Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

Objective:Using methylation characteristics of human genes to construct machine learning predictive models for screening cervical cancer and precancerous lesions.Methods:Human DNA methylation detection was performed on 224 cervical exfoliated cell specimens from the Cancer Hospital of the Chinese Academy of Medical Sciences, Tianjin Central Hospital of Gynecology Obstetrics, Xinmi Maternal and Child Health Hospital of Henan Province, West China Second Affiliated Hospital of Sichuan University, and Heping Hospital Affiliated to Changzhi Medical College collected during April 2014 and March 2015. The hypermethylated gene fragments related to cervical cancer were selected by high-density, high-association, and hypermethylated gene fragment screening and the LASSO regression algorithm. Taking cervical intraepithelial neoplasia grade 2 (CIN2) or more severe lesions as the research outcome, machine learning predictive models based on the random forest (RF), naive Bayes (NB), and support vector machine (SVM) algorithm, respectively, were constructed. A total of 144 outpatient specimens were used as the training set and 80 cervical exfoliated cell specimens from women participating in the cervical cancer screening program were used as the test set to verify the predictive models. Using histological diagnosis results as the gold standard, the detection efficacy for CIN2 or more severe lesions of the three machine learning predictive models were compared with that of the human papilloma virus (HPV) detection and cytological diagnosis.Results:In the training set of 144 cases, there were 34 cases of HPV positivity, with a positive rate of 23.61%. Cytologically, there were 37 cases diagnosed as no intraepithelial lesion or malignancy (NILM), and 107 cases diagnosed as atypical squamous cells of undetermined significance (ASC-US) or above. Histologically, there were 28 cases without cervical intraepithelial neoplasia or benign cervical lesions, 31 cases of CIN1, 18 cases of CIN2, 31 cases of CIN3, and 36 cases of squamous cell carcinoma. Seven hypermethylated gene fragments were selected from 45 genes, and three machine learning prediction models based on the RF, NB, and SVM algorithm, respectively, were constructed. In the validation set of 80 cases, there were 28 cases of HPV positivity, with a positive rate of 35.00%. Cytologically, there were 65 cases diagnosed as NILM and 15 cases as ASC-US or above. Histologically, there were 39 cases without cervical intraepithelial neoplasia or benign cervical lesions, 10 cases of CIN1, 10 cases of CIN2, 11 cases of CIN3, and 10 cases of squamous cell carcinoma. In the validation set, the area under the curve (AUC) values of the RF model, NB model, SVM model, HPV detection, and cytological diagnosis of CIN2 or above were 0.90, 0.88, 0.82, 0.68, and 0.45, respectively. The DeLong test showed that there was no statistically significant difference in the AUC values between the RF, NB, and SVM models (all P＞0.05), and the AUC values of the RF and NB models were higher than that of HPV detection (both P＜0.01), and the AUC values of the RF, NB, and SVM models were higher than that of cytological diagnosis (all P＜0.01). Compared with the NB model, the sensitivity of the RF model was similar (80.65% vs. 77.42%), but the specificity of the NB model was much higher than that of the RF model (93.88% vs. 73.47%). Conclusion:Among the machine learning prediction models for cervical cancer and precancerous lesions constructed based on human DNA methylation, the NB model has good predictive performance for CIN2 and above lesions, and may be used for screening of cervical cancer and precancerous lesions.

Objective To comparatively evaluate the diagnostic value of metagenomic next-generation sequencing(mNGS)versus conventional microbial culture in spinal infections.Methods A cross-section design was conducted on 82 consecutive patients with suspected spinal infections treated between February 2022 and January 2024 at Jiangbei Branch of First Affiliated Hospital of Army Medical University(Third Military Medical University).Microbiological culture,histopathological examination,and mNGS results from infected specimens were analyzed.Clinical diagnosis,primarily based on clinical manifestations,laboratory tests and radiologic features combined with medical history,was defined as the gold standard,and then the diagnostic performance,including sensitivity and specificity,were compared between mNGS and microbial culture.Results Among the 82 patients,definitive microbiological evidence was identified in 70 cases,and mNGS demonstrated a significantly higher detection rate than microbial culture(64 vs 36 cases,78.05％vs 43.9％,P<0.05).mNGS also obtained obviously higher sensitivity,accuracy,and negative predictive value(NPV),and notably lower positive predictive value(PPV)when compared to conventional microbial culture(all P<0.05).When stratified by infection type,mNGS obtained significantly higher sensitivity and accuracy compared to microbial culture in tuberculous spinal infections(P<0.05).For non-tuberculous spinal infections,mNGS also showed superior sensitivity to microbial culture(P<0.05).Conclusion In patients with spinal infections,mNGS demonstrates a significantly higher pathogen detection rate than conventional microbial culture.This technique can provide early and broad-spectrum pathogenic microbiological evidence for spinal infection.

Objective:To systematically analyze the disease burden of soft tissue and extraosseous sarcomas (STEOS) among individuals aged 15-49 years old worldwide and in the Chinese mainland from 1990 to 2021, and explore the relationship between socio-economic development and disease burden.Methods:Incidence, mortality and disability-adjusted life year (DALY) for STEOS in populations aged from 15 to 49 were collected from the Global Burden of Disease (GBD2021) database. The temporal trends in disease burden were quantified using the average annual percentage change (AAPC). The socio-demographic index (SDI) was employed to examine the socio-economic development.Results:The global incidence rate of STEOS among individuals aged 15-49 remained relatively stable (AAPC=-0.13, 95% CI:-0.23--0.04, P=0.299). In contrast, significant declines were observed in both mortality rate (AAPC=-0.39, 95% CI:-0.47--0.31, P<0.001) and DALY rate (AAPC=-0.46, 95% CI:-0.54--0.38, P<0.001). In the Chinese mainland, the incidence of STEOS among individuals aged 15-49 remained relatively stable (AAPC=-0.10, 95% CI:-0.31-0.10, P=0.314), while the mortality rate (AAPC=-1.42, 95% CI:-1.59--1.25, P<0.001) and DALY rate (AAPC=-1.62, 95% CI:-1.82--1.42, P<0.001) declined steadily from 1990 to 2021. In 2021, high-SDI regions reported high incidence rate (1.38/100 000, 95% UI:1.28/100 000-1.46/100 000), mortality rate (0.42/100 000, 95% UI:0.39/100 000-0.43/100 000) and DALY rate (23.05/100 000, 95% UI:21.84/100 000-24.00/100 000), while low-SDI regions reported high mortality rate (0.36/100 000, 95% UI:0.27/100 000-0.54/100 000) and DALY rate (20.50/100 000, 95% UI:15.46/100 000-30.96/100 000). Conclusion:The disease burden of STEOS worldwide and in the Chinese mainland populations aged from 15 to 49 has declined consistently. Notably, STEOS constitutes a substantial disease burden, particularly among countries and regions with high-SDI and low-SDI in 2021.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To observe the effect of robot-assisted gait training (RAGT) supplemented with intermittent theta burst stimulation (iTBS) of the cerebellum in restoring lower limb function after anterior cruciate ligament reconstruction (ACLR).Methods:Eighty ACLR patients were randomly divided into a control group, a magnetic stimulation group, a robot group and a combined group, each with 20 members. The robot and magnetic stimulation groups underwent RAGT and cerebellar iTBS before conventional training, while the combined group received iTBS followed by RAGT and then conventional training. The treatments were administered once a day, three days per week for four weeks. Before and after the intervention, the peak torque ratio of the knee flexors and extensors (H/Q), peak torque of the knee extensors (PT), and knee repositioning angle difference were measured. Knee function and balance (using the Berg Balance Scale (BBS)) were also assessed.Results:The combined group demonstrated significantly better quadriceps PT and H/Q% than the other 3 groups. Knee repositioning angle difference improved significantly in all of the groups after the treatment, with the combined group showing the smallest difference (5.00±1.21)°, significantly better than the other three groups. Lysholm and BBS scores had also improved significantly in all of the groups, with the combined group′s improvements again significantly better than those of the other groups.Conclusion:Intermittent theta burst stimulation of the cerebellum combined with robot-assisted gait training can significantly improve knee function and balance after ACLR.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective:To investigate the effect of early high-sucrose diet (eHSD) on cognitive function and its regulatory mechanism in 3×Tg-AD mice.Methods:(1) Eighteen specific-pathogen-free (SPF)-grade 2-month-old wide-type (WT) mice were randomly divided into a WT+normal chow diet (NCD) group and a WT+eHSD group, with 9 mice in each group; and 18 SPF-grade 2-month-old 3×Tg-AD mice were randomly divided into a 3×Tg-AD+NCD group and a 3×Tg-AD+eHSD group, with 9 mice in each group. At 2-5 months old, mice in the 4 groups received standard laboratory food+purified water or 30% sucrose water, followed by standard feed for all groups. At 8 months old, cognitive function was assessed by Morris water maze test; fluorescent intensity of AT8 (phosphorylated [p]-tau) and T22 (tau oligomers) in the hippocampal tissues was detected by immunofluorescent staining; concentrations of β-amyloid protein (Aβ) 42 and Aβ 40 were detected by enzyme-linked immunosorbent assay (ELISA); protein expressions of stimulator of interferon genes (STING), TANK-binding kinase 1 (TBK1), p-TBK1, and CCAAT/enhancer-binding protein β (C/EBPβ) were detected by Western blotting; activity of C/EBPβ transcription factor was detected by activity assay; mitochondrial DNA (mtDNA) content in the cytoplasm of cell was detected by real-time quantitative PCR (qPCR). (2) Eighteen SPF-grade 2-month-old 3×Tg-AD mice were randomized into a 3×Tg-AD+eHSD+H-151 group and a 3×Tg-AD+eHSD+dimethyl sulfoxide (DMSO) group, with 9 mice in each group. Mice at 2-5 months old were given standard laboratory food+30% sucrose water; they were, respectively, injected intraperitoneally with STING pathway inhibitor H-151 or DMSO at 5 months old, and continually injected until 8 months old; and then, the behavioral testing, immunofluorescent staining, ELISA, Western blotting and C/EBPβ transcription factor activity experiments were repeated as before. (3) After crossing C/EBPβ heterozygous knockout (C/EBPβ +/-) mice with 3×Tg-AD mice, 3×Tg-AD/C/EBPβ +/- mice were obtained, and 3×Tg-AD mice were used as controls; they were named 3×Tg-AD/C/EBPβ +/-+eHSD group and 3×Tg-AD+eHSD group, with 9 mice in each group. Both groups of mice were given standard laboratory food+30% sucrose water at 2-5 months old, followed by standard feed until 8 months old; and then, the behavioral testing, immunofluorescent staining, ELISA, and Western blotting experiments were repeated as before. (4) C/EBPβ transgenic mice (C/EBPβTg) were crossed with 3×Tg-AD mice to obtain C/EBPβTg/3×Tg-AD mice, and Non-Tg/3×Tg-AD mice were used as controls; they were, respectively, named as C/EBPβTg/3×Tg-AD+eHSD+H-151 group, Non-Tg/3×Tg-AD+eHSD+H-151 group, and Non-Tg/3×Tg-AD+eHSD+DMSO group, with 9 mice in each group. All 3 groups of mice were given standard laboratory food+30% sucrose water at 2-5 months old; at 5-8 months old, mice in the C/EBPβTg/3×Tg-AD+eHSD+H-151 group and Non-Tg/3×Tg-AD+eHSD+H-151 group were intraperitoneally injected with H-151, while mice in the Non-Tg/3×Tg-AD+eHSD+DMSO group were injected with DMSO; and then, the behavioral testing, immunofluorescent staining, ELISA, and Western blotting experiments were repeated as before. Results:(1) Compared with those in the WT+NCD group and WT+eHSD group, area under the latency curve of 3×Tg-AD+eHSD mice was significantly increased, and proportion of time spending in the targeted quadrant of mice in the 3×Tg-AD+NCD group and 3×Tg-AD+eHSD group was significantly decreased ( P<0.05); compared with that in the 3×Tg-AD+NCD group, proportion of time spending in the targeted quadrant in mice of the 3×Tg-AD+eHSD group was significantly reduced ( P<0.05). Compared with the 3×Tg-AD+NCD group, the 3×Tg-AD+eHSD group had significantly increased p-tau and tau oligomers, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.076 vs. 2.902±0.399; T22 fluorescent intensity: 1.000±0.145 vs. 2.495±0.273; Aβ 42: 1.000±0.167 vs.1.956±0.132; Aβ 40: 1.000±0.226 vs.1.900±0.116), significantly increased C/EBPβ protein expression and C/EBPβ transcription factor activity (1.000±0.164 vs. 1.804±0.112; 1.000±0.216 vs. 2.743±0.301), and statistically increased mtDNA level detected by D-loop1 and D-loop3 (1.000±0.234 vs. 2.800±0.210; 1.000±0.155 vs. 2.952±0.078; P<0.05). Compared with the 3×Tg-AD+NCD group, the 3×Tg-AD+eHSD group had significantly increased STING protein expression and p-TBK1/TBK1 ratio (STING: 1.000±0.192 vs. 2.093±0.081; p-TBK1/TBK1: 1.000±0.148 vs. 1.561±0.112, P<0.05). (2) Compared with the 3×Tg-AD+eHSD+DMSO group, the 3×Tg-AD+eHSD+H-151 group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, significantly decreased p-tau and tau oligomers expressions, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.142 vs. 0.538±0.057; T22 fluorescent intensity: 1.000±0.104 vs. 0.665±0.088; Aβ 42: 1.000±0.084 vs. 0.600±0.007; Aβ 40: 1.000±0.138 vs. 0.476±0.083), significantly decreased STING protein expression and p-TBK1/TBK1 ratio (STING: 1.000±0.054 vs. 0.468±0.111; p-TBK1/TBK1: 1.000±0.057 vs. 0.598±0.090), and significantly decreased C/EBPβ transcription factor activity (1.000±0.097 vs. 0.445±0.106; P<0.05). (3) Compared with the 3×Tg-AD+eHSD group, the 3×Tg-AD/C/EBPβ +/-+eHSD group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, significantly decreased p-tau and tau oligomers, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.160 vs. 0.506±0.065; T22 fluorescent intensity: 1.000±0.127 vs. 0.346±0.048; Aβ 42: 1.000±0.017 vs. 0.510±0.101; Aβ 40: 1.000±0.098 vs. 0.586±0.153), and significantly decreased C/EBPβ protein expression (1.000±0.101 vs. 0.568±0.094; P<0.05). (4) Compared with the Non-Tg/3×Tg-AD+eHSD+DMSO group, the Non-Tg/3×Tg-AD+eHSD+H-151 group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, and significantly decreased p-tau and tau oligomers expressions, Aβ 40 concentration in the hippocampus, and the Non-Tg/3×Tg-AD+eHSD+H-151 group, the C/EBPβTg/3×Tg-AD+eHSD+H-151 group had significantly decreased STING protein expression and p-TBK1/TBK1 ratio in the hippocampus ( P<0.05). Compared with the Non-Tg/3×Tg-AD+eHSD+H-151 group, the C/EBPβTg/3×Tg-AD+eHSD+H-151 group had significantly increased area under the latency curve, significantly decreased proportion of time spending in the targeted quadrant, and significantly increased p-tau and tau oligomers expressions, Aβ 40 and Aβ 42 concentration in the hippocampus ( P<0.05). Conclusion:The eHSD aggravates cognitive impairment in 3×Tg-AD mice through activating cGAS-STING-C/EBPβ pathway.

Objective To propose a low-dose CT image denoising method based on an improved Corediff model to recover the detailed features of the image and enhance the image quality.Methods An RS-Corediff model was established by modifying the key component U-Net network of the Corediff model.Firstly,the residual module was introduced in the network input stage for feature extraction;secondly,a new downsampling module was designed in the U-Net network encoder,which learned the semantic information of the feature map by convolution and maintained the learning state during the downsampling process so as to fully extract the image features;thirdly,the feature splicing processing was used to further enhance the learning effect during the upsampling process of the U-Net network decoder;finally,the convolutional kernel size was modified to adjust the sensory field during the convolutional process of the whole U-Net network structure so as to obtain rich features.The RS-Corediff model was compared with the residual encoder-decoder convolutional neural network(RED-CNN)model and the Corediff model on the public dataset AAPM 2016 in order to verify its effectiveness for low-dose CT image denoising.Results The RS-Corediff model gained advantages over the RED-CNN and Corediff models with a peak signal-to-noise ratio(PSNR)of 41.269 8,structural similarity(SSIM)of 0.953 4 and root mean square error(RMSE)of 17.568 7.Conclusion The proposed method effectively preserves the texture and details of low-dose CT images during the denoising process to improve the overall quality of the images.[Chinese Medical Equipment Journal,2025,46(5):9-13]

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.