Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Alzheimer's disease(AD)is a multifactorial degenerative disorder of the central nervous system that mainly manifests as cognitive dysfunction and loss of speech.In recent years,the zebrafish has attracted extensive attention because of its high homology with humans in terms of brain structure and function,nerve conduction,and pathogenic genes of AD.This article reviews the advantages of the zebrafish as an animal model of AD,covering topics in the pathogenesis of AD and the evaluation and screening of drugs for treatment of AD.The overall goal is to provide new insights into the pathogenesis of AD and development of novel drugs.

Objective:Through the investigation of the pathogenicity of COL4A4 heterozygous splicing mutations and the genotype-phenotype correlation in autosomal dominant Alport syndrome (ADAS), to better understand the impact of COL4A4 heterozygous splicing mutations on ADAS. Methods:The study was a case series analysis. Patients from 5 ADAS families with COL4A4 heterozygous splicing mutations detected by whole exome sequencing were recruited by three hospitals. In vivo transcriptional analysis and/or in vitro minigene splicing assay were conducted to determine the splicing patterns and assess the pathogenicity of COL4A4 heterozygous splicing mutations. Results:In the five ADAS pedigrees carrying COL4A4 heterozygous splicing mutations, four novel ADAS splicing patterns were described. In pedigree 1-4, most patients presented with continuous hematuria or/and microalbuminuria. Otherwise,the proband in pedigree 4 presented with macroalbuminuria and the proband in pedigree 1 had progressed to chronic kidney disease stage 2 at the age of 70 years old. In pedigree 5, all patients developed end-stage renal disease between 28 and 41 years old. c.735+3A>G detected in pedigree 1 and pedigree 2 and c.694-1G>C detected in pedigree 3 both led to exon 12 skipping in COL4A4, resulting in 42 nucleotides in-frame deletion (c.694_735del). c.2056+3A>G detected in pedigree 4 led to COL4A4 exon 26 skipping, which caused in-frame deletion of 69 nucleotides (c.1988_2056del). c.2716+5G>T detected in pedigree 5 led to a 360 nucleotides large in-frame deletion, including 100 bp sequence at the 3'end of exon 29,the whole sequence of exon 30 and 89 bp sequence at the 5'end of exon 31 (c.2446_2805del). Conclusions:Renal prognosis differs significantly for patients with small in-frame deletions versus large in-frame deletion splicing abnormalities. Determination of the pathogenicity and the splicing patterns of COL4A4 heterozygous splicing mutations using in vivo and in vitro transcriptional analysis may provide renal prognostic information.

Aromatase deficiency (AD) is a rare autosomal recessive genetic disease caused by loss-of-function mutations in aromatase gene (CYP19A1), leading to congenital estrogen deficiency syndrome. Both mothers of AD patients during pregnancy and female AD fetus show virilization, while male patients are usually diagnosed in adulthood due to continued height increase and metabolic abnormalities. In 2019, a patient with AD was admitted in the Second Xiangya Hospital. The patient was a 37-year-old adult male who continued to grow linearly after adulthood. His estradiol was below the measurable line, the follicle-stimulating hormone (FSH) increased, bone age delayed, epiphysis unfused, and the bone mass reduced. CYP19A1 gene detection showed that c.1093C>T, p.R365W was homozygous mutation. This disease is rare in clinic. Clinicians need to raise awareness of the disease for early diagnosis and treatment to improve the long-term prognosis of patients.
46, XX Disorders of Sex Development/genetics* ; Adult ; Aromatase/metabolism* ; Female ; Gynecomastia/genetics* ; Humans ; Infertility, Male ; Male ; Metabolism, Inborn Errors ; Mutation ; Pregnancy

The aim of the study was to develop a simple, rapid and accurate LC-MS/MS method for the determination of digoxin.Digoxin-d3 was taken as the internal standard (IS), and sample preparation was achieved by liquid-liquid extraction.Chromatographic separation was performed on a Kinetex C18 column (2.1 mm × 50 mm, 2.6 μm; Phenomenex) using an isocratic elution with merely 2 min for each sample.The mobile phase consisted of water and acetonitrile solutions, both containing 1 mmol/L ammonium acetate and 1 mmol/L formic acid (55∶45).The detection was conducted on a TripleQuadTM 4500MD mass spectrometer coupled with electrospray ionization interface under positive-ion multiple reaction monitoring mode.The transitions were m/z 798.5 → 651.3 and m/z 801.6 → 654.4 for digoxin and digoxin-d3, respectively.Results showed that the method was linear over the range of 0.100-20.0 ng/mL.The selectivity, accuracy and precision, recovery and stability of the method were all within the acceptable limits with no matrix effect.This method was successfully applied to a girl treated with digoxin with substantial improvement of therapeutic effect and elimination of toxic reaction, so it can provide valuable fuidance and reference for individualized medication in clinical practice.

Objective To apply color Doppler flow imaging (CDFI) and transcranial Doppler (TCD) to the follow-up observation of the changes of cervical vessel,intracranial hemodynamics and cerebrovascular reserve capacity (CVR) of the patients after carotid artery stent implantation.Methods Totally 96 patients with carotid artery stent implantation underwent CDFI and TCD examinations,and the changes of hemodynamics were compared before and 1 month,6 months,1 a and 2 a after implantation.Results The values of peak systolic velocity (PSV) and resistance index (RI) at the areas of carotid stenosis were lower significantly than those before implantation,while the values of PSV,pulsatility index (PI) and CVR of the middle cerebral artery were obviously higher than those before implantation (P＜0.05).There were no significant differences between the cervical and intracranial hemodynamics indexes 1 month,6 months,1 a and 2 a after treatment.Two-year follow-up found 4 cases of restenoses after implantation,and the rate for restenosis was 4.2％.Conclusion Carotid artery stent implantation improves significantly cervical and intracranial blood supply as well as CVR of the carotid stenosis patient,and CDFI combined with TCD can be used for the accurate evaluation of the efficacy and postoperative follow-up of carotid artery stent implantation.

Objective To explore the clinical efficacy and safety of recombinant human brain natriuretic peptide (rhBNP) in the treatment of acute heart failure(AHF) by observing the changes of hemodynamic parameters,cardiac function and inflammatory factors before and after treatment in the patients with AHF.Methods A total of 96 patients with AHF in our hospital from June 2012 to December 2015 were enrolled in this study and divided into the control group and observation group(n-48).The two groups were given the routine anti-heart failure treatment combined with sodium nitroprusside or rhBNP by intravenous dripping for 24 h.Fifteen cases were selected from each group for monitoring the hemodynamic change.The clinical effect was observed.The changes of heart rare,blood pressure,urine volume,cardiac function,plasma of NT-proBNP,IL-6 and hs-CRP before and after medication were observed.The occurrence of adverse reactions was also observed.Results The total effective rate of the observation group was significantly higher than that in the control group (P＜0.05).The PAP and PCWP at various time points after treatment in the observation group were significantly lower than those before treatment (P＜0.05).PAP and PCWP at various time points had statistical difference between two groups (P＜0.05).The levels of heart rate,systolic blood pressure,NT-proBNP,IL-6 and hsCRP levels after medication were significantly decreased in both groups,and the urine volume and LVEF were significantly increased (P＜0.05),and the difference between the two groups was statistically significant(P＜0.05).There was no statistically significant difference in the occurrence of adverse reactions between the two groups (P＞0.05).Conclusion The short-term efficacy of rhBNP in treating AHF is better than sodium nitroprusside,which can improve hemodynamics and cardiac function,reduces the level of inflammatory factors.

Objective To understand the prevalence of birth defects, related diseases and mental status of women during pregnancy in Shaanxi province and to analyse the major risk factors on birth defects and congenital heart disease. Possible association between maternal diseases or mental status and the risk of birth defects, was also explored. Methods A cross-sectional design was used in this study and stratified multistage random sampling method was used. The whole survey was from Jury 2013 to November 2013. Logistic regression method was used to analyze the association between maternal diseases, mental status during pregnancy and birth defects. Results The overall prevalence of birth defects was 195.04 per 10000 in Shaanxi. Among the 29121 mothers participating in this study, 51.1% developed illness and 6.8%"changed their mental status during pregnancy. After adjusting all the confounding factors, results showed that, histories of cold", fever, and intrahepatic cholestasis were (OR=1.33, 95%CI:1.10-1.61, OR=1.54, 95%CI:1.09-2.16, and OR=32.77, 95%CI:4.08-263.04) respectively, during pregnancy that related to birth defects. Self-reported unstable mental status (OR=1.60, 95%CI: 1.19-2.15) and family friction (OR=2.07, 95%CI: 1.12-3.79) were both related to the birth rates. Histories of cold and fever (OR=1.59, 95%CI:1.28-1.98;OR=1.43, 95%CI:1.48-4.00), during early pregnancy, unstable mental status during mid-pregnant period (OR=1.52, 95%CI:1.05-2.19), unstable mental status during late-pregnant period (OR=1.63, 95%CI:1.05-2.19) and family friction during late-pregnant period (OR=2.89, 95%CI:1.16-7.20) were found to be related to birth defects. Compared with those without history of cold, those with the history of cold during first (OR=1.24, 95%CI: 1.02-1.52) and second stages (OR=2.06, 95%CI: 1.30-3.26) of pregnancy were more likely to bear fetus with birth defects. Compared with those without these histories, those with histories of fever (OR=1.49, 95%CI:1.04-2.13), emotional problem (OR=1.71, 95%CI:1.19-2.45) and related diseases (OR=2.67, 95%CI: 1.32-5.39) during the first period of pregnancy were more likely to bear fetus with birth defects. Conclusion The incidence of birth defects in Shaanxi was high. Histories of cold, fever, unstable mental status and family friction during pregnancy, seemed to have increased the risks of bearing child with birth defects.