Objective:To explore the clinical characteristics and genetic variants underlying Hereditary coagulation factor Ⅴ (FⅤ) deficiency in two Chinese pedigrees.Methods:Seventeen individuals from three generations of the two pedigrees affected with FⅤ deficiency whom had visited Taizhou Hospital of Zhejiang Province respectively in March and June 2024 were recruited as study subjects. One hundred healthy individuals undergoing physical examinations have served as the controls. Relevant coagulation parameters were measured. Thrombin generation was assessed using the calibrated automated thrombogram (CAT) assay. All exons and flanking regions of the F5 gene were amplified by PCR and directly sequenced. Candidate variants were analyzed for evolutionary conservation and potential pathogenicity, and their effects on protein structure were predicted. This study was approved by the Medical Ethics Committee of Taizhou Hospital of Zhejiang Province (Ethics No.: 20230722). Results:The FⅤ activity (FⅤ: C) and antigen levels (FⅤ: Ag) of both probands showed concurrent decrease. By thrombin generation assay, both the lag time ratio and time to peak ratio were significantly increased. Genetic analysis revealed that proband A carried compound heterozygous missense variants c. 911G>A (p.Gly304Glu) and c. 1238T>C (p.Met413Thr), whilst Proband B carried compound heterozygous missense variants c. 1258G>T (p.Gly420Cys) and c. 1538G>A (p.Arg513Lys) of the F5 gene. Conservation analysis revealed that the amino acid residues p. Gly304, p. Gly420, and p. Arg513 are highly conserved across various species. Online bioinformatics tools predicted that both the p. Gly304Glu and p. Gly420Cys variants are pathogenic. Protein modeling demonstrated that all four variants can result in alterations of protein structure or disruption of hydrogen bonding. Conclusion:FⅤ deficiency in these two pedigrees can be attributed to the compound heterozygous variants p. Gly304Glu/p.Met413Thr and p. Gly420Cys/p.Arg513Lys of the F5 gene.

OBJECTIVE: To explore the clinical characteristics and genetic variants underlying Hereditary coagulation factor V (FV) deficiency in two Chinese pedigrees. METHODS: Seventeen individuals from three generations of the two pedigrees affected with FV deficiency whom had visited Taizhou Hospital of Zhejiang Province respectively in March and June 2024 were recruited as study subjects. One hundred healthy individuals undergoing physical examinations have served as the controls. Relevant coagulation parameters were measured. Thrombin generation was assessed using the calibrated automated thrombogram (CAT) assay. All exons and flanking regions of the F5 gene were amplified by PCR and directly sequenced. Candidate variants were analyzed for evolutionary conservation and potential pathogenicity, and their effects on protein structure were predicted. This study was approved by the Medical Ethics Committee of Taizhou Hospital of Zhejiang Province (Ethics No.: 20230722). RESULTS: The FV activity (FV: C) and antigen levels (FV: Ag) of both probands showed concurrent decrease. By thrombin generation assay, both the lag time ratio and time to peak ratio were significantly increased. Genetic analysis revealed that proband A carried compound heterozygous missense variants c.911G>A (p.Gly304Glu) and c.1238T>C (p.Met413Thr), whilst Proband B carried compound heterozygous missense variants c.1258G>T (p.Gly420Cys) and c.1538G>A (p.Arg513Lys) of the F5 gene. Conservation analysis revealed that the amino acid residues p.Gly304, p.Gly420, and p.Arg513 are highly conserved across various species. Online bioinformatics tools predicted that both the p.Gly304Glu and p.Gly420Cys variants are pathogenic. Protein modeling demonstrated that all four variants can result in alterations of protein structure or disruption of hydrogen bonding. CONCLUSION FV deficiency in these two pedigrees can be attributed to the compound heterozygous variants p.Gly304Glu/p.Met413Thr and p.Gly420Cys/p.Arg513Lys of the F5 gene.
Adult ; Female ; Humans ; Male ; Middle Aged ; China/ethnology* ; Factor V/chemistry* ; Factor V Deficiency/genetics* ; Heterozygote ; Pedigree ; East Asian People/genetics*

Objective:To explore the clinical characteristics and genetic variants underlying Hereditary coagulation factor Ⅴ (FⅤ) deficiency in two Chinese pedigrees.Methods:Seventeen individuals from three generations of the two pedigrees affected with FⅤ deficiency whom had visited Taizhou Hospital of Zhejiang Province respectively in March and June 2024 were recruited as study subjects. One hundred healthy individuals undergoing physical examinations have served as the controls. Relevant coagulation parameters were measured. Thrombin generation was assessed using the calibrated automated thrombogram (CAT) assay. All exons and flanking regions of the F5 gene were amplified by PCR and directly sequenced. Candidate variants were analyzed for evolutionary conservation and potential pathogenicity, and their effects on protein structure were predicted. This study was approved by the Medical Ethics Committee of Taizhou Hospital of Zhejiang Province (Ethics No.: 20230722). Results:The FⅤ activity (FⅤ: C) and antigen levels (FⅤ: Ag) of both probands showed concurrent decrease. By thrombin generation assay, both the lag time ratio and time to peak ratio were significantly increased. Genetic analysis revealed that proband A carried compound heterozygous missense variants c. 911G>A (p.Gly304Glu) and c. 1238T>C (p.Met413Thr), whilst Proband B carried compound heterozygous missense variants c. 1258G>T (p.Gly420Cys) and c. 1538G>A (p.Arg513Lys) of the F5 gene. Conservation analysis revealed that the amino acid residues p. Gly304, p. Gly420, and p. Arg513 are highly conserved across various species. Online bioinformatics tools predicted that both the p. Gly304Glu and p. Gly420Cys variants are pathogenic. Protein modeling demonstrated that all four variants can result in alterations of protein structure or disruption of hydrogen bonding. Conclusion:FⅤ deficiency in these two pedigrees can be attributed to the compound heterozygous variants p. Gly304Glu/p.Met413Thr and p. Gly420Cys/p.Arg513Lys of the F5 gene.

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive neurometabolic disease.Pathogenic mutations in ALDH5A1 genes lead to abnormalities in the structure, activity and function of succinic semialdehyde dehydrogenase, resulting in a series of neurological damage.Due to the rarity of SSADHD and the huge differences in its clinical manifestations, it often leads to misdiagnosis or delayed diagnosis, and the treatment is mainly symptomatic.There is no specific drug or treatment.In March 2024, the SSADHD consensus group, composed of SSADHD researchers from 19 institutions in 11 countries and regions, released the " Consensus Guidelines for the Diagnosis and Management of Succinic Semialdehyde Dehydrogenase Deficiency" , which elaborates on the definition, epidemiology, clinical manifestations, diagnosis, and treatment of SSADHD, aiming to standardize and unify the diagnosis and management of SSADHD.This article interprets the key contents of the guidelines, in order to provide guidance for the early screening, diagnosis and treatment of SSADHD in China.

Objective This study summarized the clinical data of IBD patients receiving upadacitinib treatment in our hospital,and provided more Chinese data to better guide the treatment of upadacitinib in Chinese IBD population.Methods Clinical data of 11 patients with IBD who received upadacitinib treatment at Anhui Provincial Hospital from March 1,2023 to September 8,2024 were retrospectively analyzed.Platelet count,ESR,CRP,disease severity score,endoscopic score,and adverse reactions were compared before treatment,at the 4th and 8th week of treatment,and clinical response rate,clinical response rate,endoscopic response rate,and endoscopic response rate were calculated.SPSS 25.0 software was used for statistical analysis.Results The platelets,ESR and CRP of patients at the 4th and 8th week after upadacitinib treatment were decreased compared with those before treatment,with statistical significance.At the 4th week,the clinical response rate was 72.72％(8/11),the clinical remission rate was 0,the clinical response rate of UC patients was 83.33％(5/6),and the clinical response rate of CD patients was 60％(3/5).At the 8th week of treatment,the clinical response rate was 100％(10/10),the clinical remission rate was 80.00％(8/10),the clinical response rate of UC patients was 100％(6/6),the clinical remission rate of UC patients was 83.33％(5/6),the clinical response rate of CD patients was 100％(4/4),and the clinical remission rate of CD was 75％(3/4).There were no adverse reactions during treatment.Three patients were re-examined by colonoscopy,all of whom were severe UC patients and achieved mucosal healing.Conclusion Upadacitinib can rapidly,effectively and sustainably control the disease in patients with moderate and severe IBD,with high safety.

Objective The aim of this study was to investigate the effect of immature neutrophils on chronic Plasmodium chabaudi(P.c)infection.Methods Single-cell sequencing combined with flow cytometry was used to detect dynamic changes in immature neutrophils and its S100A9 protein expression during P.c infection.Mice were intragastrically administered Paquinimod to deplete the immature neutrophils.Flow cytometry was used to assess its effect on the immune response against Plasmodium chabaudi.Single-cell sequencing and flow cytometry were conducted on splenocytes to examine changes of monocytes/macrophages.Results Clodronate liposomes(CLs)were administered and parasitemia and survival rates were monitored.The data showed that the frequency and number of immature neutrophils increased significantly during the chronic phase of P.c infection.Parasitemia was significantly elevated in the drug-treatment group,accompanied by a reduction in the frequency and number of immature neutrophils and monocytes.After CLs treatment,monocytes and macrophages decreased and parasitemia increased.Conclusion Taken together,a large number of immature neutrophils are newly generated during the chronic phase of Plasmodium chabaudi infection,and they may exert an anti-Plasmodium chabaudi protective role through an impact on monocytes.

Objective The aim of this study was to investigate the effect of immature neutrophils on chronic Plasmodium chabaudi(P.c)infection.Methods Single-cell sequencing combined with flow cytometry was used to detect dynamic changes in immature neutrophils and its S100A9 protein expression during P.c infection.Mice were intragastrically administered Paquinimod to deplete the immature neutrophils.Flow cytometry was used to assess its effect on the immune response against Plasmodium chabaudi.Single-cell sequencing and flow cytometry were conducted on splenocytes to examine changes of monocytes/macrophages.Results Clodronate liposomes(CLs)were administered and parasitemia and survival rates were monitored.The data showed that the frequency and number of immature neutrophils increased significantly during the chronic phase of P.c infection.Parasitemia was significantly elevated in the drug-treatment group,accompanied by a reduction in the frequency and number of immature neutrophils and monocytes.After CLs treatment,monocytes and macrophages decreased and parasitemia increased.Conclusion Taken together,a large number of immature neutrophils are newly generated during the chronic phase of Plasmodium chabaudi infection,and they may exert an anti-Plasmodium chabaudi protective role through an impact on monocytes.

Objective:To investigate the clinical and imaging features of population receiving opportunistic screening for lung cancer and in convalescent stage of COVID-19.Methods:Cross-sectional study and analysis was performed on the patients who underwent chest low-dose CT examination for cancer prevention in Cancer Hospital of Chinese Academy of Medical Sciences from December 28, 2022 to January 19, 2023. All the patients completed the COVID-19 questionnaire. A total of 334 questionnaires were sent out, all of which were recovered, and 321 valid questionnaires were collected, among them, 293 questionnaires were included in the analysis. Statistical analysis was conducted according to the questionnaire information, clinical symptoms and chest CT imaging results. The potential influencing factors of COVID-19 infection were explored, and the imaging characteristics of COVID-19 infection and early stage of lung cancer were compared.Results:A total of 293 patients underwent lung cancer screening during the convalescent stage of COVID-19 infection. A total of 231 (78.8%) cases had cough and 228 (77.8%) cases had fever. 214 (73.0%) cases still had clinical symptoms within 2 weeks after nucleic acid or antigen test showing negative, especially for cough in 171 (58.4%) cases, fatigue in 79 (25.3%) cases and sputum in 73 (24.9%) cases. There were 54 (18.4%) cases with positive chest CT changes. The main imaging findings showed that there were 46 cases with new patchy shadows, 25 cases with linear opacities, 10 cases with ground-glass opacities, 10 cases with nodular like shadows and 2 cases with consolidation, and most lesions were in the subpleural area of both lungs. Univariate analysis showed that positive CT findings were correlated with the time from positive detection of COVID-19 to screening ( P=0.026), age ( P<0.001) and underlying diseases ( P=0.006). Multivariate analysis showed that age≥65 years old ( OR=6.425, 95% CI: 2.688-15.358; P<0.001) and underlying diseases ( OR=2.292, 95% CI: 1.120-4.691; P=0.023) were risk factors for pulmonary imaging changes of COVID-19 infection. For lung cancer opportunistic screening, 36 (12.3%) cases showed ground-glass opacities in bilateral or unilateral lung lobes, among which 4 cases were suspected to be atypical adenomatous hyperplasia and 2 cases s were suspected to be early stage of lung cancer. Conclusions:Abnormal clinical symptoms and chest CT findings are still observed in the patients during the convalescent stage of COVID-19 infection. Age≥65 years, underlying diseases were the high-risk factors for the changes in chest CT imaging after COVID-19 infection. Attention should be paid to the differential diagnosis of chest CT findings between changes in the convalescent stage of COVID-19 and early stage of lung cancer.

Objective:To summarize the best evidence on exercise for the prevention and treatment of diabetic foot.Methods:A bibliometric approach was used. Systematic searches were carried out to retrieve all the publicly published evidences till July 2022 on exercise for the prevention and treatment of diabetic foot, including guidelines, evidence summary, recommended practices, expert consensus, systematic review, and original research, from foreign language databases including BMJ Best Practice, UpToDate, Joanna Briggs Institute Evidence-Based Practice Database, Cochrane Library, Embase, PubMed, Guideline International Network, National Guideline Clearinghouse, Chinese databases including China National Knowledge Infrastructure, Wanfang Database, VIP Database, China Biology Medicine disc, China Clinical Guidelines Library, and the official websites of relevant academic organizations including National Institute for Health and Care Excellence of the United Kingdom, Registered Nurses' Association of Ontario of Canada, the International Working Group on the Diabetic Foot, International Diabetes Federation, American College of Sports Medicine, American Diabetes Association, and Chinese Diabetes Society. The literature was screened and evaluated for the quality, from which the evidences were extracted and evaluated to summarize the best evidences.Results:Nine guidelines, three expert consensuses, one evidence summary (with two systematic reviews being traced), two systematic reviews, 6 randomized controlled trials were retrieved and included, with good quality of literature. Totally 33 pieces of best evidences on exercise for the prevention and treatment of diabetic foot were summarized from the aspects of appropriate exercise prevention of diabetic foot, exercise therapy of diabetic foot, precautions for exercise, health education, and establishment of a multidisciplinary limb salvage team.Conclusions:Totally 33 pieces of best evidences on exercise for the prevention and treatment of diabetic foot were summarized from 5 aspects, providing decision-making basis for clinical guidance on exercise practice for patients with diabetic foot.

Objective:To develop a risk prediction model for the recurrence of diabetic foot ulcer (DFU) in diabetic patients and primarily validate its predictive value.Methods:Meta-analysis combined with retrospective cohort study was conducted. The Chinese and English papers on risk factors related to DFU recurrence publicly published in China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and PubMed, Embase, Cochrane Library, and Web of Science, and the search time was from the establishment date of each database until March 31 st, 2022. The papers were screened and evaluated, the data were extracted, a meta-analysis was performed using RevMan 5.4.1 statistical software to screen risk factors for DFU recurrence, and Egger's linear regression was used to assess the publication bias of the study results. Risk factors for DFU recurrence mentioned in ≥3 studies and with statistically significant differences in the meta-analysis were selected as the independent variables to develop a logistic regression model for risk prediction of DFU recurrence. The medical records of 101 patients with DFU who met the inclusion criteria and were admitted to Affiliated Hospital of Guizhou Medical University from January 2019 to June 2022 were collected. There were 69 males and 32 females, aged (63±14) years. The receiver operating characteristic (ROC) curve of the predictive performance of the above constructed predictive model for DFU recurrence was drawn, and the area under the ROC curve, maximum Youden index, and sensitivity and specificity at the point were calculated. Dataset including data of 8 risk factors for DFU recurrence and the DFU recurrence rates of 10 000 cases was simulated using RStudio software and a scatter plot was drawn to determine two probabilities for risk division of DFU recurrence. Using the β coefficients corresponding to 8 DFU recurrence risk factors ×10 and taking the integer as the score of coefficient weight of each risk factor, the total score was obtained by summing up, and the cutoff scores for risk level division were calculated based on the total score × two probabilities for risk division of DFU recurrence. Results:Finally, 20 papers were included, including 3 case-control studies and 17 cohort studies, with a total of 4 238 cases and DFU recurrence rate of 22.7% to 71.2%. Meta-analysis showed that glycosylated hemoglobin >7.5% and with plantar ulcer, diabetic peripheral neuropathy, diabetic peripheral vascular disease, smoking, osteomyelitis, history of amputation/toe amputation, and multidrug-resistant bacterial infection were risk factors for the recurrence of DFU (with odds ratios of 3.27, 3.66, 4.05, 3.94, 1.98, 7.17, 11.96, 3.61, 95% confidence intervals of 2.79-3.84, 2.06-6.50, 2.50-6.58, 2.65-5.84, 1.65-2.38, 2.29-22.47, 4.60-31.14, 3.13-4.17, respectively, P<0.05). There were no statistically significant differences in publication biases of diabetic peripheral neuropathy, diabetic peripheral vascular disease, glycosylated hemoglobin >7.5%, plantar ulcer, smoking, multidrug-resistant bacterial infection, or osteomyelitis ( P>0.05), but there was a statistically significant difference in the publication bias of amputation/toe amputation ( t=-30.39, P<0.05). The area under the ROC curve of the predictive model was 0.81 (with 95% confidence interval of 0.71-0.91) and the maximum Youden index was 0.59, at which the sensitivity was 72% and the specificity was 86%. Ultimately, 29.0% and 44.8% were identified respectively as the cutoff for dividing the probability of low risk and medium risk, and medium risk and high risk for DFU recurrence, while the corresponding total scores of low, medium, and high risks of DFU recurrence were <37, 37-57, and 58-118, respectively. Conclusions:Eight risk factors for DFU recurrence are screened through meta-analysis and the risk prediction model for DFU recurrence is developed, which has moderate predictive accuracy and can provide guidance for healthcare workers to take interventions for patient with DFU recurrence risk.