway enrichment showed that IL-17 signaling pathway activated by IL-1β and MMP-1,and Th17 cell differentiation activated by IL-1β and HIF-1α were the main pathways. Animal experiments showed that Bufei Tongbi Decoction could effectively improve the degree of lung interstitial lesion and reduce the expressions of TGF-β1 and Col-Ⅲ in SLE-ILD mice (P<0.01). The expressions of IL-1β,HIF-1α and IL-17 were decreased (P<0.01). Medium and high doses of Bufei Tongbi Decoction decreased the expressions of MMP-1 and RORγt mRNA (P<0.01),and increased the expressions of IL-10 and FOXP3 mRNA (P<0.01). Bufei Tongbi Decoction could reduce the proportion of Th17 cells,increase the proportion of Treg cells,downregulate the balance of Th17/Treg (P<0.05),and improve the immune disorder. Conclusion Bufei Tongbi Decoction has the characteristics of multi-target and multi-pathway in treating SLE-ILD,and its mechanism may be related to the regulation of Th17/Treg cell balance.

[Objective]To analyze the value of grey-scale reversed T1-weighted(rT1)MRI in the detection of structur-al lesions of the sacroiliac joint(SIJ)in patients with axial spondyloarthritis(ax-SpA).[Methods]Fifty-two ax-SpA pa-tients who underwent both MRI and CT in our hospital within a week from February 2020 to December 2022 were retrospec-tively included.Both sacral and iliac side of each SIJ on oblique coronal images were divided into anterior,middle and pos-terior portion.Two radiologists reviewed independently three groups of MRI including T1-weighted imaging(T1WI),rT1 and T1WI+rT1 images to evaluate the structural lesions like erosions,sclerosis and joint space changes in each of the 6 re-gions of the SIJ.One of the radiologist did the evaluation again one month later.CT images were scored for lesions by a third radiologist and served as the reference standard.Intra-class correlation coefficients(ICC)were calculated to test the inter-and intra-reader agreement for the assessment of SIJ lesions.A Friedman test was performed to compare the lesion results of MRI and CT image findings.We examined the diagnostic performance[accuracy,sensitivity(SE)and specifici-ty]of different groups of MRI in the detection of lesions by using diagnostic test.A McNemar test was used to compare the differences of three groups of MRI findings.[Results]CT showed erosions in 71 joints,sclerosis in 65 and joint space changes in 53.Good inter-and intra-reader agreements were found in three groups of MRI images for the assessment of le-sions,with the best agreement in T1WI+rT1.There were no difference between T1WI+rT1 and CT for the assessment of all lesions,nor between rT1 and CT for the assessment of erosions and joint space changes(P>0.05).T1WI+rT1 yielded better accuracy and SE than T1WI in detection of all lesions(Accuracy erosions:90.3%vs 76.9%;SE erosions:91.6%vs 76.1%;Accu-racy sclerosis:89.4%vs 80.8%;SE sclerosis:84.6%vs 73.9%;Accuracy joint space changes:86.5%vs 73.1%;SE joint space changes:84.9%vs 60.4%;P<0.05).rT1 yielded better accuracy and SE than T1WI in detection of erosions and joint space changes(Accuracy erosions:87.5%vs 76.9%;SE erosions:88.7%vs 76.1%;Accuracy joint space changes:85.6%vs 73.1%;SE joint space changes:83.0%vs 60.4%;P<0.05).[Conclusions]In the detection of SIJ structural lesions in ax-SpA,rT1 improves the diagnostic perfor-mance and T1WI+rT1 is more superior to others.

Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria bai-calensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of bio-physical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

Objective:To provide references for finding an objective, accurate, highly repeatable and operable measurement method of the resting energy expenditure (REE) for flying personnel by taking the indirect calorimetry measured REE as the gold standard and establishing the formula for predicting REE combined with body composition indexes.Methods:Fourteen normal-size male volunteers were chosen as the subjects. The hypobaric hypoxia environment was constructed in the hypobaric chamber. The subjects were asked to complete single task (flight control) and dual task (flight control and calculation). The body weight, fat free mass (FFM), muscle mass (MM), fat mass (FM), waist-to-hip ratio (WHR), visceral fat mass (VFM) and body fat percentage (BF%) were directly measured by body composition analyzer. The respiratory frequency (RF), volume of CO 2 (VCO 2), maximal volume of O 2 (VO 2max), volume of tidal (VT), minute ventilation volume (VE), metablic equivalent (MET), REE and REE/kg/d were measured by gas metabolizer. The correlation between REE and body composition indexes was analyzed and a linear regression equation was obtained. Results:In the simulated hypobaric hypoxia environment, the RF, VCO 2, VO 2max, VE, VT, REE, REE/kg/d, MET and heart rate of the subjects increased slightly in the dual task, but there were no significant differences between the dual task and the single task (all P>0.05). REE was positively correlated with FFM and MM ( r=0.566, 0.570, P=0.035, 0.033), but not with height, FM and heart rate (all P>0.05). The prediction formula of REE in hypobaric hypoxia environment was Model A: REE=60.34×MM-1 121 ( r=0.570, P=0.033), or Model B: REE=55.34×FFM-1 073 ( r=0.566, P=0.035). There was a positive correlation between the predicted REE and the measured REE ( r=0.570, P=0.033) for Model A, and the error value was (0.032±358.170) kcal/d, P=1.00>0.05. Conclusions:FFM and MM are the main determinants of REE in normal-size subjects under hypobaric hypoxia environment. Either MM or FFM shows a good prediction effect to REE.

Objective:To provide references for finding an objective, accurate, highly repeatable and operable measurement method of the resting energy expenditure (REE) for flying personnel by taking the indirect calorimetry measured REE as the gold standard and establishing the formula for predicting REE combined with body composition indexes.Methods:Fourteen normal-size male volunteers were chosen as the subjects. The hypobaric hypoxia environment was constructed in the hypobaric chamber. The subjects were asked to complete single task (flight control) and dual task (flight control and calculation). The body weight, fat free mass (FFM), muscle mass (MM), fat mass (FM), waist-to-hip ratio (WHR), visceral fat mass (VFM) and body fat percentage (BF%) were directly measured by body composition analyzer. The respiratory frequency (RF), volume of CO 2 (VCO 2), maximal volume of O 2 (VO 2max), volume of tidal (VT), minute ventilation volume (VE), metablic equivalent (MET), REE and REE/kg/d were measured by gas metabolizer. The correlation between REE and body composition indexes was analyzed and a linear regression equation was obtained. Results:In the simulated hypobaric hypoxia environment, the RF, VCO 2, VO 2max, VE, VT, REE, REE/kg/d, MET and heart rate of the subjects increased slightly in the dual task, but there were no significant differences between the dual task and the single task (all P>0.05). REE was positively correlated with FFM and MM ( r=0.566, 0.570, P=0.035, 0.033), but not with height, FM and heart rate (all P>0.05). The prediction formula of REE in hypobaric hypoxia environment was Model A: REE=60.34×MM-1 121 ( r=0.570, P=0.033), or Model B: REE=55.34×FFM-1 073 ( r=0.566, P=0.035). There was a positive correlation between the predicted REE and the measured REE ( r=0.570, P=0.033) for Model A, and the error value was (0.032±358.170) kcal/d, P=1.00>0.05. Conclusions:FFM and MM are the main determinants of REE in normal-size subjects under hypobaric hypoxia environment. Either MM or FFM shows a good prediction effect to REE.

Objective Using network pharmacology to explore the mechanism of action of tripterygium wilfordii-white peony in the treatment of rheumatoid arthritis(RA)and validating it using an adjuvant arthritis rat model.Methods Obtain the effective ingredients of tripterygium wilfordii and white peony through TCMSP database and predict the action targets;Obtain the disease targets of RA using DisGeNET and GeneCards online database;Draw the network of"tripterygium wilfordii-white peony-active ingredient-RA"and screen the core effective components using the software Cytoscape 3.9.1;Construct the protein-protein interaction(PPI)network using String database and screen the core targets using the CytoNCA plug-in,using the Metascape database for gene enrichment analysis of common targets,and using Auto Dock Tools and Pymol software for molecular docking of core active ingredients and targets.Enzyme linked immunosorbent assay(ELISA)detection of serum tumor necrosis factor-α(TNF-α),interleukin(IL)-4,IL-6,and IL-17 levels in adjuvant arthritis rats,Western blot was used to detect the expression of phosphorylated phosphatidylinositol 3-hydroxy kinase(p-PI3K)and phosphorylated AKT protein(p-AKT),validate the results of network pharmacology analysis.Results There were a total of 61 effective ingredients in the treatment of RA with tripterygium wilfordii-white peony,with 116 targets and 191 signaling pathways involved.Animal experiments have shown that compared with the model group rats,the serum cytokine TNF-α,IL-6 and IL-17 of rats in tripterygium wilfordii-white peony group and tripterygium wilfordii extract group were significantly decreased(P<0.05),IL-4 significantly increased(P<0.05);The expression of p-PI3K and p-AKT in synovial tissue was significantly reduced(P<0.05);Compared with rats in tripterygium wilfordii extract group,the TNF-α,IL-6,IL-17,p-PI3K and p-AKT of rats in tripterygium wilfordii-white peony group were significantly reduced(P<0.05),while IL-4 was significantly increased(P<0.05).Conclusion Tripterygium wilfordii-white peony can inhibit the overexpression of phosphatidylinositol 3-hydroxy kinase(PI3K)/protein kinase B(AKT)signaling pathway,regulate cytokine release,exert anti-inflammatory effects,and ultimately treat RA through multiple active ingredients and targets.