Objective:To discuss the expression and clinical significance of inositol polyphosphate-4-phosphatase type Ⅱ(INPP4B)gene in hepatocellular carcinoma(HCC)based on The Cancer Genome Atlas(TCGA)database and experimental verification with clinical samples.Methods:Based on data from 424 clinical samples in the TCGA database(including 374 HCC tissues and 50 paracarcinoma tissues),Kaplan-Meier method and Cox regression analysis were used to evaluate the relationship between INPP4B gene and the clinical characteristics and survival prognosis of the HCC patients.The correlations between INPP4B gene and the number of 24 types of immune cells,matrix,immune cell infiltration and tumor purity in tumor tissue,and the expression level of the high-frequency mutant gene tumor protein 53(TP53)in HCC were analyzed.The clinicopathological data and paraffin-embedded tissue sections of 60 HCC patients treated with surgical resection from December 2022 to December 2023 were collected.According to clinical diagnosis,they were divided into poorly differentiated group(HCC-L group),moderately differentiated group(HCC-M group)and well-differentiated group(HCC-H group),with 20 cases in each group;20 patients during the same period who underwent biopsy and were pathologically diagnosed as non-tumor were selected as normal group,and their clinicopathologic data and liver tissue paraffin sections were collected.HE staining was used to observe the pathomorphology of HCC tissue and normal liver tissue of the subjects in various groups;immunohistochemistry method was used to detect the expressions of Ki-67 and INPP4B proteins in the HCC tissue and normal liver tissue of the subjects in various groups.Results:The TCGA database analysis results showed that compared with normal tissue,the expression level of INPP4B mRNA in HCC tissue was significantly increased(P<0.01).Compared with INPP4B low expression group,the overall survival(OS)of the patients in INPP4B high expression group was significantly prolonged(P<0.05).The univariate Cox regression analysis results showed that tumor stage,pathological stage,tumor status and residual tumor had impacts on OS of the HCC patients(P<0.05).The univariate regression analysis results showed that the INPP4B prognostic risk model score ratio was HR=0.781,95％confidence interval(CI):0.552-1.105,P=0.168.The AUC value for the impact of INPP4B on OS of the HCC patients was 0.558,indicating that the INPP4B gene prognostic risk model had certain predictive value in survival prognosis.The INPP4B mRNA expression level was not correlated with TNM stage,stage,patient gender,age,race or body mass index(BMI)(P>0.05).In tumor tissue with high and low INPP4B expression,22 types of immune cells showed statistically significant differences(P<0.05);the INPP4B mRNA expression level was positively correlated with the number of 23 types of immune cells except T helper(Th)17 cells(r>0),among which all Th cells except natural killer(NK)CD56+cells were statistically significant(P<0.01);INPP4B was significantly correlated with matrix(r=0.475),immune cell infiltration(r=0.641)and tumor purity(r=0.599)in tumor tissue(P<0.01).INPP4B was correlated with TP53(r=0.287,P<0.01).The HE staining results showed that clear and complete lobular structure,neatly arranged cells and slight inflammatory cell infiltration were observed in liver tissue of the subjects in normal group;completely destroyed lobular structure,significant hepatocellular steatosis,massive inflammatory cell infiltration,and lesions such as ballooning degeneration and small cell hyperplasia in some cells were observed in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups,and the lower the HCC differentiation degree,the more severe the tissue destruction;The immunohistochemistry results showed that compared with normal group,the expression levels of Ki-67 protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly increased(P<0.01),and the lower the differentiation degree of the HCC patients,the higher the Ki-67 positive rate.Brownish-yellow granules evenly distributed in the cells and INPP4B protein was highly expressed in liver tissue of the subjects in normal group;compared with normal group,the expression levels of INPP4B protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly decreased(P<0.01),and the lower the differentiation degree of the HCC tissue,the lower the INPP4B positive rate.Conclusion:INPP4B is a protective factor for the prognosis of HCC patients;as a new tumor suppressor gene,INPP4B may become a potential target for new drug screening in HCC treatment.

OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside （TWM） on renal injury in diabetic nephropathy （DN） rats through tumor protein p53/microRNA-214 （miR-214）/UNC-51-like kinase 1 （ULK1） axis. METHODS Male SD rats were randomly divided into normal group （n＝6） and modeling group （n＝28）； the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group， valsartan group [8.33 mg/（kg·d）] and TWM group[6.25 mg/（kg·d）]， with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline， once a day， for 6 consecutive weeks. After the last medication， liver and renal function indexes [24 h urinary total protein （24 h-UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， albumin （ALB）， alanine transaminase （ALT）]， blood lipid indexes （triglycerides， total cholesterol） and blood glucose index （fasting blood glucose） in urine/blood sample of rats were detected in each group. Renal pathologic change was observed， protein and mRNA expressions of p53， ULK1， Beclin-1 and microtubule-associated protein 1 light chain 3 （LC3）， and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group， the renal tubular epithelium of rats in the model group showed obvious edema， cell swelling， accompanied by lymphocyte infiltration； the levels of 24h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1， Beclin-1 protein and mRNA were significantly decreased or down-regulated （P＜0.01）. Compared with the model group， the histopathological damage of the kidney in rats was improved in administration groups； the levels of 24 h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 were all significantly decreased or down-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated （P＜0.01）. CONCLUSIONS TG can alleviate renal damage in DN rats， and improve their liver and renal function， as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.

Objective:To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province.Methods:A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Approval Number: 2019 Medical Ethics Review No. 67). Results:Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c. 1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c. 467G>A (p.Gly156Asp) and c. 1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c. 1297G>C (p.Ala433Pro) and c. 1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and may affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. Conclusion:The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c. 1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.

Objective:To systematically synthesize qualitative studies on healthcare professionals' experiences and needs regarding telemedicine services for diabetic foot ulcers (DFU), and to provide scientific evidence for further improvement of DFU telemedicine service systems.Methods:PubMed, Web of Science, Cochrane Library, CINAHL, Scopus, Embase, ProQuest, PsycINFO, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine disc were searched for qualitative studies on healthcare professionals' experiences and needs in the process of constructing and using DFU telemedicine service platforms. The time limit was from the inception of the databases to December 2024. The included literature was appraised according to the 2016 Joanna Briggs Institute (JBI) critical appraisal checklist for qualitative research, and the results were integrated and summarized using meta-aggregation.Results:A total of 10 studies were included, from which 30 findings were extracted, forming 11 categories, and were synthesized into four integrated findings: healthcare professionals held divergent attitudes toward DFU telemedicine services, perceived multiple benefits, faced many challenges, and had multidimensional needs.Conclusions:Telemedicine services have provided healthcare professionals with great convenience in managing DFU patients, but challenges still exist. In the future, relevant platforms and systems should be continuously improved by integrating the needs of healthcare professionals and patients, while service processes and management mechanisms should be enhanced to improve the quality of telemedicine services.

Objective To establish autoverification rules for six routine coagulation assays(PT,APTT,TT,Fib,DD,and FDP)based on the stratification of outpatients and inpatients,in accordance with CLSI AUTO-10A,AUTO-15,and WS/T 616-2018 guide-lines,and to validate the feasibility of this stratified strategy with clinical data while optimizing verification efficiency.Methods A to-tal of 323 451 coagulation test results from Zhongshan Hospital,Fudan University in 2022 were retrospectively analyzed to define auto-verification rules involving critical values,instrument flags,logical rules,historical comparison,and numerical ranges.A stratified au-toverification system was established by applying distinct rules for outpatient and inpatient populations.Subsequently,the rules were op-timized using 87 830 coagulation test results from January to March 2024,and the consistency between autoverification and manual veri-fication was prospectively evaluated using 33 968 consecutive coagulation specimens collected in April 2024.Results A stratified au-toverification system was successfully developed,comprising a total of 53 rules.The pass rate of overall verification was 77.16％(26 210/33 968),with a true-positive rate of 19.64％(6 672/33 968),a false-positive rate of 3.20％(1 086/33 968),a true-nega-tive rate of 77.16％(26 210/33 968),and no false negatives were detected.Conclusion The proposed autoverification system signifi-cantly improved verification efficiency.The stratified design based on outpatient and inpatient populations effectively minimized the risk of false negatives,and may provide a novel approach for the further development and optimization of coagulation test autoverification.

Objective:To systematically synthesize qualitative studies on healthcare professionals' experiences and needs regarding telemedicine services for diabetic foot ulcers (DFU), and to provide scientific evidence for further improvement of DFU telemedicine service systems.Methods:PubMed, Web of Science, Cochrane Library, CINAHL, Scopus, Embase, ProQuest, PsycINFO, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine disc were searched for qualitative studies on healthcare professionals' experiences and needs in the process of constructing and using DFU telemedicine service platforms. The time limit was from the inception of the databases to December 2024. The included literature was appraised according to the 2016 Joanna Briggs Institute (JBI) critical appraisal checklist for qualitative research, and the results were integrated and summarized using meta-aggregation.Results:A total of 10 studies were included, from which 30 findings were extracted, forming 11 categories, and were synthesized into four integrated findings: healthcare professionals held divergent attitudes toward DFU telemedicine services, perceived multiple benefits, faced many challenges, and had multidimensional needs.Conclusions:Telemedicine services have provided healthcare professionals with great convenience in managing DFU patients, but challenges still exist. In the future, relevant platforms and systems should be continuously improved by integrating the needs of healthcare professionals and patients, while service processes and management mechanisms should be enhanced to improve the quality of telemedicine services.

Objective:To explore the application and guiding value of bispectral index（BIS）in postoperative ventilator weaning in infants with congenital heart disease.Methods:A retrospective analysis was conducted on 81 cases of infants with congenital heart disease treated at Xuzhou Children's Hospital affiliated with Xuzhou Medical University from January 2022 to November 2023. The infants were divided into the successful weaning group（62 cases）and the failed weaning group（19 cases）based on the success of ventilator withdrawal. Univariate and multivariate Logistic analyses were performed on the clinical data of the two groups of infants，and ROC curves were plotted to analyze the predictive value of BIS for postoperative ventilator withdrawal failure in infants with congenital heart disease.Results:The mechanical ventilation time，ICU stay time，hospitalization time，and BIS values at 1 hour，2 hours，3 hours，4 hours，and 5 hours after sedation in the two groups of infants showed statistically significant differences（ P<0.05）. The results of the multivariate Logistic regression analysis indicated that BIS values at 1 hour，2 hours，3 hours，4 hours，and 5 hours after sedation are factors affecting the failure of postoperative ventilator weaning in infants with congenital heart disease（ P<0.05）. The ROC curve analysis revealed that the AUCs for predicting postoperative ventilator weaning failure in infants with congenital heart disease were 0.886，0.877，0.873，0.907，0.925，and 0.954 for BIS at 1 hour，2 hours，3 hours，4 hours，and 5 hours after sedation，and the combined prediction，respectively. The sensitivities and specificities were as follows：for BIS at 1 hour after sedation，94.7% and 67.7%；for BIS at 2 hours after sedation，84.2% and 93.5%；for BIS at 3 hours after sedation，84.2% and 83.9%；for BIS at 4 hours after sedation，89.5% and 79.0%；for BIS at 5 hours after sedation，84.2% and 85.5%；and for the combined prediction，100.0% and 90.3%. Conclusion:The use of BIS monitoring during the weaning of ventilators in infants after congenital heart disease surgery has certain predictive value for the success of the weaning process.

OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

Objective:To investigate the feasibility of deep learning based on computed tomography(CT)radiomics in improving diagnostic accuracy for pulmonary nodules.Methods:A total of 500 patients with pulmonary nodules who admitted to our hospital from January 2023 to January 2024 were selected as study subjects,and they were randomly divided into a training set(350 patients)and a test set(150 patients)as 7:3 ratio.All patients underwent CT examination,and pathological diagnosis was used as gold standard to record pulmonary nodules that were judged by clinical judgment.The radiomics features were screened from the CT images of the patients,and these features were used to construct multiple machine learning models.The predictive value of different models in diagnosing pulmonary nodules was analyzed through confusion matrices and receiver operating characteristic(ROC)curve.Results:A total of 1,594 radiomics features,including 1,195 texture features(74.97%)that was the largest ratio,334 first-order histograms(20.95%),and 65 second-order histograms(4.08%),were extracted in this study.After least absolute shrinkage and selection operator(LASSO)regression analysis and ten-fold cross-validation processing,a total of six radiomics features were screened out.The screened radiomics features were incorporated respectively into four assembled models with machine learning,including ResNet50,DenseNet121,Inception_V3 and VGG19.The constructed models were evaluated respectively using the training set and the test set.The results showed that the assembled model had the highest accuracies in both training set and the test set(96.57%and 95.33%),which area under curve(AUC)values were 0.934 and 0.923,and specificities were 81.64%and 80.52%,and sensitivities were 90.25%and 88.71%,respectively.The results of consistency test indicated that the assembled model had the best classification consistency(Kappa=0.856,P<0.001)in the constructed diagnostic model for pulmonary nodule,which was the best-performing model.Conclusion:The deep learning technique based on CT radiomics has a certain feasibility in improving the diagnostic accuracy for pulmonary nodules,and the machine learning model that is included in this study has favorable predictive value in diagnosing pulmonary nodules.In them,the assembled model that is constructed on the basis of ResNet50,DenseNet121,Inception_V3,and VGG19 has better classification ability.

Objective To establish autoverification rules for six routine coagulation assays(PT,APTT,TT,Fib,DD,and FDP)based on the stratification of outpatients and inpatients,in accordance with CLSI AUTO-10A,AUTO-15,and WS/T 616-2018 guide-lines,and to validate the feasibility of this stratified strategy with clinical data while optimizing verification efficiency.Methods A to-tal of 323 451 coagulation test results from Zhongshan Hospital,Fudan University in 2022 were retrospectively analyzed to define auto-verification rules involving critical values,instrument flags,logical rules,historical comparison,and numerical ranges.A stratified au-toverification system was established by applying distinct rules for outpatient and inpatient populations.Subsequently,the rules were op-timized using 87 830 coagulation test results from January to March 2024,and the consistency between autoverification and manual veri-fication was prospectively evaluated using 33 968 consecutive coagulation specimens collected in April 2024.Results A stratified au-toverification system was successfully developed,comprising a total of 53 rules.The pass rate of overall verification was 77.16％(26 210/33 968),with a true-positive rate of 19.64％(6 672/33 968),a false-positive rate of 3.20％(1 086/33 968),a true-nega-tive rate of 77.16％(26 210/33 968),and no false negatives were detected.Conclusion The proposed autoverification system signifi-cantly improved verification efficiency.The stratified design based on outpatient and inpatient populations effectively minimized the risk of false negatives,and may provide a novel approach for the further development and optimization of coagulation test autoverification.