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.

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 To investigate the correlation between bone mineral density(BMD)at different hip positions with muscle parameters and physical performance in middle-aged and elderly people in Kunming area.Methods 531 middle-aged and elderly volunteers were recruited from the Radiology Department of the First People's Hospital of Yunnan Province from May 2021 to April 2022.All study subjects completed the five-times-sit-to-stand test(FTSST)and hip quantitative CT(QCT)examinations.Volunteers'total hip(TH),femoral neck(FN),and intertrochanteric(IT)BMD were measured by using QCT PRO workstation and using OsiriX software to measure the area and density of their gluteus maximus muscle,gluteus medius,and minimus muscle and midthigh muscle.Divide male and female volunteers into positive and negative groups respectively based on FTSST time≥12 seconds or<12 seconds,and analyze the differences in hip BMD between the groups;Also divide male and female volunteers into three groups(50～59 years old,60～69 years old,70 years old and above)at the age of 10,and analyze the correlation between hip BMD and muscle parameters in different age and gender stratification.Control for age and BMI,and then perform partial correlation analysis on the above indicators.Results The BMD of the hip in the female FTSST positive group was lower than that in the negative group(P<0.001),while there was no statistically significant difference between the male groups(P>0.05).After adjusting for age and BMI,among males,FN BMD was positively correlated with gluteus medius and minimus muscle density in the age groups of 50～59 and 60～69(P<0.05),while TH BMD,FN BMD,and IT BMD were strongly positively correlated with gluteus medius and minimus muscle density in the age group over 70(P<0.05).For females,the correlation between hip BMD and muscle density in the age groups of 50～59 and 60～69 was weak,while BMD in all parts of the hip was not correlated with muscle density in the age group over 70(P>0.05).There was a negative correlation between TH BMD,FN BMD,and gluteus medius and minimus muscle area in the age group of 50～59 years old for males(P<0.05),while there was a significant negative correlation between TH BMD,IT BMD,and gluteus maximus area in the age group of 70 years old and above for females(P<0.05).Conclusion The BMD of various parts of the hip in the female FTSST positive group is lower than that in the negative group.The density of the gluteus medius and minimus muscle can to some extent serve as a predictive indicator of femoral neck bone strength in middle-aged and elderly men in Kunming area.

BACKGROUND:The anterior cruciate ligament has unique nonlinear mechanical properties under a complex physiological loading environment.Elastin is an important contributor to the mechanical properties of the anterior cruciate ligament,but its mechanical response to the anterior cruciate ligament under axial tension is not clear. OBJECTIVE:To quantitatively analyze the effect of elastin on the tensile mechanical response of the anterior cruciate ligament. METHODS:Elastase solution and control buffer were prepared.The porcine anterior cruciate ligament samples were prepared into small-size samples and randomly soaked in 0,0.1,1.0,2.0,5.0,and 10.0 U/mL elastase solution for 6 hours,and other small samples of the same size were soaked in 2 U/mL elastase solution for 0,1,3,6,9,and 12 hours.To determine suitable soaking conditions for elastin-targeted enzymes and verify the digestive effect,histological staining was used to compare the effects of enzyme treatment on tissue structure and composition.The ligament samples were randomly divided into elastase-treated group and PBS group,and immersed in 2 U/mL elastase solution and PBS buffer for 6 hours,respectively.A mechanical tensile test was performed before and after immersion. RESULTS AND CONCLUSION:(1)The biochemical results showed that being treated in 2 U/mL elastase solution for 6 hours could reduce the elastin content by 31.1%,and had no significant effect on other mechanical-related components in the tissue.(2)The histological results showed that elastase was able to penetrate the tissue,and the loose degree of tissue increased after treatment.(3)In the mechanical results before and after treatment,the mechanical properties of the PBS group decreased significantly,only the low-tension elastic modulus increased significantly and the initial length increased significantly in the elastase-treated group.(4)The intergroup comparison results showed that there was no significant difference between the two groups in pre-treatment,but the low-tension elastic modulus,initial slopes,saturated slopes,and initial length of the elastase-treated group after treatment were significantly higher than those in the PBS group.(5)These results suggest that elastin degradation significantly affects the biomechanical properties of the anterior cruciate ligament and further complements our understanding of the structure-function relationship of the anterior cruciate ligament.

BACKGROUND:Numerous scholars have previously researched certain greater tuberosity fractures and the procedures used to treat them.Few researchers,however,have studied the comminuted split fracture of the greater tuberosity of the humerus(Liu-Gang type IV)with rotator cuff tear in great detail. OBJECTIVE:To compare the clinical therapeutic effect of open repair position modified calcaneal plate combined with suture anchors and proximal humeral internal locking system(PHILOS)plate in the treatment of comminuted fracture of split-type greater tuberosity of humerus combined with rotator cuff tears(Liu-Gang type IV). METHODS:Case data of 30 patients with comminuted fracture of split-type greater tuberosity of humerus combined with rotator cuff tears(Liu-Gang type IV)from May 2012 to May 2022 were retrospectively analyzed.They were divided into the modified calcaneal plate combined with suture anchor group(group A)and the PHILOS with#2 Johnson group(group B),with 15 cases in each group.Intraoperative blood loss,surgical time,and incision length of all patients were recorded.Pain visual analog scale score,Constant-Murley score,as well as shoulder joint abduction,forward flexion,external rotation,and dorsal expansion activities during the last follow-up(>1 year)were evaluated. RESULTS AND CONCLUSION:(1)The surgical incision length and operation time were shorter,and blood loss was less in group A than those in group B(P<0.05).(2)No significant difference in visual analog scale score and Constant-Murley score was detected between the two groups(P>0.05).(3)During the last follow-up,forward flexion in group A was better than that in group B(P<0.05).No significant difference in abduction,external rotation,and dorsal expansion was determined between group A and group B(P>0.05).(4)In terms of complications,there was 1 case of shoulder joint pain and discomfort in group A(7%),2 cases of subacromial impingement syndrome,2 cases of upward movement of nodules,and 2 cases of shoulder joint pain(40%)in group B.There were significant differences in complication rates between the two groups(P=0.031).(5)In summary,the modified calcaneal plate combined with suture anchors in the treatment of comminuted fracture of split-type greater tuberosity of humerus combined with rotator cuff tears(Liu-Gang type IV)could better restore the forward flexion function of the shoulder joint and has a small incision,less blood loss,shorter operation time and fewer complications.

BACKGROUND:Ferroptosis and pyroptosis may play a role in the development of postmenopausal osteoporosis.There may be relevant biomarkers for the diagnosis of postmenopausal osteoporosis. OBJECTIVE:To search for the key genes related to ferroptosis and pyroptosis in postmenopausal osteoporosis using bioinformatics so as to further elucidate their biological mechanisms. METHODS:The data sets GSE56815 and GSE7429 of postmenopausal osteoporosis were downloaded from the GEO database,the national comprehensive gene expression database of the United States,and the two data sets were preprocessed.The differential expression analysis of the data was carried out by the limma package of R software,and the enrichment analysis was performed by DIVID and KOBAS.The protein-protein interaction network was mapped by STRING and Cytoscape,the Hub gene was selected by CytoHubba,and the key genes were screened by the ferroptosis database and pyroptosis database.The CIBERSORT package was used to determine the immune infiltration of postmenopausal osteoporosis samples and to analyze the correlation between key genes and immune cells RESULTS AND CONCLUSION:A total of 30 differential genes of postmenopausal osteoporosis were screened in the experimental samples,of which 9 genes were up-regulated and 21 genes were down-regulated.The enrichment of GO and KEGG pathways showed that the differences were mainly in"serine-type endopeptidase activity,""innate immune response,""special particle lumen,"and"renin secretion."The protein-protein interaction network showed the correlation of differential genes and the top 10 Hub genes with"Degree"value were selected using CytoHubba.Hub gene was intersected with the FerrDb database and cell pyroptosis dataset to obtain key genes ELANE and LCN2.Receiver operating characteristic curve and box diagram showed that the expression of ELANE and LCN2 in serum samples of postmenopausal osteoporosis was significantly lower than that in normal samples,indicating a good diagnostic value.Immune infiltration analysis showed that ELANE may be related to memory resting CD4+ T cells,M0 and M2 macrophages.LCN2 may be related to M0 macrophages.

Glaucoma is the leading irreversible blinding eye disease worldwide,and intraocular pressure(IOP)plays a key role in the occurrence and development of glaucoma.However,the underlying IOP regulatory mechanism remains un-clear.Currently,clinical IOP-lowering drugs work either by reducing aqueous humor formation or increasing aqueous hu-mor outflow with limited reduction amplitude.Recent studies demonstrate that IOP may be regulated by autonomic nerves.To understand the distribution and regulatory mechanism of autonomic nerves in the aqueous humor outflow pathway and provide new ideas for IOP-lowering study and novel drug exploration,we review the roles of the autonomic nervous system in the formation and outflow of aqueous humor in this article.

The structure and working principle of the multi-leaf collimator(MLC)optical system of Elekta linear accelerator were introduced.The causes for the faults of the MLC optical system were analyzed,and the fault repair and maintenance of the MLC optical system were summarized.References were provided for medical engineers to repair and maintain the MLC optical system.[Chinese Medical Equipment Journal,2024,45(1):76-83]