1.An Amphibians-Derived Protein Provides Novel Biotherapeutics for Various Wounds Treatment
Hao-Ran CHEN ; Nan ZHOU ; Yu-Da LIU ; Li-Hua PENG
Biomolecules & Therapeutics 2025;33(2):399-407
Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.
2.An Amphibians-Derived Protein Provides Novel Biotherapeutics for Various Wounds Treatment
Hao-Ran CHEN ; Nan ZHOU ; Yu-Da LIU ; Li-Hua PENG
Biomolecules & Therapeutics 2025;33(2):399-407
Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.
3.An Amphibians-Derived Protein Provides Novel Biotherapeutics for Various Wounds Treatment
Hao-Ran CHEN ; Nan ZHOU ; Yu-Da LIU ; Li-Hua PENG
Biomolecules & Therapeutics 2025;33(2):399-407
Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.
4.Prediction of Pulmonary Nodule Progression Based on Multi-modal Data Fusion of CCNet-DGNN Model
Lehua YU ; Yehui PENG ; Wei YANG ; Xinghua XIANG ; Rui LIU ; Xiongjun ZHAO ; Maolan AYIDANA ; Yue LI ; Wenyuan XU ; Min JIN ; Shaoliang PENG ; Baojin HUA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):135-143
ObjectiveThis study aims to develop and validate a novel multimodal predictive model, termed criss-cross network(CCNet)-directed graph neural network(DGNN)(CGN), for accurate assessment of pulmonary nodule progression in high-risk individuals for lung cancer, by integrating longitudinal chest computed tomography(CT) imaging with both traditional Chinese and western clinical evaluation data. MethodsA cohort of 4 432 patients with pulmonary nodules was retrospectively analyzed. A twin CCNet was employed to extract spatiotemporal representations from paired sequential CT scans. Structured clinical assessment and imaging-derived features were encoded via a multilayer perceptron, and a similarity-based alignment strategy was adopted to harmonize multimodal imaging features across temporal dimensions. Subsequently, a DGNN was constructed to integrate heterogeneous features, where nodes represented modality-specific embeddings and edges denoted inter-modal information flow. Finally, model optimization was performed using a joint loss function combining cross-entropy and cosine similarity loss, facilitating robust classification of nodule progression status. ResultsThe proposed CGN model demonstrated superior predictive performance on the held-out test set, achieving an area under the receiver operating characteristic curve(AUC) of 0.830, accuracy of 0.843, sensitivity of 0.657, specificity of 0.712, Cohen's Kappa of 0.417, and F1 score of 0.544. Compared with unimodal baselines, the CGN model yielded a 36%-48% relative improvement in AUC. Ablation studies revealed a 2%-22% increase in AUC when compared to simplified architectures lacking key components, substantiating the efficacy of the proposed multimodal fusion strategy and modular design. Incorporation of traditional Chinese medicine (TCM)-specific symptomatology led to an additional 5% improvement in AUC, underscoring the complementary value of integrating TCM and western clinical data. Through gradient-weighted activation mapping visualization analysis, it was found that the model's attention predominantly focused on nodule regions and effectively captured dynamic associations between clinical data and imaging-derived features. ConclusionThe CGN model, by synergistically combining cross-attention encoding with directed graph-based feature integration, enables effective alignment and fusion of heterogeneous multimodal data. The incorporation of both TCM and western clinical information facilitates complementary feature enrichment, thereby enhancing predictive accuracy for pulmonary nodule progression. This approach holds significant potential for supporting intelligent risk stratification and personalized surveillance strategies in lung cancer prevention.
5.Effect of knockdown of ARHGAP30 on proliferation and apoptosis of Siha cells
Ya-Ting PENG ; Duan LIU ; Jie MENG ; Wen-Chao LI ; Hui-Qi LI ; Hua GUO ; Mei-Lan NIU ; Qiao-Hong QIN
Chinese Pharmacological Bulletin 2024;40(5):847-853
Aim To investigate the changes in the proliferation and apoptosis of Siha cells after knocking down Rho GTPase-activating protein 30(ARHGAP30).Methods After designing specific shARHGAP30 primers and connecting them to the pLKO.1 vector,we transformed them into Escherichia coli competent cells,then co-transfecting them with lentiviral helper plasmids into HEK-293T cells.We collected and filtered cell supernatant to obtain the vi-rus to infect Siha cells.RT-qPCR and Western blot were used to detect knockdown efficiency,as well as changes in the expression of Bax and Bcl-2 after trans-fection.The CCK-8 method was employed to measure the proliferation level of cells after knockdown.Results After successful construction of a lentiviral plasmid with knockdown of the ARHGAP30 gene and establish-ment of stably transfected Siha cells,ARHGAP30 tran-scription and translation(P<0.01)in Siha cells de-creased,Bax/Bcl-2 significantly decreased(P<0.01),indicating decreased apoptosis and increased cell proliferation(P<0.01).Conclusions This study suggests the involvement of ARHGAP30 in the proliferation and apoptosis of Siha cells,and regulating the ARHGAP30 gene may interfere with the occurrence and development of cervical cancer.
6.Establishment of mice gait analysis system based on DeepLabCut algorithm to evaluate motor function of aging mice
Zhi-Hong LI ; Yi-Hua SHENG ; You LI ; Zhi-Xiang PENG ; Xing-Yao ZENG ; Xin-Li GU ; Jia-Yi TIAN ; Si-Di LI
Chinese Pharmacological Bulletin 2024;40(9):1792-1799
Aim To establish a gait analysis system based on DeepLabCut(DLC)algorithm for evaluating motor function in aged mice.Methods Based on DLC algorithm in deep learning technology,treadmill device and fully closed design were used in the system,including software and hardware.This system was applied to evaluate gait characteristics of mice due to aging un-der different movement modes.Correlation analysis was used to explore the effects of body weight and body length on gait indica-tors.Results This system realized the synchronous analysis of three-dimensional gait(lateral and ventral plane)of mice at specific gait speed,and automatically quantified 47 gait indica-tors.Using this system,it was found that during walking(15 cm·s-1),the standard deviation of body turning angle decreased,forelimb sway duration,standard deviation of knee angle,mean outward angles of left and right hind paw increased in 8 and 15 month-old mice,compared with 2-month-old mice.However,15-month-old mice showed decreased walking frequency,and in-creased stride width,total duration of double support,and knee extension and contraction distance.In addition,at trot(20 cm·s-1),15-month-old mice were unable to walk steadily,and 8-month-old mice had increased total duration of double support and mean outward angles of left hind paw,compared with 2-month-old mice.Correlation analysis revealed that indicators like walking frequency,stride width,forelimb sway duration,total duration of double support,standard deviation of knee an-gle,knee extension and contraction distance,were not affected by changes in body weight and body length.Conclusions The gait analysis system based on DLC algorithm can achieve a more sensitive,accurate and comprehensive evaluation of the gait of aged mice,distinguishing the gait characteristics of aged mice to maintain gait stability,and selecting behavioral indicators that better reflect the gait changes of aged mice.It provides a meth-odological basis for more effective assessment of efficacy and side effects of drugs for anti-aging and anti-decline of motor coordina-tion in the future.
7.Effect of berberine on regulating NF-κB p65/TGF-β1/CTGF signaling pathway in reducing renal fibrosis injury in mice
Guang-Yao LI ; Jia-Min LIANG ; Meng-Tong JIN ; Duan XI ; Peng LIU ; Peng WANG ; Rui-Hua WANG ; Qing-Qing LIU
Chinese Pharmacological Bulletin 2024;40(11):2042-2047
Aim To investigate the protective effect of berberine(BBR)on mice with unilateral ureteral obstr-uction(UUO)and explore its mechanism.Methods C57BL/6 mice were randomly divided into the sham group,UUO group,and BBR treatment groups(50,100 and 200 mg·kg-1),with eight mice in each group.Except the sham group,the other groups were subjected to left ureteral ligation to establish the UUO model.Af-ter modeling,the mice in the sham and UUO groups were fed normal saline,and the mice in the BBR treat-ment groups were fed(50,100,200)mg·kg-1 BBR by gavage for 14 days,respectively.Biochemical analy-zer was employed to detect the levels of serum creati-nine(Scr)and blood urea nitrogen(BUN).HE,Mas-son,TUNEL and immunohistochemical staining were used to observe the pathological changes of renal tis-sue.ELISA was employed to detect the expression of pro-inflammatory cytokines in renal tissue homogenate.Western blot was used to detect the protein levels of NF-κB p65,TGF-β1 and CTGF in mouse kidney.Re-sults Compared with the UUO group,the levels of Scr and BUN in the BBR group were significantly reduced.Renal injury and interstitial fibrosis were alleviated.The expression of pro-inflammatory cytokines decreased in kidney.The expression of NF-κB p65,TGF-β1 and CTGF decreased.All results showed some degree of dose dependence.Conclusion Berberine has a sig-nificant protective effect on unilateral ureteral obstruc-tion mice,and the mechanism may be that BBR has the potential to inhibit NF-κB p65/TGF-β1/CTGF signa-ling pathway,thus reducing renal inflammation and fi-brosis.
8.Meta-analysis of autologous bone grafts and bone substitute for the treatment of tibial plateau fractures
Hua GUO ; Ling-An HUANG ; Hao-Qian LI ; Li GUO ; Peng-Cui LI ; Xiao-Chun WEI
China Journal of Orthopaedics and Traumatology 2024;37(3):300-305
Objective To explore clinical efficacy of autologous bone grafts and bone substitute for the treatment of tibial plateau fractures by Meta analysis.Methods Controlled clinical studies on autogenous bone transplantation and bone substitutes in treating tibial plateau fractures published on PubMed,Web of Science,CNKI,Wanfang and other databases from January 2005 to August 2022 were searched by computer.Literature screening and data extraction were performed according to random-ized controlled trial(RCT),and the quality of RCT were evaluated by using intervention meta-analysis criteria in Cochrane man-ual.Meta-analysis of joint depression,secondary collapse rate of articular surface,blood loss,operative time and infection rate between two methods were performed by Rev Man 5.3 software.Results Seven RCT studies(424 patients)were included,296 patients in bone replacement group and 128 patients in autograft group.Operative time[MD=-16.79,95%CI(-25.72,-7.85),P=0.000 2]and blood loss[MD=-70.49,95%CI(-79.34,-61.65),P<0.000 01]between two groups had statistically differ-ences,while joint depression[MD=-0.17,95%CI(-0.91,0.58),P=0.66],secondary collapse rate of joint surface[RR=-0.74,95%CI(0.35,1.57),P=0.43],infection rate[RR=1.21,95%CI(0.31,4.70),P=0.78]between two groups had no differences.Conclusion The effects of bone substitute and autograft for the treatment of tibial plateau fracture have similar effects in terms of joint depression,secondary articular surface collapse rate and infection rate.However,compared with autologous bone trans-plantation,bone replacement could reduce blood loss and shorten operation time.
9.Identification of key genes and functions in lung metastasis of osteosarcoma based on bioinformatics
Xin WANG ; Li-Hua PENG ; Xing-Wang CHEN
China Journal of Orthopaedics and Traumatology 2024;37(7):718-724
Objective To screen the differentially expressed genes of lung metastasis of osteosarcoma by bioinformatics,and explore their functions and regulatory networks.Methods The data set of GSE14359 was screened from GEO database(http://www.ncbi.nlm.nih.gov/gds)and the differentially expressed gene(DEG)was identified using GEO2R online tool.Download osteosarcoma disease related miRNAs from the online HMMD database(http://www.cuilab.cn/hmdd)and then FunRich software was used to predict the target gene,intersects with DEG to obtains the target gene.The miRNA-mRNA rela-tionship pairs were formed according to the targeted joints,then the data was imported into Cytoscape for visualization,DAVID was used to performe GO and KEGG analysis on target genes,STRING was used to construct PPI network,Cytoscape visualiza-tion,CytoHubba plug-in screening central genes and online website for expression and survival analysis.Results Total 704 DEGs were identified,consisting of 477 up-regulated genes and 227 down regulated genes.FunRich predicted 7 888 mRNAs and 343 target genes were obtained through intersection of the two.KEGG analysis showed that it was mainly involved in focal adhesion,ECM receptor interaction,TNF signal pathway,PI3K-Akt signal pathway,IL-17 signal pathway and MAPK signal pathway.Ten central genes(CCNB1,CHEK1,AURKA,DTL,RRM2,MELK,CEP55,FEN1,KPNA2,TYMS)were identified as potential key genes.Among them,CCNB1,DTL,MELK were highly correlated with poor prognosis.Conclusion The key genes and functional pathways identified in this study may be helpful to understand the molecular mechanism of the occurrence and progression of lung metastases from osteosarcoma,and provide potential therapeutic targets.
10.Surveillance of bacterial resistance in tertiary hospitals across China:results of CHINET Antimicrobial Resistance Surveillance Program in 2022
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Wei LI ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Yanyan LIU ; Yong AN
Chinese Journal of Infection and Chemotherapy 2024;24(3):277-286
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5%were gram-positive and 70.5%were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3%,76.7%and 77.9%,respectively.Overall,94.0%of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8%of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2%in the isolates from children and 95.7%in the isolates from adults.The resistance rate to carbapenems was lower than 13.1%in most Enterobacterales species except for Klebsiella,21.7%-23.1%of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1%to 13.3%.The prevalence of meropenem-resistant strains decreased from 23.5%in 2019 to 18.0%in 2022 in Pseudomonas aeruginosa,and decreased from 79.0%in 2019 to 72.5%in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

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