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

OBJECTIVE To explore the value of microbiological rapid on-site evaluation(M-ROSE)technique in treatment of the patients with severe community-acquired pneumonia(SCAP).METHODS A total of 124 patients with SCAP who were treated in the department of respiratory and critical care medicine of The Fourth Medical Center of Chinese PLA General Hospital from Sep.2023 to Dec.2024 were enrolled in the study and were random-ly divided into the M-ROSE group and the control group in a 1∶1 ratio based on the status of M-ROSE for bron-choalveolar lavage fluid(BALF).The M-ROSE test and conventional etiological test[metagenomic next genera-tion sequencing(mNGS),smear,culture]were performed for the M-ROSE group,and the conventional etiologi-cal test was only carried out for the control group.The baseline data,symptoms and signs,C-reactive protein lev-el,treatment status and outcomes were observed and compared between the two groups of patients.RESULTS A-mong the 62 patients for whom the BALF specimens were detected with M-ROSE,45(72.58％)patients showed the consistent test result for fungi with mNGS,47(75.81％)patients showed the same test result for cocci with mNGS,and 30(48.39％)patients showed the same test result for bacilli with mNGS.The duration of the M-ROSE test was 1.50(1.50,2.00)h,shorter than that of the smear,culture and mNGS(P＜0.05).The body temperature returning to the normal and the property,volume of sputum were improved more early in days in the M-ROSE group than in the control group after the anti-infection treatment(P＜0.05);the level of inflammatory factor CRP declined more quickly in the M-ROSE group than in the control group(P＜0.05);the effective rates of treatment of the M-ROSE group were higher than those of the control group after the hospitalization for 3,5 and 7 days(P＜0.05).CONCLUSION The M-ROSE test for BALF may facilitate the rapid etiological diagnosis for the patients with SCAP in early stage,provide guidance for the anti-infection treatment strategies,and accelerate the improvement of symptoms and inflammatory factors;it has certain clinical application value.

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.

In recent years, surgical research has entered the digital era, and the dissemination of medical knowledge has also begun to confront the challenge posed by we media. When we media first emerged, most doctors in public hospitals, who focused on "medicine, education, and research", held a reserved attitude towards it. However, we media has demonstrated remarkable resilience and has continuously evolved to align with the trend of social development. Faced with the future development direction and the existing sore points, how surgeons comprehend and respond to the surging current of the times is a conundrum before us. In this article, the author has sorted out the rise and development of we media, the status of its application in the medical field, and the predicaments faced by medical we media, and has looked forward to its development to broaden the thinking of surgeons for more comprehensive innovation and development.

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 explore the value of microbiological rapid on-site evaluation(M-ROSE)technique in treatment of the patients with severe community-acquired pneumonia(SCAP).METHODS A total of 124 patients with SCAP who were treated in the department of respiratory and critical care medicine of The Fourth Medical Center of Chinese PLA General Hospital from Sep.2023 to Dec.2024 were enrolled in the study and were random-ly divided into the M-ROSE group and the control group in a 1∶1 ratio based on the status of M-ROSE for bron-choalveolar lavage fluid(BALF).The M-ROSE test and conventional etiological test[metagenomic next genera-tion sequencing(mNGS),smear,culture]were performed for the M-ROSE group,and the conventional etiologi-cal test was only carried out for the control group.The baseline data,symptoms and signs,C-reactive protein lev-el,treatment status and outcomes were observed and compared between the two groups of patients.RESULTS A-mong the 62 patients for whom the BALF specimens were detected with M-ROSE,45(72.58％)patients showed the consistent test result for fungi with mNGS,47(75.81％)patients showed the same test result for cocci with mNGS,and 30(48.39％)patients showed the same test result for bacilli with mNGS.The duration of the M-ROSE test was 1.50(1.50,2.00)h,shorter than that of the smear,culture and mNGS(P＜0.05).The body temperature returning to the normal and the property,volume of sputum were improved more early in days in the M-ROSE group than in the control group after the anti-infection treatment(P＜0.05);the level of inflammatory factor CRP declined more quickly in the M-ROSE group than in the control group(P＜0.05);the effective rates of treatment of the M-ROSE group were higher than those of the control group after the hospitalization for 3,5 and 7 days(P＜0.05).CONCLUSION The M-ROSE test for BALF may facilitate the rapid etiological diagnosis for the patients with SCAP in early stage,provide guidance for the anti-infection treatment strategies,and accelerate the improvement of symptoms and inflammatory factors;it has certain clinical application value.

In recent years, surgical research has entered the digital era, and the dissemination of medical knowledge has also begun to confront the challenge posed by we media. When we media first emerged, most doctors in public hospitals, who focused on "medicine, education, and research", held a reserved attitude towards it. However, we media has demonstrated remarkable resilience and has continuously evolved to align with the trend of social development. Faced with the future development direction and the existing sore points, how surgeons comprehend and respond to the surging current of the times is a conundrum before us. In this article, the author has sorted out the rise and development of we media, the status of its application in the medical field, and the predicaments faced by medical we media, and has looked forward to its development to broaden the thinking of surgeons for more comprehensive innovation and development.

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 construct the intracranial venous sinus thrombosis (CVST) models under plateau hypoxia by simulating plateau hypoxic condition, and further clarify the role of plateau hypoxa in CVST.Methods:Forty-eight 8-week-old male SD rats were randomly divided into sham-operated group, plateau sham-operated group, CVST group, and plateau CVST group ( n=12). CVST models in the CVST group and plateau CVST group were established by ferric chloride wet dressing, and rats in the plateau CVST group were kept in a low-pressure oxygen chamber for 2 d immediately after modeling to simulate plateau hypoxic condition at an altitude of 5,000 m (barometric pressure of 54.047 kPa, oxygen concentration of 10%-11%, and temperature of 18-23 °C). Only the bone flap and dura mater were separated in rats of the sham-operated group, without low-pressure oxygen condition or filter paper dressing. Only the bone flap and dura mater were separated in rats of the plateau sham-operated group, with plateau hypoxic condition at an altitude of 5,000 m for 2 d and without filter paper dressing. Intracranial venous sinus blood flow was detected by Doppler flowmetry before and 48 h after modeling. At 6, 24, and 48 h after modeling, 4 rats in each group were sacrificed; blood vessels at the thrombus of superior sagittal sinus (blood vessels at the superior sagittal sinus in the sham-operated group and plateau sham-operated group) were cut out and weighed; meanwhile, water contents of the brain tissues were calculated. HE staining was employed in the brain, heart, liver, lung, and kidney tissues and veins, and toluidine blue staining was peformed in the brain tissues only at 48 h after modeling. Results:(1) Doppler flowmetry indicated that intracranial venous sinus blood flow was normal in the 4 groups before modeling; intracranial venous sinus blood flow signals were normal in the sham-operated group and plateau sham-operated group and obviously weakened in the CVST group and plateau CVST group 48 h after modeling. (2) No thrombus was formed in the sham-operated group 48 h after modeling. At 6, 24 and 48 h after modeling, the thrombus in the CVST group ([15.44±1.90] mg, [12.63±1.26] mg, and [7.85±0.68] mg) and plateau CVST group ([20.38±1.67] mg, [24.93±2.37] mg, and [20.90±1.30] mg) weighted significantly heavier than those in the plateau sham-operated group ([2.55±0.38] mg, [2.19±0.30] mg, [1.75±0.31] mg), and that in the plateau CVST group weighted significantly heavier than that in the CVST group ( P<0.05); the thrombus weight in both plateau sham-operated group and CVST group decreased sequentially at 6, 24 and 48 h after modeling, with significant differences ( P<0.05); whereas, the thrombus weight in the plateau CVST group at 24 h after modeling increased compared with that at 6 h after modeling, and that at 48 h after modeling decreased compared with that at 24 h after modeling, with significant differences ( P<0.05). (3) At 6 h after modeling, the brain water contents in the sham-operated group, plateau sham-operated group, CVST group and plateau CVST group were (77.56±0.52)%, (77.57±0.92)%, (78.91±0.53)%, and (78.90±0.63)%, respectively, with statistical differences ( P<0.05); the CVST group and plateau CVST group had increased water content compared with the sham-operated group and plateau sham-operated group without significant differences ( P>0.05). At 24 and 48 h after modeling, the brain water content among the 4 groups was not statistically different ( P>0.05). (4) HE staining and toluidine blue staining indicated limited infarction, neuronal edema, and necrotic apoptosis in the brain tissues of plateau CVST group at 24 h after modeling. HE staining showed no obvious pathological changes in the myocardium, liver, lung, or kidney tissues in the 4 groups. Conclusion:CVST models can be successfully established by simulating plateau hypoxic condition through ferric chloride wet dressing and feeding in low-pressure oxygen chamber.