OBJECTIVES: To compare the anti-inflammatory, antibacterial and analgesic effects of Yinqiao Powder (YQS) formulated granules and decoction. METHODS: We first evaluated the anti-inflammatory effects of the two dosage forms of YQS in a LPS-induced RAW 264.7 cell model using RT-qPCR and Western blotting. We further constructed zebrafish models of inflammation by copper sulfate exposure, caudal fin transection, or LPS and Poly (I:C) microinjection, and evaluated anti-inflammatory effects of YQS granules and decoction by examining neutrophil aggregation and HE staining findings. In a mouse model of acute lung injury (ALI) induced by intratracheal LPS instillation, the effects of YQS gavage at 10, 15, and 20 g/kg on lung pathologies were evaluated by calculating lung wet-dry weight ratio and using HE staining, ELISA and Western blotting. The microbroth dilution method was used to evaluate the antibacterial effect of YQS. Mouse pain models established by hot plate and intraperitoneal injection of glacial acetic acid were used to evaluate the analgesic effects of YQS at 10, 15, and 20 g/kg. RESULTS: Both YQS granules and decoction significantly reduced TNF-α, IL-6, and IL-1β expressions and p-STAT3 (Tyr 705) phosphorylation level in LPS-induced RAW 264.7 cells, and obviously inhibited neutrophil aggregation in the zebrafish models. In ALI mice, YQS granules and decoction effectively ameliorated lung injury, lowered lung wet-dry weight ratio, and reduced p-STAT3 (Tyr 705) expression and TNF-α and IL-6 levels. YQS produced obvious antibacterial effect at the doses of 15.63 and 31.25 mg/mL, and significantly reduced body torsion and increased pain threshold in the mouse pain models. CONCLUSIONS The two dosage forms of TQS have similar anti-inflammatory, antibacterial and analgesic effects with only differences in their inhibitory effect on TNF-α, IL-6 and IL-1β mRNA expressions in LPS-induced RAW 264.7 cells.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Anti-Inflammatory Agents/pharmacology* ; Analgesics/pharmacology* ; RAW 264.7 Cells ; Zebrafish ; Anti-Bacterial Agents/pharmacology* ; Powders ; Tumor Necrosis Factor-alpha/metabolism* ; Acute Lung Injury/drug therapy* ; Interleukin-6/metabolism* ; Lipopolysaccharides

Objective To compare the anti-inflammatory,antitumor and anti-bacterial effects of the single extract(in granules)and the prepared drug in pieces of Forsythia Suspense(Lianqiao,a traditional Chinese herbal medicine).Methods In zebrafish embryo models of CuSO4 exposure,tail transection and LPS microinjection-induced inflammation,the anti-inflammatory effects of 10 μg/mL DEX,single extract of Forsythia Suspense,and the water extract of the prepared drug(400,600,and 800 μg/mL)were evaluated by observing neutrophil counts,RT-qPCR,HE staining and survival analysis.Zebrafish embryo models bearing different human tumor cell xenografts were used to assess the anti-tumor effect of the drugs in different dosage forms by fluorescence staining and HE staining.The microbroth dilution method was used to evaluate the antibacterial efficacy of the drugs.Results In the zebrafish embryo models of inflammation,both of the two dosage forms of Forsythia Suspense significantly inhibited neutrophil aggregation,reduced the mRNA expressions of TNF-α,IL-6,P38,Jnk,Erk and P65,and increased the survival rate of zebrafish.They both showed obvious inhibitory effects against xenografts of different human cancer cells including colon cancer cells(HCT116),pancreas adenocarcinoma cells(PANC-1),lung cancer cells(A549),liver cancer cells(Hep3B)and cervical carcinoma cells(Hela)in zebrafish embryos,and exhibited strong anti-bacterial effects at the concentration of 15.63 mg/mL.Conclusion The two dosage forms of Forsythia Suspense have similar anti-inflammatory,antitumor and antibacterial effects,but their effects for inhibiting IL-6,P65,and Jnk mRNA expressions and HCT116 cell proliferation differ significantly at low doses in zebrafish.

Objective:To invastigate the targets and signaling pathways of Gubiao Fanggan Modified Formula in regulating the defense against influenza A virus in immunosuppressed mice by network pharmacology,and the key targets were verified by immuno-suppressive mice model.Methods:TCMSP database was used to search the active ingredients of Gubiao Fanggan Modified Formula,and GeneCard,OMIM,PharmGkb databases were used to obtain the potential targets of the active ingredients to prevent influenza,and take their intersection targets were taken;STRING11.5 database was used to make protein-protein interaction network analyzed and finded the core targets;Cytoscape3.8.1 was used to build a traditional Chinese medicine-ingredient-disease target network,and GO enrichment analysis and KEGG enrichment analysis were performed.Intraperitoneal injection of cyclophosphamide was used to construct a mouse model of immune function suppression,normal group,model control group,Gubiao Fanggan Modified Formula group and oseltamivir group were set up,followed by prophylactic administration,and influenza virus intervention was performed on the fourth day.After 7 days of intragastric administration,the key targets were verified by mouse spleen index,HE staining,RT-qPCR and immunohistochemistry.Results:There were 82 active ingredients in five traditional Chinese medicines in Gubiao Fanggan Modi-fied Formula,and 72 common targets of drugs and diseases such as IL-6,TNF-α,IL-2,etc,mainly involving IL-17,TNF and AGE-RAGE signaling pathway.Gubiao Fanggan Modified Formula could increase spleen index and significantly reduce mRNA and protein expressions of IL-6 and TNF-α in spleen tissue of mice(P<0.05 or P<0.01).Conclusion:Gubiao Fanggan Modified Formula may regulate body's immune function through targets such as IL-6 and TNF-α,thereby preventing influenza virus infection.

Objective To compare the anti-inflammatory,antitumor and anti-bacterial effects of the single extract(in granules)and the prepared drug in pieces of Forsythia Suspense(Lianqiao,a traditional Chinese herbal medicine).Methods In zebrafish embryo models of CuSO4 exposure,tail transection and LPS microinjection-induced inflammation,the anti-inflammatory effects of 10 μg/mL DEX,single extract of Forsythia Suspense,and the water extract of the prepared drug(400,600,and 800 μg/mL)were evaluated by observing neutrophil counts,RT-qPCR,HE staining and survival analysis.Zebrafish embryo models bearing different human tumor cell xenografts were used to assess the anti-tumor effect of the drugs in different dosage forms by fluorescence staining and HE staining.The microbroth dilution method was used to evaluate the antibacterial efficacy of the drugs.Results In the zebrafish embryo models of inflammation,both of the two dosage forms of Forsythia Suspense significantly inhibited neutrophil aggregation,reduced the mRNA expressions of TNF-α,IL-6,P38,Jnk,Erk and P65,and increased the survival rate of zebrafish.They both showed obvious inhibitory effects against xenografts of different human cancer cells including colon cancer cells(HCT116),pancreas adenocarcinoma cells(PANC-1),lung cancer cells(A549),liver cancer cells(Hep3B)and cervical carcinoma cells(Hela)in zebrafish embryos,and exhibited strong anti-bacterial effects at the concentration of 15.63 mg/mL.Conclusion The two dosage forms of Forsythia Suspense have similar anti-inflammatory,antitumor and antibacterial effects,but their effects for inhibiting IL-6,P65,and Jnk mRNA expressions and HCT116 cell proliferation differ significantly at low doses in zebrafish.

Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide. Influenza A virus (IAV) has been found to activate multiple programmed cell death pathways, including ferroptosis. Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. However, little is known about how influenza viruses induce ferroptosis in the host cells. In this study, based on network pharmacology, we predicted the mechanism of action of Maxing Shigan decoction (MXSGD) in IAV-induced ferroptosis, and found that this process was related to biological processes, cellular components, molecular function and multiple signaling pathways, where the hypoxia inducible factor-1(HIF-1) signaling pathway plays a significant role. Subsequently, we constructed the mouse lung epithelial (MLE-12) cell model by IAV-infected in vitro cell experiments, and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage, increased reactive oxygen species (ROS) release, increased total iron and iron ion contents, decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4 (GPX4), increased expression of acyl-CoA synthetase long chain family member 4 (ACSL4), and enhanced activation of hypoxia inducible factor-1α (HIF-1α), induced nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in the HIF-1 signaling pathway. Treatment with MXSGD effectively reduced intracellular viral load, while reducing ROS, total iron and ferrous ion contents, repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway. Finally, based on animal experiments, it was found that MXSGD effectively alleviated pulmonary congestion, edema and inflammation in IAV-infected mice, and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.
Animals ; Mice ; Ferroptosis ; Network Pharmacology ; Reactive Oxygen Species ; Vascular Endothelial Growth Factor A ; Influenza A virus ; Iron ; Hypoxia

ObjectiveTo evaluate the effectiveness and consistency of three commonly used early colorectal cancer screening models for advanced colorectal adenoma as a noninvasive means， and to assess the predictive value of traditional Chinese medicine （TCM） tongue images in the models. MethodsPatients diagnosed with colorectal adenoma who underwent colonoscopy and pathological examination were selected as the study participants. Basic clinical data and tongue image were collected. The prediction models of Asia-Pacific colorectal screening （APCS） model， its revision （M-APCS） and colorectal neoplasia predict （CNP） model were applied to compare the predictive effects of the three models on advanced stage adenomas of the colon， the differences in clinical data and traditional Chinese medicine tongue characteristics among patients with different degrees of adenomas， and the similarities and differences in tongue characteristics among the models. The discriminative ability of the three risk models was evaluated using the area under the curve （AUC） and receiver operating characteristic （ROC） curves. The calibration was assessed using the Kuder-Richardson coefficient and the Hosmer-Lemeshow test for consistency analysis. ResultsA total of 227 patients with adenoma were analyzed， including 104 patients （45.82%） with advanced adenoma. In the detection of advanced adenoma， those with greasy coating （70 cases， 67.3%） were higher than those without greasy coating （34 cases， 32.7%， P＜0.05）. After multivariate analysis， the odds ratio （OR） value of non-greasy coating was 0.371 （0.204~0.673， P＜0.01）， indicating that non-greasy coating was a protective factor for advanced adenomas. Among the three risk models， the detection rate of advanced adenoma in the high-risk group with APCS was the highest （63.3%）， which was 1.49 times and 2.04 times that of the medium-risk group （42.6%） and the low-risk group （31.1%， P＜0.01）. The detection rate of advanced adenomas in high-risk groups of M-APCS and CNP was slightly higher than that in moderate or low risk groups （P＞0.05）. The proportion of yellow and greasy coating in high-risk group was higher than that in the medium-risk or low-risk group （P＜0.05）. For the ability to distinguish advanced and non-advanced adenomas， the AUC of APCS was 0.629 （95% CI： 0.556~0.702） and was higher than that of M-APCS （0.591） and CNP （0.586）. In calibration evaluation， Cronbach's alpha was 0.919 （＞0.7）， which indicated that the three models were consistent. In the correlation matrix， the correlation coefficients between APCS model and M-APCS model， and CNP model were 0.794 and 0.717， respectively， and the correlation coefficients between M-APCS model and CNP model were 0.873， Hosmer-Lemeshow χ² =2.552， P＞0.05， which suggested that the three models had good calibration ability. ConclusionAll three models demonstrate the efficiency to identify advanced colorectal adenoma， and their calibration ability is considered to be good. Among the three models， the APCS exhibits the highest recognition efficiency， however， the recognition accuracy of the APCS model needs improvement. The presence of a greasy coating is identified as one of the potential predictors of advanced adenoma. Consequently， it can be considered for inclusion in the risk model of advanced colorectal adenoma to enhance the accuracy.

Objective:To determine the effects of menopausal stage, age and other associated risk factors on symptoms of anxiety and depression among women in a community in Beijing.Methods:This study was a community-based prospective cohort. Participants who had transitioned through natural menopause, completed two or more depressive and anxiety symptoms evaluations, aged 35 to 64 years, and did not use hormone therapy were selected from the Peking Union Medical College Hospital aging longitudinal cohort of women in midlife to this analysis. The primary outcome variables were depressive and anxiety symptoms, assessed by hospital anxiety and depression scale (HADS). The generalized estimation equation was used in the statistical analysis.Results:Followed up from 2006 to 2014, 430 women and 2 533 HADS assessments were retained in the cohort. Depressive symptoms were more common than anxiety symptoms during all menopausal stages. The incidences of depressive and anxiety symptoms were 14.5% (19/191) and 3.1% (4/191) in the premenopausal -3 stage, respectively. The incidence increased in both menopausal transition and postmenopausal stage, with the highest incidence in the +1c stage [20.6% (155/751) and 8.8% (66/751), respectively]. However, these differences were not statistically significant (all P>0.05). Depressive symptoms were highest in the ≥60-<65 age group [20.8% (74/355)], and anxiety symptoms were highest in the ≥50-<55 age group [8.2% (62/754)]; but there were no statistical significances between different age groups and depressive and anxiety symptoms (all P>0.05). Multivariable analysis showed that high body mass index, low education status, and poor health status were independently associated with depressive symptoms (all P<0.05), and that poor health status, trouble falling asleep, and early awakening were independently associated with anxiety symptoms (all P<0.01). Conclusions:Depressive and anxiety symptoms are more common during menopausal transition and postmenopausal stage compared with reproductive stage. Depressive symptoms are more common than anxiety symptoms. To screen and assess depressive and anxiety symptoms in perimenopausal women is essential, especially for women with high risk factors.

Objective:To observe the interobserver agreement of classification of macular degeneration in severe pathological myopia (PM) by ophthalmologists with different clinical experience.Methods:A retrospective study. From January 2019 to December 2021, 171 eyes of 102 patients with severe PM macular degeneration who were examined at Eye Center of Beijing Tongren Hospital of Capital Medical University were included in the study. The clinical data such as age, gender, axial length, spherical equivalent power, fundus color photography, and optical coherence tomography (OCT) were collected in detail. Six independent ophthalmologists (A, B, C, D, E, F) classified each fundus photography based on META-PM and ATN classification of atrophy (A) system and interobserver agreement was assessed by Kappa statistics. According to the classification standard of traction (T) in the ATN classification, the OCT images were interpreted and classified, in which T0 was subdivided into retinal pigment epithelium (RPE) and choroidal thinning, choroidal neovascularization (CNV) with partial RPE and choroidal atrophy, RPE, and choroidal atrophy. Lamellar macular hole can't be classified by ATN system, which was defined as TX. Kappa ( κ) test was used to analyze the consistency of classification results between physicians A, B, C, D, E and F. κ value ≤0.4 indicates low consistency, 0.4 < κ value ≤ 0.6 indicates moderate consistency, and κ value >0.6 indicates strong consistency. Results:Among the 171 eyes of 102 cases, there were 20 males with 37 eyes (19.6%, 20/102), and 82 females with 134 eyes (80.4%, 82/102); age was 61.97±8.78 years; axial length was (30.87±1.93) mm; equivalent spherical power was (-16.56±7.00) D. Atrophy (A) classification results in META-PM classification and ATN classification, the consistency of physician A, B, C, D, E and physician F were 73.01%, 77.19%, 81.28%, 81.28%, 88.89%; κ value were 0.472, 0.538, 0.608, 0.610, 0.753, respectively. In the ATN classification, the T0, T1, T2, T3, T4, and T5 were in 109, 18, 11, 12, 9, and 8 eyes, respectively; TX was in 4 eyes.Conclusions:There are differences in the consistency of classification of severe PM macular lesions among physicians with different clinical experience, and the consistency will gradually improve with the accumulation of clinical experience.

Objective:To evaluate the value of synthetic MRI combined with DWI in the diagnosis of benign and malignant breast lesions.Methods:The data of 184 consecutive patients with suspected breast lesions in Yunnan Cancer Hospital from July to September 2019 were prospectively analyzed. All patients were randomly assigned to training group ( n=110) and validation group ( n=74), and underwent conventional MRI and synthetic MRI respectively before and after contrast injection. At the maximum slice of the lesion, the ROI was drawn along the edge and recorded as "tumor". In the solid area with the most obvious tumor enhancement, the second ROI was drawn and recorded as "local". At the same time, ADC values (ADC local and ADC tumor) and relaxation time values (T local and T tumor) were measured. T and T + represented the relaxation time value of the ROI pre-and post-contrast scanning. ΔT% represented the relative change rate in T value between pre-and post-contrast scanning.The rank sum test was used to test the quantitative parameters of benign and malignant breast lesions in the training group and the validation group, and the variables with P<0.05 were included in the binary logistic regression analysis to screen the independent variables and establish the prediction model. The area under ROC curve was used to evaluate the discrimination of parameters and models. The clinical applicability of model was analyzed by decision curve analysis (DCA). Results:In the training group, univariate analysis showed that there were significant differences in T 1tumor, T 1+tumor, ΔT 1% tumor, T 2local, T 2+local, T 2tumor and T 2+tumor, ADC local, ADC tumor between benign and malignant breast lesions ( P<0.05). Multivariate logistic regression analysis showed that T 1+tumor, ΔT 1% tumor, T 2tumor, ADC local, ADC tumor were independent variables in the diagnosis of breast cancer. The relaxation time model (model A: T 1+tumor, ΔT 1% tumor, T 2tumor) and ADC model (model B: ADC local, ADC tumor) established by combining the above variables had the same diagnostic efficiency (AUC=0.905, 0.914, Z=-1.874, P=0.062), and the multi-parameter combination model (model C: T 1+tumor, ΔT 1% tumor, T 2tumor, ADC local, ADC tumor) had the highest diagnostic efficiency (AUC=0.965). DCA analysis showed that when the threshold probability ranges between 21%-99% (training cohort) and 15%-99% (validation cohort), the net benefit of model C was better than model A and B. Conclusion:The multi-parameter combined prediction model established based on the relaxation time value and ADC can identify breast cancer efficiently and can be used as an auxiliary diagnostic tool.

Chloroquine and hydroxychloroquine were primarily used to treat malaria. With continuous research on their mechanism of action, their application range has gradually expanded to treat serious infectious diseases, rheumatic immune diseases, tumors, etc. Chloroquine and hydroxychloroquine are the two most attractive drugs developed in the past 50 years, and their efficacy in the treatment of various non-malaria diseases has been increasingly recognized by researchers. The results of in-depth research show that chloroquine and hydroxychloroquine have antiviral effects against coronavirus, influenza virus and Ebola virus, have significant clinical efficacy in the treatment of rheumatoid diseases such as systemic lupus erythematosus and rheumatoid arthritis, and can enhance the drug sensitivity of tumor cells by combining with classic anticancer drugs. The main adverse reaction of hydroxychloroquine is eye damage, especially retinopathy. Therefore, patients treated with this drug should undergo regular eye examinations. In this review paper, the chemical structure, pharmacokinetics, application status and pharmaceutical care of chloroquine and hydroxychloroquine were summarized. This paper looks forward to providing help for the rational use of these two drugs in the future.