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.

Acute-on-chronic liver failure （ACLF） refers to severe liver dysfunction that occurs on the basis of chronic liver diseases， and it is characterized by rapid disease progression， poor prognosis， and high mortality rate. In recent years， inflammatory markers have become a research hotspot due to their significant role in assessing the prognosis of ACLF. This article reviews the advances in the application of inflammatory markers in assessing the prognosis of ACLF， such as systemic immune inflammatory index， lymphocyte-white blood cell ratio， neutrophil-lymphocyte ratio， and C-reactive protein， and discusses their clinical value and future research directions， in order to provide a theoretical basis for the early intervention and prognosis management of ACLF patients.

OBJECTIVE To provide a reference for improving the drug patent linkage system. METHODS Data on drug names， drug types， abbreviated new drug application （ANDA） acceptance numbers， registration classifications， and applicant names were obtained from the patent certifications and patent information disclosure modules of China’s patent information registration platform for marketed drugs. The data collection period was from July 4， 2021， to September 30， 2023. The analysis focused on the annual distribution of patent certifications for the ANDA varieties included in the statistics， the proportion of different registration classifications， the details of the type Ⅳ certifications， the remaining validity periods of the corresponding patents for the type Ⅲ certifications， and the number of manufacturers for the same variety. RESULTS Among the ANDA varieties analyzed， type Ⅰ certifications predominated （accounting for 86.53%）， while types Ⅱ， Ⅲ and Ⅳ certifications each accounted for approximately 4% to 5%. In the three registration classifications， type Ⅰ certifications in registration classification 3 accounted for as high as 98.55%， and in registration classification 4， type Ⅰ certifications accounted for 79.65%， while types Ⅱ， Ⅲ and Ⅳ certifications each accounted for around 7%. In terms of the detailed type of the Ⅳ certifications， type Ⅳ of article 2 certifications had a large proportion （79.23%） and showed a slight upward trend， whereas the challenges of type Ⅳ of article 1 certifications were few. The remaining validity period of the patents corresponding to type Ⅲ certifications was excessively long， with a median of 18 months. The proportion of the same variety with fewer than 5 manufacturers was 36.44%， while those with more than or equal to 20 manufacturers accounted for 14.75%. CONCLUSIONS The ANDA system in China has been orderly integrated with the drug patent linkage system in practice. It is recommended to optimize aspects such as patent certifications registration and objection mechanisms， the effective approval dates for ANDA with type Ⅲ certifications， and incentive measures for type Ⅳ of article 1 certifications， thereby further standardizing the ANDA process and guiding the high-quality development of generic drugs.

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.

To construct a recombinant expression system for a single-domain antibody targeting the urease of Helicobacter pylori(Hp),this study employed several strategies.First,using artificial intelligence(AI)auxiliary tools such as Pymol,I-TASSER,and ClussPro2,the molecular interactions between different antibodies and Hp urease subunit B(UreB)were analyzed.The fully humanized single-domain antibody UreBAb was identified as the primary research target.Next,the UreBAb gene sequence was optimized based on Escherichia coli codon preferences,and was inserted into expression vectors such as pET28a and pE-SUMO.The resulting recombinant expression strains were obtained by transforming Escherichia coli Rosetta(DE3).Recombinant antibody proteins were prepared through IPTG induction,and its activity was detected using extracted Hp urease as the antigen.SDS-PAGE analysis confirmed the correct expression of both UreBAb and SUMO-UreBAb,with protein yields of 0.34 mg/mL and 0.41 mg/mL,respectively.Unidirectional immunodiffusion experiments further confirmed that both recombinant antibodies exhibited strong affinity for Hp UreB antigen,with inhibition rates of 51.27%and 74.07%,respectively.Additionally,leveraging artificial intelligence tools such as AlphaFold2,cluspro2,mCSM-AB,OSPREY,and FoldX,the study evaluated and analyzed key binding sites and mutational strategies affecting the stability of the antigen-antibody complex.Subsequently,nine UreBAb evolution mutants were constructed,and their binding activities with the antigen were enhanced.Among these,the I107W mutant showed the most significant improvement,achieving a 24.95%increase compared to the wild-type UreBAb.This research lays a solid foundation for the development of fully humanized single-domain antibodies against Hp.

Unicorn lotus is a plant tuber in the araceae family, which has therapeutic effects such as dispelling cold and dampness, dispelling wind and phlegm, and treating stroke. However, acute poisoning of fresh Unicorn lotus has been rarely reported domestically and internationally. This article reports a case of poisoning caused by chewing unicorn lotus. The patient experienced numbness in the lips, swelling and rupture of the oral cavity, continuous salivation, difficulty swallowing and obvious burning sensation in the throat, accompanied by shortness of breath and mild hypoxemia. After receiving comprehensive treatments such as oxygen therapy, electrocardiographic monitoring, cleaning of necrotic oral mucosa, anti infection, inhibition of oral salivary secretion, and nutritional support, the patient finally recovered and was discharged.

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 investigate the risk factors of postoperative recurrence in patients with primary brain glioma and to construct a prediction model.Methods:A total of 98 patients with primary brain glioma treated by radical surgery in Nanchong Central Hospital from January 2018 to January 2021 were retrospectively included, and were divided into recurrent group (40 cases) and non-recurrent group (58 cases) according to whether there was recurrence or not during the follow-up period. The independent influencing factors for postoperative recurrence in patients with primary brain glioma were evaluated by multivariate logistic regression. Logistic prediction model of postoperative recurrence risk of patients with primary brain glioma was established, and the predictive efficacy of each index was calculated by receiver operator characteristic (ROC) curve.Results:There were statistically significant differences between recurrent group and non-recurrent group in glioma World Health Organization (WHO) grade ( χ2=12.48, P<0.001), isocitrate dehydrogenase (IDH) 1/2 mutation ( χ2=13.24, P<0.001), mean platelet volume (MPV) ( t=5.34, P<0.001), and MPV/platelet count (PLT) ( t=9.73, P<0.001). Multivariate analysis showed that WHO grade Ⅲ-Ⅳ ( OR=8.54, 95% CI: 1.62-44.99, P=0.011), IDH1/2 wild type ( OR=9.08, 95% CI: 1.68-49.19, P=0.010), low MPV ( OR=0.46, 95% CI: 0.21-0.99, P=0.048) and low MPV/PLT ( OR=0.02, 95% CI: 0.01-0.03, P<0.001) were independent risk factors for postoperative recurrence in patients with primary brain glioma. The logistic prediction model based on the above indicators was logit ( P) =11.78+2.15×WHO grade+2.21×IDH1/2 mutation situation-0.78×MPV-200.70×MPV/PLT ( R2=0.785). The ROC curve analysis results showed that WHO grade, IDH1/2 mutation, MPV, MPV/PLT, and logistic prediction model P-value could all be used to predict the risk of postoperative recurrence in patients with primary brain glioma; The areas under the curve were 0.681, 0.684, 0.783, 0.920 and 0.964, respectively. In the area under ROC curve comparison of each indicator, the predictive performance of the logistic regression model P-value was significantly higher than that of other indicators (all P<0.05) . Conclusion:Postoperative recurrence in patients with primary brain glioma may be related to glioma WHO grade, IDH1/2 mutation and platelet related laboratory indexes. The model constructed based on the above indicators can be used to predict the recurrence risk in patients with primary brain glioma after surgery.

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.

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.