OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Aim To investigate the impact of Cinobu-facini on the proliferation,invasion,and apoptosis of HepG2 cells and the underlying mechanism.Methods The proliferation of HepG2 cells was assessed using the CCK-8 method following treatment with Cinobufaci-ni.The invasion capability of HepG2 cells was evalua-ted through Transwell assay after exposure to Cinobufa-cini.The apoptosis rates of HepG2 cells post Cinobufa-cini intervention were measured using flow cytometry,and the expression levels of VEGF in the culture medi-um of HepG2 cells were determined using enzyme-linked immunoassay.Furthermore,qRT-PCR and Western blot analyses were conducted to assess the im-pact of Cinobufacini on mRNA and protein expression levels related to the CXCL5/FOXD1/VEGF pathway.The interaction between CXCL5 and FOXD1 was inves-tigated via co-immunoprecipitation.Results Cinobufa-cini treatment led to a gradual decrease in HepG2 cell viability in a dose-dependent manner compared to the control group(P＜0.05).Moreover,Cinobufacini sig-nificantly suppressed HepG2 cell invasion(P＜0.05)while enhancing cell apoptosis(P＜0.05).Notably,Cinobufacini exhibited inhibitory effects on the CX-CL5/FOXD1/VEGF pathway,as evidenced by re-duced expression of related mRNA and proteins(P＜0.05).FOXD1 was identified as the binding site of CXCL5.Overexpression of CXCL5 resulted in in-creased proliferation and VEGF secretion by HepG2 cells(P＜0.05),and increased expression of FOXD1 and VEGF(P＜0.05).However,Cinobufacini inter-vention effectively inhibited liver cancer cell prolifera-tion and invasion(P＜0.05),promoted apoptosis(P＜0.05),reduced VEGF secretion by HepG2 cells(P＜0.05),and downregulated the expression of CXCL5 and FOXD1 in HepG2 cells(P＜0.05);but com-pared with the unexpressed group of Cinobufacini,its ability to inhibit cell activity was weakened(P＜0.05),and its ability to inhibit the expression of CX-CL5,FOXD1,and VEGF was weakened(P＜0.05).Conclusion Cinobufacini may inhibit HepG2 cell pro-liferation and invasion and promote HepG2 cell apopto-sis by regulating the CXCL5/FOXD1/VEGF pathway.

Objective To observe the therapeutic effect and mechanism of Astragaloside Ⅳ liposomes for influenza A virus infection in mice.Methods Fifty BALB/c mice were randomly divided into normal group(10 mice)and modeling group(40 mice).The modeling group mice were injected with A/PR/8/34(H1N1)influenza virus liquid via nasal drip.The modeling mice were randomly divided into model group,Oseltamivir group,and Astragaloside Ⅳ Liposomes high-and low-dose groups,with 10 mice in each group.The drug was administered by gavage two hours after infection for five days continuously.The appearance of the mice was observed,the body mass,survival condition and lung index as well as viral load in lung were assessed,pathological feature of lung tissue was observed by hematoxylin-eosin(HE)staining method,and mRNA expression levels of monocyte chemoattractant protein 1(MCP-1),macrophage inflammatory protein 1β(MIP-1β),and interferon γ(IFN-γ),CXC chemokine ligand 1(CXCL-1),interleukin(IL)-6,and IL-1β in lung tissues were detected by quantitative polymerase chain reaction(qPCR)method.Enzyme-linked immunosorbent assay(ELISA)was performed to detect the contents of granulocyte-macrophage colony-stimulating factor(GM-CSF)and regulated on activation normal T-cell expressed and secreted(RANTES)in mouse lung tissue.Results Compared with the normal group,mice in the model group showed significant decrease of body mass,shortened survival time(P＜0.001),significantly increased lung index(P＜0.001),significantly increased viral load in lung(P＜0.001),and significantly increased mRNA expression levels of MIP-1β,IFN-γ,CXCL-1,IL-6,IL-1β and MCP-1 in lung tissue(P＜0.05 or P＜0.001),and the structure destruction of lung tissue could be seen in pathology.Compared with the model group,mice in the Astragaloside Ⅳ liposomes high-dose group showed that the decrease in body mass was slowed down,the survival time and survival rate were higher(P＜0.05),and the lung index was significantly decreased(P＜0.05),the viral load in lung was decreased(P＜0.001)and the mRNA expression levels of MIP-1β,IFN-γ,CXCL-1,IL-6,IL-1β and MCP-1 in lung tissue were decreased,and the alveolar structure was relatively intact,and a little connective tissue hyperplasia was seen.Conclusion Astragaloside Ⅳ liposomes can improve the survival time and reduce the viral load of lung tissue in mice with influenza A virus infection,and its mechanism may be related to the inhibition of the expression of inflammatory factors,thus playing an antiviral role.

Objective To prepare paclitaxel-natural borneol complex,and to explore the prescription and preparation process of paclitaxel-natural borneol complex drug-loaded submicroemulsion,and its in vitro anti-tumor effect.Methods The Paclitaxel-natural borneol complex was prepared by grinding method and identified by Fourier Transform infrared spectroscopy(FT-IR)and differential scanning calorimetry(DSC).The compound drug-loaded submicroemulsion was prepared using a two-step high-pressure emulsification method.The single-factor investigation and the orthogonal experimental design were applied to optimize the formulation and preparation process.MTT assay,cell cloning assay,and cell scratch assay were used to evaluate the effect of this preparation on HCT-116 cells.Results The infrared spectral absorption peaks of taxol-natural borneol complex at 3 312.76 cm-1 and 3 513.92 cm-1 disappeared,and DSC analysis showed that a new absorption peak of taxol-natural borneol complex appeared at 154.56 ℃,indicating that taxol be coupled with natural borneol to form a new complex.The optimal prescription was 0.44％active pharmaceutical ingredient[paclitaxel-natural borneol(1∶3)],10％medium chain triglyceride,3％emulsifier[egg yolk lecithin-Poloxam 188(1∶2)],2％glycerol,0.3％oleate.The optimal process was emulsification at 80 ℃,60 MPa high pressure homogenization 10 times.The half inhibitory concentration(IC50)was 0.75 μg·mL-1 by MTT asssy in cell.In the cell cloning assay,the scratch healing area of blank control group,paclitaxel raw material and paclitaxel/natural borneol submicroemulsion were(36.44±3.35)％,(13.59±9.28)％,(8.30±4.09)％,respectively.The results were statistically significant(P＜0.05).In the plate cloning experiment,the cell cloning rates of blank control group,paclitaxel bulk drug group and submicroemulsion group were(37.92±0.729)％,(9.16±1.335)％and(3.36±1.065)％,respectively,the differents were statistically significant(P＜0.05).Conclusion This submicroemulsion has reasonable prescription,feasible process and good stability.Cell experiments showed that the submicronemulision effectively inhibits the proliferation and migration of HCT-116 cells,suggesting its potential as a promising antitumor agent.

This article aimed to summarise the clinical experience of Professor XIONG Jibai in treating henoch-schonlein purpura （HSP） from the perspective of "simultaneous treatment of wind and blood". HSP was devided into acute phase and transitional phase in clinic. It was considered that the wind pathogen exists throughout the disease course， and the treatment is guided by the "four methods of treating blood" in TANG Rongchuan's Treatise on Blood Syndromes - Blood Vomiting （《血证论·吐血》）， which are stanching bleeding， expelling stasis， tranquilising blood， and tonifying blood. In the acute phase， wind-heat damaging collateral symdrome and blood-heat frenetic flow syndrome are common， which could be treated by the method of cooling blood to dispel wind， and eliminating stasis to stop bleeding， with self-prescribed modified Ziping Xiaofeng Powder （紫萍消风散）； in the transitional phase， syndrome of effulgent fire due to yin deficiency and syndrome of qi deficiency failing to control are common， which could be treated by the method of tranquilising blood and tonifying deficiency， with modified Zhibai Dihuang Decoction （知柏地黄汤） and Guipi Decoction （归脾汤）. At the same time， it is believed that wind-related medicinal has the function of eliminating stasis， stanching bleeding， and cooling blood， and the wind-related medicinal should be used throughout the treatment.

Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.

ObjectiveTo explore the possible mechanism of Bimin Formula （鼻敏方） in treating lung-spleen qi deficiency syndrome of allergic rhinitis （AR） with high mucin secretion. MethodsThirty-four SD rats were randomly divided into a blank group （8 rats）， a model group （8 rats）， a low-dose Bimin Formula group （8 rats）， and a high-dose Bimin Formula group （10 rats）. Except for the blank group， the other groups were subjected to AR lung-spleen qi deficiency rat models induced by smoking， gavage of Ginkgo biloba leaf extract， and ovalbumin. After modeling， rats in the low- and high-dose Bimin Formula groups were given Bimin Formula concentrate （concentration of 2.16 g/ml） by gavage at doses of 1.08 g/100 g and 2.16 g/100 g， respectively， while rats in the model group were given 0.5 ml/100 g of normal saline by gavage， once daily for 28 days； the blank group was not intervened. Behavioral assessments were performed after intervention. ELISA was used to detect the levels of peripheral blood total immunoglobulin E （IgE）. HE staining was used to observe the pathological changes of nasal mucosa epithelium in rats， while immunohistochemistry was used to detect the expression of transmembrane protein 16A （TMEM16A） and mucin 5AC （MUC5AC） protein in nasal mucosa. Western Blot was used to detect the expression of nuclear factor kappa B （NF-κB） protein， and RT-PCR was used to detect the expression of TMEM16A， MUC5AC， and NF-κB mRNA in nasal mucosa. ResultsHE staining showed that the nasal mucosa epithelial cell structure in the blank group was intact without shedding， swelling， or necrosis； the nasal mucosa epithelial tissue of rats in the model group was thickened and partially shed， with infiltration of eosinophils and lymphocytes visible； the pathological changes in nasal mucosa tissue of rats in the high- and low-dose Bimin Formulagroups were improved， and more improvement was showen in the high-dose group. Compared with those in the blank group， the behavioral scores and peripheral blood total IgE levels of rats in the model group significantly increased， as well as the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosa （P＜0.05 or P＜0.01）. Compared with those in the model group， the behavioral scores and peripheral blood total IgE levels of rats in the high-dose Bimin Formula group decreased， and the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosaalso decreased （P＜0.05 or P＜0.01）； the behavioral scores and peripheral blood total IgE levels of rats in the low-dose Bimin Formula group were reduced， and the expression of TMEM16A and MUC5AC proteins and mRNA in nasal mucosa， as well as the expression of NF-κB protein decreased （P＜0.05 or P＜0.01）， but the difference in NF-κB mRNA expression was not statistically significant （P＞0.05）. Compared with the low-dose Bimin Formula group， the expression of NF-κB protein in the high-dose group decreased （P＜0.01）. ConclusionBimin Formula may improve the symptoms and high mucus secretion of AR lung-spleen qi deficiency by regulating the TMEM16A/NF-κB/MUC5AC signaling pathway in nasalmucosa.

Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ² test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ²=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ²=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.
Male ; Female ; Humans ; Retrospective Studies ; Pancreatitis, Acute Necrotizing/complications* ; Acute Disease ; Intraabdominal Infections/complications* ; Necrosis/complications* ; Treatment Outcome

Humans ; Fibrosarcoma/surgery* ; Sarcoma ; Temporal Bone ; Soft Tissue Neoplasms/surgery*