Objective:To explore the significance of genetic diagnosis, clinical characteristics and treatment of congenital renal diabetes insipidus with arginine vasopressin receptor 2 ( AVPR2). Methods:Clinical data of three patients diagnosed as diabetes insipidus were retrospectively analyzed.Results:The three cases were 3-month, 5-month and 6-month male infants, respectively. The main manifestations were repeated fever and growth retardation with hypernatremia. Polydipsia, polyuria and persistent hypogravity uria appeared during the course . In case 1, the AVPR2 exon c.613_c.614del resulted in amino acid change p.Y205Cfs*53. The proband mother was a mutation carrier of AVPR2 gene, and the child was hemizygous and the mother was heterozygous. In case 2, there was a hemizygotic mutation in AVPR2 gene: c.255C>A(p.SP85Glu), which appeared to be a missense mutation. The father had no mutation, the mother had a heterozygous mutation, the aunt had no mutation, and the eldest brother had a hemizygous mutation. There was one hemizygotic variation in the AVPR2 gene in patient 3: c.167G>A(P.LY56ASP), which was a missense mutation. The father had no mutation, the mother had a heterozygous mutation. The minimum allele frequencies of the gene variants in case 2 and case 3 were not recorded in the reference population gene frequency database. The urine volume of 3 children was significantly reduced after treatment with hydrochlorothiazide and amiloride.After genetic test, all three cases were diagnosed as congenital renal diabetes insipidus caused by AVPR2 gene mutation. Conclusion:Genetic testing benefits to the early diagnosis of congenital renal diabetes insipidus.

Objective To investigate the presumed correlation between lactate level and clearance during extracorporeal life support(ECLS)and death in elderly cardiac intensive care patients.Methods A total of 93 elderly cardiac intensive care patients who received ECLS in Department of Critical Care Medicine,Xiangya Medical College Affiliated Changsha Hospital,Central South University,from March 2019 to October 2024 were retrospectively included to manage low cardiac production syndrome after major cardiac surgery.According to hospital outcomes,the patients were divided into a death group(n=45)and a survival group(n=48).Blood lactate measurements were performed every 4 hours from the beginning of ECLS treatment to calculate peak lactate and lactate clearance rate(LCR).Routine ICU scores,such as sequential organ failure score(SOFA)and reactive organ dysfunction(ROD)score,and postoperative complications were recorded.Results The death group received larger amounts of packed red blood cell concentrate,fresh frozen plasma and platelet concentrate,and exhibited higher ratios of norepinephrine and epinephrine administration and higher incidences of re-thoracotomy and hemolytic episodes when compared with the survival group(P＜0.05,P＜0.01).At the end of ECLS,higher SOFA and ROD scores were observed in the death group(P＜0.01).The death group also demonstrated higher lactate level from venoarterial ECLS(P＜0.001)and increased median peak lactate level,but lower median LCR than the survival group(P＜0.01).Multivariate logistic analysis showed that peak lactate and LCR were independent prognostic factors in the elderly cardiac ICU patients(P＜0.05,P＜0.01).The AUC value(95％CI)of peak lactate and LCR in predicting patient outcomes was 0.723(95％CI:0.615-0.831)and 0.846(95％CI:0.761-0.932),respectively,and the value of their combination in predicting in-hospital death was 0.846(95％CI:0.762-0.931),with a sensitivity of 0.629 and a specificity of 0.937.Conclusion Lactate level and its clearance rate during ECLS can affect the survival rate of elderly cardiac intensive care patients.Peak lactate and LCR can predict the prognosis of elderly cardiac intensive care patients,and can be used as prognostic indicators for clinical monitoring.

Objective To investigate the role and mechanism of AMP-activated protein kinase(AMPK)in regulating mitochondrial function and cardiomyocyte injury in sepsis.Methods Forty Balb/c mice were randomly divided into four groups:Sham group(n=10),Sham+5-aminoimidazole-4-carboxamide ribonucleotide(AICAR)group(n=10),CLP group(n=10),and CLP+AICAR group(n=10).A sepsis mouse model was established through cecal ligation and puncture(CLP).Echocardiography and histological analysis were used to assess sepsis-induced cardiac injury.Neonatal rat cardiomyocytes(NRCMs)were incubated with lipopolysaccharide(LPS)(10 μg/mL)for 24 h to induce an in vitro sepsis model,and treated with AICAR.Mitochondrial function and dynamics were assessed by using Western blotting,enzyme-linked immunosorbent assay(ELISA),and immunofluorescence assays.Results Compared with the Sham group,AMPK expression in the myocardial tissue of CLP mice was significantly reduced(P<0.05).Compared with the CLP group,AMPK expression in the CLP+AICAR group was significantly increased(P<0.05).Survival analysis showed that CLP led to a high mortality rate(～60％ ),while AICAR treatment significantly improved the survival rate of CLP mice(P<0.05).Compared with the Sham group,cardiac output(CO),stroke volume(SV),and left ventricular end-diastolic volume(LVEDV)were significantly decreased in the CLP group(P<0.05),while left ventricular posterior wall systolic(LVPWs)and left ventricular posterior wall thickness(LVPWd)were significantly increased(P<0.05).AICAR treatment alleviated the cardiac dysfunction induced by CLP.Compared with the CLP group,mitochondrial size and the number of mitochondrial cristae in the myocardial tissue of CLP+AICAR group mice were significantly increased(P<0.05),while DHE fluorescence intensity and the number of TUNEL-positive cells were significantly reduced(P<0.05).Compared with the LPS group,ATP production,mitochondrial respiration rate,and complex Ⅰ,Ⅱ,and Ⅲ activities in NRCMs of the LPS+AICAR group were significantly increased(P<0.05),while mitochondrial and cytoplasmic ROS levels were significantly reduced(P<0.05).Compared with the control group,mitochondrial size in NRCMs of the LPS group was significantly reduced(P<0.05),while Bax and Caspase-3 expression,as well as mitochondrial fission index,were significantly increased(P<0.05),and these changes were mitigated by AICAR(P<0.05).Conclusion AMPK plays a crucial role in maintaining cardiac function and mitigating septic myocardial injury by regulating mitochondrial structure and function,energy metabolism,oxidative stress,and apoptosis.

Objective To evaluate the prognostic value of syndecan-1,VE-cadherin,and neuron-specific enolase(NSE)in elderly patients with sepsis-associated encephalopathy(SAE).Methods Elderly patients with septic shock admitted to the ICU of the First Hospital of Changsha between January 2022 and August 2024 were enrolled in this study.Serum levels of syndecan-1,VE-cadherin,and NSE were measured on the first and third days following ICU admission in these elderly patients with septic shock.The optimal cut-off values,sensitivity,and specificity of syndecan-1,VE-cadherin,and NSE for predicting SAE were further analyzed.Results Ninety-six elderly patients with septic shock were enrolled in this study,comprising 40 cases in the SAE group and 56 cases in the non-SAE group.Sequential organ failure assessment scores,acute physiology and chronic health evaluation scores,and 28-day mortality rates were significantly higher in the SAE group compared to the non-SAE group(P<0.05).The serum levels of syndecan-1,VE-cadherin,and NSE on both the first and third days were significantly elevated in the SAE group compared to the non-SAE group(P<0.05).Elevated serum levels of syndecan-1,VE-cadherin,and NSE on the third day were identified as independent risk factors for SAE.On the third day,serum syndecan-1 levels(AUC=0.798,95%CI:0.709～0.886,optimal cutoff=160.80 ng/mL,sensitivity=71.43%,specificity=72.50%),serum VE-cadherin levels(AUC=0.847,95%CI:0.768～0.927,optimal cut-off=2,429.00 ng/mL,sensitivity=78.57%,specificity=82.50%),and serum NSE levels(AUC=0.765,95%CI:0.670～0.861,optimal cutoff=14.24 ng/mL,sensitivity=53.57%,specificity=92.50%)were all effective predictors of SAE.Notably,the combination of syndecan-1,VE-cadherin,and NSE(AUC=0.877,95%CI:0.806～0.949,sensitivity=85.71%,specificity=80.00%)demonstrated superior performance in predicting SAE.Conclusions Secondary SAE in elderly patients with septic shock is closely associated with blood-brain barrier dysfunction and brain injury.The serum levels of syndecan-1,VE-cadherin,and NSE on the third day demonstrated significant predictive value for SAE.Moreover,the combined assessment of syndecan-1,VE-cadherin,and NSE exhibited superior performance in predicting SAE.

Objective To evaluate the prognostic value of syndecan-1,VE-cadherin,and neuron-specific enolase(NSE)in elderly patients with sepsis-associated encephalopathy(SAE).Methods Elderly patients with septic shock admitted to the ICU of the First Hospital of Changsha between January 2022 and August 2024 were enrolled in this study.Serum levels of syndecan-1,VE-cadherin,and NSE were measured on the first and third days following ICU admission in these elderly patients with septic shock.The optimal cut-off values,sensitivity,and specificity of syndecan-1,VE-cadherin,and NSE for predicting SAE were further analyzed.Results Ninety-six elderly patients with septic shock were enrolled in this study,comprising 40 cases in the SAE group and 56 cases in the non-SAE group.Sequential organ failure assessment scores,acute physiology and chronic health evaluation scores,and 28-day mortality rates were significantly higher in the SAE group compared to the non-SAE group(P<0.05).The serum levels of syndecan-1,VE-cadherin,and NSE on both the first and third days were significantly elevated in the SAE group compared to the non-SAE group(P<0.05).Elevated serum levels of syndecan-1,VE-cadherin,and NSE on the third day were identified as independent risk factors for SAE.On the third day,serum syndecan-1 levels(AUC=0.798,95%CI:0.709～0.886,optimal cutoff=160.80 ng/mL,sensitivity=71.43%,specificity=72.50%),serum VE-cadherin levels(AUC=0.847,95%CI:0.768～0.927,optimal cut-off=2,429.00 ng/mL,sensitivity=78.57%,specificity=82.50%),and serum NSE levels(AUC=0.765,95%CI:0.670～0.861,optimal cutoff=14.24 ng/mL,sensitivity=53.57%,specificity=92.50%)were all effective predictors of SAE.Notably,the combination of syndecan-1,VE-cadherin,and NSE(AUC=0.877,95%CI:0.806～0.949,sensitivity=85.71%,specificity=80.00%)demonstrated superior performance in predicting SAE.Conclusions Secondary SAE in elderly patients with septic shock is closely associated with blood-brain barrier dysfunction and brain injury.The serum levels of syndecan-1,VE-cadherin,and NSE on the third day demonstrated significant predictive value for SAE.Moreover,the combined assessment of syndecan-1,VE-cadherin,and NSE exhibited superior performance in predicting SAE.

Objective To investigate the role and mechanism of AMP-activated protein kinase(AMPK)in regulating mitochondrial function and cardiomyocyte injury in sepsis.Methods Forty Balb/c mice were randomly divided into four groups:Sham group(n=10),Sham+5-aminoimidazole-4-carboxamide ribonucleotide(AICAR)group(n=10),CLP group(n=10),and CLP+AICAR group(n=10).A sepsis mouse model was established through cecal ligation and puncture(CLP).Echocardiography and histological analysis were used to assess sepsis-induced cardiac injury.Neonatal rat cardiomyocytes(NRCMs)were incubated with lipopolysaccharide(LPS)(10 μg/mL)for 24 h to induce an in vitro sepsis model,and treated with AICAR.Mitochondrial function and dynamics were assessed by using Western blotting,enzyme-linked immunosorbent assay(ELISA),and immunofluorescence assays.Results Compared with the Sham group,AMPK expression in the myocardial tissue of CLP mice was significantly reduced(P<0.05).Compared with the CLP group,AMPK expression in the CLP+AICAR group was significantly increased(P<0.05).Survival analysis showed that CLP led to a high mortality rate(～60％ ),while AICAR treatment significantly improved the survival rate of CLP mice(P<0.05).Compared with the Sham group,cardiac output(CO),stroke volume(SV),and left ventricular end-diastolic volume(LVEDV)were significantly decreased in the CLP group(P<0.05),while left ventricular posterior wall systolic(LVPWs)and left ventricular posterior wall thickness(LVPWd)were significantly increased(P<0.05).AICAR treatment alleviated the cardiac dysfunction induced by CLP.Compared with the CLP group,mitochondrial size and the number of mitochondrial cristae in the myocardial tissue of CLP+AICAR group mice were significantly increased(P<0.05),while DHE fluorescence intensity and the number of TUNEL-positive cells were significantly reduced(P<0.05).Compared with the LPS group,ATP production,mitochondrial respiration rate,and complex Ⅰ,Ⅱ,and Ⅲ activities in NRCMs of the LPS+AICAR group were significantly increased(P<0.05),while mitochondrial and cytoplasmic ROS levels were significantly reduced(P<0.05).Compared with the control group,mitochondrial size in NRCMs of the LPS group was significantly reduced(P<0.05),while Bax and Caspase-3 expression,as well as mitochondrial fission index,were significantly increased(P<0.05),and these changes were mitigated by AICAR(P<0.05).Conclusion AMPK plays a crucial role in maintaining cardiac function and mitigating septic myocardial injury by regulating mitochondrial structure and function,energy metabolism,oxidative stress,and apoptosis.

Objective:To explore the significance of genetic diagnosis, clinical characteristics and treatment of congenital renal diabetes insipidus with arginine vasopressin receptor 2 ( AVPR2). Methods:Clinical data of three patients diagnosed as diabetes insipidus were retrospectively analyzed.Results:The three cases were 3-month, 5-month and 6-month male infants, respectively. The main manifestations were repeated fever and growth retardation with hypernatremia. Polydipsia, polyuria and persistent hypogravity uria appeared during the course . In case 1, the AVPR2 exon c.613_c.614del resulted in amino acid change p.Y205Cfs*53. The proband mother was a mutation carrier of AVPR2 gene, and the child was hemizygous and the mother was heterozygous. In case 2, there was a hemizygotic mutation in AVPR2 gene: c.255C>A(p.SP85Glu), which appeared to be a missense mutation. The father had no mutation, the mother had a heterozygous mutation, the aunt had no mutation, and the eldest brother had a hemizygous mutation. There was one hemizygotic variation in the AVPR2 gene in patient 3: c.167G>A(P.LY56ASP), which was a missense mutation. The father had no mutation, the mother had a heterozygous mutation. The minimum allele frequencies of the gene variants in case 2 and case 3 were not recorded in the reference population gene frequency database. The urine volume of 3 children was significantly reduced after treatment with hydrochlorothiazide and amiloride.After genetic test, all three cases were diagnosed as congenital renal diabetes insipidus caused by AVPR2 gene mutation. Conclusion:Genetic testing benefits to the early diagnosis of congenital renal diabetes insipidus.

Objective To investigate the presumed correlation between lactate level and clearance during extracorporeal life support(ECLS)and death in elderly cardiac intensive care patients.Methods A total of 93 elderly cardiac intensive care patients who received ECLS in Department of Critical Care Medicine,Xiangya Medical College Affiliated Changsha Hospital,Central South University,from March 2019 to October 2024 were retrospectively included to manage low cardiac production syndrome after major cardiac surgery.According to hospital outcomes,the patients were divided into a death group(n=45)and a survival group(n=48).Blood lactate measurements were performed every 4 hours from the beginning of ECLS treatment to calculate peak lactate and lactate clearance rate(LCR).Routine ICU scores,such as sequential organ failure score(SOFA)and reactive organ dysfunction(ROD)score,and postoperative complications were recorded.Results The death group received larger amounts of packed red blood cell concentrate,fresh frozen plasma and platelet concentrate,and exhibited higher ratios of norepinephrine and epinephrine administration and higher incidences of re-thoracotomy and hemolytic episodes when compared with the survival group(P＜0.05,P＜0.01).At the end of ECLS,higher SOFA and ROD scores were observed in the death group(P＜0.01).The death group also demonstrated higher lactate level from venoarterial ECLS(P＜0.001)and increased median peak lactate level,but lower median LCR than the survival group(P＜0.01).Multivariate logistic analysis showed that peak lactate and LCR were independent prognostic factors in the elderly cardiac ICU patients(P＜0.05,P＜0.01).The AUC value(95％CI)of peak lactate and LCR in predicting patient outcomes was 0.723(95％CI:0.615-0.831)and 0.846(95％CI:0.761-0.932),respectively,and the value of their combination in predicting in-hospital death was 0.846(95％CI:0.762-0.931),with a sensitivity of 0.629 and a specificity of 0.937.Conclusion Lactate level and its clearance rate during ECLS can affect the survival rate of elderly cardiac intensive care patients.Peak lactate and LCR can predict the prognosis of elderly cardiac intensive care patients,and can be used as prognostic indicators for clinical monitoring.

Objective To explore the curative effect of hydrocortisone ascorbic acid,vitamin C and vitamin B1(HAT)therapy on septic shock and its influence on the time of vasoactive drug application,hemodynamic parameters and short-term prognosis.Methods According to different treatment plans,92 patients with septic shock were divided into the HAT group and the routine treatment group,46 cases in each group.The routine treatment group was given routine treatments[anti-infection,fluid replacement,stabling blood pressure and continuous renal replacement therapy(CRRT)],while the HAT group was additionally given HAT therapy.All patients were treated continuously for 3 d.The indexes related the curative effect,scores of acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)and sequential organ failure assessment(SOFA),levels of mean arterial pressure(MAP),heart rate(HR),central arterial pressure(CAP),D-lactic acid(D-Lac),creatinine(Cr),hypersensitive C-reactive protein(hs-CRP)and procalcitonin(PCT)before and after treatment,incidence of adverse reactions and 28 d survival rate by follow-up were compared between the two groups.Results The circulation stabilization time,use time of vasoactive drugs and hormones,mechanical ventilation time,CRRT time,treatment time in ICU and total hospitalization time were shorter in the HAT group than those in the routine treatment group(P<0.05).After 7 d of treatment,scores of APACHE Ⅱ and SOFA,levels of HR,D-Lac,Cr,hs-CRP and PCT were lower in the HAT group than those in the routine treatment group,while MAP and CAP were higher than those in the routine treatment group(P<0.05).The 28-day survival rate was 65.22％in the HAT group,which was higher than that in the routine treatment group(45.65％,P<0.05).Conclusion HAT therapy can improve clinical curative effect in patients with septic shock,shorten use time of vasoactive drugs,improve hemodynamic parameters and short-term prognosis.

Systemic juvenile idiopathic arthritis is one of the common rheumatic and immune diseases in children. It has a sudden onset, obvious systemic symptoms, and lung involvement. However, systemic juvenile idiopathic arthritis with an early manifestation of pulmonary ground-glass opacities combined with macrophage activation syndrome is rare. The clinical data of a child with systemic juvenile idiopathic arthritis with pulmonary ground-glass shadow and macrophage activation syndrome who was admitted to Hubei Maternal and Child Health Care Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology in December 2021 were analyzed retrospectively in order to improve the understanding of rheumatic diseases and pulmonary lesions. The child was admitted to the hospital for 10 days due to rash and fever. Thoracic CT showed scattered ground glass like shadows in both lungs due to the prevention and control screening of COVID-19 pneumonia epidemic situation. After admission, the child was still repeatedly flaccid with high fever, accompanied by dysfunction of both lower limbs. The knee joint MRI found that there was synovitis in the knee joint, and various laboratory indicators suggested macrophage activation syndrome. After that, systemic juvenile idiopathic arthritis was diagnosed. After being treated with methylprednisolone, cyclosporine and topzumab, the clinical remission and the ground-glass shadow of the lung basically disappeared. Through the analysis of this case, it is suggested that clinicians should not ignore other diseases that cause ground glass shadow in the lung during the current epidemic of COVID-19.