ObjectiveTo improve the accuracy of discrete element method in simulating the processing of traditional Chinese medicine（TCM） powder system under low shear conditions. MethodsIn this study， extract powders of Tongsaimai tablets and Qige granules were used as the research objects， the angle of repose（AOR） and effective angle of internal friction of the two materials were determined by AOR test method and shear cell test method. Based on the Hertz-Mindlin with JKR V2 contact model and particle scaling theory， taking the particle-particle restitution coefficient（A）， particle-particle static friction coefficient（B）， particle-particle rolling friction coefficient（C）， particle-steel restitution coefficient（D）， particle-steel static friction coefficient（E）， particle-steel rolling friction coefficient（F） and Johnson-Kendall-Roberts（JKR） surface energy（G） as test factors， the simulated contact parameters of Tongsaimai tablets extract powder were first calibrated with a single reference value using AOR as the reference value， and then the simulated contact parameters of Tongsaimai tablets extract powder as well as Qige granules extract powder were co-calibrated with AOR and effective angle of internal friction as the joint reference value， respectively. Then， Plackett-Burman design was used to screen the critical contact parameters that have a significant effect on the simulated reference value， and the steepest ascent design was used to determine the optimal range of the critical contact parameters， finally， the regression model between the critical contact parameters and the simulated reference values was established through the design of the response surface test， and the critical contact parameters were calibrated based on the regression model and the desirability function approach. ResultsThe optimal combination of discrete elemental contact parameters A-G for Tongsaimai tablets extract powder under a single reference value was 0.100， 0.718， 0.616， 0.100， 0.400， 0.250 and 0.075 J·m^-2， which was validated to have relative errors of 0.10% and -8.64% for the simulated AOR and the simulated effective angle of internal friction， respectively. And the optimal combination of discrete elemental contact parameters A-G for Tongsaimai tablets extract powder at the joint reference values was 0.100， 0.682， 0.598， 0.100， 0.521， 0.294 and 0.075 J·m^-2， which was verified to have relative errors of 0.10% and -0.18% for the simulated AOR and the simulated effective angle of internal friction， respectively. The optimal combination of discrete elemental contact parameters A-G for Qige granules extract powder at the joint reference values was 0.150， 0.370， 0.330， 0.150， 0.500， 0.500 and 0.100 J·m^-2， which was verified to have relative errors of 2.70% and -1.30% for the simulated AOR and the simulated effective angle of internal friction， respectively. Compared with the single reference value method， the joint calibration method not only increased the number of the critical contact parameters for characterizing particle-device interactions， but also was more accurate and reliable. ConclusionCompared with the results of single reference value calibration， the results obtained by the method of joint calibration of discrete element simulation contact parameters with AOR and effective angle of internal friction as the reference values are more accurate， which can provide more accurate and reliable simulation physical property data for the simulation experiments of TCM extract powder under low shear process conditions.

Objective:To evaluate the effect of nursing specialist nurses′ assistance on the ability of nursing home nurses to maintain venous catheter under the vision of combination of medical care and nursing care, providing reference for carrying out specialized nursing assistance work in grassroots hospitals.Methods:This study was an experimental study. According to Miller′s pyramid theory, a model of specialist nurse assistance was established with specialized technology as the core. From January to December 2021, three nursing hospitals in Suzhou were assisted. Convenience sampling method was used to investigate the ability of intravenous catheter maintenance, the incidence of central venous catheter maintenance defects, the incidence of central venous catheter complications and unplanned extubation, and the satisfaction of doctors and patients before and after help.Results:Totally 86 nurses were included, aged (33.17 ± 2.31) years old. After the help, the theoretical and operational skill scores of nurses in the nursing home were (89.77 ± 2.11) and (92.75 ± 1.62) points, respectively, which were significantly higher than those before the help (60.84 ± 2.71) and (79.81 ± 1.68) points, and the differences were statistically significant ( t=-84.96, -52.12, both P<0.05). Among the maintenance defects of central venous catheter in nursing homes, incomplete labeling, film wrapping, blood seepage, catheter discounting, non-standard film fixing, and incomplete information of extended care were 9.95% (21/211), 8.53% (18/211), 2.84% (6/211), 6.16% (13/211), 4.74% (10/211), 2.37% (5/211) after help, all lower than 50.57% (89/176), 43.18% (76/176), 14.20% (25/176), 25.57% (45/176), 18.18% (32/176), 11.93% (21/176) before help. The differences were statistically significant ( χ2 values were 14.00 to 77.81, all P<0.05). The incidence of medical adhesive related skin injury, catheter obstruction complications and unplanned extubation were 4.44% (4/90), 3.33% (3/90) and 2.22% (2/90), respectively, which were lower than 20.51% (16/78), 15.38% (12/78) and 11.54% (9/78) before help. The differences were statistically significant ( χ2=8.81, 6.06, 4.50, all P<0.05). Doctors′ satisfaction with nurses and patients′ satisfaction with nursing work were 96.43%(27/28) and 93.75%(45/48), respectively, both higher than 71.43%(20/28) and 72.73%(32/44) before help, and the differences were statistically significant respectively ( χ2=4.77, 5.97, both P<0.05). Conclusions:From the perspective of combination of medical care and nursing care, the maintenance and assistance of intravenous catheters by the team of intravenous therapy nurses in nursing hospitals can effectively reduce the incidence of central venous catheter complications and unplanned extubation, improve the maintenance ability of intravenous catheters of nurses in nursing hospitals, and help to improve the quality of nursing care in nursing hospitals.

Objective To explore the mechanism by which diazepam alleviates lipopolysaccharide(LPS)-induced pyroptosis and inflammation to delay the progression of pulmonary fibrosis.Methods MRC-5 cells challenged with LPS were treated with diazepam and transfected with a let-7a-5p mimic alone or co-transfected with pc-DNA-MYD88.The changes in cellular expressions of inflammatory factors were analyzed with ELISA,and the expressions of fibrosis-and pyroptosis-related proteins were detected using Western blotting.In the animal experiment,C57BL/6 mice were randomized for treatment with LPS,LPS+diazepam,LPS+diazepam+let-7a-5p mimic,LPS+diazepam+ST2825(a MYD88 inhibitor),or LPS+diazepam+let-7a-5p mimic+pc-DNA-MYD88,and pulmonary fibrosis and pulmonary expression of α-SMA were examined using Masson staining and immunofluorescence staining,respectively.Results LPS exposure of MRC-5 cells significantly downregulated let-7a-5p expression,up-regulated MYD88 expression,increased the levels of IL-4,IL-6,TGF-β and TNF-α,and enhanced the expressions of fibrosis-related proteins(Col-I,Col-III,and α-SMA)and pyroptosis-related proteins(NLRP3,caspase-1,ASC,and GSDMD-N).Diazepam treatment of LPS-stimulated cells effectively inhibited the expressions of inflammation-related factors and the fibrosis-and pyroptosis-related proteins.In C57BL/6 mice,diazepam treatment obviously alleviated LPS-induced pulmonary fibrosis and reduced and pulmonary expression of α-SMA,and these effects were further enhanced by treatment with let-7a-5p mimic or ST2825,but the effect of let-7a-5p mimic was significantly attenuated by MYD88 over-expression.Conclusion Diazepam can negatively regulate MYD88 by upregulating the expression of let-7a-5p to inhibit LPS-induced pyroptosis and inflammatory response,thereby alleviating lung fibrosis in mice.

Objective To investigate the effects of linoleic acid(LA)on the diversity and structure of intestinal flora in mice.Methods Twelve SPF grade male C57BL/6J mice at 7 weeks were randomly divided into control group(CTRL group)and linoleic acid group(LA group).One day before the linoleic acid diet was supplemented,the normal food was removed from the LA group and the mice in the LA group were fasted for one night,so that the LA diet was more acceptable to the mice in the LA group,and LA was given on the day of the experiment recording,and the feed was updated at any time to ensure that the mice could eat freely until the end of modeling.After 12 weeks of modeling,mouse feces were collected,and mixed samples were collected for every two mice feces,and then 16sRNA high-throughput sequencing was performed to analyze intestinal flora structure,Alpha and Beta diversity.Results 16sRNA high-throughput sequencing showed that LA intervention damaged the richness and diversity of intestinal flora.The results of principal component analysis showed that the composition of flora in CTRL group was different from that in LA group.At gate level,the relative abundance of Actinobacteria in LA group increased(P＜0.01).At the genus level,the relative abundance of L.Duchennei in the LA group decreased(P＜0.05),but the relative abundance of Bifidobacterium,Faecalibaculum and Erysipelotrichaceae in the LA group increased(all P＜0.01).Conclusion LA intervention could reduce the richness and diversity of intestinal flora in mice,and adjust the structure of intestinal flora.There were significant differences between beneficial bacteria and pathogenic bacte-ria in intestinal flora after LA intervention,which provided certain basis for the treatment of bioactive compounds of linoleic acid and the therapeutic adjustment of intestinal microorganisms as targets.

ObjectiveTo observe the spontaneous testicular tumors in interferon receptor-deficient mice (AG129) and provide a basis for further research using this mouse strain. MethodsThe AG129 mouse population was bred in an SPF barrier environment and reproduced normally. Among the 3-week-old weaned mice, we found that one male mouse had an abnormally enlarged testis, while none of the other mice in the same litter exhibited a similar condition. The spontaneous testicular tumor in this mouse was continuously monitored. The mouse was euthanized and dissected at 9 weeks of age. The gross morphology of the tumor was observed, and the tissue was then embedded in paraffin and sectioned for hematoxylin and eosin (HE) staining. ResultsAfter several weeks of observation, the tumor tissue gradually increased in size as the mice aged. Upon dissection, the tumor tissue was encapsulated in a smooth capsule. After opening the capsule, the tumor tissue was irregular in shape, with some areas being hard and others soft. The results of HE staining showed that the tumor tissue developed from tissues derived from multiple germ layers, with nerve tissue, bone tissue, muscle tissue, and adipose tissue inside, exhibiting an irregular morphological structure. ConclusionBased on the tumor development, gross morphological structure, and the HE staining results of the pathological sections, the tumor in this mouse was preliminarily diagnosed as an immature teratoma.

Objective To explore the application value of serum CXC chemokine ligand 12(CXCL12)and CXC chemokine receptor 4(CXCR4)detection combined with Doppler ultrasound in the diagnosis of dangerous placenta previa.Methods A sum of 90 patients with dangerous placenta previa admitted to Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine in Hebei from June 2020 to January 2023 were collected as research subjects.According to the postpartum pathological results,they were grouped into the placental implantation group(n=38)and the non placental implantation group(n=52),while another 90 healthy pregnant women(with placenta attached to the anterior wall of the uterus)who underwent pregnancy examination in Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine in Hebei and matched with the patient's gestational age were regarded as the control group.The serum levels of CXCL12 and CXCR4 in each group were compared.ROC curve was applied to analyze the diagnostic efficacy of serum CXCL12 and CXCR4 levels for placental implantation.Using postoperative pathological results as the gold standard,the fourfold table method was applied to calculate the diagnostic efficacy of serum CXCL12 and CXCR4 combined with Doppler ultrasound in the occurrence of placental implantation.Results The serum levels of CXCL12(2.75±1.26 ng/ml,5.82±2.14 ng/ml,10.24±3.58 ng/ml)and CXCR4(1.84±0.78 ng/ml,4.47±1.83 ng/ml,8.32±2.763 ng/ml)in the control group,non placental implantation group and placental implantation group were increased successively,and the differences were significant(F=158.998,199.141,all P＜0.05).The detection of serum CXCL12 and CXCR4 combined with Doppler ultrasound in the diagnosis of placental implantation had an AUC of 0.948,and sensitivity and specificity were 92.11％and 86.54％,respectively,which was better than CXCL12,CXCR4,and Doppler ultrasound alone predicting separately(Z=2.266,2.682,3.472,P=0.023,0.007,0.001).Conclusion The expression levels of serum CXCL12 and CXCR4 in patients with dangerous placenta previa are increased.The combination of serum CXCL12 and CXCR4 with Doppler ultrasound may have good diagnostic efficacy for the occurrence of placental implantation in dangerous placenta previa patients.

Objective To explore the mechanism by which diazepam alleviates lipopolysaccharide(LPS)-induced pyroptosis and inflammation to delay the progression of pulmonary fibrosis.Methods MRC-5 cells challenged with LPS were treated with diazepam and transfected with a let-7a-5p mimic alone or co-transfected with pc-DNA-MYD88.The changes in cellular expressions of inflammatory factors were analyzed with ELISA,and the expressions of fibrosis-and pyroptosis-related proteins were detected using Western blotting.In the animal experiment,C57BL/6 mice were randomized for treatment with LPS,LPS+diazepam,LPS+diazepam+let-7a-5p mimic,LPS+diazepam+ST2825(a MYD88 inhibitor),or LPS+diazepam+let-7a-5p mimic+pc-DNA-MYD88,and pulmonary fibrosis and pulmonary expression of α-SMA were examined using Masson staining and immunofluorescence staining,respectively.Results LPS exposure of MRC-5 cells significantly downregulated let-7a-5p expression,up-regulated MYD88 expression,increased the levels of IL-4,IL-6,TGF-β and TNF-α,and enhanced the expressions of fibrosis-related proteins(Col-I,Col-III,and α-SMA)and pyroptosis-related proteins(NLRP3,caspase-1,ASC,and GSDMD-N).Diazepam treatment of LPS-stimulated cells effectively inhibited the expressions of inflammation-related factors and the fibrosis-and pyroptosis-related proteins.In C57BL/6 mice,diazepam treatment obviously alleviated LPS-induced pulmonary fibrosis and reduced and pulmonary expression of α-SMA,and these effects were further enhanced by treatment with let-7a-5p mimic or ST2825,but the effect of let-7a-5p mimic was significantly attenuated by MYD88 over-expression.Conclusion Diazepam can negatively regulate MYD88 by upregulating the expression of let-7a-5p to inhibit LPS-induced pyroptosis and inflammatory response,thereby alleviating lung fibrosis in mice.

Based on the standards of modern Chinese medicinal materials, literature and records of ancient books, this article reviewed the preliminary processing of Aucklandiae Radix and processing of its decoction pieces. There are some problems in the records of the initial processing of Aucklandiae Radix, such as lack of specific parameters, inconsistent processing sequence, unclear removal methods of fibrous roots and soil, inconsistent cutting specifications, drying methods and temperature. Different processing methods of Aucklandiae Radix decoction pieces can lead to differences in the content of their index components. From the initial processing of the producing area to softening, slicing, and then secondary drying, it may increase production costs and time, and lead to the loss of active components. There are more than 20 kinds of processing methods in ancient books, such as stirfrying, baking, simmering, grinding juice and so on. However, only paper simmering, bran stirfrying and Coptidis Rhizoma processing are commonly used at present, and other processing methods have great exploration space. Referring to the research results of freshcut processing of other Chinese materia medica containing volatile components, it is considered that the key to ensure the quality of Chinese materia medica and decoction pieces is to formulate a standardized process flow of freshcut processing of Aucklandiae Radix.

AIM:To analyze the occurrence and clinical characteristics of adverse drug reactions(ADR)induced by four programmed cell death pro-tein 1(PD-1)inhibitors according to literature re-ports,and to provide reference for clinical safe medication.METHODS:PubMed,CNKI,and Wan-fang,and other databases were searched to collect case reports of adverse reactions caused by four PD-1 inhibitors,including camrelizumab,sintilimab,toripalimab,and tislelizumab.RESULTS:A total of 105 eligible literature reports were retrieved from the databases at home and abroad(as of June 1,2022),including 42 reports on camrelizumab with 47 patients,29 reports on sintilimab with 30 pa-tients,21 reports on toripalimab with 24 patients and 13 reports on tislelizumab with 15 patients.Among them,there were 76 males(65.5％)and 40 females(34.5％),with a gender ratio of 1.9:1.0.The age range was between 29 to 84 years old,and the onset of ADR mainly occurred within 4 months af-ter the first use of PD-1 inhibitors.Immune-related adverse reactions were mainly manifested as skin and its attachment(41 cases,34.5％),endocrine sys-tem(25 cases,21.0％),and cardiovascular system(22 cases,18.5％).Most patients improved after symptomatic and supportive treatment.CONCLU-SION:Immune-related adverse effects(irAEs)may occur at any time during treatment with the four PD-1 inhibitors,among these the skin system is most frequently affected,followed by the cardiovas-cular and endocrine systems.This suggests the im-portance of individualized drug administration and stringent control over indications in clinical prac-tice.Close monitoring throughout immunotherapy is essential to minimize or prevent irAEs,thus en-suring patient safety in medication usage.

Bladder perfusion is one of the main methods for the treatment of bladder cancer. In order to further improve the standardization of bladder cancer bladder perfusion operation for nursing staff, this paper, guided by evidence-based methods, formed the expert consensus on the whole process management of bladder perfusion for bladder cancer through Delphi expert consultation and expert demonstration meeting, and provided guidance for the standardization of clinical nursing practice and management institutionalization of bladder cancer bladder perfusion from seven aspects, namely, perfusion environment, operators, drug allocation, operation process, adverse reactions, health education and continuous nursing.