AIM To evaluate the quality of Changmaile Capsules(Ⅰ).METHODS The analysis was performed on a 35℃ thermostatic Thermo Scientific AccucoreTM XL C18 column(4.6 mm×250 mm,4 μm),with the mobile phase comprising of methanol-acetonitrile-0.5% phosphoric acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelengths were set at 230,280 nm.The contents of gastrodin,danshensu,quercetin-3-O-β-D-glucose-7-O-β-D-gentiobioside,3′-hydroxypuerarin,puerarin,3′-methoxypuerarin,puerarin apioside,daidzin,rosmarinic acid,lithospermic acid,ononin,daidzein,salvianolic acid B,calycosin,paeoniflorin and isoquercitrin were determined,after which HPLC fingerprints were established,along with the calculation of similarities.RESULTS Sixteen constituents showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 87.4%-103.9% with the RSDs of 0.54%-3.10% .At 230 nm,the fingerprints of ten batches of samples demonstrated similarities of 0.954-0.999,which displayed obvious differences at 280 nm.3′-Hydroxypuerarin,puerarin,3′-methoxypuerarin,puerarin apioside,daidzin and daidzein were main differential constituents,paeoniflorin and isoquercitrin exhibited stable contents in various batches of samples.CONCLUSION This simple,accurate and reliable method can be used for the quality control of Changmaile Capsules(Ⅰ).

Objective To investigate the effect of silencing E6-associated protein(E6AP)on the level of p53 protein in human papilloma virus(HPV)negative cervical cancer cells(C33A cells).Methods The siRNA sequence silencing E6AP(siE6AP)and silencing control disordered siRNA sequence(siControl)were transfected into C33A cells with the mediation of LipofectamineTM2000 transfection reagent respectively.The silencing effect of siRNA on E6AP and the expression of p53and cleaved-caspase-3 proteins were detected by Western blot.Results The levels of E6AP protein in C33A cells of siE6AP group were significantly lower(t =-4.597,P<0.05),while the levels of p53 and cleaved-caspase-3 proteins were significantly higher than those of siControl group(t = 4.533 and 7.099 respectively,each P<0.05).Conclusion Silencing of E6AP significantly increased the expression of p53 protein in C33A cells,indicating that silencing of E6AP may restore the activity and function of p53 protein in C33A cells.

To investigate the crucial role of particle size in the biological effects of nanoparticles, a series of mesoporous silica nanoparticles (MSNs) were prepared with particle size gradients (50, 100, 150, 200 nm) with the traditional Stober method and adjusting the type and ratio of the silica source. The correlation between toxicity and size-caused biological effects were then further examined both in vitro and in vivo. The results indicated that the prepared MSNs had a uniform size, good dispersal, and ordered mesoporous structure. Hemolytic toxicity was found to be independent of particle size. At the cellular level, MSNs with smaller particle sizes were more readily internalized by cells, which initiated to more intense oxidative stress, therefor inducing higher cytotoxicity, and apoptosis rate. In vivo studies demonstrated that MSNs primarily accumulated in the liver and kidneys of mice. Pharmacokinetic analysis revealed that larger MSNs were eliminated more efficiently by the urinary system than smaller MSNs. The mice's body weight monitoring, blood tests, and pathological sections of major organs indicated good biocompatibility for MSNs of different sizes. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Zhejiang Chinese Medical University. Overall, this study prepared MSNs with a particle size gradient to investigate the correlation between toxicity and particle size using macrophages and endothelial cells. The study also examined the biosafety of MSNs with different particle sizes in vivo and in vitro, which could help to improve the safety design strategy of MSNs for drug delivery systems.

Objective: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE)-hepatic arterial infusion chemotherapy (HAIC)-targeted-immune quadruple therapy in patients with intermediate and advanced-stage hepatocellular carcinoma (HCC). Methods: 101 patients with intermediate and advanced stage HCC were enrolled according to the inclusion and exclusion criteria, and then they were divided into a combination group and a control group. Patients in the combination group was treated with TACE-HAIC-targeted-immune quadruple therapy, while the control group was only treated with TACE therapy. The overall survival (OS), progression-free survival (PFS), and treatment-related adverse reactions were statistically analyzed in the two groups of patients. Statistical analysis was carried out by t-test, χ² test, rank sum test, Kaplan-Meier curve, log-rank test, Cox regression (or proportional hazards model) analysis according to different data. Results: The tumor objective response rate and disease control rate as evaluated by mRECIST 1.1 criteria in the combination group were 80% and 94%, respectively, which were significantly higher than those in the control group, 41.2% (P<0.001) and 74.5% (P=0.007). The OS and PFS of the combination group were 15.6 months [95%CI 11.3-NA ] and 8.8 months [95%CI 6.9-12.0], respectively, which were significantly better than the control group at 6.1 months [95%CI 5.3-6.6] (P<0.001) and 3.2 months [95%CI 3.0-3.6] (P<0.001). Gastric ulcer incidence was significantly higher in the combination group (9/50, 18%) than that in the control group (2/51, 3.9%) (P=0.023). Conclusion TACE-HAIC-targeted-immune quadruple therapy is a more effective treatment mode for intermediate and advanced-stage HCC than TACE alone, and attention should be paid to the monitoring of target immune-related adverse reactions.
Humans ; Carcinoma, Hepatocellular/pathology* ; Chemoembolization, Therapeutic ; Liver Neoplasms/pathology* ; Retrospective Studies ; Infusions, Intra-Arterial ; Treatment Outcome

Objective To investigate the effects of CTNND2 knockout on cerebellar neuronal development and motor function in mice, as well as its possible mechanisms. Methods The mice were divided into two groups (n = 10 in each group), all of them were 7 weeks old : wild-type (WT) C57BL/6J mice were treated as control group, and homozygous of CTNND2 knockout (CTNND2 7) mice were treated as experimental group, the genotype of CTNND2 7 mice were detected with PCR. The motor function of two groups were detected by beam walking test, hanging wire test and gait analysis test. The changes of cerebellar Purkinje cells were detected by immunofluorescence staining and Golgi staining. Western blotting was performed to detect the expression levels of synapse-associated proteins phosphorylated synapsin 1 (p-Synl), synapsin 1 (Synl), ELKS and postsynaptic density protein 95(PSD95), as well as phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), protein kinase B (Akt), phosphorylated mammalian target of rapamycin (p-mTOR) and mammalian target of rapamycin (mTOR). Results Compared with the WT mice, except the increase in time to traverse the beam, there was a decrease in the proportion of pass on the beam, or latency to fall from the hanging wire, or score of hanging wire, or fore-stride length and hind-stride length of CTNND2 7 mice. There was also a decrease in numbers of Purkinje cells and its dendritic arborization in cerebellum of CTNND2 7 mice. The ratio of p-Synl/ Synl, p-Akt/Akt and p-mTOR/mTOR, as well as the expression levels of ELKS, PSD95 and PI3K were lower than those of WT mice. Conclusion CTNND2 knockout can affect the number and dendritic architecture of Purkinje cells, as well as synthesis of synapse-associated proteins in cerebellum by down-regulating PI3K/Akt/mT0R signaling pathway, resulting in cerebellar developmental disorder, thereby affecting motor function of mice.

It is reported that a patient who committed suicide by oral hydrochloric acid was misdiagnosed as "dichlorvos poisoning". The original pesticide bottle was tested to be strong acid, and the nursing process was finally successful. The focus of care includes: Do a good job of emergency care for tracheal intubation and digestive tract, oral care for infection prevention and nutritional support in the advanced stage of the disease, prevention of venous thrombosis in the lower limbs, psychological care during the rehabilitation period, and continued care after discharge.

It is reported that a patient who committed suicide by oral hydrochloric acid was misdiagnosed as "dichlorvos poisoning". The original pesticide bottle was tested to be strong acid, and the nursing process was finally successful. The focus of care includes: Do a good job of emergency care for tracheal intubation and digestive tract, oral care for infection prevention and nutritional support in the advanced stage of the disease, prevention of venous thrombosis in the lower limbs, psychological care during the rehabilitation period, and continued care after discharge.

Setariae Fructus Germinatus (Guya) is a commonly used traditional Chinese medicine, which has been used for thousands of years. In ancient and modern books and works, the name is often confused because of its complicated relationship with the origin. In order to clarify the name and source of Guya, the authors examined the name, origin and processing history of Guya through consulting ancient Chinese herbal books, modern Chinese medicine monographs, calendar edition of Chinese Pharmacopoeia and the processing standards of various provinces, and found that different regions in China used Guya according to their local habits, resulting in the foreign body of the same name of Guya, lacking a unified standard. It is suggested that changing the name of Guya to Suya is more practical, and is conducive to the quality standard research and clinical accurate application of Guya.

Objective: To observe the effect of modified Erchentang on the expression of interleukin-19 (IL-19), interleukin-20 (IL-20)and their receptor IL-20R₁, IL-20R₂ in bronchioles of rats with chronic obstructive pulmonary disease (COPD), and to explore the molecular mechanism of modified Erchentang on anti-inflammatory of COPD. Method: The model of rat with COPD was established by cigarette smoke combined with lipopolysaccharide (LPS). The experimental rats were randomly divided into 6 groups:normal group, model group, modified Erchentang high, medium and low dose group, and Jizhitangjiang group. Normal group and model group fed with normal saline 4 mL · d^-1, modified Erchentang high, middle, low dosage group(20,10,5 g · kg^-1 · d^-1).The dosage of Jizhitangjiang group was 12 g · kg^-1 · d^-1, all groups were given intragastric administration for 14 days, twice a day. To observe the general situation of rats.To evaluate the pulmonary function of rats. To detect the contents of IL-10, IL-19 and IL-20 in serum by enzyme-linked immunosorbent assay (ELISA).To observe the pathological changes of bronchiole tissue by light microscopy.To detect the expression of IL-20R₁ and IL-20R₂ in bronchiole tissue by immunohistochemistry. Result: Compared with normal group, peak expiratory flow(PEF), forced expiratory volume in one second(FEV₁), forced vital capacity (FVC), and FEV₁/FVC in model group were significantly increased (P<0.05), the content of IL-19, IL-20 in serum significantly increased(P<0.05), the content of IL-10 in serum was significantly decreased (P<0.05), the expression of IL-20R₁ and in bronchioles tissue significantly increased (P<0.05). Compared with model group, the PEF, FEV₁, FVC, FEV₁/FVC of Jizhitangjiang group, modified Erchentang high, medium and low dosage group were significantly increased(P<0.05).The content of IL-19, IL-20 in serum significantly decreased(P<0.05), the content of IL-10 in serum was significantly increased (P<0.05), the expression of IL-20R₁ and IL-20R₂ in bronchioles tissue was significantly decreased (P<0.05). Conclusion: Modified Erchentang can improve the lung function and protect the tissue structure of bronchioles in COPD rats, which may be related to the inhibition of the expression of IL-19, IL-20 and their receptor IL-20R₁, IL-20R₂ in bronchioles of rats with modified Erchentang.