Objective:To explore the genetic etiology of fetal skeletal dysplasia using whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) techniques, and the feasibility of using WES as the first-tier method for such fetuses.Methods:Seventy four fetuses with skeletal dysplasia detected by prenatal ultrasound at the Genetic Testing Center of the Women and Children′s Hospital Affiliated to Qingdao University from January 2020 to August 2024 were selected as the study subjects. Fetal muscle and peripheral blood samples of the pregnant women and their spouses were collected and subjected to WES analysis. CNV-seq was carried out on all fetal muscle tissue samples. And the results were compared with the CNVs indicated by WES. Genetic etiologies were analyzed across different subtypes of skeletal dysplasia. And the feasibility of using WES as the first-tier genetic test for similar fetuses was assessed, in addition with a systematic cost-effectiveness analysis. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: QFELL-YJ-2024-201).Results:A total of 50 fetuses were diagnosed, which yielded a diagnostic rate of 67.57%. These included 6 chromosomal aneuploidies, 4 chromosomal CNVs and 40 monogenic disorders. The monogenic diseases had involved 46 variant sites in 23 pathogenic genes, among which 12 were unreported previously, including MYH3: c. 735T>C, ALPL: c. 1324C>T, NEK9: c. 1973G>A, MAGEL2: c. 2024_2025del, LMBR1: c. 423+ 4914A>C, NEB: c. 21273_21276del, COL1A1: c. 2651G>C and c. 2758G>C, ASPM: c. 2473delinsGA, TBX5: c. 704G>A, DYNC2H1: c. 10893del, and DYNC2I2: c. 1270C>T. Substantial concordance was reached between WES-derived CNV calls and CNV-seq findings. No clinically significant CNV was exclusively detected by CNV-seq. Cost-effectiveness modeling demonstrated that implementing WES as the first-tier genetic testing method could reduce the total expenditure when WES unit cost remained below 6.4 folds that of the CNV-seq. Conclusion:Genetic variants including single nucleotide variations (SNV) of monogenic disorders, chromosomal aneuploidies and genomic CNVs are important causes for fetal skeletal dysplasia. WES is an accurate and efficient method for analyzing the etiology of fetal skeletal dysplasia, particularly in those with a family history of similar phenotype or maternal history of adverse pregnancies.

OBJECTIVE: To explore the genetic etiology of fetal skeletal dysplasia using whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) techniques, and the feasibility of using WES as the first-tier method for such fetuses. METHODS: Seventy four fetuses with skeletal dysplasia detected by prenatal ultrasound at the Genetic Testing Center of the Women and Children's Hospital Affiliated to Qingdao University from January 2020 to August 2024 were selected as the study subjects. Fetal muscle and peripheral blood samples of the pregnant women and their spouses were collected and subjected to WES analysis. CNV-seq was carried out on all fetal muscle tissue samples. And the results were compared with the CNVs indicated by WES. Genetic etiologies were analyzed across different subtypes of skeletal dysplasia. And the feasibility of using WES as the first-tier genetic test for similar fetuses was assessed, in addition with a systematic cost-effectiveness analysis. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: QFELL-YJ-2024-201). RESULTS: A total of 50 fetuses were diagnosed, which yielded a diagnostic rate of 67.57%. These included 6 chromosomal aneuploidies, 4 chromosomal CNVs and 40 monogenic disorders. The monogenic diseases had involved 46 variant sites in 23 pathogenic genes, among which 12 were unreported previously, including MYH3: c.735T>C, ALPL: c.1324C>T, NEK9: c.1973G>A, MAGEL2: c.2024_2025del, LMBR1: c.423+4914A>C, NEB: c.21273_21276del, COL1A1: c.2651G>C and c.2758G>C, ASPM: c.2473delinsGA, TBX5: c.704G>A, DYNC2H1: c.10893del, and DYNC2I2: c.1270C>T. Substantial concordance was reached between WES-derived CNV calls and CNV-seq findings. No clinically significant CNV was exclusively detected by CNV-seq. Cost-effectiveness modeling demonstrated that implementing WES as the first-tier genetic testing method could reduce the total expenditure when WES unit cost remained below 6.4 folds that of the CNV-seq. CONCLUSION Genetic variants including single nucleotide variations (SNV) of monogenic disorders, chromosomal aneuploidies and genomic CNVs are important causes for fetal skeletal dysplasia. WES is an accurate and efficient method for analyzing the etiology of fetal skeletal dysplasia, particularly in those with a family history of similar phenotype or maternal history of adverse pregnancies.
Humans ; Exome Sequencing/methods* ; Female ; Pregnancy ; DNA Copy Number Variations/genetics* ; Genetic Testing/methods* ; Prenatal Diagnosis/methods* ; Adult ; Male ; Fetus ; Bone Diseases, Developmental/diagnosis* ; Ultrasonography, Prenatal

Objective To evaluate the application value of dermatoscope combined with rapid frozen section examination in the treatment of head and facial skin tumors.Methods A retrospective analysis was performed on 123 patients with head and facial skin masses admitted to Affiliated Jinhua Hospital,Zhejiang University School of Medicine from June 2019 to December 2023.Patients were divided into two groups according to their wishes.Patients in group A underwent preoperative dermoscopy combined with intraoperative rapid frozen section examination,and patients in group B underwent preoperative skin biopsy combined with intraoperative rapid frozen section examination.The diagnostic accuracy of two methods was compared.Results There were 81 patients in group A,including 39 basal cell carcinoma,25 squamous cell carcinoma,8 solar keratosis,5 seborrheic keratosis and 4 verrucous nevus.There were 42 patients in group B,including 25 basal cell carcinoma,13 squamous cell carcinoma and 4 solar keratosis.Both groups of patients successfully completed the operation,postoperative follow-up 6 months no recurrence.The accuracy of dermoscopy in the diagnosis of head and facial skin masses was 91.36％,and the accuracy of skin biopsy was 100％.There was no statistical significance between them(x2=2.407,P=0.121).Conclusion In surgical treatment of head and facial skin tumors,the diagnostic accuracy of preoperative dermoscopy combined with intraoperative rapid frozen section examination is high,and it is worthy of clinical promotion.

OBJECTIVE To detect the common pathogens for the patients with eczematous dermatitis and analyze associations between the pathogens and the clinical stages.METHODS A total of 206 patients with eczematous der-matitis who were treated in Jinhua Central Hospital from Jan.2014 to Jan.2024 were enrolled in the study and were divided into the secondary skin lesion group with 92 cases and the non-secondary skin lesion group with 114 cases according to the characteristics of the lesions.Meanwhile,the people who received physical examination and had no history of eczematous dermatitis were chosen as the control group with 91 cases.The distribution and den-sity of the common pathogens were compared among the three groups and among the patients with different clini-cal stages(the acute stage,the subacute stage and the chronic stage)of eczematous dermatitis.The scores of skin lesion were compared among the patients.RESULTS Staphylococcus aureus,Staphylococcus epidermidis and Malassezia were dominant among the isolated pathogens;both the positive rates of pathogens and the densities of pathogens,from the high to the low,were as follows:the secondary skin lesion group＞the non-secondary skin lesion group＞the control group(P＜0.05).The isolation rate of S.aureus of the secondary skin lesion group and the non-secondary skin lesion group were higher than that of the control group(P＜0.05);the isolation rate of Malassezia of the secondary skin lesion group was higher than that of the non-secondary skin lesion group(P＜0.05).The score of skin lesion of the patients detected positive for pathogens was higher than that of the patients detected negative(P＜0.05).Among the patients detected positive for pathogens,the score of skin lesion of the a-cute stage patients was higher than that of the subacute stage patients and the chronic stage patients(P＜0.05);the isolation rates of S.aureus and Malassezia and the density of pathogens of the acute stage patients were higher than those of the chronic stage patients(P＜0.05),and the density of pathogens of the subacute stage patients was higher than that of the chronic stage patients(P＜0.05).CONCLUSIONS S.aureus,S.epidermidis and Malassezia are the common pathogens isolated from the patients with eczematous dermatitis.The positive rates and densities of pathogens are higher among the patients with secondary skin lesions,and the infections with the pathogens are associated with the severity of skin lesion and the clinical stage.

OBJECTIVE To detect the common pathogens for the patients with eczematous dermatitis and analyze associations between the pathogens and the clinical stages.METHODS A total of 206 patients with eczematous der-matitis who were treated in Jinhua Central Hospital from Jan.2014 to Jan.2024 were enrolled in the study and were divided into the secondary skin lesion group with 92 cases and the non-secondary skin lesion group with 114 cases according to the characteristics of the lesions.Meanwhile,the people who received physical examination and had no history of eczematous dermatitis were chosen as the control group with 91 cases.The distribution and den-sity of the common pathogens were compared among the three groups and among the patients with different clini-cal stages(the acute stage,the subacute stage and the chronic stage)of eczematous dermatitis.The scores of skin lesion were compared among the patients.RESULTS Staphylococcus aureus,Staphylococcus epidermidis and Malassezia were dominant among the isolated pathogens;both the positive rates of pathogens and the densities of pathogens,from the high to the low,were as follows:the secondary skin lesion group＞the non-secondary skin lesion group＞the control group(P＜0.05).The isolation rate of S.aureus of the secondary skin lesion group and the non-secondary skin lesion group were higher than that of the control group(P＜0.05);the isolation rate of Malassezia of the secondary skin lesion group was higher than that of the non-secondary skin lesion group(P＜0.05).The score of skin lesion of the patients detected positive for pathogens was higher than that of the patients detected negative(P＜0.05).Among the patients detected positive for pathogens,the score of skin lesion of the a-cute stage patients was higher than that of the subacute stage patients and the chronic stage patients(P＜0.05);the isolation rates of S.aureus and Malassezia and the density of pathogens of the acute stage patients were higher than those of the chronic stage patients(P＜0.05),and the density of pathogens of the subacute stage patients was higher than that of the chronic stage patients(P＜0.05).CONCLUSIONS S.aureus,S.epidermidis and Malassezia are the common pathogens isolated from the patients with eczematous dermatitis.The positive rates and densities of pathogens are higher among the patients with secondary skin lesions,and the infections with the pathogens are associated with the severity of skin lesion and the clinical stage.

Objective To evaluate the application value of dermatoscope combined with rapid frozen section examination in the treatment of head and facial skin tumors.Methods A retrospective analysis was performed on 123 patients with head and facial skin masses admitted to Affiliated Jinhua Hospital,Zhejiang University School of Medicine from June 2019 to December 2023.Patients were divided into two groups according to their wishes.Patients in group A underwent preoperative dermoscopy combined with intraoperative rapid frozen section examination,and patients in group B underwent preoperative skin biopsy combined with intraoperative rapid frozen section examination.The diagnostic accuracy of two methods was compared.Results There were 81 patients in group A,including 39 basal cell carcinoma,25 squamous cell carcinoma,8 solar keratosis,5 seborrheic keratosis and 4 verrucous nevus.There were 42 patients in group B,including 25 basal cell carcinoma,13 squamous cell carcinoma and 4 solar keratosis.Both groups of patients successfully completed the operation,postoperative follow-up 6 months no recurrence.The accuracy of dermoscopy in the diagnosis of head and facial skin masses was 91.36％,and the accuracy of skin biopsy was 100％.There was no statistical significance between them(x2=2.407,P=0.121).Conclusion In surgical treatment of head and facial skin tumors,the diagnostic accuracy of preoperative dermoscopy combined with intraoperative rapid frozen section examination is high,and it is worthy of clinical promotion.

Objective:To explore the genetic etiology of fetal skeletal dysplasia using whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) techniques, and the feasibility of using WES as the first-tier method for such fetuses.Methods:Seventy four fetuses with skeletal dysplasia detected by prenatal ultrasound at the Genetic Testing Center of the Women and Children′s Hospital Affiliated to Qingdao University from January 2020 to August 2024 were selected as the study subjects. Fetal muscle and peripheral blood samples of the pregnant women and their spouses were collected and subjected to WES analysis. CNV-seq was carried out on all fetal muscle tissue samples. And the results were compared with the CNVs indicated by WES. Genetic etiologies were analyzed across different subtypes of skeletal dysplasia. And the feasibility of using WES as the first-tier genetic test for similar fetuses was assessed, in addition with a systematic cost-effectiveness analysis. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: QFELL-YJ-2024-201).Results:A total of 50 fetuses were diagnosed, which yielded a diagnostic rate of 67.57%. These included 6 chromosomal aneuploidies, 4 chromosomal CNVs and 40 monogenic disorders. The monogenic diseases had involved 46 variant sites in 23 pathogenic genes, among which 12 were unreported previously, including MYH3: c. 735T>C, ALPL: c. 1324C>T, NEK9: c. 1973G>A, MAGEL2: c. 2024_2025del, LMBR1: c. 423+ 4914A>C, NEB: c. 21273_21276del, COL1A1: c. 2651G>C and c. 2758G>C, ASPM: c. 2473delinsGA, TBX5: c. 704G>A, DYNC2H1: c. 10893del, and DYNC2I2: c. 1270C>T. Substantial concordance was reached between WES-derived CNV calls and CNV-seq findings. No clinically significant CNV was exclusively detected by CNV-seq. Cost-effectiveness modeling demonstrated that implementing WES as the first-tier genetic testing method could reduce the total expenditure when WES unit cost remained below 6.4 folds that of the CNV-seq. Conclusion:Genetic variants including single nucleotide variations (SNV) of monogenic disorders, chromosomal aneuploidies and genomic CNVs are important causes for fetal skeletal dysplasia. WES is an accurate and efficient method for analyzing the etiology of fetal skeletal dysplasia, particularly in those with a family history of similar phenotype or maternal history of adverse pregnancies.

Objective:To observe any effect of exercise preconditioning on the levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in the brain tissue of rats after induced cerebral ischemia and reperfusion, and how it might promote angiogenesis.Methods:Thirty-six male Sprague-Dawley rats were randomly divided into a sham-operation group, a model group and an exercise preconditioning group, each of 12. After adaptive running training for 3 days, the exercise preconditioning group ran daily for 30 minutes at 15m/min for 14 days, while the other two groups did not exercise. Middle cerebral artery occlusion and reperfusion were then induced in the model and exercise preconditioning groups using the modified Zea-Longa suture method. Rats in the sham-operation group were only cut open to expose the right carotid artery. Right after the modeling, and again 24 hours later neurological deficit was evaluated using the Zea-Longa score and modified neurological severity scoring (mNSS). Infarct sizes were measured using 2, 3, 5-triphenyl tetrazolium chloride staining. Any morphological changes were noted using hematoxylin and eosin (HE) staining, and the expression of CD31 protein, hypoxia-inducible factor-1α and vascular endothelial growth factor in the ischemic cerebral cortex were quantified immunohistochemically.Results:Right after the modelling, compared with the sham-operation group, the average Zea-Longa scores of the model and exercise groups had increased significantly, but were not significantly different from each other. Twenty-four hours later the average Zea-Longa score, mNSS score and relative cerebral infarction area of the model group had increased significantly compared with the sham-operation group, while the exercise preconditioning group′s averages had decreased significantly. The HE staining showed that compared with the sham-operation group, pathological changes such as loose tissue, reduced number of nerve cells, nucleolysis, and vacuolization of the cerebral cortex on the ischemic side were found in the model group. Compared with the model group, the pathological changes in the exercise preconditioning group were less serious. The levels of CD31 protein, HIF-1α and VEGF in the ischemic cerebral cortexes of the model group had by then increased significantly. But compared with the model group, those levels had increased more in the exercise preconditioning group.Conclusion:Exercise preconditioning can effectively promote angiogenesis after cerebral ischemia and reduce chronic injury. That may be related to the activation of the HIF-1α and/or VEGF signaling pathways.

ObjectiveTo observe the clinical efficacy of modified Shenqi Pill （肾气丸） plus Tongdu Tiaoshen Acupuncture （通督调神针刺） in the treatment of neurogenic bladder after spinal cord injury of kidney-yang deficiency syndrome. MethodsForty-six patients were randomly divided into 23 cases each in the control group and the treatment group. Both groups were given conventional treatment， i.e. oral methylcobalamin tablets （0.5 mg each time， 3 times a day） and paraplegic conventional acupuncture （once a day， 6 consecutive days a week）. The control group was given simple bladder function rehabilitation training on the basis of the conventional treatment； and the treatment group was given modified Shenqi Pill orally （1 dose a day， 150 ml each time， taken warmly in morning and evening） and Tongdu Tiaoshen Acupuncture （once a day， 6 consecutive days per week） in addition to what were given to the control group. The treatment course lasted for 4 weeks. The 24 h urination frequency， 24 h urine leakage frequency， 24 h single urine volume， bladder residual urine volume， international lower urinary tract symptom （LUTS） score， traditional Chinese medicine （TCM） syndrome score were compared between the two groups， and clinical effectiveness and TCM syndrome effectiveness were compared between the two groups after treatment. ResultsTwenty patients in each group were finally analyzed in this study. The number of 24 h urination， the number of 24 h urine leakage， bladder residual urine volume， LUTS score， and the TCM syndrome scores decreased after treatment in both groups， and the 24 h single urine volume increased （P＜0.01）； and much more improvement was found of each index in the treatment group than in the control group （P＜0.05 or P＜0.01）. The total clinical effectiveness and TCM syndrome effectiveness in the treatment group was 85.00% （17/20） respectively， which were statistically significantly higher than 45.00% （the total clinical effectiveness， 9/20） and 60.00% （TCM syndrome effectiveness， 12/20） in the control group （P＜0.01）. ConclusionModified Shenqi Pill plus Tongdu Tiaoshen Acupuncture can signi-ficantly improve the clinical symptoms of neurogenic bladder patients after spinal cord injury of kidney-yang deficiency syndrome， having better effectiveness than simple bladder function rehabilitation training， and its mechanism may be related to the improvement of the injured nerve function innervating the bladder.

Objective To explore the clinical efficacy and safety of azithromycin sequential therapy combined with risk management in the treatment of mycoplasmal pneumonia pneumonia(MPP)in children.Methods MPP children admitted to the Department of Pediatrics of Quzhou People's Hospital from March 2023 to November 2023 were retrospectively selected,and divided into a study group(azithromycin sequential therapy combined with risk management)and a control group(azithromycin sequential therapy combined with routine care)according to different intervention methods.The clinical efficacy,inflammatory cytokines[interleukin-6(IL-6),interleukin-17(IL-17),and tumor necrosis factor-α(TNF-α)],incidence of MPP-related complications,and incidence of drug-related adverse reactions(DRAR)in the two groups after treatment were observed and compared.Results A total of 119 children with MPP were included in the study,with 57 in the study group and 62 in the control group.The clinical efficacy of children with MPP in the study group was significantly higher than that in the control group(P＜0.05).There was no significant difference in IL-6,IL-17,and TNF-α between the two groups before treatment(P＞0.05);after treatment,both groups showed significant decreases in IL-6,IL-17,and TNF-α compared with before treatment,and these indicators of the study group were lower than thsoe of the control group(P＜0.05).The incidence of MPP-related complications in children in the study group was lower than that in the control group(P＜0.05),and there was no significant difference in the incidence of adverse drug reactions between the two groups(P＞0.05).In addition,the satisfaction of MPP children's family members in the study group with nursing care was significantly higher than that in the control group(P＜0.05).Conclusion The clinical efficacy of azithromycin sequential therapy combined with risk management in the treatment of pediatric MPP is significant,which can regulate the expression of inflammatory cytokines,reduce MPP-related complications,and improve clinical efficacy and family satisfaction with nursing care.