1.Progress in Disease-Syndrome-Integrated Mouse Models of Lung Cancer
Yulei ZHAO ; Bingbing HAN ; Xingxin WANG ; Guangjian YANG ; Yajie WANG ; Xiaoyong TANG
Laboratory Animal and Comparative Medicine 2026;46(4):531-540
Lung cancer has the highest mortality rate among malignant tumors worldwide, posing a severe threat to human health. Traditional Chinese medicine (TCM) offers unique advantages in treating lung cancer, with disease-syndrome-integrated animal models serving as a critical component of TCM lung cancer research. According to TCM pathogenesis, lung cancer is classified as a pattern of underlying deficiency with superficial excess. Clinically, it is often categorized into syndromes such as qi and yin deficiency, lung-spleen qi deficiency, lung yin deficiency, qi stagnation and blood stasis, and phlegm-heat obstructing the lungs. Treatment should fundamentally adhere to the principle of "strengthening the healthy qi and expelling pathogenic factors". This paper systematically reviews literature from 2005 to 2025 on disease-syndrome-integrated animal models for lung cancer. It summarizes the theoretical basis and establishment methods of four core disease-syndrome-integrated models: qi-yin deficiency pattern, spleen qi deficiency pattern, qi stagnation and blood stasis pattern, and kidney deficiency pattern. Further discussion covers their evaluation systems and limitations. Additionally, modeling approaches for other patterns including yang deficiency, spleen deficiency, and qi deficiency with blood stasis are summarized, with evaluation methods categorized by behavioral characteristics and biochemical indicators. Analysis reveals that current models predominantly use C57BL/6 mice, exhibiting issues such as insufficient clinical relevance, complex modeling procedures, numerous confounding factors, and a low degree of standardization. Future improvements to disease-syndrome-integrated lung cancer animal models could include using clustered regularly interspaced short palindromic repeats (CRISPR) technology to establish organoid–patient-derived xenograft models; developing controllable composite stress systems and standardized stimulus models, such as gradient-controlled alternating cold/heat chambers and programmed dietary regulation systems, to reduce nonspecific interference; and developing multidimensional dynamic modeling techniques by integrating clinical big data, including metabolomics and imaging features, to design dynamic intervention protocols, thereby providing more precise and reliable experimental tools for elucidating the mechanisms of TCM in lung cancer prevention and treatment.
2.Experimental study on the method of establishing a pig left lung orthotopic transplantation model
Heng ZHAO ; Jinteng FENG ; Shan GAO ; Rui ZHAO ; Hongyi WANG ; Ye SUN ; Yixing LI ; Haotian BAI ; Runyi TAO ; Bin HE ; Zhiyu WANG ; Yanpeng ZHANG ; Borui SUN ; Shuo LI ; Guangjian ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(08):1275-1281
Objective To explore the method for establishing a pig left lung orthotopic transplantation model. Methods A total of 4 male Yorkshire pigs weighing (40.0±2.5) kg underwent surgical procedures, including anesthesia, tracheal intubation, donor lung procurement, and recipient lung transplantation. Histological morphology and blood gas analysis of the transplanted lungs were assessed 2 hours after reperfusion to evaluate the histological changes and function of the transplanted lungs. Results The pigs underwent left lung in situ transplantation, effectively simulating conditions relevant to human lung transplantation. Two hours after the transplantation, arterial blood gas analysis showed that arterial partial pressure of oxygen was 155.4-178.6 mm Hg, arterial partial pressure of carbon dioxide was 53.1-62.4 mm Hg, and the oxygenation index was 310.8-357.2 mm Hg. Hematoxylin and eosin staining indicated a low degree of pulmonary edema and minimal cellular infiltration. Conclusion The pig left lung orthotopic transplantation model possesses strong operability and stability. Researchers can replicate this model according to the described methods and further conduct basic research and explore clinical translational applications.
3.Research progress in the application of supercooling preservation technology in graft preservation
Heng ZHAO ; Jinteng FENG ; Bangrui YU ; Yixing LI ; Haotian BAI ; Haishui HUANG ; Guangjian ZHANG
Organ Transplantation 2025;16(3):394-403
Supercooling preservation technology, as a groundbreaking innovation in the field of organ preservation, significantly reduces the metabolic rate of cells and inhibits ice crystal formation by placing organs in a low-temperature environment near or below the freezing point. This technology extends the preservation time of organs and maintains their biological activity. Compared with the traditional low-temperature preservation at 4 °C, supercooling preservation effectively avoids cell damage and the accumulation of metabolic products, demonstrating significant advantages in the preservation of cells, tissues and organs. In recent years, important progress has been made in the optimization of cryoprotectants, the application of antifreeze proteins, the improvement of vitrification technology, and the development of nanotechnology-based rewarming techniques. These advancements provide new pathways to address the challenges of toxicity, ice crystal formation and uneven rewarming rates during supercooling preservation. This review summarizes the basic principles of supercooling preservation, the application of key technologies, and their practical effects in organ transplantation. It also analyzes the challenges of toxicity and rewarming efficiency, aiming to provide theoretical support and research directions for the future optimization of organ low-temperature preservation technology and its clinical application.
4.Discussion on right lung volume reduction techniques in lung transplantation surgery
Hongyi WANG ; Yixing LI ; Jinteng FENG ; Heng ZHAO ; Yanpeng ZHANG ; Shan GAO ; Jizhao WANG ; Shuo LI ; Guangjian ZHANG
Organ Transplantation 2025;16(6):907-913
Objective To investigate the clinical effects of different right lung volume reduction techniques when the donor lung is oversized and mismatched with the recipient. Methods Clinical data of 10 recipients who underwent right lung volume reduction lung transplantation at the First Affiliated Hospital of Xi'an Jiaotong University from October 2022 to June 2024 were collected, including gender, age, primary disease type, and type of transplantation. A retrospective analysis was performed on postoperative complications within 90 days, duration of mechanical ventilation, hospital stay, and survival status to explore the impact of different volume reduction techniques on the survival rate of lung transplant recipients. Results A total of 10 right lung volume reduction recipients were included in this study, with 2 cases of upper lobe reduction, 7 cases of middle lobe reduction, and 1 case of lower lobe reduction. Three recipients developed airway complications (one each with upper, middle, and lower lobe reduction). The 30-day survival rate was 90% and the 1-year survival rate was 70%. One recipient with upper lobe reduction died of septic shock during the perioperative period, one with lower lobe reduction died of airway anastomotic fistula 2 months after surgery, and one with middle lobe reduction died of renal insufficiency 1 year after surgery. All 7 recipients with middle lobe reduction successfully passed the perioperative period, with one case of airway anastomotic stenosis (1/7). The average duration of mechanical ventilation was 71 hours, and the average hospital stay was 26 days. The 30-day survival rate was 7/7, and the 1-year survival rate was 6/7. Conclusions Middle lobe reduction in right lung transplantation surgery has the advantages of low incidence of airway complications, good safety, and minimal loss of lung function, and may be a better right lung volume reduction option with potential for application.
5.Action mechanism by which fibronectin type Ⅲ domain-containing protein 5 inhibits macrophage pyroptosis
Guangjian ZHAO ; Danan LIU ; Bo ZHOU ; Yao WANG
Chinese Journal of Tissue Engineering Research 2024;28(25):4005-4012
BACKGROUND:Fibronectin type Ⅲ domain-containing protein 5(FNDC5)is a muscle factor that can regulate glucose and lipid metabolism,and exert anti-inflammatory,anti-oxidative effects and improvement in insulin resistance.Moreover,FNDC5 could control various cell pyroptosis. OBJECTIVE:To explore the effect and potential mechanism of FNDC5 on macrophage pyroptosis. METHODS:(1)After completing the construction of the lentivirus virus overexpressing FNDC5 or silencing FNDC5,the THP-1 cells were transfected with the lentivirus vector.The result of transfection was detected by the expression of green fluorescence,qPCR,and western blot assay.(2)Phorbol ester induced THP-1 cells to differentiate into macrophages.Oxidized low-density lipoprotein(ox-LDL)was added to induce the cell pyroptosis model.There were six groups,i.e.,NC group,ox-LDL group,ox-LDL+MOCK1 group,ox-LDL+Ov-FNDC5 group,ox-LDL+MOCK2 group,and ox-LDL+shFNDC5 group.(3)The level of cell pyroptosis was evaluated by Hoechst 33342/propidium iodide fluorescence double staining and lactate dehydrogenase release assay.The expression levels of related molecules in THP-1 cells were analyzed by qPCR and western blot assay.The interleukin-18 and interleukin-1β in cell supernatant were detected by ELISA. RESULTS AND CONCLUSION:Compared with the ox-LDL+MOCK1 group,overexpression of FNDC5 significantly reduced the pyroptosis rate of macrophages and the release levels of lactate dehydrogenase,interleukin-1β and interleukin-18,significantly inhibited the mRNA expression of NF-κB p65,NF-κB p50,NLRP3,ASC,Caspase-1,and GSDMD,and significantly inhibited the protein expression of NF-κB p65,NF-κB p50,NLRP3,ASC,cleaved Caspase-1 and GSDMD-N.Compared with the ox-LDL+MOCK2 group,the silence of FNDC5 showed the opposite result.These findings suggest that FNDC5 attenuates pyroptosis in macrophages by inhibiting the NF-κB/NLRP3 pathway.
6.A study on the association between exposure of uric acid accumulation and risks of acute pancreatitis
A'fang SU ; Guangjian LI ; Yunshui ZHANG ; Xiujuan ZHAO ; Shouling WU ; Xiaozhong JIANG
The Journal of Practical Medicine 2024;40(14):2009-2014
Objective To investigate the correlation between exposure of uric acid accumulation and the risks of acute pancreatitis(AP)in the population in Kailuan Group.Methods A prospective study was performed based on thesubjects receiving annual physical examination during 2006 to 2010 in Kailuan Group.All of them had no AP history but had complete data on UA.The starting point of follow-up was when the subjects completed the health examination in 2010,and the end point was new AP events,deaths or the end of follow-up(2021-12-31).Exposure of uric acid accumulation(cumUA)was calculated according to the average values of uric acid measured in each two consecutive physical examinations and the intervalbetween these two consecutive physical examinations.The cumulative incidences of AP indifferent subgroups(determined by the quartile of cumUA)were described using Kaplan-Meier product limit-method and compared by log-rank test.Multivariate Cox proportional hazards regression model was used to analyze the impacts of different cumUA subgroups on new occurrence of AP events.Results A total of 55,799 subjects were included in this study.The subjects were divided into four groups according to the quartile of cumUA.Sex ratio,average age,BMI,systolic blood pressure(SBP),diastolic blood pressure(DBP),FPG,TC,TG,LDL-C,HDL-C,smoking,alcohol consumption,education≥9 years,physical exercise,history of hypertension,and history of cholelithiasis differed significantly among the groups(P<0.05),there was no difference in diabetes history among the 4 groups(P=0.30).153 patients developed AP during an average follow-up of(10.52±1.75)years,the incidence rates were 1.65,2.76,2.13 and 3.96 per 10 000 person-year in the Q1,Q2,Q3and Q4,respectively(P<0.01).After adjusting sex,age,TC,TG,eGFR,smoking,alcohol consumption,education,physical activity,and history of hypertension,diabetes,or cholelithiasis,Multivariate analysis showed a significantly increased risk in Q4(HR=1.77,95%CI:1.07~2.92)as comparing with Q1.After excluding deaths during the follow-up period,Multivariate Cox regression analysis was performed again in Q4 HR=1.75(95%CI:1.04~2.95).Conclusions With the increase of cumUA exposure,both morbidity and risk of AP occur-rence have the tendency of rising.
7.COVID-19 after lung transplantation: Four case reports
Hongyi WANG ; Yixing LI ; Heng ZHAO ; Yanpeng ZHANG ; Shan GAO ; Jizhao WANG ; Yilong ZHAO ; Shuo LI ; Guangjian ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(11):1697-1702
From December 2022 to January 2023, 4 lung transplant recipients (3 males and 1 female, aged 52-60 years, all received transplantation less than 1 year) were hospitalized in the Department of Thoracic Surgery of the First Affiliated Hospital of Xi'an Jiaotong University due to COVID-19 after surgery. The clinical manifestations were mostly characterized by elevated body temperature accompanied by shortness of breath, and indicators such as heart rate, oxygen saturation, and oxygenation index could reflect the severity of the condition. The therapy was timely adjusted to immunosuppressive drugs, upgraded oxygen therapy, anti-bacterial and anti-fungal therapy, prone ventilation, general treatment, and anticoagulant therapy, depending on the situation. Finally, 3 patients were cured and discharged from hospital, and 1 died.
8.Analysis of Clinical Epidemiological Characteristics of 15,967 Lung Cancer Surgery Patients in Yunnan Cancer Hospital from 2013 to 2022.
Ruke TANG ; Yujie LEI ; Lianhua YE ; Guangqiang ZHAO ; Xudong XIANG ; Gaofeng LI ; Guangjian LI ; Xi WANG ; Ying CHEN ; Kaiyun YANG ; Xiaobo CHEN ; Jiapeng YANG ; Min ZHAO ; Bingquan XIANG ; Qiubo HUANG ; Guangcan LUO ; Hongwei ZHANG ; Yunchao HUANG
Chinese Journal of Lung Cancer 2024;27(12):911-918
BACKGROUND:
Lung cancer is a disease with a high incidence rate in Yunnan province, yet there is a paucity of large-scale studies on its clinical epidemiology. This research aims to investigate the epidemiological characteristics of patients who underwent lung cancer surgery at Yunnan Cancer Hospital over the past decade, thereby providing a theoretical basis for the prevention and treatment of lung cancer.
METHODS:
Clinical data were collected from 15,967 patients who underwent lung cancer surgery at Yunnan Cancer Hospital between 2013 and 2022. A statistical analysis was conducted on the patients' general data, surgical information, pathological types of lung cancer, and other clinical epidemiological characteristics.
RESULTS:
Among the 15,967 cases of lung cancer, 46.3% were male and 53.7% were female, with the male-to-female ratio ranging from 0.68 to 1.61:1. The median age was 56 years (interquartile range: 49-63), and 37.0% of the patients were in the age group of 50-59 years. Since 2017, there has been an annual increase in the proportion of patients under the age of 60 years. The smoking status of the patients showed that 28.1% were smokers and 71.9% were non-smokers. Qujing city accounted for 41.4% and Kunming city for 23.2% of the cases in Yunnan province, with 29.6% of patients originating from Xuanwei and Fuyuan areas of Qujing city. The distribution of affected lung lobes was as follows: right upper lobe 28.2%, right middle lobe 6.3%, right lower lobe 20.1%, left upper lobe 22.7%, and left lower lobe 16.4%. The use of thoracoscopic surgery increased from 30.8% to 96.3%, with single-port thoracoscopic surgery comprising 61.3%. Lobectomy was performed in 64.2% of cases, wedge resection in 17.2%, and segmentectomy in 12.2%. The proportion of lobectomy decreased from 83.1% to 46.1%. The proportion of patients in stages 0-I increased from 43.5% to 82.8%, while stages II-IV decreased from 56.5% to 17.2%. Adenocarcinoma increased from 75.6% to 88.3%, and squamous cell carcinoma decreased from 21.5% to 8.6%. Among adenocarcinoma patients, 60.9% were female. Among sguamous cell carcinoma patients, 90.6% were male. The peak age for adenocarcinoma was 50-59 years, and for squamous cell carcinoma, it was 60-69 years. The smoking rate was higher among squamous cell carcinoma patients (65.9%) compared to adenocarcinoma patients (22.3%). Adenocarcinoma patients had a higher proportion in stages 0-I (76.3%), while squamous cell carcinoma patients were more prevalent in stages II-III (64.1%).
CONCLUSIONS
The findings indicate an increasing proportion of female patients with adenocarcinoma, a younger age of onset, a higher proportion of non-smoking lung cancer patients, and an increased proportion of stages 0-I lung cancer. These trends may reflect the epidemiological characteristics of patients undergoing lung cancer surgery in Yunnan and surrounding areas over the past decade.
Humans
;
Female
;
Male
;
Lung Neoplasms/pathology*
;
Middle Aged
;
China/epidemiology*
;
Aged
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Adult
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Aged, 80 and over
9.The role of dapagliflozin in ox⁃LDL⁃triggered pyroptosis of THP⁃1 ⁃derived foam cells
Caiwei Gong ; Guangjian Zhao ; Danan Liu ; Hangjun Ou ; Quanwei Zhao ; Hui Li
Acta Universitatis Medicinalis Anhui 2023;58(8):1366-1373
Objective :
To investigate the role of dapagliflozin ( DAPA) in ox⁃LDL⁃induced pyroptosis of human myeloid leukemia monocytes (THP⁃1) derived foam cells .
Methods :
THP⁃1 ⁃derived foam cell pyroptosis model was constructed by ox⁃LDL⁃induced THP⁃1derived macrophages . The experimental groups were set as follows : the blank control group(NC) , the ox⁃LDL group(ox⁃LDL) , and the drug intervention group(ox⁃LDL + DAPA) . Oil Red Ostaining was used to detect the foam cell levels of macrophages . The cell proliferation and toxicity assay kit was used to detect the effect of DAPA on foam cell viability . Hoechst 33342/propidium iodide(PI) double staining was used to detect THP⁃1 derived foam cell pyroptosis . Cell immunofluorescence double staining was used to detect the effect of DAPA on the expression of pyroptosis key factor Caspase⁃1 in foam cells . The activity of lactate dehydrogenase (LDH) in the cell culture medium was detected using a microplate enzyme⁃linked immunosorbent assay. qRT⁃PCR and Western blot were used to detect the mRNA and protein expression levels of Nod⁃like receptor pyrindomain containing 3 (NLRP3) , cystein⁃containing aspartate⁃specific protease⁃1( Caspase⁃1 ) , apoptosis⁃associated⁃speck⁃like protein containing CARD(ASC) ,gasdermin⁃D (GSDMD) , interleukin(IL) Ⅳ18 and IL⁃1β , respectively .
Results :
The CCK⁃8 assay indicated that the optimal intervention concentration of DAPA was 10 μmol/L. Oil Red O staining confirmed the successful construction of the THP⁃1 ⁃derived foam cell pyroptosis model . Compared with the blank control group , the expression levels of NLRP3 , Caspase⁃1 , ASC , GSDMD , IL⁃18 , IL⁃1β mRNA and protein significantly increased in ox⁃LDL group(P < 0. 05) , as well as the number of PI⁃positive cells and LDH activity(P < 0. 05) , the fluorescence intensity of Caspase⁃1 and the number of redlipid droplets in the cytoplasm of the cells . However , these effects were significantly reversed after DAPA intervention in the ox⁃LDL + DAPA group(P < 0. 05) .
Conclusion
DAPA inhibits ox⁃LDL⁃induced pyroptosis in THP⁃1 ⁃derived foam cells .
10.Short-term efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy for the treatment of non-small cell lung cancer
Yixing LI ; Heng ZHAO ; Bohao LIU ; Jizhao WANG ; Yanpeng ZHANG ; Chendong GUO ; Chuchen ZHAO ; Kun FAN ; Hongyi WANG ; Runyi TAO ; Zhiyu WANG ; Jia ZHANG ; Junke FU ; Guangjian ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(03):369-374
Objective To explore the short-term efficacy and safety of pembrolizumab combined with chemotherapy in the neoadjuvant treatment of non-small cell lung cancer. Methods The clinical data of 11 male patients with non-small cell lung cancer who underwent pembrolizumab combined with neoadjuvant chemotherapy in the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to June 2021 were retrospectively analyzed. The average age of the patients was 52.0-79.0 (62.0±6.9) years. The imaging data and pathological changes before and after neoadjuvant treatment were compared, and adverse reactions during neoadjuvant treatment were recorded. Objective remission rate (ORR) and main pathological remission rate (MPR) and pathological complete remission rate (pCR) were the main observation endpoints. Results After preoperative neoadjuvant therapy with pembrolizumab combined with platinum or paclitaxel, all patients successfully underwent thoracoscopic radical resection of lung cancer. The ORR was 72.7%, and the MPR was 81.8%. Among them, 45.5% of patients achieved pCR. The main adverse reactions were hypoalbuminemia, decreased appetite and nausea. The mortality rate within 30 days after surgery was 0, and no tumor metastasis was observed. Conclusion Pembrolizumab combined with neoadjuvant chemotherapy is safe and feasible to treat non-small cell lung cancer, and the short-term efficacy is beneficial.


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