ObjectiveTo investigate the effect and mechanism of simvastatin pretreatment on kidney ischemia reperfusion injury （IRI） in mice. MethodsFifteen male C57BL/6 mice aged 6-8 weeks were divided into three groups： Sham operation group （Sham group）， kidney IRI group （IR group）， and simvastatin pretreatment+kidney IRI group （SIM group）. Hematoxylin-eosin （HE） staining of kidney tissue and detection of serum creatinine （SCr） and lactate dehydrogenase （LDH） were used to evaluate kidney injury. The levels of superoxide dismutase （SOD）， reduced glutathione （GSH）， malondialdehyde （MDA） and reactive oxygen species （ROS） were detected to evaluate oxidative stress. The contents of ferrous iron （Fe²⁺） and ferric iron （Fe³⁺） in kidney tissue were detected， and the morphological changes of mitochondria were observed by transmission electron microscope. The relative expression levels of Kruppel-like factor 2 （KLF2）， glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， and acyl-coa synthetase long chain family member 4 （ACSL4） protein in kidney tissue were detected. ResultsCompared with the IR group， the SIM group had significantly reduced renal tubular injury and decreased contents of Scr and LDH in serum （P < 0.001）. It also showed increased expression of SOD and GSH and decreased expression of MDA and ROS （P < 0.01）. Simvastatin pretreatment reduced the contents of Fe²⁺ and Fe³⁺ in the tissues （P < 0.01） and alleviated mitochondrial damage. It also promoted the expression of KLF2 （P < 0.01）， up-regulated the expression of ferroptosis-related protective proteins GPX4 and SLC7A11， and down-regulated the expression of ferroptosis-related damage protein ACSL4 （P < 0.05）. ConclusionSimvastatin pretreatment may inhibit kidney ferroptosis by promoting the expression of KLF2 to alleviate kidney IRI.

Sepsis is a clinical syndrome resulting from infection followed by inflammation and is one of the significant causes of mortality worldwide. The underlying reason is the host′s uncontrolled inflammatory response to an infection, which leads to multiple organ dysfunction. It not only aggravates the condition, but also leads to a poor prognosis. Neutrophils are involved in many physiological and pathological processes in the human body and are forerunners to reach the site of infection/inflammation for clearing the infection and resolute the inflammation during sepsis. In addition, under the stimulation of pathogens, neutrophils can release a special network structure containing a variety of protein components and DNA as the skeleton, which is named neutrophil extracellular traps (NETs). Although NETs can kill pathogens, excess NETs have a significant influence on the pathogenesis of sepsis-induced multiple organ damage, including lung, kidney, and liver damage. This review aims to introduce the role of NETs in sepsis and organ dysfunction, hoping to provide new ideas for the treatment of sepsis.

Glycogen storage disease type Ⅱ,also known as Pompe disease,is an autosomal recessive metabolic myopathy with pulmonary hypertension as a rare complication.We reported a case of pulmonary hypertension in adult with late-onset glycogen storage disease type Ⅱ.Her arterial blood gas results indicated type Ⅱ respiratory failure,lung function indicated severe restricted ventilation dysfunction,sleep monitoring indicated severe sleep apnea hypopnea,severe nocturnal hypoxemia,echocardiography-derived systolic pulmonary pressure was 62 mmHg(1 mmHg=0.133 kPa),electromyography indicated myogenic lesion,and whole exon sequencing indicated GAA gene mutation.Supportive therapy and enzyme replacement therapy are applied in this patient.

Objectives:To observe the effectiveness and safety of recombinant human brain natriuretic peptide(rhBNP)for the treatment of patients with right heart failure caused by pulmonary arterial hypertension(PAH).Methods:A total of 421 patients with right heart failure caused by PAH who were hospitalized in Fuwai Hospital from January 2019 to June 2024 were retrospectively included in this study.All patients were treated with rhBNP on top of conventional therapy.24 h urine volume,body weight,liver and renal function index,electrolyte,uric acid,red blood cell distribution width(RBCDW),cardiac function,blood pressure and heart rate before and after the treatment of rhBNP were compared.Clinical symptoms,signs and the occurrence of adverse events during treatment were also observed.Results:Compared with baseline,after treatment with rhBNP,the 24 h urine volume increased.The levels of body weight,transaminase,total bilirubin,direct bilirubin,uric acid,RBCDW,systolic blood pressure,heart rate,and N-terminal pro-B-type natriuretic peptide significantly decreased(all P<0.05).There were no statistically significant differences in the levels of serum creatinine,and tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio(both P>0.05).Dyspnea and lower limbs edema were improved in 75.2%cases(227/302)and 66.9%cases(281/420)respectively.The incidence of adverse events and severe adverse events during rhBNP treatment were 1.2%(5/421)and 0.5%(2/421)respectively.Conclusions:Adding rhBNP on top of standard medication can effectively increase 24 h urine volume,reduce body weight,improve some prognostic indicators,improve the clinical symptoms and signs of heart failure without negatively affecting the renal function in right heart failure patients caused by PAH.Blood pressure should be closely monitored during the treatment process.

Chronic thromboembolic pulmonary hypertension is characterised by the persistent obstruction of the proximal pulmonary arteries by organized thrombi and peripheral microvascular disease,which can lead to right-sided heart failure and mortality.Pulmonary endarterectomy enables complete removal of visible obstructive elements within the pulmonary arteries and is recommended for operable patients.Nevertheless,over 40%of patients are precluded from pulmonary endarterectomy because of factors such as surgically inaccessible lesions,compromised general health status,or concurrent comorbidities or still with residual pulmonary hypertension after pulmonary endarterectomy.For inoperable patients or those with residual pulmonary hypertension after pulmonary endarterectomy,balloon pulmonary angioplasty is an effective therapeutic option,which could significantly improve the hemodynamic,exercise tolerance and outcome of the patients.With the emerging accumulation of clinical experience and evidence,2022 European Society of Cardiology/European Respiratory Society guidelines of pulmonary hypertension recommend balloon pulmonary angioplasty as an alternative therapeutic option for these patients.However,different types of lesions may have their own lesion characteristics,the strategy and device of balloon pulmonary angioplasty should thus be individually considered for different lesions,in fact,the success rate of treatment and the incidence rate of complications are varied significantly.Therefore,the aim of this review is to comprehensively summarize the existing studies on balloon pulmonary angioplasty treatment strategies for different types of lesions and the management of complications to provide guidance and reference for clinicians.

OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of a family with Dentinogenesis imperfecta type Ⅰ(DGI-Ⅰ). METHODS: Clinical data were collected from a patient with DGI-Ⅰ admitted to the Reproductive Medicine Department of the Affiliated Hospital of Jining Medical University in March 2024. Clinical and familial data were retrospectively collected. Peripheral blood samples (5 mL each) were obtained from the proband and her family members for genomic DNA extraction, followed by whole-exome sequencing (WES) and Sanger sequencing validation. The pathogenicity of the detected variants was assessed according to the Classification Standards and Guidelines for Genetic Variants formulated by the American Society of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines"). The study was approved by the Ethics Committee of the Affiliated Hospital of Jining Medical University (Ethics No. 2024-08-C012), and written informed consent for clinical research were obtained from all participants. RESULTS: The proband, a 35-year-old female, presented with translucent yellow primary teeth and progressive browning, darkening, and loss of permanent teeth, without skeletal abnormalities. Affected family members exhibited similar phenotypes. Genetic testing revealed a heterozygous COL1A2 variant (c.1503+1G>A) in the patient and other affected members, while unaffected family members all lacked this variant. Based on the ACMG Guidelines, this variant was classified as likely pathogenic (PM4 + PP1_Strong + PM2_Supporting). CONCLUSION The COL1A2 c.1503+1G>A heterozygous variant is the disease-causing mutation in this family. Above finding has expanded the mutational spectrum of the COL1A2 gene and provided a basis for genetic counseling and diagnosis in similar cases.
Humans ; Female ; Dentinogenesis Imperfecta/genetics* ; Collagen Type I/genetics* ; Adult ; Pedigree ; Mutation ; Male ; Phenotype ; Exome Sequencing

AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.

Objective:To investigate the clinical phenotype and genetic characteristics of a family with Dentinogenesis imperfecta type Ⅰ(DGI-Ⅰ).Methods:Clinical data were collected from a patient with DGI-Ⅰ admitted to the Reproductive Medicine Department of the Affiliated Hospital of Jining Medical University in March 2024. Clinical and familial data were retrospectively collected. Peripheral blood samples (5 mL each) were obtained from the proband and her family members for genomic DNA extraction, followed by whole-exome sequencing (WES) and Sanger sequencing validation. The pathogenicity of the detected variants was assessed according to the Classification Standards and Guidelines for Genetic Variants formulated by the American Society of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the " ACMG Guidelines" ). The study was approved by the Ethics Committee of the Affiliated Hospital of Jining Medical University (Ethics No. 2024-08-C012), and written informed consent for clinical research were obtained from all participants.Results:The proband, a 35-year-old female, presented with translucent yellow primary teeth and progressive browning, darkening, and loss of permanent teeth, without skeletal abnormalities. Affected family members exhibited similar phenotypes. Genetic testing revealed a heterozygous COL1A2 variant (c.1503+ 1G>A) in the patient and other members, while unaffected family all members lacked this variant. Based on the ACMG Guidelines, this variant was classified as likely pathogenic(PM4 + PP1_Strong + PM2_Supporting). Conclusion:The COL1A2 c. 1503+ 1G>A heterozygous variant is the disease-causing mutation in this family. Above finding has expanded the mutational spectrum of the COL1A2 gene and provided a basis for genetic counseling and diagnosis in similar cases.

AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.

Glycogen storage disease type Ⅱ,also known as Pompe disease,is an autosomal recessive metabolic myopathy with pulmonary hypertension as a rare complication.We reported a case of pulmonary hypertension in adult with late-onset glycogen storage disease type Ⅱ.Her arterial blood gas results indicated type Ⅱ respiratory failure,lung function indicated severe restricted ventilation dysfunction,sleep monitoring indicated severe sleep apnea hypopnea,severe nocturnal hypoxemia,echocardiography-derived systolic pulmonary pressure was 62 mmHg(1 mmHg=0.133 kPa),electromyography indicated myogenic lesion,and whole exon sequencing indicated GAA gene mutation.Supportive therapy and enzyme replacement therapy are applied in this patient.