Objective:To investigate the clinical characteristics and genetic etiology of a primary familial brain calcification (PFBC) family, and analyze the pathogenic mechanism of MYORG gene variants. Methods:A 17-year-old female who presented to the Second Affiliated Hospital of Zhejiang University School of Medicine on 13 May 2024 with " paroxysmal limb twitching for 1 day" was enrolled. The patient and her parents underwent clinical evaluation and neuroimaging. Peripheral blood was collected for whole exome sequencing (WES). Candidate variants were confirmed by Sanger sequencing and interpreted using the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as the ACMG Guidelines). This study was approved by Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (Ethics No. 2020-674). Results:① The patient experienced epileptic seizures. Cranial CT revealed multiple calcifications in the bilateral basal ganglia and cerebellum, with a total calcification score of 23. ② WES identified compound heterozygous variants in MYORG: c. 337_348dup (p.Leu113_Arg116dup), a known pathogenic variant, and c. 1268T>G (p.Val423Gly). Segregation analysis showed that the father carried the c. 337_348dup heterozygous variant, whereas the mother carried the c. 1268T>G heterozygous variant. ③ According to ACMG guidelines, the c. 1268T>G variant was classified as "likely pathogenic" (PM2_Supporting + PM3_Supporting + PP1_Supporting + PP3_Moderate + PP4_Supporting). Conclusion:The novel compound heterozygous MYORG variants c. 337_348dup and c.1268T>G have broadened the mutational spectrum of the MYORG gene and further supported compound heterozygosity as an important genetic mechanism in MYORG-related PFBC.

OBJECTIVE: To investigate the clinical characteristics and genetic etiology of a primary familial brain calcification (PFBC) family, and analyze the pathogenic mechanism of MYORG gene variants. METHODS: A 17-year-old female who presented to the Second Affiliated Hospital of Zhejiang University School of Medicine on 13 May 2024 with "paroxysmal limb twitching for 1 day" was enrolled. The patient and her parents underwent clinical evaluation and neuroimaging. Peripheral blood samples were collected for whole exome sequencing (WES). Candidate variants were confirmed by Sanger sequencing and interpreted using the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as the ACMG Guidelines). This study was approved by Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (Ethics No. 2020-674). RESULTS: The patient experienced epileptic seizures. Cranial CT revealed multiple calcifications in the bilateral basal ganglia and cerebellum, with a total calcification score of 23. WES identified compound heterozygous variants in MYORG: c.337_348dup (p.Leu113_Arg116dup), a known pathogenic variant, and c.1268T>G (p.Val423Gly). Segregation analysis showed that the father carried the c.337_348dup heterozygous variant, whereas the mother carried the c.1268T>G heterozygous variant. According to ACMG guidelines, the c.1268T>G variant was classified as "likely pathogenic" (PM2_Supporting + PM3_Supporting + PP1_Supporting + PP3_Moderate + PP4_Supporting). CONCLUSION The novel compound heterozygous MYORG variants c.337_348dup and c.1268T>G have broadened the mutational spectrum of the MYORG gene and further supported compound heterozygosity as an important genetic mechanism in MYORG-related PFBC.
Adolescent ; Female ; Humans ; Brain Diseases/genetics* ; Calcinosis/genetics* ; Exome Sequencing ; GPI-Linked Proteins/genetics* ; Mutation ; Pedigree ; Glycoside Hydrolases

Iron deficiency and anemia are common and are associated with poor prognosis in patients with heart failure.Previous studies have found that oral iron supplementation cannot improve quality of life and activity tolerance in patients with heart failure.In recent years,a large number of studies have demonstrated that sodium-glucose cotransporter 2 inhibitor(SGLT2i)can improve the prognosis of patients with heart failure.Researchers have found that they can stimulate erythropoietin secretion,inhibit sympathetic overactivation,inhibit inflammatory response,improve iron absorption and utilization,and inhibit ferroptosis.This article summerizes the effect of SGLT2i on iron metabolism in patients with heart failure,so as to explore possible ways to improve iron deficiency and anemia in patients with heart failure.

Iron deficiency and anemia are common and are associated with poor prognosis in patients with heart failure.Previous studies have found that oral iron supplementation cannot improve quality of life and activity tolerance in patients with heart failure.In recent years,a large number of studies have demonstrated that sodium-glucose cotransporter 2 inhibitor(SGLT2i)can improve the prognosis of patients with heart failure.Researchers have found that they can stimulate erythropoietin secretion,inhibit sympathetic overactivation,inhibit inflammatory response,improve iron absorption and utilization,and inhibit ferroptosis.This article summerizes the effect of SGLT2i on iron metabolism in patients with heart failure,so as to explore possible ways to improve iron deficiency and anemia in patients with heart failure.

Objective:To investigate the clinical characteristics and genetic etiology of a primary familial brain calcification (PFBC) family, and analyze the pathogenic mechanism of MYORG gene variants. Methods:A 17-year-old female who presented to the Second Affiliated Hospital of Zhejiang University School of Medicine on 13 May 2024 with " paroxysmal limb twitching for 1 day" was enrolled. The patient and her parents underwent clinical evaluation and neuroimaging. Peripheral blood was collected for whole exome sequencing (WES). Candidate variants were confirmed by Sanger sequencing and interpreted using the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as the ACMG Guidelines). This study was approved by Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (Ethics No. 2020-674). Results:① The patient experienced epileptic seizures. Cranial CT revealed multiple calcifications in the bilateral basal ganglia and cerebellum, with a total calcification score of 23. ② WES identified compound heterozygous variants in MYORG: c. 337_348dup (p.Leu113_Arg116dup), a known pathogenic variant, and c. 1268T>G (p.Val423Gly). Segregation analysis showed that the father carried the c. 337_348dup heterozygous variant, whereas the mother carried the c. 1268T>G heterozygous variant. ③ According to ACMG guidelines, the c. 1268T>G variant was classified as "likely pathogenic" (PM2_Supporting + PM3_Supporting + PP1_Supporting + PP3_Moderate + PP4_Supporting). Conclusion:The novel compound heterozygous MYORG variants c. 337_348dup and c.1268T>G have broadened the mutational spectrum of the MYORG gene and further supported compound heterozygosity as an important genetic mechanism in MYORG-related PFBC.

Although the artificial intelligence diagnosis technology of traditional Chinese medicine(TCM)is constantly developing,the existing intelligent syndrome differentiation models can only output the diagnosis results and cannot display the reasoning process of TCM diagnosis.They do not have the interpretability of TCM diagnostic knowledge and are difficult to truly reflect the process of TCM's syndrome differentiation.This can be a long-standing problem that has puzzled the academic community.This article elaborates on the development process and technical characteristics of intelligent diagnosis in traditional Chinese medicine,explores multiple key technologies and bottlenecks in current research in reasoning of TCM's Syndrome Differentiation,and factors affecting diagnosis.A novel intelligent diagnosis model architecture that can infer and explain the process of TCM'ssyndrome differentiation was proposed,and the implementation process of the model and algorithm was explained,and detailed data instance analysis was conducted.This article will provide new methods for the development of intelligent syndrome differentiation of TCM and open up new research ideas for clinical decision-making assistance of TCM.

Objective To investigate the prevalence and influencing factors of HIV/AIDS patients with hyperlipidemia before and after receiving antiviral therapy in Wuhan. Methods A retrospective cohort study was used to analyze the data of HIV/AIDS patients in Wuhan from 2004 to 2021. Elevated levels of either TG or TC were determined as hyperlipidemia. Logistic regression model was used to analyze the influencing factors of baseline hyperlipidemia, and Cox proportional risk model was used to analyze the influencing factors of new-onset hyperlipidemia after receiving antiviral therapy. Results A total of 7 562 HIV/AIDS patients were enrolled, 30.61% (2 315/7 562) with hyperlipidemia at baseline and 69.39% (5 247/7 562) without hyperlipidemia. The mean person-years of follow-up for those patients without hyperlipidemia at baseline were 3.48, of whom 33.14% (1 739/5 247) developed hyperlipidemia during follow-up, with an overall density of 9.53/100 person-years. Multivariate logistic regression analysis showed that age ≥30 years and BMI ≥24 kg/m² were positively correlated with baseline hyperlipidemia, while CD4 cell count ≥ 200 μL was negatively correlated with baseline hyperlipidemia. Multivariate Cox model analysis showed that new-onset hyperlipidemia after receiving antiviral therapy was significantly positively correlated with BMI between 18.5-23.9 and ≥24 kg/m², the initial antiviral treatment regimen containing LPV/r, efavirenz and other factors A baseline CD4 cell count of 200 to 349 cells /μL was negatively correlated with new-onset hyperlipidemia. Conclusion HIV/AIDS patients with high BMI and an initial antiviral regimen including Kaletra or efavirenz have a significantly higher risk of hyperlipidemia. Follow-up monitoring of blood lipid in these patients should be strengthened.

In this paper,a new method for catalytic synthesis of chalcones from substituted acetophenone and substituted benzaldehyde in polyphosphoric acid/concentrated sulfuric acid system was proposed,and the reaction conditions were optimized. The results showed that the optimized reaction conditions were determined as polyphosphoric acid of 5 equiv. and concentrated sulfuric acid of 20 equiv.,with 1,4-dioxane as solvent at 90 °C for 2 h under nitrogen protection. Twelve chalcones were synthesized with good yield. All target compounds were characterized by IR,HRMS,1H NMR and 13C NMR.

Objective: To explore the genetic basis for a pedigree affected with X-linked adrenoleukodystrophy presenting as spastic paraplegia of the lower limbs. Methods: Genomic DNA was extracted from peripheral blood samples of the patient and his mother. Potential variant was detected with a panel for genes associated with spastic paraplegia. Candidate variant was verified by PCR and Sanger sequencing. Results: Both the proband and his mother presented with walking difficulty. A previously known variant, c. 623T>A (p.V208E), was identified in the ABCD1 gene mapped on chromosome X in both. Conclusion X-link adrenoleukodystrophy should be taken into account as a possible diagnosis for this pedigree.

Objective: To explore the genetic basis of a patient with early-onset Parkinson disease from a consanguineous family. Methods: Homozygosity mapping and Sanger sequencing of cDNA were used to identify the causative mutation. Results: A homozygous missense variation (c.56C>G, p. Thr19Arg) in the PARK7 gene was identified in the patient. In silico analysis suggested the c. 56C>G variation to be pathogenic. Conclusion Homozygous c. 56C>G variation of the PARK7 gene was the disease-causing variation in this family.