Objective:To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS).Methods:An adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was enrolled as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X).Results:Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c. 206+ 2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the patients mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+ PM2_Supporting). Conclusion:The heterozygous splice site variant c. 206+ 2T>G of the SMAD3 gene probably underlay the disease of this patient. The discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.

OBJECTIVE: To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS). METHODS: A adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X). RESULTS: Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c.206+2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the proband's mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION The heterozygous splice site variant c.206+2T>G of the SMAD3 gene probably underlay the disease in this patient. Above discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.
Adult ; Humans ; Male ; Exome Sequencing ; Loeys-Dietz Syndrome/genetics* ; Mutation ; Pedigree ; Smad3 Protein/genetics*

Objective:To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS).Methods:An adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was enrolled as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X).Results:Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c. 206+ 2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the patients mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+ PM2_Supporting). Conclusion:The heterozygous splice site variant c. 206+ 2T>G of the SMAD3 gene probably underlay the disease of this patient. The discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.

Objective·To explore the efficacy and safety of compound amino acid capsules in the treatment of malnutrition and calcium and phosphorus metabolism disorders in maintenance hemodialysis patients.Methods·In this prospective,randomized,controlled,single-center study,forty maintenance hemodialysis patients from Renji Hospital,Shanghai Jiao Tong University School of Medicine were randomly divided into two groups,the treatment group(n=21)and the control group(n=19).The treatment group was given oral compound amino acid capsules on the basis of regular hemodialysis treatment,while the control group received no special nutritional intervention.Serum albumin,prealbumin,hemoglobin,ferritin,calcium,phosphorus,1,25-(OH)2-D3 and intact parathyroid hormone levels were analyzed every 3 months,and the incidence of adverse events including death,cardio-cerebrovascular accidents and vascular access failure was recorded.The total follow-up period was 9 months.Results·Serum albumin and prealbumin in the treatment group at 6-month and 9-month were significantly higher than the baseline parameters(albumin,t=3.574,5.599,both P<0.05;prealbumin,t/Z=-2.485,2.921,both P<0.05).Albumin in the control group increased at 9-month with a lower amplification compared to the treatment group(t=3.877,P=0.001),while the difference of prealbumin showed no statistical significance during follow-up.Hemoglobin and serum ferritin in the treatment group started to increase at 3-month(hemoglobin,t=2.192;ferritin,t=2.994;both P<0.05).Phosphorus in treatment group decreased at 3-month and 9-month(t/Z=-2.743,-2.103,both P<0.05),while phosphorus in the control group remained relatively stable during the first 6 months and increased at 9-month(Z=-2.178,P=0.029).Calcium and 1,25-(OH)2-D3 in the treatment group at 3-month and 6-month were significantly higher than the baseline parameters(calcium,t=4.581,4.922,both P=0.000;1,25-(OH)2-D3 t/Z=4.504,-2.374,both P<0.05),while the increase in blood calcium in the control group was significantly smaller than that in the treatment group during the same period.1,25-(OH)2-D3 in the control group showed no significant improvement.There was no significant difference in intact parathyroid hormone level,incidence of adverse events and other laboratory examination results between the two groups.Conclusion·Compound amino acid capsules can ameliorate the nutrition status and regulate calcium and phosphorus metabolism effectively and safely in maintenance hemodialysis patients.

OBJECTIVE To investigate the potential of low-frequency, low-power ultrasound to enhance the transdermal absorption and efficacy of ketoprofen gel. METHODS Ketoprofen gel was used as a model drug to compare the in vitro transdermal permeation of ultrasound treated group and untreated group. Additionally, a rat model of collagen-induced inflammation provided a basis for evaluating pharmacodynamic differences. Pharmacokinetic studies further elucidated the effects of ultrasound on ketoprofen gel's penetration process. RESULTS Ultrasound treatment enhanced the cumulative transdermal permeation of ketoprofen gel by 3.5-fold over 24 hours compared to untreated. Significant pharmacokinetic improvements in AUC0-t from (4289.02±763.58)ng·h·mL−1 to (11301.10±3386.30)ng·h·mL−1 and a reduction in Tmax from (6.0±1.4)h to (3.0±2.0)h. Ultrasound notably improved the gel's anti-inflammatory effects in the rat model, effectively and rapidly reducing inflammation-induced swelling. CONCLUSION Low-frequency, low-power ultrasound can significantly improve the amount and rate of transdermal absorption of ketoprofen gel and enhance its pharmacological potency, from the aspects of skin permeation tests, pharmacodynamic evaluation, and pharmacokinetic studies, which is an effective penetration enhancer for transdermal administration of ketoprofen gel.

Systemic application of effective antifungal drugs is the basic treatment for pulmonary mycosis,meanwhile,drug spraying under bronchoscope is one of the most important treatment options for tracheal,bronchial and pulmonary mycosis.Compared with bronchoscopic drug injection,indwelling guided drug injection cannula through nasal suspension with or without anchoring has more advantages in the treatment of pulmonary mycosis,including the ability to connect to a syringe pump for continuous and slow injection of drugs,which can avoid repeatedly performing bronchoscopy.This article describes the standard operating procedure of indwelling nasal cannula with or without anchoring for the treatment of pulmonary mycosis.

Recognizing upper airway obstruction and stenosis is critical to determine the subsequent treatment options in patients with obstructive sleep apnea(OSA).Drug-induced sleep endoscopy(DISE)is a 3D visual evaluation technology for the anatomical structure of the upper respiratory tract of OSA patients during"sleeping"state after being anesthetized.The dynamic situation of upper respiratory tract obstruction and collapse can be observed safely and quickly through endoscopy,which provides important reference for formulating surgical methods and positive airway pressure(PAP)intervention treatments.With the assistance of polysomnography(PSG),DISE plays an important role in optimizing individualized treatment plans for OSA.The present article introduces the technical operating points of PSG-assisted drug-induced sleep endoscopic positive airway pressure titration.

Objective:To explore whether anlotinib or bevacizumab has better efficacy in patients with recurrent glioblastoma.Methods:The clinical characteristics and treatment data of patients with recurrent glioblastoma admitted to Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine,were collected retrospectively.All patients received maximal resection of the tumor combined with postoperative adjuvant radiotherapy and chemotherapy,and the recurrence was detected by head contrast-enhanced MRI.According to the choice of anti-vascular therapy,the patients were divided into anlotinib group and bevacizumab group.Survival curves were drawn to compare the overall survival time of the two groups of patients,and subgroup analysis was performed according to the basic information of the patients and whether they received temozolomide chemotherapy or radiotherapy after recurrence.Results:A total of 37 patients were enrolled in the study,19 in the anlotinib group and 18 in the bevacizumab group.The median overall survival time was 16.3 months,with 19.6 months in the anlotinib group and 12.8 months in the bevacizumab group.However,survival analysis showed that there was no significant difference in survival time between the anlotinib group and the bevacizumab group(P=0.88).Further subgroup analysis showed that there was no significant difference in survival time between the two groups in all subgroups.Conclusion:This study provided an initial indication of the efficacy of anlotinib in patients with recurrent glioblastoma and suggested that oral anlotinib may be a viable option for patients who were unable to tolerate bevacizumab or who had.

Objective:To explore whether anlotinib or bevacizumab has better efficacy in patients with recurrent glioblastoma.Methods:The clinical characteristics and treatment data of patients with recurrent glioblastoma admitted to Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine,were collected retrospectively.All patients received maximal resection of the tumor combined with postoperative adjuvant radiotherapy and chemotherapy,and the recurrence was detected by head contrast-enhanced MRI.According to the choice of anti-vascular therapy,the patients were divided into anlotinib group and bevacizumab group.Survival curves were drawn to compare the overall survival time of the two groups of patients,and subgroup analysis was performed according to the basic information of the patients and whether they received temozolomide chemotherapy or radiotherapy after recurrence.Results:A total of 37 patients were enrolled in the study,19 in the anlotinib group and 18 in the bevacizumab group.The median overall survival time was 16.3 months,with 19.6 months in the anlotinib group and 12.8 months in the bevacizumab group.However,survival analysis showed that there was no significant difference in survival time between the anlotinib group and the bevacizumab group(P=0.88).Further subgroup analysis showed that there was no significant difference in survival time between the two groups in all subgroups.Conclusion:This study provided an initial indication of the efficacy of anlotinib in patients with recurrent glioblastoma and suggested that oral anlotinib may be a viable option for patients who were unable to tolerate bevacizumab or who had.

OBJECTIVE To explore the relationship between the ANKK1 rs1800497 polymorphism and atypical antipsychotic drug-induced metabolic syndrome （MS）. METHODS Totally 94 patients with schizophrenia were included， and ANKK1 rs1800497 genotypes of patients were detected by micro-fluorescence immunoassay； social demographic information， clinical characteristics and other data were collected. The χ2 test was used to compare the correlation between the sex of patients and the occurrence of MS， and the correlation between gene polymorphism and the occurrence of MS and its risk factors.RESULTS Totally 94 patients included 24 cases （25.53%） of GG， 51 cases （54.26%） of GA and 19 cases of AA （20.21%）. Among them， there were 45 cases （47.87%） of MS， and the incidence of MS in male was higher than that in female （P＜0.05）. Genotype analysis showed that ANKK1 rs1800497 polymorphism was not associated with MS （P＝0.452）. ANKK1 rs1800497 A allele was significantly associated with hyperglycemia （χ2＝4.379， P＝0.036）， while it was not related to abdominal obesity， hypertension， high level of TG and low level of HDL-C （P＞0.05）， suggesting that for patients with schizophrenia， allele A was a relative risk factor for inducing hyperglycemia [OR＝2.008，95%CI（1.039， 3.881）]. CONCLUSIONS ANKK1 rs1800497 polymorphism has no correlation with the induction of MS by atypical antipsychotics， while the schizophrenia patients with A allele are more likely to induce hyperglycemia. The incidence of MS in male patients is significantly higher than that in female patients.