OBJECTIVE: To assess the relationship between blood pressure reactivity index (BPRI) and in-hospital mortality risk in patients with sepsis-associated acute kidney injury (SA-AKI). METHODS: A retrospective cohort study was conducted to collect data from patients admitted to the intensive care unit (ICU) and clinically diagnosed with SA-AKI between 2008 and 2019 in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database in the United States. The collected data included demographic characteristics, comorbidities, vital signs, laboratory parameters, sequential organ failure assessment (SOFA) and simplified acute physiology scoreII(SAPSII) within 48 hours of SA-AKI diagnosis, stages of AKI, treatment regimens, mean BPRI during the first and second 24 hours (BPRI_0_24, BPRI_24_48), and outcome measures including primary outcome (in-hospital mortality) and secondary outcomes (ICU length of stay and total hospital length of stay). Variables with statistical significance in univariate analysis were included in LASSO regression analysis for variable selection, and the selected variables were subsequently incorporated into multivariate Logistic regression analysis to identify independent predictors associated with in-hospital mortality in SA-AKI patients. Restricted cubic spline (RCS) analysis was employed to examine whether there was a linear relationship between BPRI within 48 hours and in-hospital mortality in SA-AKI patients. Basic prediction models were constructed based on the independent predictors identified through multivariate Logistic regression analysis, and receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive performance of each basic prediction model before and after incorporating BPRI. RESULTS: A total of 3 517 SA-AKI patients admitted to the ICU were included, of whom 826 died during hospitalization and 2 691 survived. The BPRI values within 48 hours of SA-AKI diagnosis were significantly lower in the death group compared with the survival group [BPRI_0_24: 4.53 (1.81, 8.11) vs. 17.39 (5.16, 52.43); BPRI_24_48: 4.76 (2.42, 12.44) vs. 32.23 (8.85, 85.52), all P < 0.05]. LASSO regression analysis identified 20 variables with non-zero coefficients that were included in the multivariate Logistic regression analysis. The results showed that respiratory rate, temperature, pulse oxygen saturation (SpO₂), white blood cell count (WBC), hematocrit (HCT), activated partial thromboplastin time (APTT), lactate, oxygenation index, SOFA score, fluid balance (FB), BPRI_0_24, and BPRI_24_48 were all independent predictors for in-hospital mortality in SA-AKI patients (all P < 0.05). RCS analysis revealed that both BPRI showed "L"-shaped non-linear relationships with the risk of in-hospital mortality in SA-AKI patients. When BPRI_0_24 ≤ 14.47 or BPRI_24_48 ≤ 24.21, the risk of in-hospital mortality in SA-AKI increased as BPRI values decreased. Three basic prediction models were constructed based on the identified independent predictors: Model 1 (physiological indicator model) included respiratory rate, temperature, SpO₂, and oxygenation index; Model 2 (laboratory indicator model) included WBC, HCT, APTT, and lactate; Model 3 (scoring indicator model) included SOFA score and FB. ROC curve analysis showed that the predictive performance of the basic models ranked from high to low as follows: Model 3, Model 2, and Model 1, with area under the curve (AUC) values of 0.755, 0.661, and 0.655, respectively. The incorporation of BPRI indicators resulted in significant improvement in the discriminative ability of each model (all P < 0.05), with AUC values increasing to 0.832 for Model 3+BPRI, 0.805 for Model 2+BPRI, and 0.808 for Model 1+BPRI. CONCLUSIONS BPRI is an independent predictor factor for in-hospital mortality in SA-AKI patients. Incorporating BPRI into the prediction model for in-hospital mortality risk in SA-AKI can significantly improve its predictive capability.
Humans ; Acute Kidney Injury/mortality* ; Sepsis/complications* ; Retrospective Studies ; Hospital Mortality ; Prognosis ; Blood Pressure ; Intensive Care Units ; Male ; Female ; Length of Stay ; Middle Aged ; Aged ; Adult ; Logistic Models

Objective To observe the therapeutic effect and mechanism of allicin on uremic-induced myocardial injury in rats.Methods Twenty-four rats were randomly divided into sham-operated group,model group,and low-,and high-dose allicin groups,with six rats in each group.Except for the sham-operated group,the uremic-induced myocardial injury model was constructed using the 5/6 nephrectomy method in all other groups of rats.After successful modeling,corresponding interventions were carried outed.At the end of the intervention,the renal function of rats was observed,the cardiac mass index was calculated,the levels of serum high-sensitive cardiac troponinⅠ(hs-cTnI)and creatine kinase isoenzyme(CK-MB)were detected by enzyme-linked immunosorbent assay(ELISA),the pathological changes of rat cardiac tissues were observed by hematoxylin-eosin(HE)staining,the changes of autophagosomes and autolysosomes were observed by transmission electron microscopy,and the protein expressions of PTEN-induced putative kinase 1(PINK1)and E3 ubiquitin protein ligase(Parkin)in myocardial tissues were detected by Western Blot.Results Compared with the sham-operated group,the serum creatinine(SCr),blood urine nitrogen(BUN),cardiac mass index,CK-MB and hs-cTnI in rats in the model group were elevated(P<0.05),the pathological damage of cardiac tissues were obvious,and the autophagosomes and autolysosomes were decreased,and PINK1 and Parkin protein expressions in myocardial tissues were decreased(P<0.05);compared with the model group,SCr,BUN,cardiac mass index,CK-MB and hs-cTnI in allicin low-and hogh-dose groups were decreased,the changes of pathological damage of cardiac tissues were relieved,the autophagosomes and autolysosomes were increased,and PINK1 and Parkin protein expressions in myocardial tissues were increased(P<0.05).Conclusion Allicin can reduce myocardial injury in uremic rats,and its mechanism may be related to the up-regulation of PINK1/Parkin-mediated mitochondrial autophagy.

Myocardial injury is the leading cause of death in uremic patients.PINK 1/Parkin-mediated mitochondrial autophagy is involved in the progression of myocardial injury.In recent years,pathogenic turbidity has been gradually accepted as a representative of a new type of toxic pathogens by the researchers of traditional Chinese medicine(TCM).This paper sorts out literature about pathogenic turbidity,analyzes the etiological and pathogenic characteristics of pathogenic turbidity,and suggests that the pathogenesis of uremia-induced myocardial injury can be more comprehensively clarified from the perspective of healthy-qi deficiency resulting in latent pathogenic turbidity.In the patients with uremia,the down-regulation of PINK1/Parkin causes the weakening of mitochondrial autophagy,which leads to the elevation of levels of reactive oxygen species(ROS)and inflammatory factors,and eventually causes the injury of myocardial cell.The above pathogenic mechanism is similar to the process of traditional Chinese medicine(TCM)in which the deficiency of the healthy-qi(in particular kidney deficiency)results in the production of the pathogenic turbidity(showing as dampness,blood stasis,phlegm,toxin and so on)and then causes the pathogenic turbidity hide in vessels and collaterals and gradually injure the heart vessels,and eventually results in the deficiency of heart vessels.The mitochondrial autophagy mechanism mediated by the PINK1/Parkin pathway is suitalbe for explaining the TCM pathogenesis of uremia-induced myocardial injury,characterized by healthy-qi deficiency resulting in latent pathogenic turbidity,and also is suitable for interpretating the principle of supporting healthy-qi to eliminate pathogenic turbidity for treating uremia-induced myocardial injury.Under the guidance of the theory of health y-qi deficiency and turbid pathogens in TCM,the development of specific PINK 1/Parkin agonists may expand the approach for the treatment of uremia-induced myocardial injury.

Objective To investigate the role and prognostic value of matrix metalloproteinase-7(MMP7)in the migration and immune cell infiltration of hepatocellular carcinoma.Methods MMP7_siRNA for downregulating the target gene MMP7 and pMMP7 for upregulating MMP7 were constructed and were used to transfect hepatocellular carcinoma cell line(MHCC97H).RT-qPCR and Western Blot were used to measure the mRNA and protein expression levels of the target gene in cells.Scanning electron microscopy and Transwell assay were used to observe the changes in cell pseudopodia and migration ability,and bioinformatics methods were used to investigate the correlation of MMP7 with immune cells and immune infiltration score in TCGA and TIMER databases in patients with hepatocellular carcinoma,as well as the association between MMP7 and the prognosis of patients with hepatocellular carcinoma.The Spearman method was used for correlation analysis.Sanger Box online tool was used to assess the value of MMP7 in the overall survival curve and disease-specific survival of hepatocellular carcinoma.The Kaplan-Meier method was used to plot survival curves,and the Log-rank test was used for comparison of prognosis between different samples.Results After MHCC97H cells were transfected with MMP7_siRNA or pMMP7,there was a significant reduction or increase in the expression of the target gene MMP7;after downregulation of MMP7,there were significant reductions in the number and length of the pseudopodia,while after MMP7 overexpression,there were significant increases in the number and length of filopodia with radial arrangement.The Transwell chamber assay showed that MMP7_siRNA2 significantly reduced the migration ability of cells(P<0.05),and there was a significant increase in migration ability after pMMP7 transfection.The expression of MMP7 was significantly correlated with B lymphocytes(r=0.37,P<0.05),CD4+T lymphocytes(r=0.40,P<0.05),neutrophils(r=0.49,P<0.05),macrophages(r=0.49,P<0.05),and dendritic cells(r=0.47,P<0.05).In the TCGA database,the patients with hepatocellular carcinoma were divided into MMP7 high expression group with 267 patients and MMP7 low expression group with 146 patients based on overall survival,and the results showed that the MMP7 high expression group had a significantly shorter overall survival time than the MMP7 low expression group(P<0.05);based on the disease-specific survival time,the patients were divided into MMP7 high expression group with 257 patients and MMP7 low expression group with 145 patients,and the analysis showed that the MMP7 high expression group also had a significantly shorter disease-specific survival time than the MMP7 low expression group(P<0.05).Conclusion MMP7 promotes the migration of hepatocellular carcinoma cells and plays a major role in immune cell infiltration,and the expression of MMP7 is also significantly associated with the prognosis of hepatocellular carcinoma.

Objective:To explore the clinical characteristics and genetic basis for a child with global developmental delay and autism.Methods:A child who had presented at West China Second University Hospital of Sichuan University on April 13, 2021 was selected as the study subject. Clinical manifestations, laboratory examination and result of genetic testing were analyzed.Results:The main symptoms of the child had included cognitive, language and motor delay, autism and epilepsy. Electroencephalogram revealed multiple focal discharges in both waking and sleeping stages, with the remarkable one seen at the sleeping stage. Cranial MRI showed pachygyria and local cortical thickening, Whole exome sequencing (WES) revealed that the child has harbored a heterozygous c. 1589_1595dup (p.Gly533Leufs*143) frameshifting variant in the TBR1 gene (OMIM 604616). Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PS2+ PVS1_Supporting+ PM2_Supporting). After treated with levetiracetam and rehabilitation training, the child did not have seizure in the past 5 months, and his motor development has also significantly improved. Conclusion:The c. 1589_1595dup variant of the TBR1 gene probably underlay the disease in this patient.

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment.However,the sensitivity of existing detection techniques is not sufficient,and the criteria for evaluating optimal force have not been yet established.Here,by employing 3D finite element analysis methodology,we found that the apical distal region(A-D region)of mesial roots is particularly sensitive to orthodontic force in rats.Tartrate-resistant acidic phosphatase(TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams(g),leading to alveolar bone resorption and tooth movement.When the force reached 80 g,TRAP-positive osteoclasts started appearing on the root surface in the A-D region.Additionally,micro-computed tomography revealed a significant root resorption at 80 g.Notably,the A-D region was identified as a major contributor to whole root resorption.It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement,inclination,and hyalinization.These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model.Collectively,our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients'orthodontic treatment.

Objective:To systematically evaluate the effect of different durations of prone ventilation on the efficacy of patients with acute respiratory distress syndrome (ARDS).Methods:A computer search was conducted in databases including PubMed, Cochrane Library, Embase, CNKI, Wanfang Database, VIP Database, and China Biomedical Literature Database for studies on prone ventilation for the treatment of adult patients with ARDS published from the establishment of the database to September 2023. Studies were categorized into ≤24 hours group and > 24 hours group based on the duration of prone ventilation. Outcome indicators included mortality, the length of intensive care unit (ICU) stay, incidence of pressure ulcers, and operation of tracheotomy. Two researchers independently screened the literature, extracted information, and evaluated the risk of bias of the included literature. The quality of the included literature was assessed using the NOS scale, and the effect of different durations of prone ventilation on the efficacy of ARDS was analyzed by Meta-analysis.Results:A total of 517 patients from 4 papers were finally included, including 249 patients with prone ventilation duration ≤24 hours and 268 patients with prone ventilation duration > 24 hours. All 4 studies were cohort studies, and the overall inclusion of literature assessed for methodological quality indicated high study quality and low risk of bias. Meta-analysis showed that there were no significantly differences in mortality [relative risk ( RR) = 1.02, 95% confidence interval (95% CI) was 0.79 to 1.31, P = 0.88], the length of ICU stay [mean difference ( MD) = -2.68, 95% CI was -5.30 to - 0.05, P = 0.05] between the prone ventilation duration ≤ 24 hours group and prone ventilation duration > 24 hours group. Compared with the prone ventilation duration ≤24 hours group, the incidence of pressure ulcers ( RR = 0.76, 95% CI was 0.59 to 0.98, P = 0.04) and the operation of tracheotomy ( RR = 0.71, 95% CI was 0.53 to 0.94, P = 0.02) were significantly increased in the prone ventilation duration > 24 hours group. Conclusions:The duration of prone ventilation had no significant effect on the mortality and the length of ICU stay in ARDS patients, but prone ventilation for > 24 hours increased the incidence of pressure ulcers and the operation of tracheotomy, which still needs to be further verified by a large number of studies due to the small number of included studies.

OBJECTIVE: To explore the clinical feature and genetic variant of a child with autosomal recessive Charlevoix-Saguenay type spastic ataxia (ARSACS). METHODS: Clinical data of a child who was admitted to the West China Second Hospital of Sichuan University on April 30, 2021 was collected. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The child, a 3-year-and-3-month-old female, had a complain of "walking instability for over a year". Physical and laboratory examination revealed progressive and aggravated gait instability, increased muscle tone of the right limbs, peripheral neuropathy of the lower limbs, and thickening of retinal nerve fiber layer. The results of WES revealed that she has harbored a maternally derived heterozygous deletion of exons 1 to 10 of the SACS gene, in addition with a de novo heterozygous c.3328dupA variant in exon 10 of the SACS gene. Based on the ACMG guidelines, the exons 1-10 deletion was rated as likely pathogenic (PVS1+PM2_Supporting), and the c.3328dupA was rated as a pathogenic variant (PVS1_Strong+PS2+PM2_Supporting). Neither variant was recorded in the human population databases. CONCLUSION The c.3328dupA variant and the deletion of exons 1-10 of the SACS gene probably underlay the ARSACS in this patient.
Female ; Humans ; Heat-Shock Proteins/genetics* ; Muscle Spasticity/genetics* ; Mutation ; Spinocerebellar Ataxias/pathology* ; Child, Preschool

Humans ; COVID-19 ; HIV Infections/drug therapy* ; Risk Factors

Objective:To compare the effects of intensive and standard blood pressure control on the outcomes of patients with acute ischemic stroke in the anterior circulation who have successfully recanalized after endovascular therapy (EVT).Methods:A multicenter, open-label, blinded-endpoint, randomized controlled design was used. Patients with anterior circulation stroke received EVT and successfully recanalized in Nanjing First Hospital, Nanjing Medical University and several branch hospitals from July 2020 to October 2022 were prospectively included. They were randomly divided into the intensive blood pressure control group (target systolic blood pressure [SBP] 100-120 mmHg) or the standard blood pressure control group (target SBP 121-140 mmHg). The blood pressure of both groups needs to achieve the target within 1 h and maintain for 72 h. The primary outcome endpoint was outcome at 90 d, and the good outcome was defined as a score of 0-2 on the modified Rankin Scale. Secondary outcome endpoints included early neurological improvement, symptomatic intracranial hemorrhage (sICH) within 24 h, and death and serious adverse events within 90 d.Results:A total of 120 patients were included, including 63 in the intensive blood pressure control group and 57 in the standard blood pressure control group. There was no statistically significant difference in baseline characteristics between the two groups. The SBP at 72 h after procedure was 122.7±8.1 mmHg in the intensive blood pressure control group and 130.2±7.4 mmHg in the standard blood pressure control group, respectively. There were no significantly differences in the good outcome rate (54.0% vs. 54.4%; χ2=0.002, P=0.963), the early neurological improvement rate (45.2% vs. 34.5%; χ2=1.367, P=0.242), the incidence of sICH (6.3% vs. 3.5%; P=0.682), mortality (7.9% vs. 14.0%; χ2=1.152, P=0.283) and the incidence of serious adverse events (12.7% vs. 15.8%; χ2=0.235, P=0.628) at 90 d between the intensive blood pressure control group and the standard blood pressure control group. Conclusion:In patients with anterior circulation stroke and successful revascularization of EVT, early intensive blood pressure control don’t improve clinical outcomes and reduce the incidence of sICH.