1.Application of Recombinant Collagen in Biomedicine
Huan HU ; Hong ZHANG ; Jian WANG ; Li-Wen WANG ; Qian LIU ; Ning-Wen CHENG ; Xin-Yue ZHANG ; Yun-Lan LI
Progress in Biochemistry and Biophysics 2025;52(2):395-416
Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.
2.Research progress on strategies to target intestinal microbiota to improve drug resistance in tumor immunotherapy
Hui-ling LI ; Bi-qing LIU ; Ying-nan FENG ; Xin HU ; Lan ZHANG ; Xian-zhe DONG
Acta Pharmaceutica Sinica 2025;60(2):260-268
A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.
3.The effects and mechanisms of silica on alveolar epithelial cell apoptosis
Yali LAN ; Wenyao SU ; Zhiming HU ; Ping WANG ; Bizhu ZHANG ; Na ZHAO
China Occupational Medicine 2025;52(1):10-16
Objective To investigate the effects and mechanisms of silica dust on the apoptosis of alveolar epithelial cell (AEC) through in vitro and animal experiments. Methods i) In vitro experiment. A549 cells were stimulated with 100 mg/L silica suspension for 0, 12, 24 and 48 hours. The cell apoptosis rate was detected by flow cytometry. ii) Animal experiment. Specific pathogen-free male C57BL/6 mice were randomly divided into control, 14-day, 28-day, and 56-day groups, with five mice in each group. The mice in the control group were sacrificed at 56 days after being treated with 40.0 μL 0.9% sodium chloride solution, and the mice in the last three groups were sacrificed at 14, 28 and 56 days after being treated with 40.0 μL silica suspension with a mass concentration of 125 g/L via tracheal exposure method. The lung tissues of mice were collected to measure lung organ coefficients. Masson staining was used to detect the degree of pulmonary fibrosis, and Ashcroft scores were evaluated. The apoptosis of AEC in mice was observed by TUNEL immunofluorescence assay. iii) The mRNA relative expression of apoptosis-related genes in A549 cells and mouse lung tissue was detected using reverse transcription and real-time fluorescence quantitative polymerase chain reaction. Results i) In vitro experiment. The apoptosis rate of A549 cells increased with longer silica exposure (all P<0.05). The relative expression of B cell lymphoma-2 (BCL-2) mRNA in A549 cells in 24 h group and 48 h group decreased (both P<0.05), and the relative expression of BCL-2 associated X protein (BAX) mRNA increased (both P<0.05), compared with 0 h group. The mRNA relative expression of caspase (CASP) -3 and CASP-9 in A549 cells increased with longer silica exposure (all P<0.05). ii) Animal experiment. The lung organ coefficients and Ashcroft score in mice progressively increased (all P<0.05), the degree of pulmonary fibrosis was gradually aggravated, and TUNEL positive cells in lung tissue were gradually increased, while Bax, Casp-3 and Casp-9 mRNA relative expression increased with longer silica exposure (all P<0.05). Conclusion Silica dust may cause pulmonary fibrosis by inducing apoptosis of AEC, with a time-dependent effect. The mechanism may be related to the effect of silica dust on mitochondrial apoptosis through Bcl-2/Bax/Caspase-3 signaling pathway.
4.Disease Burden of Malignant Tumors Among Residents of Kunshan City, Jiangsu Province, 2006–2021
Zhouquan FAN ; Wenbin HU ; Yixu JIN ; Lyulin LU ; Jie ZHOU ; Lan TONG ; Wei QIN
Cancer Research on Prevention and Treatment 2025;52(5):411-417
Objective To analyze the burden of disease of malignant tumors in Kunshan City from 2006 to 2021. Methods The global burden of disease research methodology was applied. The indicators of cancer incidence, mortality, and disability-adjusted life years (DALYs) in Kunshan were calculated using the data from the Tumor Registry System and Death Registry System in Kunshan. The changes in cancer were compared. Results In 2021, the number of incidences and deaths and the DALYs of cancer were
5.Application of blood conservation measures with different red blood cell transfusion volumes in obstetrics and their impact on postpartum outcomes
Huimin DENG ; Fengcheng XU ; Meiting LI ; Lan HU ; Xiao WANG ; Shiyu WANG ; Xiaofei YUAN ; Jun ZHENG ; Zehua DONG ; Yuanshan LU ; Shaoheng CHEN
Chinese Journal of Blood Transfusion 2025;38(5):691-698
Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL(OR=1.699)(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma(FFP), cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.
6.The role of the gut-lung axis in paraquat-induced lung injury in mice
Zhiming HU ; Yali LAN ; Yiru QIN ; Ping WANG ; Na ZHAO
China Occupational Medicine 2025;52(2):135-142
Objective To explore the mechanism of the gut-lung axis in paraquat-induced lung injury in mice, with a focus on analyzing the changes in intestinal gene expression and their potential roles. Methods Specific pathogen-free C57BL/6 wild-type mice were randomly divided into control, low-dose, and high-dose groups, with 10 mice in each group. Mice in the three groups received a single intragastric administration of paraquat solution at doses of 0, 25, or 50 mg/kg body weight. The mice were euthanized on day 21. Lung histopathological changes were assessed, and the differentially expressed genes (DEGs) in the intestinal tissues of mice in these two groups were analyzed through transcriptomics. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore potential mechanisms of the gut-lung axis in paraquat-induced lung injury and fibrosis. Results Paraquat exposure induced dose-dependent pulmonary injury and fibrosis in the mice. The Ashcroft score of lung tissue was higher in the mice of low-dose group than that in the control group (P<0.05). Both the lung organ coefficient and Ashcroft score of lung tissues in the mice of high-dose group were higher than those in the control group and the low-dose group (all P<0.05). The result of transcriptomic analysis showed 146 DEGs, including 91 upregulated and 55 downregulated genes, in intestinal tissues of mice in the low-dose group, and 57 DEGs, including 47 upregulated and 10 downregulated genes in the high-dose group, compared with the control group. Notably, 19 DEGs were commonly altered in both low- and high-dose groups. The result of GO enrichment analysis showed that the DEGs were primarily involved in biological processes including "immune response", "oxidative stress" and "cell differentiation". The result of KEGG enrichment analyses showed that DEGs were primarily involved in key processes including "oxidative stress response path way", "immune response path way" and "digestion and absorption path way". Conclusion Paraquat exposure alters intestinal gene expression, particularly in genes in biological processes related to immune responses and oxidative stress. These changes may mediate inflammatory signaling via the gut-lung axis and contribute to the development of paraquat-induced pulmonary fibrosis.
7.External validation of the model for predicting high-grade patterns of stage ⅠA invasive lung adenocarcinoma based on clinical and imaging features
Yu RONG ; Nianqiao HAN ; Yanbing HAO ; Jianli HU ; Yajin NIU ; Lan ZHANG ; Yuehua DONG ; Nan ZHANG ; Junfeng LIU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1096-1104
Objective To externally validate a prediction model based on clinical and CT imaging features for the preoperative identification of high-grade patterns (HGP), such as micropapillary and solid subtypes, in early-stage lung adenocarcinoma, in order to guide clinical treatment decisions. Methods This study conducted an external validation of a previously developed prediction model using a cohort of patients with clinical stage ⅠA lung adenocarcinoma from the Fourth Hospital of Hebei Medical University. The model, which incorporated factors including tumor size, density, and lobulation, was assessed for its discrimination, calibration performance, and clinical impact. Results A total of 650 patients (293 males, 357 females; age range: 30-82 years) were included. The validation showed that the model demonstrated good performance in discriminating HGP (area under the curve>0.7). After recalibration, the model's calibration performance was improved. Decision curve analysis (DCA) indicated that at a threshold probability>0.6, the number of HGP patients predicted by the model closely approximated the actual number of cases. Conclusion This study confirms the effectiveness of a clinical and imaging feature-based prediction model for identifying HGP in stage ⅠA lung adenocarcinoma in a clinical setting. Successful application of this model may be significant for determining surgical strategies and improving patients' prognosis. Despite certain limitations, these findings provide new directions for future research.
8.Comparative burden of disease attributable to high BMI in Kunshan City between 2012-2023
Zhouquan FAN ; Wenbin HU ; Yixu JIN ; Lulin LU ; Jie ZHOU ; Lan TONG ; Wei QIN
Journal of Public Health and Preventive Medicine 2025;36(5):40-44
Objective To analyze and compare the disease burden of high BMI in Kunshan City in different periods, and to provide a scientific basis for the prevention and control of overweight and obesity in Kunshan City. Methods Using the global burden of disease research method, the number of deaths attributable to high BMI and attributable YLL in Kunshan City were calculated using the survey data of chronic diseases and their risk factors and the data of the death registration system in Kunshan City. Results In 2023, R5.46% of deaths in Kunshan City were attributed to high BMI, with 345 attributable deaths, and attributable mortality rate and standardized attributable mortality rate were 39.16/100 000 and 33.82/100 000, Rrespectively. Attributable YLL rate and standardized attributable YLL rate were 692.35/100 000 and 604.46/100 000, respectively. High BMI caused a loss of 0.52 years of life expectancy per capita. Compared with 2012, PAF, standardized attributable mortality rate, standardized attributable YLL rate and life expectancy loss per capita of high BMI in 2023 increased by 121.95%, 100.71%, 57.05%, and 100%, respectively. Among different genders, PAF increased by 91.05% for males and 161.97% for females from 2012 to 2023. Among different diseases, cardiovascular and cerebrovascular diseases and cancers had the highest attributable disease burden, while diabetes, chronic kidney disease and Alzheimer's disease all had a significant increase. Conclusion The burden of disease attributable to high BMI has risen dramatically in Kunshan City, and the adverse health effects of overweight and obesity need to be reduced through scientific weight loss and comprehensive practical measures.
9.Comparative burden of disease attributable to high BMI in Kunshan City between 2012-2023
Zhouquan FAN ; Wenbin HU ; Yixu JIN ; Lulin LU ; Jie ZHOU ; Lan TONG ; Wei QIN
Journal of Public Health and Preventive Medicine 2025;36(5):40-44
Objective To analyze and compare the disease burden of high BMI in Kunshan City in different periods, and to provide a scientific basis for the prevention and control of overweight and obesity in Kunshan City. Methods Using the global burden of disease research method, the number of deaths attributable to high BMI and attributable YLL in Kunshan City were calculated using the survey data of chronic diseases and their risk factors and the data of the death registration system in Kunshan City. Results In 2023, R5.46% of deaths in Kunshan City were attributed to high BMI, with 345 attributable deaths, and attributable mortality rate and standardized attributable mortality rate were 39.16/100 000 and 33.82/100 000, Rrespectively. Attributable YLL rate and standardized attributable YLL rate were 692.35/100 000 and 604.46/100 000, respectively. High BMI caused a loss of 0.52 years of life expectancy per capita. Compared with 2012, PAF, standardized attributable mortality rate, standardized attributable YLL rate and life expectancy loss per capita of high BMI in 2023 increased by 121.95%, 100.71%, 57.05%, and 100%, respectively. Among different genders, PAF increased by 91.05% for males and 161.97% for females from 2012 to 2023. Among different diseases, cardiovascular and cerebrovascular diseases and cancers had the highest attributable disease burden, while diabetes, chronic kidney disease and Alzheimer's disease all had a significant increase. Conclusion The burden of disease attributable to high BMI has risen dramatically in Kunshan City, and the adverse health effects of overweight and obesity need to be reduced through scientific weight loss and comprehensive practical measures.
10.Different Effects of Fresh and Dried Dendrobium Huoshanense on Chronic Atrophic Gastritis
Mengqing HU ; Xinyu YANG ; Weihan GONG ; Huiqun XIE ; Lan HAN ; Daiyin PENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):29-39
ObjectiveTo compare the protective effects of water extracts from fresh and dried Dendrobium huoshanense on gastric mucosa in chronic atrophic gastritis (CAG). MethodsMale SD rats (n=72) were randomly divided into 9 groups, with 8 rats in each group, which were normal group, model group, Yangwei Shu (4 g·kg-1) group, low-, medium-, and high-dose fresh D. huoshanense (3.5, 7, and 14 g·kg-1) groups, and low-, medium-, and high-dose dried D. huoshanense (0.7, 1.4, 2.8 g·kg-1) groups. The CAG rat model was successfully established by inducing with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and other factors for a total of 11 weeks. Then, the rats were intervened with fresh and dried D. huoshanense for 4 weeks. The serum and gastric tissues of the rats were collected. The changes in gastric juice secretion volume and gastric acid pH value in each group were observed. The gastric mucosal injury was observed by naked eyes and hematoxylin-eosin(HE) staining. The gastric mucus secretion level was determined by Alcian blue and periodic acid-Schiff staining(AB-PAS) staining. The expression levels of tight junction proteins Occludin and ZO-1 in gastric tissues were determined by immunofluorescence. The expression levels of serum pepsinogen Ⅰ (PG Ⅰ), pepsinogen Ⅱ (PG Ⅱ), gastrin 17 (G-17), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). The expression levels of aquaporin 1 (AQP1), aquaporin 3 (AQP3), and aquaporin 4 (AQP4) in gastric tissues were determined by Western blot. ResultsCompared with the normal group, the model group showed an obviously reduced gastric juice secretion volume (P0.05), significantly increased gastric acid pH value (P0.01), gastric mucosa with obvious atrophy, and a significantly reduced gastric mucus secretion volume (P0.01). The expression of Occludin and ZO-1 in the gastric mucosal barrier was significantly decreased (P0.01). The levels of PG Ⅰ and PG Ⅱ in the serum were obviously decreased (P0.05, P0.01), and the levels of G-17, IL-1β, IL-6, and TNF-α were significantly increased (P0.01). The expression level of AQP1 in the gastric tissue was significantly upregulated (P0.01), and the expression levels of AQP3 and AQP4 were significantly downregulated (P0.01). Compared with the model group, each drug administration group could improve the gastric mucosal atrophy of CAG model rats to varying degrees, obviously increase the gastric juice secretion volume of the model rats (P0.05, P0.01), significantly decrease the gastric acid pH value (P0.01), obviously increase the gastric mucus secretion volume (P0.05, P0.01), obviously decrease the expression levels of G-17, IL-6, IL-1β, and TNF-α (P0.05, P0.01), obviously increase the expression levels of Occludin, ZO-1, PG Ⅰ, and PG Ⅱ (P0.05, P0.01), obviously upregulate the expression levels of AQP3 and AQP4 (P0.05, P0.01), and obviously downregulate the expression level of AQP1 (P0.05, P0.01). ConclusionThe water extracts of fresh and dried D. huoshanense can exert therapeutic effects on CAG by improving gastric mucosal injury, reducing inflammation, and regulating water metabolism. Moreover, the dried D. huoshanense has a better effect.


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