Objective: To explore the brain-predicted age difference (Brain-PAD) in patients with type 2 diabetes mellitus (T2DM) by a machine learning prediction model based on structural magnetic resonance ( sMRI) in the Southwest University Adult Lifespan Dataset (SALD) , and to reveal the relationship between Brain-PAD and dura- tion of T2DM and cognition . Methods: Group comparisons about demographic variables and cognitive function were conducted respectively in local database of 104 T2DM patients and 83 healthy controls (HC) . The prediction model via Gaussian process regression (GPR) was constructed by training sMRI data of 329 healthy volunteers in SALD , then its performance was validated and evaluated . Furthermore , Brain-PAD ( predicted age-chronological age) in the local database was calculated . Group comparisons of Brain-PAD between T2DM patients and HCs were conducted by Mann-Whitney U test. Finally , Pearson correlation coefficient (r) was calculated between Brain-PAD and duration of disease and cognition . Results: Poor performance in auditory verbal learning test (AVLT)-delayed recall , AVLT-recognition , symbol digital modalities test (SDMT) (P < 0. 05) , and increased Brain-PAD were ob- served in T2DM patients , compared with HCs [1 . 619 ( - 4. 001 , 8. 272) years vs - 1 . 289 ( - 4. 128 , 4. 134) years , Z = 2. 056 , P = 0. 034] . Notably , the median of Brain-PAD in T2DM group was positive , indicating that the brain of T2DM patient maybe relatively “older”than his chronological age . Brain-PAD in T2DM group was as- sociated with performance in AVLT-immediate recall ( r = 0. 291 , P = 0. 003) , AVLT-delayed recall ( r = 0. 248 , P = 0. 011) , SDMT( r = 0. 376 , P = 0. 001) and trail making test (TMT)-A ( r = - 0. 206 , P = 0. 036) . However , the relationships between Brain-PAD and duration of T2DM were not explored . Conclusion Decreased cognitive function in patients with T2DM is demonstrated in this study . The machine learning prediction model based on sMRI supports the identification of brain aging objectively in patients with T2DM .

BACKGROUND:Studies have shown that metformin has anti-inflammatory,anti-tumor,anti-aging and vasoprotective effects,and can inhibit the progression of osteoarthritis,but its specific mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism of metformin on cartilage protection in a rat model of osteoarthritis. METHODS:Forty male Sprague-Dawley rats were randomly divided into four groups(n=10 per group):blank,control,sham-operated,and metformin groups.The blank group did not undergo any surgery.In the sham-operated group,the joint cavity was exposed.In the model group and the metformin group,the modified Hulth method was used to establish the osteoarthritis model.At 1 day after modeling,the rats in the metformin group were given 200 mg/kg/d metformin by gavage,and the model,blank,and sham-operated groups were given normal saline by gavage.Administration in each group was given for 4 weeks consecutively.Hematoxylin-eosin staining,toluidine blue staining,and safranin O-fast green staining were used to observe the morphological structure of rat knee joints.Immunohistochemical staining and western blot were used to detect the protein expression of SOX9,type Ⅱ collagen,a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),Beclin1,P62,phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(AKT),p-AKT,mammalian target of rapamycin(Mtor),and p-Mtor in rat cartilage tissue. RESULTS AND CONCLUSION:The results of hematoxylin-eosin,toluidine blue and safranin O-fast green staining showed smooth cartilage surface of the knee joints and normal histomorphology in the blank group and the sham-operated group,while in the model group,there was irregular cartilage surface of the knee joint and cartilage damage,with a decrease in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.In the metformin group,there was a significant improvement in the damage to the structure of the cartilage in the knee joints of the rats,and the cartilage surface tended to be smooth,with an increase in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.Immunohistochemistry staining and western blot results showed that compared with the control and sham-operated groups,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the model group was significantly decreased(P<0.05).Conversely,the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly increased(P<0.05).Furthermore,compared with the model group,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the metformin group was significantly increased(P<0.05),while the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly decreased(P<0.05).To conclude,Metformin can improve the autophagy activity of chondrocytes and reduce the degradation of cartilage matrix in osteoarthritis rats by inhibiting the activation of PI3K/AKT/Mtor signaling pathway,thus exerting a protective effect on articular cartilage.

Objective:To investigate whether biochanin A(BCA)has a protective effect against dextran sodium sulfate(DSS)-in-duced ulcerative colitis(UC)in mice.Methods:Thirty C57BL/6N mice were randomly divided into normal control group,DSS model group,sulfasalazine(SASP)-positive drug control group,and low/medium/high-dose(5 mg/kg,10 mg/kg,and 20 mg/kg)BCA groups.The mouse model of UC was induced by administering 2.5%DSS aqueous solution for 7 days.During the experimental period,both the normal control and model groups were given 0.5%carboxymethyl cellulose sodium solution daily by gavage.The positive control group was given 100 mg/kg SASP,while the BCA groups were given BCA suspensions at doses of 5 mg/kg,10 mg/kg,and 20 mg/kg.The ad-ministration lasted for 10 days.Body weight changes and fecal status of the mice were recorded every day;the colon was dissected,col-lected,and measured for its length.The colon was stained with Hematoxylin-Eosin for pathomorphological study.Quantitative poly-merase chain reaction was used to determine the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)in the colon.Immunofluorescence was used to determine the expression of tight junction proteins,zonula occluden-1(ZO-1)and occludin,in the colon.Results:It showed that 5 mg/kg and 10 mg/kg BCA significantly alleviated weight loss in mice with UC,while 5 mg/kg,10 mg/kg,and 20 mg/kg BCA reduced the disease activity index scores.Additionally,BCA showed similar effects to SASP in improving the structure and reducing the shortening of the colon in mice with UC.Compared with the model group,all BCA groups had significantly decreased TNF-α(P=0.024、P=0.060、P=0.003)and IL-6(P=0.002、P<0.001、P<0.001)and significantly increased IL-10(P=0.006、P=0.003、P<0.001),with varying degrees of up-regulated expression of tight junction proteins.Conclusion:BCA can effectively alleviate DSS-induced symptoms,reduce intes-tinal damage,and protect the intestinal barrier in mice with UC.

Objective:To explore the genetic basis for a girl with primary microcephaly and growth retardation.Methods:A girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278).Results:DNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c. 2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene. Conclusion:Based on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.

OBJECTIVE: To explore the genetic basis for a girl with primary microcephaly and growth retardation. METHODS: A girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278). RESULTS: DNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c.2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene. CONCLUSION Based on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.
Female ; Humans ; Cell Cycle Proteins ; Heterozygote ; Microcephaly/genetics* ; Mutation ; Nerve Tissue Proteins/genetics* ; Pedigree

Objective:To explore the genetic basis for a girl with primary microcephaly and growth retardation.Methods:A girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278).Results:DNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c. 2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene. Conclusion:Based on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.

To examine the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) and investigate the horizontal transmission of blaKPC and blaNDM genes for the prevention and treatment of CRKP. A total of 49 clinically isolated CRKP strains were retrospectively analyzed from January to December 2022 at The First Hospital of Hunan University of Chinese Medicine. Phenotypic screening was performed using modified carbapenem inactivation assay (mCIM) and EDTA-carbapenem inactivation assay (eCIM). Polymerase chain reaction (PCR) was utilized to identify carbapenem resistance genes, β-lactamase resistance genes, and virulence genes, while multi-locus sequence analysis (MLST) was employed to assess the homology of CRKP strains. Conjugation experiments were conducted to infer the horizontal transmission mechanism of blaKPC and blaNDM genes. The results showed that the study included 49 CRKP strains, with 44 carrying blaKPC and 8 carrying blaNDM, Three strains were identified as blaKPC+ blaNDM-CRKP. In this study, 28 out of 49 CRKP strains (57.2%) were found to carry virulence genes. Additionally, one CRKP strain tested positive in the string test and was found to carry both Aerobactin and rmpA virulence genes. MLST results revealed a total of 5 ST types, with ST11 being predominant (41/49, 83.7%). Successful conjugation was observed in all 3 blaKPC-CRKP strains, while only 1 out of 3 blaNDM-CRKP strains showed successful conjugation. The transconjugant exhibited significantly reduced susceptibility to imipenem and cephalosporin antibiotics. In conclusion, the resistance mechanism of CRKP in this study is primarily attributed to the production of KPC enzymes, along with the presence of multiple β-lactamase resistance genes. Additionally, there is a local prevalence of hv-CRKP and blaKPC+ blaNDM-CRKP. blaKPC and blaNDM can be horizontally transmitted through plasmids, with varying efficiency among different strains.

Objective To discuss the value of clinical radiomic nomogram(CRN)and deep convolutional neural network(DCNN)in distinguishing atypical pulmonary hamartoma(APH)from atypical lung adenocarcinoma(ALA).Methods A total of 307 patients were retrospectively recruited from two institutions.Patients in institu-tion 1 were randomly divided into the training(n=184:APH=97,ALA=87)and internal validation sets(n=79:APH=41,ALA=38)in a ratio of 7∶3,and patients in institution 2 were assigned as the external validation set(n=44:APH=23,ALA=21).A CRN model and a DCNN model were established,respectively,and the performances of two models were compared by delong test and receiver operating characteristic(ROC)curves.A human-machine competition was conducted to evaluate the value of AI in the Lung-RADS classification.Results The areas under the curve(AUCs)of DCNN model were higher than those of CRN model in the training,internal and external validation sets(0.983 vs 0.968,0.973 vs 0.953,and 0.942 vs 0.932,respectively),however,the differences were not statistically significant(p=0.23,0.31 and 0.34,respectively).With a radiologist-AI com-petition experiment,AI tended to downgrade more Lung-RADS categories in APH and affirm more Lung-RADS cat-egories in ALA than radiologists.Conclusion Both DCNN and CRN have higher value in distinguishing APH from ALA,with the former performing better.AI is superior to radiologists in evaluating the Lung-RADS classification of pulmonary nodules.

To examine the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) and investigate the horizontal transmission of blaKPC and blaNDM genes for the prevention and treatment of CRKP. A total of 49 clinically isolated CRKP strains were retrospectively analyzed from January to December 2022 at The First Hospital of Hunan University of Chinese Medicine. Phenotypic screening was performed using modified carbapenem inactivation assay (mCIM) and EDTA-carbapenem inactivation assay (eCIM). Polymerase chain reaction (PCR) was utilized to identify carbapenem resistance genes, β-lactamase resistance genes, and virulence genes, while multi-locus sequence analysis (MLST) was employed to assess the homology of CRKP strains. Conjugation experiments were conducted to infer the horizontal transmission mechanism of blaKPC and blaNDM genes. The results showed that the study included 49 CRKP strains, with 44 carrying blaKPC and 8 carrying blaNDM, Three strains were identified as blaKPC+ blaNDM-CRKP. In this study, 28 out of 49 CRKP strains (57.2%) were found to carry virulence genes. Additionally, one CRKP strain tested positive in the string test and was found to carry both Aerobactin and rmpA virulence genes. MLST results revealed a total of 5 ST types, with ST11 being predominant (41/49, 83.7%). Successful conjugation was observed in all 3 blaKPC-CRKP strains, while only 1 out of 3 blaNDM-CRKP strains showed successful conjugation. The transconjugant exhibited significantly reduced susceptibility to imipenem and cephalosporin antibiotics. In conclusion, the resistance mechanism of CRKP in this study is primarily attributed to the production of KPC enzymes, along with the presence of multiple β-lactamase resistance genes. Additionally, there is a local prevalence of hv-CRKP and blaKPC+ blaNDM-CRKP. blaKPC and blaNDM can be horizontally transmitted through plasmids, with varying efficiency among different strains.

Objective To explore the value of combined prediction model based on clinical and CT radiomics features in discriminating atypical pulmonary hamartoma(APH)from atypical lung adenocarcinoma(ALA).Methods A total of 290 patients with APH and ALA confirmed by pathology were retrospectively selected.250 patients from the First Affiliated Hospital of Anhui Medical University were randomly assigned into a training set(APH=91,ALA=84)and an internal validation set(APH=39,ALA=36)at a ratio of 7∶3,and other 40 patients from the First Affiliated Hospital of USTC were assigned as an external validation set(APH=21,ALA=19).The independent model and multivariate logistic regression combined model were constructed using the selected clinical-CT features and radiomics features,respectively,and a nomogram was drawn.Receiver operating characteristic(ROC)curve and DeLong test were used to evaluate and compare the performances of the models.Results The area under the curve(AUC)of the combined model established by 3 clinical-CT features and 4 radiomics features in the training set was 0.980,which was higher than that of clinical-CT model(AUC=0.885,P＜0.001)and radiomics model(AUC=0.975,P=0.042).The AUC of the combined model in the internal and external validation sets(0.963 vs 0.917)were also higher than those of clinical-CT model(0.858 vs 0.774)and radiomics model(0.953 vs 0.897),respectively.Conclusion The combined prediction model based on clinical and CT radiomics features can improve the differential diagnosis ability of APH and ALA.