In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.

Pancreatic cancers (PCs) is a common malignant tumor with poor prognosis in the digestive system. Its main treatment methods include surgery, radiotherapy, chemotherapy, and targeted therapy. The early diagnosis rate of hidden onset of PCs is low, and most patients have already lost the opportunity to undergo surgery when diagnosed with PCs. Chemotherapy is still the main treatment for advanced PCs, but the use of chemotherapy drugs in PCs can easily lead to drug resistance. The most significant feature that distinguishes PCs from other tumors is its rich and dense matrix, which not only hinders drug penetration but also impedes the infiltration of immune cells. The above reasons have led to a very low survival rate of PCs patients. Therefore, drug delivery systems are very important in the diagnosis and treatment of PCs. They can improve drug delivery, enhance biological barrier penetration, reduce side effects, and combine multiple treatment methods. Therefore, the treatment prospects of PCs are very broad. Currently, drug delivery systems widely applied in PCs primarily include nanodrug delivery systems, tumor microenvironment-targeted drug delivery system, immunotherapy drug delivery system, gene therapy drug delivery system, and combination therapy drug delivery system that synergize multiple therapeutic modalities. Emerging drug delivery systems (DDSs) have revolutionized PCs treatment by addressing these challenges through multiple mechanisms. Nanoformulations improve drug solubility, prolong circulation time, and reduce systemic toxicity via passive/active targeting. Smart DDSs responsive to PCs-specific stimuli enable extracellular matrix degradation, tumor-associated fibroblasts reprogramming, and vascular normalization to enhance drug accessibility. Last but not least, carrier systems loaded with myeloid-derived suppressor cell inhibitors or T cell activators can reverse immunosuppression and potentiate immunotherapy efficacy. Advanced platforms co-deliver chemotherapeutics with immunomodulators, gene-editing tools, or sonodynamic agents to achieve synergistic antitumor effects. These platforms aim to address critical challenges in PCs treatment, such as enhancing drug bioavailability, overcoming stromal barriers, reprogramming immunosuppressive niches, and achieving multi-mechanistic antitumor effects. This article provides a systematic summary and prospective analysis of the current development status, latest cutting-edge advances, opportunities, and challenges of the above-mentioned drug delivery systems in the field of PCs therapy.

OBJECTIVE To systematically evaluate the efficacy and safety of tislelizumab in the treatment of advanced non- small cell lung cancer （NSCLC）. METHODS Computerized searches were conducted in PubMed， Embase， the Cochrane Library， CNKI， Wanfang and other Chinese and English databases to collect randomized controlled trials （RCTs） on tislelizumab for advanced NSCLC. The search period was from the establishment of the databases to December 2024. After strictly screening the literature， extracting data and conducting quality evaluations in accordance with the inclusion and exclusion criteria， a meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. RESULTS A total of 18 RCTs involving 2 337 patients were included， with 1 283 in the experimental group and 1 054 in the control group. The meta-analysis results showed that the objective response rate [RR＝1.61， 95%CI （1.48， 1.75）， P＜0.000 01]， disease control rate [RR＝1.21， 95%CI （1.13， 1.29）， P＜0.000 01]， progression free survival [HR＝0.55， 95%CI （0.45， 0.66）， P＜0.000 01]， and overall survival [HR＝0.78， 95%CI（0.62， 0.97）， P＝0.03] were significantly better in the experimental group than in the control group. There was no statistically significant difference in the incidence of adverse reactions between the two groups [RR＝1.00， 95%CI （0.73， 1.37）， P＝1.00]； among the common adverse reactions， only the incidence of liver function impairment was significantly higher in the experimental group than in the control group [RR＝1.30， 95%CI （1.10， 1.54）， P＜0.01]. CONCLUSIONS Tislelizumab in combination with chemotherapy or targeted drugs significantly improves the efficacy in patients with advanced NSCLC without increasing the risk of adverse reactions overall. However， liver function should be closely monitored during treatment.

Diabetic kidney disease(DKD)is a high incidence microvascular complication caused by diabetes mellitus(DM).Persistent high glucose induces oxidative stress in the body.nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1)can play an anti-inflammatory and anti-oxidative role by inhibiting the accumulation of extracellular matrix in glomerular mesangium,inhibiting epithelial-mesenchymal transition in renal tubular epithelial cells,and inhibiting iron apoptosis,so as to improve renal function damage and delay the process of DKD.This article reviews the relationship between Nrf2/HO-1 pathway and DKD and the effect of traditional Chinese medicine active ingredients on DKD through Nrf2/HO-1 signaling pathway,in order to provide a basis for the development of new drugs.

ObjectiveTo explore the protective effect and mechanism of Yangxin Dingji capsules on isoproterenol （ISO）-induced ventricular arrhythmia in SD rat cardiomyocytes based on the transforming growth factor-β activated kinase 1 （TAK1）-mitogen-activated protein kinase kinase 3 （MKK3）-p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodFifty male SPF-grade SD rats were randomly divided into a normal group， a model group， a propranolol group， a low-dose Chinese medicine group， and a high-dose Chinese medicine group. The ventricular arrhythmia model was constructed using the ISO "6+1" method. The propranolol group received propranolol at 0.015 g·kg^-1·d^-1. The Chinese medicine groups received Yangxin Dingji capsules at doses of 0.5、 2 g·kg^-1·d^-1， respectively. The normal and model groups were given an equal volume of 0.9% NaCl solution. Electrocardiogram （ECG） changes in SD rats were recorded using the BL-420F biological function experimental system. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the heart. Serum levels of cardiac troponin I （cTnI）， creatine kinase-MB （CK-MB）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and transforming growth factor-β₁ （TGF-β₁） were measured using enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of IL-1β and TNF-α was assessed using real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Reactive oxygen species （ROS） expression was detected using immunofluorescence. Protein expression levels of TAK1， phosphorylated TAK1 （p-TAK1）， MKK3， phosphorylated MKK3 （p-MKK3）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， IL-1β， and TNF-α were measured using Western blot or immunohistochemistry. ResultCompared with normal group， the model group showed significant ventricular arrhythmia in ECG， with an increased arrhythmia score （P<0.01）. Pathological damage to myocardial tissue was evident， and serum levels of cTnI， CK-MB， IL-1β， TNF-α， and TGF-β₁ were elevated （P<0.01）. The mRNA and protein expression of IL-1β and TNF-α in myocardial tissue was also increased （P<0.01）. ROS level and protein expression of p-TAK1， p-MKK3， p-p38 MAPK， and p-NF-κB were elevated in myocardial tissue （P<0.01）. In the propranolol and Chinese medicine groups， the incidence of sustained ventricular tachycardia （SVT） and arrhythmia scores were significantly reduced compared to model group （P<0.05， P<0.01）. Pathological damage to cardiomyocytes was alleviated， and levels of myocardial injury markers and inflammatory factors in serum and myocardial tissue were decreased. The ROS level in myocardial tissue was also reduced （P<0.01）， with a noticeable reduction in related molecules in the p38 MAPK pathway （P<0.05， P<0.01）. ConclusionThe expression of p38 MAPK pathway molecules was up-regulated in myocardial tissue of ISO-induced ventricular arrhythmia rats. Yangxin Dingji capsules may inhibit cardiac inflammation damage by regulating the expression of related molecules in the p38 MAPK pathway， thereby exerting a protective effect on myocardial cells， with TAK1 being a potential target.

Abstract The choroid is a multifunctional dynamic structure located between the sclera and the Bruch membrane, which may be involved in the regulation of eye growth and the development of myopia. Choroidal thickness may serve as an important biomarker for predicting the development of myopia and the effectiveness of myopia control treatments in children and adolescents. The study reviews and summarizes the physiological structure and measuring methods of the choroid, and discusses its influencing factors including age, physiological changes, refractive status, axial length, drug effects, optical environment and so on. The review points out the potential applications of choroidal thickness in myopia research among children and adolescents.

Objective:To evaluate the effects of recombinant human thrombopoietin (rhTPO) on platelet count (PLT) and liver function in acute liver failure (ALF) rats by observing the dynamic changes of PLT, thrombopoietin (TPO) and liver function during ALF.Methods:Twenty-four male Sprague-Dawley (SD) rats were divided into model group, TPO group and interleukin-11 (IL-11) group using a random number table method, with eight rats in each group. All rats were intraperitoneally injected with D-galactosamine (D-GalN, 1?500 mg/kg, dosed within 72 hours) to induce the ALF model. After modeling, rats in TPO group was received subcutaneous injection of 15 μg/kg of rhTPO for 5 days, and rats in IL-11 group was received subcutaneous injection of 0.45 mg/kg of IL-11 for 5 days. Venous blood samples were collected before and at 1, 3, 5, 7 and 12 days after molding for whole blood cell detection. The level of TPO in serum was detected by enzyme-linked immunosorbent assay (ELISA). Liver function indexes including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and albumin (ALB) were measured before and at 1, 3 and 5 days after modeling. The rats were sacrificed 12 days after the modeling, and the pathological changes of liver tissue were observed by hematoxylin-eosin (HE) staining.Results:Two rats in each group died within 24-48 hours after modeling. HE staining showed that all three groups of ALF rats showed large flake necrosis of hepatocytes, disorder of hepatic lobular structure, mesh scaffold collapse, hepatic sinus congestion and hemorrhage, and flake infiltration of inflammatory cells on day 12 after modeling. The levels of serum ALT, AST and TBil of rats in each group were significantly increased 1 day after modeling and then decreased. The level of ALB decreased significantly on the first day after modeling and then increased, but there was no significant difference in the trend of liver function indexes among the three groups. PLT in the three groups decreased rapidly on day 1 after modeling, and then recovered gradually with the improvement of liver function. The PLT of the TPO group rose to the peak value 7 days after molding and was significantly higher than that of the model group [PLT (×10 9/L): 1?673.3±347.5 vs. 855.3±447.0, P < 0.05], while there was no significant difference between the IL-11 group and the model group [PLT (×10 9/L): 1?350.3±386.6 vs. 855.3±447.0, P > 0.05]. The level of serum TPO of the three groups increased significantly on day 1 after modeling, then decreased, and dropped to the lowest value on day 5, but there was no significant difference in the trend of serum TPO level among the three groups. Conclusions:PLT in ALF rats decreased rapidly in the early stage and recovered gradually with the improvement of liver function, and the serum TPO level increased first and then decreased. Injection of rhTPO can significantly increase PLT in ALF rats, but has no significant effect on liver function and survival rate.

OBJECTIVE To improve the quality evaluation method of Platycodonis Radix, to study the differences in the quality of three-years-old Platycodonis Radix under different harvesting periods, and to determine the optimal harvesting period of Platycodonis Radix. METHODS The leachate, ash, moisture, refractive index and the content of six saponins were used as the quality evaluation indexes. The differences between the herbs of Platycodonis Radix at different harvesting periods were characterized with the help of mathematical and statistical methods. And link the entropy weight method, gray correlation analysis and TOPSIS method were combined to obtain the statistical analysis of the relevant indexes and the quality ranking information of the herbs in different harvesting periods. RESULTS There were significant differences between the quality evaluation indexes of three-years-old Platycodonis Radix at different harvesting periods. The added multi-indicator testing had improved the quality evaluation system of Platycodonis Radix and enhanced the "Drug properties-Effectiveness" linkage of the herbs. And the results of the comprehensive quality evaluation model showed that the herbs harvested around October 21 (Frost’s Descent) were ranked best in terms of comprehensive index. CONCLUSION In order to ensure the quality of Platycodonis Radix, the best harvesting period for three-years-old Platycodonis Radix is determined around the "Frost’s Descent" season, taking into account the characteristics of the herbs' appearance and the material basis of herbs.

This study constructed a LHCGR-CRE-luc-HEK293 transgenic cell line according to the activation of the cAMP signaling pathway after recombinant human chorionic gonadotropin binding to the receptor. The biological activity of recombinant human chorionic gonadotropin was assayed using a luciferase assay system. The relative potency of the samples was calculated using four-parameter model. And the method conditions were optimized to validate the specificity, relative accuracy, precision and linearity of the method. The results showed that there was a quantitative potency relationship of human chorinonic gonadotropin (hCG) in the method and it was in accordance with the four-parameter curve. After optimization, the conditions were determined as hCG dilution concentration of 2.5 μg·mL^-1, dilution ratio of 1∶4, cell number of 10 000-15 000 cells/well, and induction time of 6 h. The method had good specificity, relative accuracy with relative bias ranging from -8.9% to 3.4%, linear regression equation correlation coefficient of 0.996, intermediate precision geometric coefficient of variation ranging from 3.3% to 15.0%, and linearity range of 50% to 200%. This study successfully established and validated a reporter gene method to detect hCG biological activity, which can be used for hCG biological activity assay and quality control.

Objective:This study was designed to explore the distribution pattern of TCM syndrome types in patients with Chronic Kidney Disease (CKD) stage 3-5 without alternative treatment after objective collection of TCM quad-diagnostic instruments.Methods:The four-diagnostic instruments of Chinese medicine were used to collect the four-diagnostic information of patients with stage CKD 3-5 non-alternative treatment for syndrome determination, and the correlation between TCM syndrome and basic disease characteristics of patients was analyzed.Results:The distribution of TCM syndrome types in 464 patients with CKD 3-5 stage non-substitution therapy was based on deficiency syndrome, and had both standard and solid syndrome. Qi-deficiency syndrome was the most common type, accounting for 24.6% (114/464), followed by kidney-yang deficiency syndrome, heart-qi deficiency syndrome, kidney-yin deficiency syndrome, heart-blood deficiency syndrome, spleen-yang deficiency syndrome and lung-yin deficiency syndrome. The positivism type of this deficiency is blood stasis, dampness-heat, moisture, turbidity and turbidity toxicity. There was no significant difference in gender and age distribution among patients with different CKD stages ( P>0.05), but the proportion of deficiency syndrome gradually increased with the increase of age. There were differences in the distribution of primary deficiency syndrome in different CKD stages ( χ2=57.48, P<0.001), but no difference in the distribution of primary deficiency syndrome ( χ2=2.59, P=0.957). Conclusions:According to the four diagnostic instrument of traditional Chinese medicine, the distribution of TCM syndrome types in patients with stage CKD3-5 non-alternative treatment is based on deficiency syndrome, combined with deficiency of primary and solid syndrome. The syndrome types in CKD3 stage were mainly qi deficiency and kidney qi deficiency, while the TCM syndrome types in CKD stage 4 were qi deficiency and kidney Yang deficiency. With the progression of the disease, the TCM syndromes of stage 5 CKD were mainly heart-qi deficiency and kidney-yang deficiency.