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.

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.

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 provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi (HHRY) pills for endometriosis-associated dysmenorrhea. Methods: This study constitutes a multicenter, randomized, double-blind, placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period. A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio. The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale (VAS) scores and quality of life, whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain, duration of pain episodes (in days), frequency and quantity of the consumption of ibuprofen sustained-release capsules (or other non-steroidal anti-inflammatory drugs), and days off work/study for staff/student due to dysmenorrhea, ovarian cyst, and/or pelvic nodule size. The safety was monitored throughout the treatment period. All the analyses were based on the intention-to-treat principle. For continuous outcomes, simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups, with categorical data expressed as the number and percentage of occurrences. Differences were compared using the chi-square test or Fisher's exact test. The predefined analysis was adjusted for concomitant treatment, a variable considered to be associated with outcomes but unaffected by treatment allocation. Estimates of treatment effects were reported with 95% confidence intervals. Two-tailed P values ≤ .05 were considered statistically significant. Conclusion Positive results from this trial, upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

Purpose To explore the clinicopathological features of cholangitis lenta.Methods The clinical data of 12 patients with cholangitis Lenta were collected,HE staining,his-tochemical staining and immunohistochemistry were used to de-tect the clinicopathological changes in 12 cases of cholangitis lenta,and the relevant literature was reviewed.Results All the 12 patients with cholangitis Lenta had acute history and ab-normal liver function,9 cases(75.0％)had abnormal white blood cell count,11 cases(91.7％)had abdominal infection,8 cases(66.7％)had systemic inflammatory response syndrome(SIRS)and 8 cases(66.7％)were diagnosed as sepsis.The common pathological manifestations included spotty necrosis(100％),piecemeal necrosis(100％),confluent necrosis(75.0％),bridging necrosis(66.7％),hepatocyte and capil-lary cholestasis(75.0％),and mild edema in portal area(33.3％).12 cases showed proliferation of bile ductules around the portal area,inspissated bile in dilated bile ductules and no cholestasis in interlobular bile ducts.12 cases had the basis of primary liver disease.2 patients(16.7％)died after being transferred to another hospital for treatment,and 10 patients(83.3％)survived,which lasted for 7 to 55 months.Conclu-sion Cholangitis Lenta shows unique clinical manifestations and morphological features,it is often accompanied by underly-ing diseases.The pathological manifestation of cholangitis Lenta in liver biopsy suggests that patients may have sepsis and/or ab-dominal infection,and therefore its diagnosis should be com-bined with clinical features,laboratory examination and imaging manifestations.

Dendrobium is one of the valuable Chinese herbs in China,and Dendrobium officinale is the top grade of Dendrobium,which is recorded in many ancient medical texts as having the efficacy of treating diabetes.Modern pharmacological research shows that Dendrobium has the effects of anti-tumor,anti-fatigue,immune regulation,anti-aging,and regulation of glycolipid metabolism.In clinical application,Dendrobium officinale also has the function of balancing glucose and lipid metabolism,improving insulin resistance,promoting insulin secretion,improving the function of islet cells,and has a certain role in the prevention and treatment of diabetic complications.At present,there is a lack of systematic review of the pharmacological mechanism of Dendrobium officinale in the treatment of diabetes.In order to understand the pharmacological action of Dendrobium officinale in the treatment of diabetes more comprehensively,and to provide a reference for further pharmacological research,so that it can be better applied in clinics,this paper reviews the research progress of the pharmacological mechanism of Dendrobium officinale in the treatment of diabetes.

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 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.