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28 August 2025, Volume 45 Issue 8 Previous Issue   
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Basic research
Clinical research
Evidence-based medicine
Review
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Basic research

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Regulatory effect of FGF2 on the expression of R-spondin 1 in mouse intestinal stromal cells LI Jingcong, ZHAO Han, LIN Qiaowen, SUN Hongxiang, SU Bing, WU Ningbo 2025, 45 (8):  939-948.  doi: 10.3969/j.issn.1674-8115.2025.08.001 Abstract ( 323 )   HTML ( 32 )   PDF (3937KB) ( 1027 )   Objective ·To preliminarily investigate the regulatory effect and underlying mechanism of fibroblast growth factor 2 (FGF2) on R-spondin 1 (Rspo1) expression in CD34+CD81+ stromal cells from the mouse colon. Methods ·Colonic CD45-CD326-CD31-GP38+CD81+Rspo1-tdTomato+ stromal cells were sorted from Rspo1-tdTomato reporter mice by flow cytometry and subsequently cultured in vitro. The expression of surface protein markers was evaluated by flow cytometry after 14 d of culture. qPCR was employed to quantify Rspo1 expression in response to stimulation with FGF2, FGF9, epidermal growth factor (EGF), platelet-derived growth factor-bb (PDGF-bb), insulin-like growth factor 1 (IGF1), or hepatocyte growth factor (HGF). RNA sequencing and bioinformatic analyses were used to identify the signaling pathways underlying FGF2-mediated regulation of Rspo1, followed by preliminary validation with pathway-specific inhibitors and qPCR. Results ·After 14 d of culture, the sorted colonic stromal cells retained expression of CD34, CD81, and glycoprotein GP38, while remaining negative for other lineages markers CD45, CD326, and CD31. qPCR revealed that 20 ng/mL FGF2 significantly suppressed Rspo1 expression, whereas the other tested growth factors exerted no notable effect. RNA sequencing and bioinformatic analysis indicated that mitogen-activated protein kinase (MAPK) signaling pathway played a key role in the regulatory effect of FGF2 on Rspo1. qPCR further demonstrated that pretreatment with U0126, an inhibitor of mitogen extracellular kinase 1/2 (MEK1/2), reversed FGF2-mediated suppression of Rspo1 expression. Conclusion ·FGF2 may inhibit Rspo1 expression in mouse colonic CD34+CD81+ stromal cells via the MEK1/2-extracellular regulated protein kinase 1/2 (ERK1/2) signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Effects of telomerase gene therapy on pressure overload-induced heart failure in mice HE Suhui, ZHAO Yinlong, CHANG Alex Chia Yu 2025, 45 (8):  949-956.  doi: 10.3969/j.issn.1674-8115.2025.08.002 Abstract ( 262 )   HTML ( 12 )   PDF (4524KB) ( 674 )   Objective ·To investigate the therapeutic effect of telomerase gene therapy (JV001) on heart failure induced by transverse aortic constriction (TAC) in mice. Methods ·Male C57BL/6J mice were randomly divided into sham operation group (Sham group) , model group (TAC group), and JV001 treatment group (TAC+JV001 group). An adeno-associated virus 9 (AAV9) vector containing the catalytic inactivation (D868A) and nuclear export phosphorylation (Y707F) mutations in the human telomerase reverse transcriptase (hTERT) gene (AAV9-modhTERT, named JV001) was intravenously administered to TAC animals at a single dose of 4×1012 gc/kg. The Sham group and the TAC group received equivalent volumes of saline via tail vein injection. Six weeks after administration, the expression of JV001 in the heart was determined by real-time quantitative PCR (RT-qPCR). Murine cardiac functions were assessed using echocardiography. Physiological indexes of mice were recorded for calculating heart weight/body weight ratio (HW/BW) and heart weight/tibial length ratio (HW/TL). Cardiac hypertrophy was assessed using hematoxylin-eosin (HE) staining and wheat germ agglutinin (WGA) staining. Cardiac collagen deposition was observed by Masson staining. The expressions of myocardial hypertrophy-related genes (Nppa, Nppb, Myh7, Myh6) and myocardial fibrosis-related genes (Col1a1, Col3a1, Ctgf) were detected by RT-qPCR. Results ·High levels of modhTERT mRNA were expressed in the hearts of mice at 6 weeks post-injection. Compared with sham-operated mice, TAC mice exhibited significantly reduced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). Compared to TAC mice, TAC+JV001 mice exhibited a significant improvement in LVEF and LVFS. Concurrently, there was a downregulation in the HW/BW and HW/TL in TAC+JV001 mice compared to TAC mice. Furthermore, JV001 treatment reduced the mean cardiomyocyte cross-sectional area and improved the expression levels of myocardial hypertrophy-related genes, including Nppa, Nppb, Myh7 and Myh6. Additionally, JV001 treatment ameliorated the TAC-induced increase in myocardial interstitial fibrosis and reduced the elevated expression levels of myocardial fibrosis-related genes, including Col1a1, Col3a1, and Ctgf. Conclusion ·AAV9-modhTERT treatment can alleviate TAC-induced cardiac dysfunction, cardiac hypertrophy, and fibrosis in mice. Figures and Tables | References | Related Articles | Metrics

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Ubiquitination and degradation of RPTPα mediated by MARCH9 ZHANG Yuqin, AIHEMAITI Yilixiati, WANG Yanli, YANG Zhi, HUANG Jian 2025, 45 (8):  957-968.  doi: 10.3969/j.issn.1674-8115.2025.08.003 Abstract ( 236 )   HTML ( 10 )   PDF (4566KB) ( 370 )   Objective ·To investigate the molecular mechanisms and biological functions of the E3 ubiquitin ligase membrane-associated RING-CH 9 (MARCH9) in regulating the ubiquitination of receptor protein tyrosine phosphatase alpha (RPTPα). Methods ·Western blotting was employed to identify the ubiquitination type of RPTPα and to evaluate the regulatory effect of MARCH9 on its ubiquitination level; Comparative analysis of RPTPα protein stability was performed among wild-type MARCH9, catalytically inactive MARCH9 mutants (MARCH9 S198A or MARCH9-HC/CC), and endogenous MARCH9 knockdown via shRNA. Proteasome inhibitor MG132, autophagy inhibitor 3-MA, and lysosomal inhibitor chloroquine (CQ) were used to determine the degradation pathway of MARCH9-mediated RPTPα ubiquitination. The mechanism underlying 43 ℃ heat shock-induced RPTPα degradation was explored. Stable lung cancer cell lines with MARCH9 single-knockdown (H1299-shMARCH9) and MARCH9/RPTPα double-knockdown (H1299-shMARCH9-shRPTPα) were established using lentiviral vectors. CCK-8 proliferation assay, colony formation assay, and soft agar assay were conducted to evaluate the effects of MARCH9 or RPTPα on lung cancer cell proliferation and clonogenicity. Vasculogenic mimicry formation assay and scratch wound healing assay were performed to assess the impacts on tumor cell invasion and migration. Subcutaneous xenograft models in nude mice were established to examine in vivo tumorigenicity. Bioinformatics analysis was used to compare the expression differences and prognostic correlations of MARCH9 and RPTPα in lung cancer patients. Results ·RPTPα predominantly underwent K63-linked poly-ubiquitination, which was significantly enhanced by MARCH9 overexpression. Wild-type MARCH9, but not its catalytic mutants, markedly reduced RPTPα protein stability, while endogenous MARCH9 knockdown increased RPTPα levels. CQ, not MG132 or 3-MA, restored RPTPα stability, indicating that MARCH9 mediated lysosomal degradation of RPTPα through ubiquitination. Heat shock at 43 ℃ specifically enhanced MARCH9-RPTPα interaction, promoting RPTPα degradation. Functional assays revealed that, compared to control H1299 cells, MARCH9-knockdown cells exhibited elevated RPTPα levels, accelerated proliferation, enhanced clonogenicity and invasive capacity, and increased tumorigenicity in nude mice. These phenotypes could be reversed by double knockdown of MARCH9/RPTPα. Bioinformatics analysis demonstrated that high RPTPα expression correlated with poor prognosis and tumor metastasis in lung cancer patients, while MARCH9 showed inverse correlations. Conclusion ·MARCH9 mediates K63-linked ubiquitination-dependent lysosomal degradation of phosphatase RPTPα, providing new insights into developing RPTPα-targeted cancer therapeutic strategies. Figures and Tables | References | Related Articles | Metrics

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Microenvironmental profiles of wound tissues with accelerated healing properties by HAMA hydrogel JIANG Qianyu, YAO Chengcheng, JI Ping, WANG Ying 2025, 45 (8):  969-980.  doi: 10.3969/j.issn.1674-8115.2025.08.004 Abstract ( 328 )   HTML ( 13 )   PDF (6238KB) ( 1175 )   Objective ·To explore the roles of hyaluronic acid methacryloyl (HAMA) hydrogel in skin wound healing and to characterize the microenvironmental landscape at wound sites. Methods ·A full-thickness skin excision model was established in mice, which were randomly divided into a control group (n=3) and a HAMA group (n=3). The wound in the HAMA and control groups were covered with 100 μL of HAMA hydrogel and 100 μL of phenyl-2,4,6-trimethylbenzoylphosphonic acid lithium (LAP), respectively. Both groups were then irradiated with a UV lamp for 20 s. The residual wound areas was measured on days 0, 3, 7, 10, and 14. Wound healing effects of HAMA hydrogel were analyzed by measuring the residual wound area and through H-E staining. Single-cell RNA sequencing technology was utilized to analyze the cellular profile of local wound skin tissues at day 14 post-injury. Immunofluorescence assay was used to detect the levels of type I collagen, type Ⅲ collagen, F4/80, CD206, and CD86 in the wound sites. The mRNA expression levels of Arg1, Nos2, Itgam, and Itgb2 in the mouse macrophage cell line Raw264.7 co-cultured with HAMA hydrogel for 24 h were detected by RT-qPCR. The fibroblasts and macrophages in the local skin of the mouse wound on day 14 were analyzed using the Seurat package, and the communication between fibroblasts and macrophages was analyzed using the CellChat package. Results ·Mice treated with HAMA hydrogel exhibited a significantly faster rate of wound healing process compared to the control group. At day 14, wounds in the HAMA-treated mice had already healed, while those in the control group remained unhealed. Single-cell RNA sequencing analysis revealed a remarkable increase in the proportion of fibroblasts in the skin tissues of HAMA-treated wounds. The proportion of the Col3a1-high-expressing fibroblast subset increased (90.2%) compared to the control group (79.8%), while the proportion of the Col1a1-high-expressing fibroblast subset decreased (5.7% vs 15.9%). Immunofluorescence analysis confirmed that the level of type Ⅲ collagen in the wound tissues of the HAMA group was significantly higher than that in the control group (P=0.035), while the level of type Ⅰ collagen was significantly lower (P=0.044). Although there was no significant difference in the proportions of macrophages in the wound tissues between the HAMA-treated and control groups, scRNA sequencing data and in vitro experiments using Raw264.7 cells showed that HAMA hydrogel could induce the expression of Arg1 and decrease the expression of Nos2 in the macrophages (P<0.001). Additionally, macrophages in the HAMA-treated wounds expressed higher levels of CD206 and lower levels of CD86 (P=0.042, P=0.011). The results of the CellChat analysis showed that, compared to the control group, increased communication intensity was observed between macrophages and fibroblasts subsets at the wound sites in the mice of HAMA group. Conclusion ·The microenvironment after HAMA hydrogel treatment is conducive to skin wound healing, characterized by a local aggregation of anti-inflammatory macrophages and fibroblasts that secrete type Ⅲ collagen. Figures and Tables | References | Related Articles | Metrics

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Role of CARD9 in macrophage M1 polarization in severe acute pancreatitis rats WANG Lin, XU Ping, ZHANG Qiaoting, TIAN Jun, LOU Xiaoli, WANG Jing 2025, 45 (8):  981-989.  doi: 10.3969/j.issn.1674-8115.2025.08.005 Abstract ( 213 )   HTML ( 11 )   PDF (3627KB) ( 757 )   Objective ·To investigate the role of caspase recruitment domain-containing protein 9 (CARD9) in regulating macrophage polarization in a rat model of severe acute pancreatitis (SAP). Methods ·SD rats were divided into 4 groups: Control group, SAP group, SAP+CARD9 shRNA group, and SAP+Control shRNA group with six rats in each group. The SAP rats transfected with CARD9 shRNA were established by injecting CARD9 shRNA adenovirus 48 hours before the SAP model was induced. The pancreatic tissues, peripheral blood, and peritoneal macrophages were collected 12 hours after the model was established. The expressions of CARD9 gene and CARD9 protein in peritoneal macrophages and pancreatic tissues were measured by real-time PCR and Western blotting. The expressions of TNF-α, IL-6, IL-10 and Arg-1 mRNA were detected by real-time PCR and the polarization types of peritoneal macrophages were detected by flow cytometry. Results ·The expressions of CARD9 gene and CARD9 protein in peritoneal macrophages in CARD9 shRNA rats were significantly lower than those in SAP rats and interference control rats, which confirmed the success of CARD9 interference model. Compared with SAP rats, CARD9 shRNA rats had significantly reduced degree of inflammation and pathological scores; the mRNA levels of TNF-α, and IL-6 in peritoneal macrophages were significantly decreased; meanwhile, the mRNA levels of IL-10 and Arg-1 were increased, and the changes in TNF-α and IL-6 were significantly higher than those of IL-10 and Arg-1. The proportion of M1 macrophages was significantly reduced, and the ratio of M1/M2 was significantly decreased. The expression level of CARD9 mRNA in peritoneal macrophages was positively correlated with the proportion of M1 macrophages and the mRNA levels of TNF-α and IL-6. Conclusion ·CARD9 is involved in regulating macrophage polarization in SAP rats, and it mainly regulates M1 polarization. Inhibition of CARD9 expression can reduce M1 macrophage polarization and reduce the inflammatory response in SAP rats. Figures and Tables | References | Related Articles | Metrics

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Effect of in situ hypoxia-inducing hydrogelon extracellular matrix secretion in the nucleus pulposus ZHOU Xingdie, CHEN Zehao, LÜ Zhendong, ZHANG Yuhui, LIU Li 2025, 45 (8):  990-1000.  doi: 10.3969/j.issn.1674-8115.2025.08.006 Abstract ( 187 )   HTML ( 8 )   PDF (7392KB) ( 568 )   Objective ·To construct an interpenetrating network hydrogel (HMGL) that can induce hypoxia in situ, investigate its effects on promoting the secretion of extracellular matrix in nucleus pulposus cells (NPCs), and evaluate its potential in the treatment of intervertebral disc degeneration. Methods ·HMGLs capable of long-term in situ hypoxiainduction were prepared by a two-step polymerization method. Hypoxic hydrogels with laccase concentrations of 5 U/mL and 10 U/mL, namely HMGL-5 and HMGL-10, were constructed, whereas a hyaluronic acid methacryloyl (HAMA) hydrogel served as the control. The molecular structures of HAMA and gelatin grafted with vanillin (GelVA) were verified by 1H nuclear magnetic resonance spectra (1H NMR) and Fourier transform infrared spectroscopy (FTIR). The microstructures of the hydrogels were observed by scanning electron microscope (SEM), and the mechanical properties of the hydrogels were tested by a rotational rheometer and a dynamic mechanical analyzer (DMA). The induced hypoxic behaviors of the hydrogels were detected by an oxygen consumption fluorescent probe. The biocompatibility of the hydrogels was tested by live/dead staining and the cell counting kit 8 (CCK-8) assay, and the expression of hypoxia-inducible factor-1α (HIF-1α) and type Ⅱ collagen (Col Ⅱ) in NPCs was detected by immunofluorescence staining. A rat model of intervertebral disc degeneration was established, and hydrogels loaded with NPCs were injected into degenerated intervertebral discs to evaluate their repair effects. Disc height and disc water content changes were detected by X-ray imaging and magnetic resonance imaging (MRI), and the integrity of disc structure and proteoglycan levels were detected by histological staining. Results ·Structural characterization demonstrated that the materials had been successfully prepared. SEM showed that the three hydrogels all had a loose and porous structure, and their elastic moduli increased with the decrease of pore size. Hypoxia test results indicated that the hypoxia-inducing ability of HMGL-10 hydrogel was the strongest. In vitro experimental results showed that the three hydrogels all had good biocompatibility. Compared with the HAMA hydrogel, the HIF-1α of NPCs was significantly activated in the HMGL-10 hydrogel. The expression levels of HIF-1α and Col Ⅱ in the HMGL-10 hydrogel group were 3.38 and 4.15 times higher than those in the HAMA hydrogel group. In vivo experimental results showed that the integrity, height, and water content of the intervertebral discs in the hypoxia hydrogel group were all superior to those in the other treatment groups. Conclusion ·The in situ hypoxia-inducing hydrogel effectively activates HIF-1α, promotes extracellular matrix secretion, and demonstrates superior regenerative potential for intervertebral disc repair. Figures and Tables | References | Related Articles | Metrics

Clinical research

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A single-center retrospective cohort study of rituximab combined with glucocorticoids in the treatment of high-risk primary membranous nephropathy ZHAO Keke, LI Hui, ZHANG Chong 2025, 45 (8):  1001-1008.  doi: 10.3969/j.issn.1674-8115.2025.08.007 Abstract ( 282 )   HTML ( 8 )   PDF (2135KB) ( 268 )   Objective ·To evaluate and compare the clinical efficacy and safety of rituximab (RTX) monotherapy and RTX combined with glucocorticoids in the treatment of high-risk primary membranous nephropathy (PMN). Methods ·A retrospective cohort study was conducted to include 87 high-risk PMN patients who received RTX treatment in Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, between December 2018 and February 2024. Patients were divided into RTX monotherapy group and RTX combined with glucocorticoid group (combination therapy group) according to their treatment regimens. After adjusting for confounding factors using propensity score matching (PSM), intention-to-treat (ITT) and per-protocol (PP) analyses were performed to evaluate the primary efficacy outcomes. Results ·A total of 58 patients were included after PSM, with 29 in each group. At 12 months after treatment, ITT analysis showed that the overall remission and complete remission (CR) of RTX monotherapy were 72.41% and 20.69% respectively, compared to 79.31% and 55.17% in the combination therapy group. The difference in CR rates between the two groups was statistically significant (P=0.007). The differences in serum creatinine, blood urea nitrogen, and estimated glomerular filtration rate (eGFR) were not statistically significant. However, the 24-hour urinary protein levels in the combination therapy group were significantly lower than those in the RTX monotherapy group (P=0.024). PP analysis showed that the CR rate of the combination therapy group was also significantly higher than that of the RTX monotherapy group (P=0.026). During follow-up, serum creatinine levels and eGFR remained stable in both groups. The incidence of adverse events was comparable between the two groups, with no statistically significant differences. Conclusion ·Compared with RTX monotherapy, RTX combined with glucocorticoids significantly improves the CR rate in high-risk PMN patients without increasing the incidence of adverse events. This combination regimen appears to be an effective treatment strategy, though its long-term efficacy and safety warrant further confirmation through large-scale prospective studies. Figures and Tables | References | Related Articles | Metrics

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Development and clinical application of a machine learning-driven model for metabolite-based diagnosis of small cell lung cancer HUANG Xin, LIU Jiahui, YE Jingwen, QIAN Wenli, XU Wanxing, WANG Lin 2025, 45 (8):  1009-1016.  doi: 10.3969/j.issn.1674-8115.2025.08.008 Abstract ( 236 )   HTML ( 12 )   PDF (2349KB) ( 292 )   Objective ·To develop an early diagnostic model for small cell lung cancer (SCLC) based on differences in serum metabolite expression profiles between patients with SCLC and those with benign pulmonary diseases, using machine learning algorithms. Methods ·Serum samples were collected from 29 SCLC patients and 67 patients with benign lung diseases at Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, as the training cohort. An independent external validation cohort included 20 SCLC patients and 40 patients with benign lung diseases from Gansu Provincial Cancer Hospital. A total of 69 serum metabolites were quantitatively analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The XGBoost Classifier was employed to rank metabolite importance, and a forward feature selection strategy based on XGBoost was used to identify a subset of key metabolites. Diagnostic models were constructed using AdaBoost, random forest (RF), and light gradient boosting machine (LGBM) algorithms. Model performance was assessed using receiver operating characteristic (ROC) curves and the area under the curve (AUC), and validated on the external test cohort. Results ·Principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) of the training cohort revealed distinct metabolic profiles between SCLC and benign lung disease patients. Based on feature importance rankings, six key metabolites were selected to construct the MTB-6 diagnostic model. Among the models, AdaBoost achieved the best performance, with an AUC of 0.943, sensitivity of 75.0%, and specificity of 90.9% in the training cohort. In the external test cohort, the model demonstrated robust performance with an AUC of 0.921, sensitivity of 80.0%, and specificity of 87.5%. Conclusion ·The MTB-6 model, based on six serum metabolites and the AdaBoost algorithm, exhibits excellent diagnostic performance and holds potential for the differential diagnosis of SCLC and benign pulmonary diseases. Figures and Tables | References | Related Articles | Metrics

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Clinical study on osteogenic effect of sticky bone and autologous iliac cancellous bone graft in repairing unilateral alveolar cleft YU Zuyin, LIU Yiyun, XIE Jiahui, CAI Ming, SHEN Guofang 2025, 45 (8):  1017-1026.  doi: 10.3969/j.issn.1674-8115.2025.08.009 Abstract ( 223 )   HTML ( 9 )   PDF (4294KB) ( 621 )   Objective ·To explore the clinical efficacy and safety of sticky bone [deproteinized porcine bone mineral granules combined with advanced platelet-rich fibrin (A-PRF) and liquid platelet-rich fibrin (L-PRF)] in the repair of unilateral alveolar cleft. Methods ·Patients diagnosed with unilateral alveolar cleft who met the inclusion and exclusion criteria were recruited from December 1,2023 to August 31,2024. The patients were randomly divided into 2 groups. The experimental group received sticky bone grafts, and the control group received autologous iliac cancellous bone grafts for alveolar cleft repair. The primary efficacy index was the bone resorption rate at 6 months post-surgery, calculated by measuring the grafted bone volume immediately after surgery and at 6 months using Simplant Pro 17.01 software based on patients' computed tomography data collected before surgery, immediately after surgery, and 6 months post-surgery. Secondary efficacy indices included bone density at 6 months after surgery, the occurrence of postoperative complications in patients, and the scores on the oral health-related quality of life scale. Prism 10 software was used for data analysis, and t-test and Pearson correlation analysis methods were adopted. Results ·Seventeen patients with unilateral alveolar cleft were included in the experimental group, and 15 in the control group. The remaining bone volume in the experimental group at 6 months after surgery was more than that in the control group. The bone resorption rate in the experimental group was 33.24%±17.16%, significantly lower than 66.31%±17.98% in the control group (P<0.001). One patient in the experimental group had vestibular mucosal dehiscence accompanied by bone powder discharge 2 weeks after surgery; 3 patients in the control group had vestibular mucosal dehiscence accompanied by cancellous bone discharge 1 month after surgery, with one case of grafted bone necrosis 4 months after surgery. The bone density in the experimental group at 6 months after surgery was significantly higher than that in the control group (P<0.001), and the scores on the oral health-related quality of life scale were lower. Conclusion ·Compared with iliac cancellous bone, when sticky bone is used in the treatment of patients with unilateral alveolar cleft, it shows a lower bone resorption rate and higher bone density, indicating better osteogenic ability. Fewer number of complications and lower scores on the oral health-related quality of life scale suggest greater safety, thereby supporting its strong potential for clinical promotion and application. Figures and Tables | References | Related Articles | Metrics

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Molecular epidemiology of Klebsiella pneumoniae isolated from children JIANG Jie, ZHANG Hong, LUN Heyuan, PAN Fen, YU Fangyuan, HE Ping 2025, 45 (8):  1027-1034.  doi: 10.3969/j.issn.1674-8115.2025.08.010 Abstract ( 273 )   HTML ( 5 )   PDF (1605KB) ( 988 )   Objective ·To analyze the molecular epidemiological characteristics of Klebsiella pneumoniae isolated from children, including the distribution of serotypes, resistance genes, and virulence genes, to provide a scientific basis for the prevention and treatment strategies of Klebsiella pneumoniae infections in children. Methods ·A total of 133 non-duplicate strains of Klebsiella pneumoniae clinically isolated from Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, from April 2023 to April 2024, were collected. Antimicrobial susceptibility testing was performed by using the Vitek-2 Compact system. Capsular polysaccharide K antigen serotypes (K types) were determined by wzy-dependent initiator (wzi) gene sequencing. Resistance genes were detected by the colloidal gold method. Virulence genes and lipopolysaccharide O antigen serotypes (O types) were identified by PCR method. Results ·Among the 133 strains of Klebsiella pneumoniae, a total of 50 strains of carbapenem-resistant Klebsiella pneumoniae (CRKP) were detected, mainly distributed in the neonatal ward and intensive care unit (ICU). CRKP exhibited high resistance to most antimicrobial agents, and the main type of carbapenemase gene was blaNDM (34/50, 68.00%), followed by co-carriage of blaNDM+blaOXA-48 (10/50, 20.00%) and blaKPC (6/50, 12.00%). Serotype analysis revealed that the 50 CRKP strains could be divided into 8 K types and 6 O types. The most common K type was KL17 (30/50, 60.00%), followed by KL105 (10/50, 20.00%) and KL47 (5/50, 10.00%). The most common O type was O4 (30/50, 60.00%), followed by O3b (7/50, 14.00%, ), O3/O3a (6/50, 12.00% ), and OL101 (5/50, 10.00%). Significant correlations were identified between KL47 and OL101 serotypes (KL47:OL101), between KL17 and O4 serotypes (KL17:O4), and between KL1/KL2 and O1 serotypes (KL1/KL2:O1). Conclusion ·The CRKP strains infecting children primarily carry blaNDM-type carbapenemase genes, showing a significant difference compared to CRKP-infected adults. The detection rate of CRKP in the neonatal ward is significantly higher than those in other departments, suggesting that infection prevention and control measures in this ward need to be strengthened. Figures and Tables | References | Related Articles | Metrics

Evidence-based medicine

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Deciphering the protective role of AZGP1 in heart failure through Mendelian randomization LI Long, ZHAO Xia, JIN Shan, LI Zeying, LÜ Fuqiang, PANG Lijuan, LIU Kejian 2025, 45 (8):  1035-1045.  doi: 10.3969/j.issn.1674-8115.2025.08.011 Abstract ( 279 )   HTML ( 7 )   PDF (4628KB) ( 948 )   Objective ·To investigate the causal relationship between plasma zinc-alpha-2-glycoprotein 1 (AZGP1) and heart failure (HF) by using Mendelian randomization (MR) analysis and experimental validation. Methods ·A two-sample MR analysis was performed to assess the causal relationship between AZGP1 and HF by integrating large-scale genome-wide association study (GWAS) data on plasma proteins and HF. The inverse-variance weighted (IVW) method was employed as the primary analytical approach, supplemented by MR-Egger regression, weighted median, and simple median methods. Horizontal pleiotropy was tested by using MR-PRESSO global test and MR-Egger intercept analysis. Colocalization analysis was conducted to validate genetic locus overlap. Additionally, a clinical cohort (84 HF patients and 68 healthy controls) was analyzed, with plasma AZGP1 levels quantified by enzyme-linked immunosorbent assay (ELISA). Results ·MR analysis showed that elevated plasma AZGP1 levels were significantly associated with reduced HF risk (OR=0.82, 95%CI 0.75‒0.90, P=1.70×10-5). Colocalization analysis confirmed that AZGP1 expression and HF shared causal genetic variants (posterior probability for H4=0.69). Sensitivity and reverse MR analyses supported the robustness of the results. ELISA confirmed that plasma AZGP1 levels were significantly lower in HF patients compared to healthy controls, reinforcing its protective role in HF. Conclusion ·This study demonstrates AZGP1 exerts a protective causal effect on HF and may serve as a potential biomarker for HF treatment. Figures and Tables | References | Related Articles | Metrics

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Research progress on milk-derived exosomes in sarcopenia TANG Wenjing, JIA Jie, YANG Kefeng, MAO Xuanxia, SONG Fangfang 2025, 45 (8):  1046-1052.  doi: 10.3969/j.issn.1674-8115.2025.08.012 Abstract ( 278 )   HTML ( 9 )   PDF (2270KB) ( 1234 )   Milk-derived exosomes are nanoscale extracellular vesicles naturally present in mammalian milk and are rich in proteins, lipids, nucleic acids, and bioactive metabolites. They exhibit biological activities such as anti-inflammatory, antioxidant, and immunomodulatory effects. Owing to their unique advantages of low immunogenicity, excellent biocompatibility, stability, and natural targeting ability, milk-derived exosomes have emerged as promising natural nanocarriers, garnering significant attention in disease treatment and nutritional interventions. Sarcopenia, characterized by reduced skeletal muscle mass and diminished strength, is closely associated with aging, chronic inflammation, and oxidative stress. Recent studies have highlighted the potential role of milk-derived exosomes in combating sarcopenia. These exosomes can increase myotube diameter, enhance muscle mass and fiber cross-sectional area, and improve exercise performance metrics such as grip strength. Potential mechanisms may include promoting muscle anabolism, improving mitochondrial function through antioxidant mechanisms, and modulating the inflammatory microenvironments. However, challenges remain in their application for sarcopenia at present, such as the unclear mechanisms of key bioactive components [e.g., microRNAs (miRNAs), L-ornithine, and milk fat globule-epidermal growth factor 8 (MFG-E8)], and the targeting and stability of delivery systems need to be optimized. Future research should focus on the functional analysis of components in exosomes, optimization of delivery systems, and preclinical validation to promote their practical application in managing age-related muscle health. Figures and Tables | References | Related Articles | Metrics

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Application of single-cell RNA sequencing in bone regeneration HUANG Zihan, HUANG Xinzhi 2025, 45 (8):  1053-1058.  doi: 10.3969/j.issn.1674-8115.2025.08.013 Abstract ( 300 )   HTML ( 6 )   PDF (1313KB) ( 322 )   Bone regeneration is pivotal for restoring bone homeostasis, involving the coordinated collaboration of diverse cell types in a complex and heterogeneous process. Elucidating the molecular mechanisms at each stage to develop novel bone regeneration strategies represents a key direction in this field. Traditional high-throughput sequencing examines bulk transcriptomes, losing cellular-level resolution. Single-cell RNA sequencing (scRNA-seq) technology enables the analysis of subpopulation heterogeneity by revealing RNA expression profiles at the single-cell level. Based on single-cell atlases, researchers can further employ specific algorithms to simulate cellular differentiation trajectories, facilitating more profound mechanistic investigations. Utilizing this technology, critical cell subpopulations involved in long bone and craniofacial bone regeneration have been identified, characteristic cellular markers and potential diagnostic indicators have been defined, regenerative differences under inflammatory or aging conditions have been compared, the osteogenic mechanisms involved in guided bone regeneration procedures have been explored, and the differential bone-promoting effects of various biomaterials have been revealed. This review summarizes the applications of scRNA-seq in long bone and craniofacial bone regeneration, as well as in bone tissue engineering. It highlights its contributions in deciphering cellular heterogeneity, gene regulation, and microenvironmental interactions, consolidates key cell subpopulations and their functions identified through sequencing, and discusses current research limitations. Furthermore, it outlines future prospects for this technology in bone regeneration research, offering new perspectives for subsequent studies. Figures and Tables | References | Related Articles | Metrics

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Research status of ultrasound parameters and blood indicators in predicting fetal growth restriction LIANG Shuyuan, YE Baoying, CHENG Weiwei 2025, 45 (8):  1059-1065.  doi: 10.3969/j.issn.1674-8115.2025.08.014 Abstract ( 316 )   HTML ( 17 )   PDF (1321KB) ( 1319 )   Fetal growth restriction (FGR) refers to the failure of a fetus to reach the level of growth potential determined by its genetic potential. It is a common obstetric complication, occurring in 5% to 10% of pregnancies. As a major risk factor for perinatal death and adverse neonatal outcomes, early prediction of FGR is crucial for optimizing pregnancy management. Existing evidence suggests that FGR is significantly associated with a variety of adverse pregnancy outcomes, including intrauterine hypoxia, preterm birth, neonatal asphyxia, and even neonatal mortality. It may also affect long-term neurological development and increase the risk of metabolic diseases in adulthood. Its pathogenesis is complex, which may involve placental blood flow perfusion insufficiency and genetic factors. Ultrasound parameters are the main basis for the diagnosis of FGR, among which fetal biological and hemodynamic parameters are of great value. Elevated umbilical artery blood flow resistance index, absent or reversed end-diastolic blood flow, and placental insufficiency are associated with the severity of FGR. However, approximately 10% of fetuses diagnosed by ultrasound as having FGR are later confirmed to be healthy small-for-gestational-age (SGA) infants after birth, and this false positive result may lead to unnecessary clinical interventions. Currently, there is no recognized accurate prediction model for FGR in clinical practice. Future research should focus on establishing unified diagnostic criteria and developing multi-index joint prediction tools based on artificial intelligence (AI). Early prediction and intervention for FGR are of great significance to improve perinatal outcomes. This paper reviewed the predictive value of ultrasound parameters, blood indicators, and their integration with AI for FGR, in order to provide a basis for clinical decision-making. References | Related Articles | Metrics

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Clinical analysis and literature integration study of cystic fibrosis complicated by allergic bronchopulmonary aspergillosis HE Chen, YAN Silei, ZHOU Weitao, LING yong, YU Ningning, JIANG Kun, QIAN Liling 2025, 45 (8):  1066-1073.  doi: 10.3969/j.issn.1674-8115.2025.08.015 Abstract ( 271 )   HTML ( 4 )   PDF (2092KB) ( 602 )   Objective ·To explore the diagnostic and treatment methods for patients with cystic fibrosis (CF) complicated by allergic bronchopulmonary aspergillosis (ABPA), and to enhance clinicians' understanding of these two diseases. Methods ·A retrospectively analysis was conducted on the clinical data of 5 patients with CF complicated by ABPA admitted to the Department of Respiratory Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, from July 2023 to August 2024. A literature search was performed in PubMed, Web of Science, Cochrane Library, and CNKI for studies published in the past 10 years regarding the co-existence of these diseases. Clinical manifestations, treatment courses, and current epidemiological research were summarized and analyzed. Results ·Common symptoms of patients with CF complicated by ABPA included aggravated cough and expectoration, wheezing, fever, and dyspnea. Whole-exome aequencing indicated mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and an increase in the concentration of chloride ions in sweat. The levels of total serum immunoglobulin E (IgE) and Aspergillus fumigatus-specific IgE increased, and chest computed tomography (CT) showed bronchiectasis and mucus plugging. CF complicated by ABPA is often missed or misdiagnosed for asthma. In China, ABPA is often diagnosed before CF, whereas in Caucasian populations CF is typically diagnosed first. Initial treatment usually involves long-term oral administration of antifungal drugs such as voriconazole combined with glucocorticoids such as prednisone. For patients with frequent relapses or severe side effects, alternative antifungal agents or omalizumab therapy may be considered. Co-infection with Pseudomonas aeruginosa is common, often requiring intravenous antibiotics such as cefoperazone-sulbactam. Current epidemiological research focuses mainly on clinical characteristics, treatment regimens, and novel diagnostic methods. Conclusion ·ABPA and CF have overlapping symptoms. Accurate diagnosis of CF complicated by ABPA requires genetic testing, sweat chloride measurement, chest CT, and serological tests. The coexistence of these diseases often leads to missed, delayed, or incorrect diagnosis, increasing patient burden. Present epidemiological studies mainly address clinical characteristics with a lack of targeted clinical drug trials for this patient population. Figures and Tables | References | Related Articles | Metrics

Case report

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Case report of severe aplastic anemia complicated by multiple Bacillus cereus infections ZHOU Huiru, ZHANG Liqin, ZHANG Xiaoxing, SUN Zhijiang 2025, 45 (8):  1074-1078.  doi: 10.3969/j.issn.1674-8115.2025.08.016 Abstract ( 154 )   HTML ( 3 )   PDF (5074KB) ( 435 )   Patients with severe aplastic anemia (SAA) often present with neutropenia, and are particularly susceptible to infections, especially following immunosuppressive therapy. Bacillus cereus is a ubiquitous, opportunistic pathogen capable of colonizing healthy individuals and causing infections through various routes. Neutropenia is a common feature in many hematologic disorders, placing affected patients at higher risk for Bacillus cereus infections. This report describes a rare case of Bacillus cereus bacteremia with multiple abscesses in a patient with SAA during the neutropenic phase following immunosuppressive therapy. Given the rarity of such presentations, relevant literature was reviewed and the diagnostic and treatment process was analyzed in detail, with the aim of providing clinical insights and improving the management of similar cases. Figures and Tables | References | Related Articles | Metrics