1.Construction of a full-cycle management model for T2DM patients led by clinical pharmacists
Yuanyuan JIANG ; Guimei ZHENG ; Yaohua CAO ; Zeyu XIE ; Weiling CAO
China Pharmacy 2026;37(1):92-98
OBJECTIVE To establish a full-cycle management model for type 2 diabetes mellitus (T2DM) patients led by clinical pharmacists. METHODS Based on literature research, a basic framework and items of full-cycle management model led by clinical pharmacists were initially formulated. The Delphi method was adopted to conduct questionnaire inquiries among 26 experts to determine the specific implementation items of the model. The analytic hierarchy process (AHP) method was used to determine the weight values of items at all levels, and the reliability and validity of the model items were analyzed. RESULTS The recovery rates of the two rounds of expert consultation questionnaires were 86.67% and 100%, respectively, and the expert authority coefficient was 0.88. Kendall’s concordance coefficients of the tertiary-level items were 0.064 and 0.084, respectively, and the P values from the χ 2 tests were all less than 0.05; the consistent ratios of the judgment matrices for all levels of AHP model were all less than 0.1. The established full-cycle management led by clinical pharmacists comprised three primary-level items (pharmacy service pathway for T2DM patients during hospitalization, pharmacy management pathway for hypoglycemia in T2DM inpatients, and the pharmacy follow-up pathway for T2DM discharged patients, with weights of 0.098, 0.568 and 0.334, respectively), twelve secondary-level items (e.g. pharmaceutical care during hospitalization for 1 to 2 days, admission assessment and education, with weights ranging from 0.143 to 0.333) and thirty-seven tertiary-level items (e.g. assessment of medication compliance, verification of the medication plan for discharge, with weights ranging from 0.068 to 0.750). Cronbach’s α coefficients for primary-level items and the overall questionnaire were 0.762, 0.879, 0.928 and 0.951, respectively. The item-level and scale-level content validity indexes were 0.967 and 0.808, respectively. CONCLUSIONS A full-cycle management model for T2DM patients led by clinical pharmacists has been constructed successfully, demonstrating high scientificity and reliability.
2.Ameliorative effect and mechanism of Forsythia suspensa-Lonicera japonica herb pair on acute lung injury via regulating serum exosomal miRNA
Zhaohua CHEN ; Shumin XIE ; Wanshun CHANG ; Yuqing HAN ; Yanwen CHEN ; Yanhui ZHU ; Mingzhuo CAO ; Haiying HUANG
China Pharmacy 2026;37(3):305-310
OBJECTIVE To study the ameliorative effect and mechanism of Forsythia suspensa-Lonicera japonica herb pair on acute lung injury (ALI) based on serum exosomal microRNA (miRNA). METHODS The rats were randomly divided into a blank group (normal saline), model group (nomal saline), and F. suspensa-L. japonica herb pair group (2.55 g/kg), with 10 rats in each group. Except for the blank group, the other groups were used to establish an ALI model by intratracheal dripping of 5 mg/ mL lipopolysaccharides. After modeling, each group was given relevant medicine/normal saline intragastrically, once a day, for 3 consecutive days. After the last medication, the pathological status of lung tissue was observed; lung wet-to-dry weight ratio and leukocyte counts in bronchoalveolar lavage fluid (BALF) were determined. The levels of inflammatory factors [tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), IL-10] in BALF were determined. Exosomes were isolated from rat serum, and high- throughput sequencing technology was employed to screen differentially expressed miRNA within the exosomes, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Based on the screened differentially expressed miRNA and the enriched KEGG pathways, in vitro cellular experiments were conducted for validation. RESULTS The animal experimental results demonstrated that after intervention with the F. suspensa-L. japonica herb pair, the wet-to-dry weight ratio, the number of leukocytes in BALF, as well as the levels of TNF-α and IL-1β in BALF of ALI rats were all significantly reduced (P<0.01), while the level of IL-10 was significantly increased (P<0.01). The results of high-throughput sequencing experiments revealed that the F. suspensa-L. japonica herb pair could significantly up-regulate the expressions of miR-345-3p, miR-194-5p, miR-653-5p, and others in exosomes. Among them, the KEGG pathways involved in the target genes of differentially expressed miRNA included the hypoxia-inducible factor-1(HIF-1) signaling pathway, among others. The results of cellular E-mail:huang.haiying@126.com validation experiments showed that overexpressed miR-345-3p could significantly elevate the level of IL-10 in the cell supernatant (P<0.01), while significantly reducing the levels of TNF-α and IL-1β in the cell supernatant, as well as the mRNA and protein expression levels of protein kinase B1, phosphatidylinositol 3- kinase, and HIF-1α (P<0.01). CONCLUSIONS F. suspensa-L. japonica herb pair can alleviate inflammatory responses and thereby exert a therapeutic effect in improving ALI by up-regulating the expression of miR-345-3p in serum exosomes and inhibiting the activity of the HIF-1 signaling pathway.
3.Mechanisms of Qiaobai cold compress solution in improving acne vulgaris based on transcriptomics and experiment
Zhenjiang XIE ; Weina ZHU ; Liangliang CAO ; Fuqiong ZHOU ; Shupan ZHANG ; Bingwen ZHOU ; Yinsheng CHEN ; Wen LI ; Ying ZHAO
China Pharmacy 2026;37(4):425-430
OBJECTIVE To investigate the mechanism by which Qiaobai cold compress solution (QBCS) improves acne vulgaris (AV) based on transcriptomics and animal experiments. METHODS Rats were randomly divided into a blank control group ( n =6) and a modeling group ( n =30). AV models were established in the modeling group by topical application of oleic acid to the inner surface of both ears, combined with subcutaneous injection of Cutibacterium acnes suspension into the auricle. Successfully modeled rats were further divided into the model group, positive control group (Tretinoin cream, 0.045 g/kg), and QBCS low-, medium-, high-dose groups [3.55, 7.11, 14.22 g/kg (calculated by the amount of crude drug) ] , with 6 rats in each group. Rats in each d rug group were treated with the corresponding drugs once daily for 14 consecutive days. After the final administration, changes in the appearance of the ears and histopathological changes in the ear tissues were observed, and serum levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β, were measured. Auricular tissues from the blank control group, model group and QBCS medium-dose group were collected for transcriptome sequencing. Differential expressed genes (DEGs) were screened and subjected to Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, followed by validation using real-time quantitative polymerase chain reaction and Western blot assay. RESULTS Compared with the model group, rats in all QBCS groups showed alleviated auricular acne symptoms, with reduced epidermal thickening, sebaceous gland hyperplasia, and inflammatory cell infiltration. Serum levels of TNF-α (except for the QBCS low-dose group), IL-6 (except for the QBCS low-dose group) and IL-1β were significantly decreased ( P <0.05). A total of 590 DEGs were identified (blank control group vs. model group), and 596 DEGs were identified (model group vs. QBCS medium-dose group). Above DEGs (blank control group vs. model group) were mainly enriched in Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signaling pathways, etc. Validation experiments showed that, compared with model group, low-, medium- and high-dose of QBCS reduced, to varying degrees, the mRNA expression of TNF-α, TLR2, interferon-γ and CXC chemokine ligand 8 in the auricular tissues of AV rats, increased the mRNA expression of peroxisome-proliferator-activated receptor gamma and tumor protein 53, and inhibited the phosphorylation of NF-κB p65 protein as well as the expressions of TLR2 and myeloid differentiation primary response protein 88(MyD88) ( P <0.05). CONCLUSIONS QBCS can alleviate auricular inflammation and skin lesions in AV rats. This effect may be related to inhibition of the TLR/MyD88/NF-κB signaling pathway, thereby suppressing the expression of downstream inflammatory factors such as TNF-α.
4.Preparation and activity identification of hepatitis B core protein virus-like particles containing PD-1 B cell epitopes
XIE Nuotong1,2 ; CAO Xinyu1,3 ; ZHOU Li4 ; LI Yulin1 ; ZHANG Nan5 ; ZHANG Xinwei3 ; WANG Yunlong1,3
Chinese Journal of Cancer Biotherapy 2026;33(2):140-146
[摘 要] 目的:建立一种以乙型肝炎病毒核心蛋白(HBc)病毒样颗粒(VLP)为骨架,嵌合PD-1 B细胞表位的重组颗粒蛋白,研究其对小鼠结直肠癌(CRC)的抑制效果。方法:设计PD-1 HBc VLP质粒并导入BL21(DE3)获得重组PD-1 HBc VLP表达菌株后,通过优化培养温度,实现蛋白可溶性表达,经硫酸铵沉淀、Sepharose 4 Fast Flow尺寸排阻层析和DEAE阴离子树脂层析纯化获得高纯度的PD-1 HBc VLP。采用电泳、WB、HPLC及电镜手段对其表达水平、蛋白纯度、颗粒形成率、形态特征及抗原结合活性等特征进行系统表征,ELISA测定免疫小鼠后的血清效价,评价其免疫原性,构建CT26细胞CRC小鼠移植瘤模型,通过监测PD-1 HBc VLP治疗后小鼠体质量和肿瘤体积变化,评估PD-1 HBc VLP抗肿瘤活性。结果:在28 ℃条件下,可溶性目的蛋白表达量占总蛋白的10.27%,多步纯化后目的蛋白纯度为(91.77 ± 0.62)%,分子量为23 000,电镜测定粒径为(31.90 ± 1.88) nm,粒径仪测定粒径为(30.66 ± 0.62) nm,多分散指数(PDI)为(0.18 ± 0.05)。WB结果显示,PD-1 HBc VLP重组蛋白可分别与HBc VLP抗血清和PD-1抗体结合。ELISA结果显示,经PD-1 HBc VLP 3次免疫后,第14天小鼠血清中总抗体效价为1∶640 000,其中抗PD-1的效价为1∶40 000。抗肿瘤实验表明,PD-1 HBc VLP组小鼠的肿瘤抑制率为(27.99 ± 2.98)%,对照组在45 d全部死亡,PD-1 HBc VLP组中位生存期延长20 d。结论:成功制备了以HBc VLP为骨架,嵌合PD-1 B细胞表位的PD-1 HBc VLP,且对小鼠结直肠癌有治疗效果。
5.Safety of endoscopic variceal ligation and endoscopic cyanoacrylate injection in treatment of esophagogastric varices in patients with liver cirrhosis and influencing factors for postoperative bleeding
Luyao JIA ; Baoying CAO ; Chunming HUANG ; Biao XIE ; Hongbo GAO ; Chuo LI ; Qinghua HUANG
Journal of Clinical Hepatology 2026;42(2):356-361
ObjectiveTo investigate the risk factors for bleeding within 5 days and 2 weeks after endoscopic variceal ligation (EVL) or endoscopic cyanoacrylate injection (ECI) for the treatment of esophagogastric varices in patients with liver cirrhosis, as well as the safety of EVL/ECI in patients with thrombocytopenia. MethodsA total of 489 patients with liver cirrhosis and esophagogastric varices who underwent EVL/ECI in Guangzhou Eighth People’s Hospital, Guangzhou Medical University, from January 2018 to December 2023 were enrolled as subjects, and according to the presence or absence of bleeding after surgery, they were divided into bleeding group and non-bleeding group. The risk factors for bleeding within 5 days and 2 weeks after surgery were analyzed. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test or the continuity-corrected chi-square test was used for comparison of categorical data between groups; the receiver operating characteristic (ROC) curve was plotted to determine the cut-off value of MELD score; a multivariate logistic regression analysis was used to identify the independent risk factors for postoperative bleeding. ResultsThere were no significant differences in the bleeding rates within 5 days and 2 weeks after EVL/ECI between the 386 patients with a platelet count of ≥50×109/L and the 103 patients with a platelet count of (25 — 49)×109/L (5 days: 1.94% vs 2.85%, P=0.870; 2 weeks: 2.91% vs 4.92%, P=0.544). The overall bleeding rate was 2.66% (13/489) and 4.50% (22/489), respectively, within 5 days and 2 weeks after EVL/ECI. The multivariate logistic regression analysis showed that MELD score was an independent risk factor for bleeding within 5 days (odds ratio [OR]=3.726, 95% confidence interval [CI]: 1.214 — 11.429, P=0.021) and 2 weeks (OR=5.760, 95%CI: 1.779 — 18.651, P=0.003) after EVL/ECI, while hemoglobin (Hb) was a protective factor against bleeding within 5 days (OR=0.972, 95%CI: 0.948 — 0.996, P=0.025) and 2 weeks (OR=0.976, 95%CI: 0.957 — 0.995, P=0.016) after surgery; portal vein tumor thrombus (OR=2.667, 95%CI: 1.000 — 7.117, P=0.050) was an independent risk factor for bleeding within 2 weeks after surgery, while platelet count [(25 — 49)×10⁹/L] was not a risk factor for postoperative bleeding (P>0.05). ConclusionBoth EVL and ECI have good safety in patients with liver diseases and grade 3 thrombocytopenia. MELD score is an independent risk factor for bleeding within 5 days and 2 weeks after EVL/ECI, while Hb is a protective factor; portal vein tumor thrombus is an independent risk factor for bleeding within 2 weeks after surgery.
6.Mechanism of Yishen Tongluo Formula regulating the TLR4/MyD88/NF-κB signaling pathway to ameliorate pyroptosis in diabetic nephropathy mice
Yifei ZHANG ; Zijing CAO ; Zeyu ZHANG ; Xuehui BAI ; Jingyi TANG ; Junyu XI ; Jiayi WANG ; Yiran XIE ; Yuqi WU ; Xi GUO ; Zhongjie LIU ; Weijing LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):21-33
Objective:
To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway.
Methods:
Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue.
Results:
Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated.
Conclusion
Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.
7.Yishen Tongluo Prescription Ameliorates Oxidative Stress Injury in Mouse Model of Diabetic Kidney Disease via Nrf2/HO-1/NQO1 Signaling Pathway
Yifei ZHANG ; Xuehui BAI ; Zijing CAO ; Zeyu ZHANG ; Jingyi TANG ; Junyu XI ; Shujiao ZHANG ; Shuaixing ZHANG ; Yiran XIE ; Yuqi WU ; Zhongjie LIU ; Weijing LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):41-51
ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease (DKD) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) signaling pathway. MethodsSpecific pathogen-free (SPF) male C57BL/6 mice were assigned into a control group (n=10) and a modeling group (n=50). The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group, a semaglutide (40 μg·kg-1) group, and high-, medium-, and low-dose (18.2, 9.1, 4.55 g·kg-1, respectively) Yishen Tongluo prescription groups, with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured, and the kidney index (KI) was calculated. Serum levels of creatinine (SCr), blood urea nitrogen (BUN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin, periodic acid-Schiff, periodic acid-silver methenamine, and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty acid-binding protein (L-FABP), nitric oxide synthase (NOS), glutathione (GSH), total antioxidant capacity (T-AOC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 (Keap1) and malondialdehyde (MDA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group, the DKD model group showed rises in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with glomerular hypertrophy, renal tubular dilation, thickened basement membrane, mesangial expansion, and collagen deposition. Additionally, the model group showed elevated levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, lowered levels of GSH and T-AOC, up-regulated expression of MDA and Keap1, and down-regulated expression of Nrf2, HO-1, NQO1, and glutamate-cysteine ligase catalytic subunit (GCLC) (P<0.05). Compared with the model group, the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with alleviated pathological injuries in the renal tissue. In addition, the three groups showed lowered levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, elevated levels of GSH and T-AOC, down-regulated expression of MDA and Keap1, and up-regulated expression of Nrf2, HO-1, NQO1, and GCLC (P<0.05). ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway, mitigating oxidative stress, and reducing renal tubular injuries.
8.Signal mining and analysis of adverse drug events of tirzepatide
Zeyu XIE ; Zhuoru LIANG ; Guimei ZHENG ; Weiling CAO ; Jisheng CHEN
China Pharmacy 2025;36(8):956-960
OBJECTIVE To identify and analyze adverse drug event (ADE) signals associated with tirzepatide based on the FDA Adverse Event Reporting System (FAERS) database, providing a reference for clinical medication safety. METHODS ADE reports from January 1, 2022, to June 30, 2024, with tirzepatide as the primary suspected drug, were extracted from the FAERS database. Medical Dictionary for Regulatory Activities was used to systematically categorize the selected system organ class (SOC) and preferred term of ADE. Signal mining and analysis were performed using the reporting odds ratio method and the proportional reporting ratio method. RESULTS A total of 39 229 ADE reports related to tirzepatide were obtained, including 3 934 severe ADE reports (10.03%). The majority of severe ADE reports were related to hospitalization or prolonged hospitalization (3.82%), involving 131 positive ADE signals. Among the reports with documented patient gender and age, 26 195 were female (66.77%), 7 869 were male (20.06%), and the majority of patients were aged 18-64 years (54.26%). The top three most frequently reported ADE were injection site pain, nausea, and injection site hemorrhage. Strong ADE signals not mentioned in the tirzepatide instruction included injection site coldness, starvation ketoacidosis, injection site hemorrhage, hunger, elevated adrenaline, injection site skin cracking, binge eating, skin laxity, intestinal sepsis, lack of satiety, and dysesthesia. Subgroup analysis for patient’s gender and age showed differences in the proportion of ADE reports across different SOC. Male patients or those aged≥65 years had a higher risk of gastrointestinal system disorders compared to female patients or those aged <65 years. CONCLUSIONS In clinical use of tirzepatide, in addition to monitoring ADE listed in the instruction, attention should also be paid to ADE not mentioned in the instruction, such as injection site coldness, starvation ketoacidosis, injection site hemorrhage, elevated adrenaline, and intestinal sepsis, to ensure patient safety.
9.Rapid health technology assessment of tirzepatide for diabetes mellitus type 2 and long-term weight management
Zeyu XIE ; Yinuo LIU ; Zhuoru LIANG ; Yaohua CAO ; Guimei ZHENG ; Weiling CAO
China Pharmacy 2025;36(9):1141-1146
OBJECTIVE To evaluate the efficacy, safety and cost-effectiveness of tirzepatide for diabetes mellitus type 2 (T2DM) and long-term weight management, and provide evidence-based basis for clinical drug treatment and health insurance policy formulation. METHODS Computer searches were conducted in Embase, PubMed, the Cochrane Library, CNKI and health technology assessment (HTA) official website from their inception to October 1st 2024 to collect HTA report, systematic review/ meta-analysis and pharmacoeconomic study on tirzepatide for the treatment of T2DM or for weight management. After data extraction and quality evaluation, descriptive analysis was performed on the research results. RESULTS Totally 18 papers were included, including 14 systematic reviews/meta-analyses and 4 pharmacoeconomics studies, and no HTA report was retrieved. In terms of efficacy, most results showed that the tirzepatide 10 mg and 15 mg were significantly better than other glucagon-like peptide-1 (GLP-1) receptor agonists in reducing glycosylated hemoglobin, body weight, and waist circumference (P<0.05). In terms of safety, compared with other GLP-1 receptor agonists, tirzepatide did not increase the incidence of gastrointestinal-related adverse events (AE), the incidence of AE of grade ≥3, or the incidence of severe hypoglycemia (P>0.05). However, tirzepatide 15 mg may significantly increased the incidence of hypoglycemia and the rate of discontinuation due to adverse reactions (P< 0.05). In terms of cost-effectiveness, based on the background of foreign pharmacoeconomic studies, tirzepatide was more cost- effective compared to semaglutide and liraglutide in the treatment of T2DM or for weight management. CONCLUSIONS Tirzepatide at doses of 10 mg and 15 mg has good efficacy and safety for the treatment of T2DM and for long-term weight management. However, when using the 15 mg dose of tirzepatide, close monitoring is required due to the risk of hypoglycemia and discontinuation due to adverse reactions it may pose. Based on pharmacoeconomic studies conducted abroad results, tirzepatide exhibits economic advantages.
10.Shaoyaotang Containing Serum Mediates Fas/FasL Pathway to Inhibit Lipopolysaccharide Induced Inflammation and Apoptosis of Caco-2 Cells
Yuting YANG ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Nianjia XIE ; Bo ZOU ; Daguang CHEN ; Erle LIU ; Yi LU ; Zhaowen LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):62-69
ObjectiveTo investigate the effects of different concentrations of Shaoyaotang-containing serum on lipopolysaccharide (LPS)-induced inflammation of human colorectal adenocarcinoma (Caco-2) cells by inhibiting apoptosis via activating the tumor necrosis factor (TNF) receptor superfamily member 6 (Fas)/Fas ligand (FasL) pathway. MethodsCaco-2 cells were allocated into blank, model (LPS, 10 mg·L-1), Shaoyaotang-containing serum (5%, 10%, 15%, 20%), and Fas inhibitor (KR-33493, 20 mmol·L-1) groups. Except the blank group, the other groups were stimulated with 10 mg·L-1 LPS for 24 h for the modeling of inflammation. After successful modeling, the blank, Fas inhibitor, and model groups were treated with blank serum, and the Shaoyaotang-containing serum groups were treated with the serum samples at corresponding concentrations for 24 h. The Fas inhibitor group was subjected to KR-33493 pretreatment for 1 h. Cell proliferation and viability were examined by the cell-counting kit-8 (CCK-8) method. The levels of interleukin (IL)-6, IL-1β, and TNF-α were measured by enzyme-linked immunosorbent assay. Apoptosis was detected by flow cytometry. The protein and mRNA levels of Fas, FasL, cysteinyl aspartate-specific proteinase (Caspase)-3, Caspase-9, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), respectively. ResultsCompared with the blank group, the model group presented a decrease in cell survival rate (P<0.01). Compared with that in the model group, the cell survival rate showed no significant change in the 5% Shaoyaotang-containing serum group but increased in the 10%, 15%, and 20% Shaoyaotang-containing serum groups (P<0.01). Since there was no statistical difference between the 5% Shaoyaotang-containing serum group and the model group, 10%, 15%, and 20% Shaoyaotang-containing sera were selected for the follow-up study. Compared with the blank group, the model group showed risen levels of IL-6, IL-1β, and TNF-α (P<0.01), an increased apoptosis rate (P<0.01), up-regulated protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.01), and down-regulated protein and mRNA levels of Bcl-2 (P<0.01). Compared with the model group, the Fas inhibitor group and the 10%, 15%, and 20% Shaoyaotang-containing serum groups showed declined levels of IL-6, IL-1β, and TNF-α (P<0.01), decreased apoptosis rates (P<0.01), down-regulated protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.05, P<0.01), and up-regulated protein and mRNA levels of Bcl-2 (P<0.05, P<0.01). In addition, the 15% and 20% Shaoyaotang-containing serum groups had lower levels of IL-6, IL-1β, and TNF-α (P<0.05, P<0.01), lower apoptosis rates (P<0.05, P<0.01), lower protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.05, P<0.01), and higher protein and mRNA levels of Bcl-2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can reduce the content of inflammatory factors in Caco-2 cells, down-regulate the protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax, and up-regulate the protein and mRNA levels of Bcl-2 under the intervention of LPS by regulating the Fas/FasL pathway and inhibiting the apoptosis of intestinal epithelial cells in ulcerative colitis.


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