1.Analysis of clinical use of drugs for lung cancer treatment in a hospital
Shuang LIU ; Yanqiu WU ; Hongbin YI ; Liping KUAI ; Dongyan XU ; Jianhua TANG
Journal of Pharmaceutical Practice and Service 2026;44(3):152-159
Objective To compare and analyze the changes in the use of lung cancer therapeutic drugs before and after the national initiation of health insurance negotiations, and to study the impact of a series of policies on the use of lung cancer drugs. Methods Descriptive statistical methods were used analyze the basic situation of lung cancer patients and the changes of corresponding therapeutic drugs in Peking University People's Hospital from 2014 to 2020, as well as to the hospital procurement data of lung cancer therapeutic drugs in the database of the Chinese Medicine Economic Information. Results From 2014 to 2020, the total cost per capita of lung cancer patients showed a trend of first increasing and then decreasing, increasing before the national drug negotiation and gradually decreasing after the negotiation. After 2017, the use of small ATC categories such as VEGF/VEGFR inhibitors and EGFR tyrosine kinase inhibitors increased significantly, along with a rise in the number of monoclonal antibody varieties. The DDDs of osimertinib, anlotinib, alectinib, crizotinib and other drugs in the medical insurance list increased significantly, and the average daily cost decreased significantly. Conclusion The number of hospitalization days for lung cancer patients had continued to shorten in recent years, and the structure of drug use had changed significantly. The adjustment of the medical insurance catalog had led to more innovative lung cancer drugs showing the trend of volume up and price down.
2.Preparation and hydrolytic activity analysis of dual-catalytic-triad PETase
Qiudong SU ; Xining YAO ; Feng QIU ; Feng WANG ; Shuang ZHANG ; Ke XU ; Shengli BI ; Yanhai WANG
Acta Universitatis Medicinalis Anhui 2026;61(3):546-551
ObjectiveTo prepare a recombinant PETase with a dual-catalytic-triad and to evaluate its efficiency in the biodegradation of polyethylene terephthalate (PET). MethodsBased on the crystal structure of wild-type PETase, point mutations (T88H/L117D) were introduced via site-directed mutagenesis. The recombinant protein was prepared using prokaryotic expression and chromatography purification techniques. The enzymatic hydrolysis of the mutant PETase was assessed by relatively quantifying the products mono (2-hydroxyethyl) terephthalate (MHET) and terephthalic acid (TPA). ResultsBoth wild-type and mutant PETases accumulated as inclusion bodies, accounting for approximately 20% of the total bacterial protein. After solubilization in urea, the proteins were eluted at 300 mmol/L imidazole during affinity chromatography purification, with concentrations of 1.824 and 1.833 mg/mL and purities of 83.11% and 84.32%, respectively. Subsequent anion-exchange chromatography yielded highly pure enzymes in the 200 mmol/L NaCl fraction: 2.776 mg/mL (96.86% purity) for the wild type and 1.967 mg/mL (95.13% purity) for the mutant. Following refolding, the final concentrations were 0.484 mg/mL for the wild type and 0.991 mg/mL for the mutant. Hydrolysis assays revealed that the mutant released MHET and TPA at (237.67±17.00)% and (197.33±12.01)% of the wild-type levels, respectively. ConclusionThe T88H/L117D dual-catalytic-triad PETase is successfully prepared and it significantly enhanced PET-degrading activity, thus, it′s a promising biocatalyst for PET bioremediation.
3.Analysis of Clinical and Phenomics Characteristics of Patients with Phlegm-Stasis Binding Syndrome and Its Accompanied Patterns in Stable Angina Pectoris of Coronary Heart Disease
Chongchai LI ; Han LI ; Zheng LI ; Zeng LI ; Yushi ZHOU ; Yuhan AO ; Shuang XU ; Xue WANG ; Yaoyao SUN ; Dongning WU ; Hongcai SHANG ; Mingxue ZHANG
Journal of Traditional Chinese Medicine 2026;67(14):1514-1522
ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris (SAP) of coronary heart disease (CHD). MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome, 125 cases of qi deficiency-accompanied syndrome, 38 cases of qi stagnation-accompanied syndrome, and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine (TCM) patterns. Data of patients with different TCM patterns were collected, including general condition, TCM symptoms, blood lipids, coagulation function, immune indicators, and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection (VIP) ≥1 and fold change (FC) ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group, with a relatively high proportion of males. Regarding TCM symptoms, patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse, chest pain, and chest tightness; in patients with qi deficiency-accompanied syndrome, fatigue, chest pain, and weak pulse were most common; in patients with qi stagnation-accompanied sydnrome, wiry-choppy or wiry-slippery pulse, chest pain, and symptoms that increase or decrease with emotional changes, belching, or flatulence were most common; in patients with toxin accumulation-accompanied syndrome, bitter taste in the mouth, chest tightness, irritability, restlessness or manic delirium, and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters (P<0.05), whereas no statistically significant difference was found in blood lipid levels and immune indicators (P>0.05).Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine, leucine, and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin (FC = 3.58) and oxypurinol (FC = 124.50). Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine (FC = 2.62) and D-mannosamine (FC = 2.99). Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine (FC = 7.83) and canrenone (FC = 8.94). ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders, amino acid metabolism abnormalities, and multiple immune indicators activation, which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.
4.Analysis of Clinical and Phenomics Characteristics of Patients with Phlegm-Stasis Binding Syndrome and Its Accompanied Patterns in Stable Angina Pectoris of Coronary Heart Disease
Chongchai LI ; Han LI ; Zheng LI ; Zeng LI ; Yushi ZHOU ; Yuhan AO ; Shuang XU ; Xue WANG ; Yaoyao SUN ; Dongning WU ; Hongcai SHANG ; Mingxue ZHANG
Journal of Traditional Chinese Medicine 2026;67(14):1514-1522
ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris (SAP) of coronary heart disease (CHD). MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome, 125 cases of qi deficiency-accompanied syndrome, 38 cases of qi stagnation-accompanied syndrome, and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine (TCM) patterns. Data of patients with different TCM patterns were collected, including general condition, TCM symptoms, blood lipids, coagulation function, immune indicators, and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection (VIP) ≥1 and fold change (FC) ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group, with a relatively high proportion of males. Regarding TCM symptoms, patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse, chest pain, and chest tightness; in patients with qi deficiency-accompanied syndrome, fatigue, chest pain, and weak pulse were most common; in patients with qi stagnation-accompanied sydnrome, wiry-choppy or wiry-slippery pulse, chest pain, and symptoms that increase or decrease with emotional changes, belching, or flatulence were most common; in patients with toxin accumulation-accompanied syndrome, bitter taste in the mouth, chest tightness, irritability, restlessness or manic delirium, and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters (P<0.05), whereas no statistically significant difference was found in blood lipid levels and immune indicators (P>0.05).Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine, leucine, and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin (FC = 3.58) and oxypurinol (FC = 124.50). Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine (FC = 2.62) and D-mannosamine (FC = 2.99). Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine (FC = 7.83) and canrenone (FC = 8.94). ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders, amino acid metabolism abnormalities, and multiple immune indicators activation, which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.
5.Renal Protective Effect of Tongxinluo Submicron Powder on Mice with Diabetic Kidney Disease Based on PANoptosis
Huinan XU ; Haorui XU ; Tao LIU ; Shuang SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(17):155-163
ObjectiveTo investigate the role and underlying mechanisms of Tongxinluo submicron powder in regulating renal PANoptosis, alleviating pathological injury in diabetic kidney disease (DKD), reducing urinary albumin excretion, and improving renal function in DKD mice. MethodsSix 6-week-old male C57BL/Ks mice were assigned into the normal group. Eighteen 6-week-old male BKS-db;Nos3KO mice were randomly divided into three groups: model group, Tongxinluo group (0.75 g·kg-1·d-1), and dapagliflozin group (0.001 g·kg-1·d-1), and were administered by gavage for 12 consecutive weeks. General conditions of the mice were observed. At weeks 0, 4, 8, and 12 after administration, body weight, fasting blood glucose (FBG), urine albumin-to-creatinine ratio (UACR), and urinary albumin excretion rate (AER) were measured. After treatment, mice were anesthetized for sample collection. Blood was obtained by orbital enucleation and centrifuged to collect supernatant. Serum creatinine (SCr), urea (UREA), β2-microglobulin (β2-MG), retinol-binding protein (RBP), and serum cystatin C (CysC) were measured. Renal histopathological changes were evaluated using hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and Masson's trichrome staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α). Serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were also measured. Western blot analysis was performed to quantify the expression of key PANoptosis-related proteins in renal tissue, including Z-DNA-binding protein 1 (ZBP1), Caspase-1, cleaved Caspase-1, gasdermin D (GSDMD) and its N-terminal fragment (GSDMD-N), Caspase-8, cleaved Caspase-8, Caspase-3, cleaved Caspase-3, mixed lineage kinase domain-like protein (MLKL), and phosphorylated MLKL (p-MLKL). ResultsCompared with the normal group, the model group showed significant obesity and continuously increased blood glucose levels (P<0.05). Renal function indicators (UREA, β2-MG, CysC) were significantly increased (P<0.05), and urinary albumin excretion indicators (UACR, AER) were markedly elevated (P<0.05). Renal histopathology showed enlarged glomeruli, diffuse thickening of the basement membrane, and significant expansion of the mesangial matrix. Masson staining revealed extensive blue collagen fiber deposition, suggesting glomerulosclerosis and interstitial fibrosis. Meanwhile, serum levels of inflammatory cytokines (IL-1β, IL-18, and TNF-α) were significantly increased (P<0.05). SOD and GSH-Px levels were decreased, while MDA levels were increased (P<0.05). The expression of key PANoptosis-related proteins (ZBP1, cleaved Caspase-1, GSDMD, GSDMD-N, cleaved Caspase-8, Caspase-3, cleaved Caspase-3, and p-MLKL) in renal tissue was significantly upregulated (P<0.05). After intervention, compared with the model group, renal function indicators (UREA, β2-MG, CysC) and urinary albumin excretion indicators (UACR, AER) in the Tongxinluo group were significantly decreased (P<0.05), and all were superior to those in the dapagliflozin group (P<0.05). Renal pathological injury was markedly alleviated, with reduced mesangial proliferation and collagen fiber deposition. In addition, serum levels of IL-1β, IL-18, and TNF-α were significantly decreased (P<0.05). SOD and GSH-Px levels were increased, while MDA levels were decreased (P<0.05). Western blot results showed that the expression of key PANoptosis-related proteins (ZBP1, cleaved Caspase-1, GSDMD, GSDMD-N, cleaved Caspase-8, Caspase-3, cleaved Caspase-3, and p-MLKL) in renal tissue was significantly downregulated (P<0.05). ConclusionTongxinluo submicron powder can inhibit renal PANoptosis in DKD mice, alleviate renal inflammatory response and pathological injury, reduce urinary albumin excretion, and improve renal function.
6.Cytotoxicity Studies of Light-oxygen-voltage (LOV) Domain Photosensitizers
Shuang XU ; Ben WAN ; Na SHA ; Kai-Hong ZHAO
Progress in Biochemistry and Biophysics 2025;52(2):487-500
ObjectiveAt present, the most commonly used photosensitizers in photodynamic therapy are still chemical photosensitizers, such as porphyrin and methylene blue, in order to specifically target cellular tissues, and thus poison cells, chemical photosensitizers need to use antibody conjugation or a transgenically encoded tag with affinity for the modified photosensitizing ligand, e.g. FlAsH, ReAsh or Halo Tag. Gene-encoded photosensitizers can directly poison cells by targeting specific cell compartments or organelles. However, currently developed gene-encoded photosensitizers have low reactive oxygen species production and low cytotoxicity, so it is necessary to continue to develop and obtain photosensitizers with higher reactive oxygen species production for the treatment of microbial infections and tumors. MethodsIn this study, we developed a photosensitizer LovPSO2 based on the light-oxygen-voltage (LOV) structural domain of phototropin-1B-like from Oryza sativa japonica. LovPSO2 was expressed in E. coli BL21(DE3) and purified to obtain protein samples, the purified protein samples were added 3 µmol/L singlet oxygen probe of SOSG and 5 µmol/L superoxide anion probe of DHE after fixed to A445=0.063±0.003, respectively, then measured every 2 min of singlet oxygen production for 10 min and every 1 min of superoxide anion production for 5 min under blue light irradiation at 445 nm, 70 µmol·m-2·s-1. ResultsThe results showed that LovPSO2 could produce a large amount of singlet oxygen under blue light irradiation at 445 nm, 70 µmol·m-2·s-1, and its singlet oxygen quantum yield was 0.61, but its superoxide anion yield was low, so in order to improve the superoxide anion yield of LovPSO2, a mutant with a relatively high superoxide anion yield was obtained by further development and design on its basis LovPRO2. The stability of proteins is crucial for research in drug development and drug delivery, among others. Temperature and light are the key factors affecting the production of reactive oxygen species (ROS) by photosensitive proteins and their stability, while the temperature in cell culture and mammals in vivo is about 37°C, and the temperature inside tumor cells is about 42-45°C. Therefore, we further analyzed the photostability of miniSOG, SOPP3, LovPSO2, and LovPRO2 and their thermostability at 37℃ and 45℃. The analysis of proteins thermostability showed that LovPSO2 and LovPRO2 had better thermostability at 37℃ and 45℃, respectively. Analysis of the photostability of the proteins showed that LovPRO2 had better photostability. In addition, to further determine the phototoxic effects of photosensitizers, LovPSO2 and LovPRO2 were expressed in E. coli BL21(DE3) and HeLa cells, respectively. The results showed that LovPSO2 and LovPRO2 had better phototoxicity to E. coli BL21(DE3) under blue light irradiation, and the cellular phototoxicity lethality was as high as 90% after 30 min of continuous light irradiation, but the phototoxicity was weaker in HeLa cells. The reason for this result may be that the intracellular environment exacerbated the photobleaching of FMN encapsulated by LovPSO2 and LovPRO2, respectively, which attenuated the damage of reactive oxygen species to animal cellular tissues, limiting its use as a mechanistic tool to study oxidative stress. ConclusionLovPSO2 and LovPRO2 can be used as antibacterial photosensitizers, which have broader application prospects in the food and medical fields.
7.The effect of different doses of butolphinol on levels of serum prolactin, serotonin and lipid hydrogen peroxide after cesarean section
Yongning ZHU ; Danni XU ; Shuang YANG ; Ning XIE ; Na XIAN ; Zhi JIA
Chinese Journal of Postgraduates of Medicine 2025;48(6):510-515
Objective:To analyze the effects of different doses of butorphanol on prolactin, serotonin and lipid hydrogen peroxide after cesarean section.Methods:A total of 124 women who underwent cesarean section in the Affiliated Hospital of Jining Medical University from January 2023 to January 2024 were prospectatively selected as study subjects, and divided into the study group 1 (41 cases), study group 2 (41 cases) and study group 3 (42 cases) according to random number table method. All three groups underwent patient-controlled analgesia after surgery, and 0.2 mg fentanyl was used as analgesic drug. However, the doses of butorphanol were 100 mg/L in the study group 1, 120 mg/L in the study group 2, and 140 mg/L in the study group 3. The level of PRL and first lactation time before and after surgery were compared among the three groups at different time points, serotonin and LHP levels were compared among the three groups at different time points after surgery, Ramsay and visual analog scale (VAS) scores were compared among the three groups at different time points after surgery, and the occurrence of adverse reactions and satisfaction with analgesic effect were compared among the three groups.Results:At 24, 48 and 72 h after operation, the level of PRL in the study group 3 was higher than that in the study group 2 and study group 1: (383.02 ± 47.57) μg/L vs. (376.39 ± 46.83), (302.88 ± 41.38) μg/L; (412.38 ± 40.22) μg/L vs. (394.82 ± 38.30), (315.09 ± 37.93) μg/L; (434.39 ± 39.39) μg/L vs. (427.48 ± 40.27), (344.39 ± 42.78) μg/L, there were statistical differences ( P<0.05). The first lactation time in the study group 2 and study group 3 was lower than that in the study group 1: (50.31 ± 6.52), (49.54 ± 6.27) h vs. (53.91 ± 8.42) h, there was statistical difference ( P<0.05). At 2 h (T 1), 12 h (T 2), 24 h (T 3) and 48 h (T 4) after surgery, the levels of serotonin in the study group 3, study group 2 and study group 1 were increased successively, and the levels of LHP were decreased successively, there were statistical differences ( P<0.05). At 30 min after surgery (T 0), T 1, T 2, T 3 and T 4, the Ramsay score in the study group 3, study group 2 and study group 1 were increased successively, and the VAS score were decreased successively, there were statistical differences ( P<0.05). There was no significant difference in the incidence of adverse reactions among the three groups ( P>0.05). The total satisfaction of study group 3 was higher than that of study group 2 and study group 1: 92.86%(39/42) vs. 73.17%(30/41), 68.29%(28/41), there was statistical difference ( Z = 2.52, P = 0.008). Conclusions:Butorphanol 140 mg/L has a more significant analgesic effect after cesarean section, and can improve the levels of serum PRL, serotonin and LHP, reduce the occurrence of adverse reactions, and improve the satisfaction of analgesia
8.Correlation of FBXL5 and IREB2 with iron homeostasis and efficacy of neoadju-vant chemotherapy in colorectal cancer
Miaomiao WANG ; Ruizhe ZHANG ; Xiaoyang XU ; Shuang HE ; Feifei WEN ; Yangyang LI ; Shuhua WU
Chinese Journal of Clinical and Experimental Pathology 2025;41(10):1280-1290
Purpose The current study aims to elucidate the interrelationships among IREB2,FBXL5,iron ho-meostasis,and the therapeutic efficacy of neoadjuvant chemotherapy.Methods A total of 97 samples,classified into colorectal cancer neoadjuvant chemotherapy-resistant and-sensitive groups,along with their corresponding paracancer-ous normal mucosa were collected.The expression levels of FBXL5,IREB2,TFRC and FTH1 were detected by immu-nohistochemistry,Werstern blot and RT-qPCR.The contents of ferroptosis-related markers Fe2+,MDA,ROS and GSH were detected by applying the kit,and the levels of these markers were analyzed.The relationship between each factor in different colorectal cancer tissues and tumor regression rate and prognosis of neoadjuvant chemotherapy were ana-lyzed.Results(1)The expression of IREB2,FBXL5,TFRC and FTH1 in colorectal cancer was higher than that in normal intestinal mucosa(P<0.05),and the expression of FBXL5 and FTH1 in colorectal cancer drug-resistant group was lower than that in the sensitive group,whereas the expression of IREB2 and TFRC was higher than that in the sen-sitive group(P<0.05);(2)The correlation analysis showed a positive correlation between the expression of IREB2 and TFRC in the drug-resistant group,and a negative correlation with the expression of FBXL5 and FTH1 in the drug-resistant group.TFRC expression in the colorectal cancer resistance group were positively correlated(P<0.05)and negatively correlated with the expression of FBXL5 and FTH1(P<0.05);(3)the content of Fe2+and GSH was high-er than that of the sensitivity group in the colorectal cancer resistance group,and the level of ROS was lower than that of the sensitivity group(P<0.05);(4)Fe2+was positively correlated with the expression of IREB2,TFRC,and neg-atively correlated with the expression of FBXL5 and FTH1,and was negatively correlated with the expression of FBXL5 and FTH1.FTH1 expression were both negatively correlated(P<0.05);(5)tumor regression rate was positively cor-related with the expression of FBXL5 and FTH1,and negatively correlated with the expression of IREB2 and TFRC,as well as positively correlated with the level of ROS,and negatively correlated with Fe2+and GSH(P<0.05);(6)The expression of IREB2 and TFRC was positively correlated with tumor diameter and lymph node metastasis,and the ex-pression of FBXL5 and FTH1 was negatively correlated with tumor diameter and lymph node metastasis,and the expres-sion of FBXL5 was also negatively correlated with the depth of tumor infiltration(P<0.05);(7)Kaplan-Meier analy-sis showed that lymph node metastasis,FBXL5,IREB2,TFRC,FTH1,and TRG grading were closely related to the prognosis of colorectal cancer patients(P<0.05).Cox multivariate regression analysis indicated that lymph node me-tastasis,high expression of IREB2 and TFRC,low expression of FBXL5 and FTH1,and low tumor regression grade(TRG)were risk factors for the ineffectiveness of neoadjuvant chemotherapy in colorectal cancer patients.Conclusion FBXL5 and IREB2 are not only associated with high iron homeostasis,but also closely related to the efficacy and prognosis of neoadjuvant chemotherapy for colorectal cancer.In the future,they may become new targets for the treat-ment of colorectal cancer and improve the prognosis of patients.
9.Mechanism of Regulating MK2 to Improve Bone Marrow Inflammatory Damage after Hematopoietic Stem Cell Transplantation.
Zhao-Hui WANG ; Bo LONG ; Yu-Han WANG ; Zhi-Ting LIU ; Zi-Jie XU ; Shuang DING
Journal of Experimental Hematology 2025;33(5):1453-1460
OBJECTIVE:
To investigate the role of MK2 inhibitor MMI-0100 on inflammatory response after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and related mechanisms.
METHODS:
An allo-HSCT mouse model was established. Recipient rats were randomly divided into BMT+NaCl group and BMT+MMI-0100 group, and were injected with NaCl and MMI-0100 every day after transplantation, respectively. Samples of the two groups were collected on d 7 and 14, femur paraffin sections were stained with HE, and pathological changes in the bone marrow cavity were observed under the light microscope. The gene and protein expression levels of pro-inflammatory cytokines IL-1β and IL-18 were detected by qPCR and Western blot. Macrophage typing was detected by flow cytometry. The expression levels of NLRP3 and Caspase-1 were detected by Western blot.
RESULTS:
Inflammatory cell infiltration in the bone marrow cavity was significantly reduced in the BMT+MMI-0100 group. Western blot results showed that the protein expression levels of IL-1β and IL-18 in the BMT+MMI-0100 group were decreased compared to the BMT+NaCl group on day 7 and day 14 (all P <0.01). The qPCR results showed that compared to the BMT+NaCl group, the IL-18 gene expression levels in the BMT+MMI-0100 group were significantly reduced on day 7 and day 14 (both P <0.01). In the BMT+MMI-0100 group, the expression level of IL-1β gene decreased on day 7 (P <0.05), but increased and was higher than that in the BMT+NaCl group on day 14 (P <0.05). Flow cytometry results showed that the expression of M1 macrophages and M1/M2 ratio decreased in the BMT+MMI-0100 group compared to BMT+NaCl group (all P <0.05). Western blot results showed that the protein expression levels of NLRP3 and Caspase-1 in the BMT+MMI-0100 group were lower than those in the BMT+NaCl group (all P <0.05).
CONCLUSION
MMI-0100 can ameliorate bone marrow inflammatory injury after allo-HSCT and may act by reducing NLRP3 expression to promote M2 polarization.
Animals
;
Interleukin-1beta/metabolism*
;
Rats
;
Interleukin-18/metabolism*
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
Mice
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Inflammation
;
Bone Marrow/pathology*
;
Protein Serine-Threonine Kinases/metabolism*
;
Intracellular Signaling Peptides and Proteins/antagonists & inhibitors*
;
Caspase 1/metabolism*
;
Macrophages
;
Transplantation, Homologous
10.Arthroscopic tissue engineering scaffold repair for cartilage injuries.
Zhenlong LIU ; Zhenchen HOU ; Xiaoqing HU ; Shuang REN ; Qinwei GUO ; Yan XU ; Xi GONG ; Yingfang AO
Journal of Peking University(Health Sciences) 2025;57(2):384-387
OBJECTIVE:
To standardize the operative procedure for tissue-engineered cartilage repair, by demonstrating surgical technique of arthroscopic implantation of decalcified cortex-cancellous bone scaffolds, and summarizing the surgical experience of the sports medicine department team at Peking University Third Hospital.
METHODS:
This article elaborates on surgical techniques and skills, focusing on the unabridged implantation technology and surgical procedure of decalcified cortex-cancellous bone scaffolds under arthroscopy: First, the patient was placed in the supine position. After anesthesia had been established, the surgeon established an arthroscope and explored the damaged area under the scope. After confirming the size and location of the injury site, the surgeon cleaned the damaged cartilage, and also trimmed the edges of the cartilage to ensure that the cut surface was smooth and stable. the surgeon performed the micro-fracture surgery in the area of cartilage injury, and then measured the size of the injured area under the scope. Next, the surgeon manually trimmed the tissue-engineered scaffold based on the measurements taken under the arthroscope, and then directly implanted the scaffold using a sleeve. A honeycomb-shaped fixator was used to implant absorbable nails to fix the scaffold. After the scaffold was installed, the knee was repeatedly flexed and extended for 10-20 times to ensure stability and range of motion. Finally, the arthroscope was withdrawn and the wound was closed.
RESULTS:
Decalcified cortex-cancellous bone scaffolds possessed unparalleled advantages over synthetic materials in terms of morphology and biomechanics. The cancellous bone part of the scaffold provided a three-dimensional, porous space for cell growth, while the cortical bone part offered the necessary mechanical strength. The surgery was performed entirely under arthroscopy to minimize invasiveness to the patient. Absorbable pins were used for fixation to ensure the stability of the scaffold. This technique could effectively improve the prognosis of the patients with cartilage injuries and standardized the surgical procedures for arthroscopic tissue-engineered scaffold operations in the patients with cartilage damage.
CONCLUSION
With the standard arthroscopic tissue-engineered scaffold repair technique, it is possible to successfully repair damaged cartilage, alleviate symptoms in the short term, and provide a more ideal long-term prognosis. The author and their team explain the surgical procedures for tissue-engineered scaffolds under arthroscopy, with the aim of guiding future clinical practice.
Tissue Engineering/methods*
;
Humans
;
Tissue Scaffolds
;
Arthroscopy/methods*
;
Cartilage, Articular/surgery*

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