Screening and mechanism of the best treatment of red light and silver ion dressing for treatment of chronic non-healing wounds / 中国组织工程研究

BACKGROUND:Red light irradiation and silver ion dressing are mostly used to treat chronic difficult healing wounds clinically,but the optimal irradiation time of red light irradiation and silver ion dressing for chronic non-healing wounds,and the combination of different silver ion dressings have not been determined. OBJECTIVE:To investigate the optimal irradiation time and dressing combination of red light and silver ion dressing in the therapy of chronic non-healing wounds. METHODS:The chronic non-healing wound model was made by applying Staphylococcus aureus on the whole skin defect and subcutaneous hydrocortisone injection in SD rats.72 rat models were randomly divided into 4 groups with 18 rats in each group by random number table method.The rats were treated on the basis of standard dressing change and the following therapy:A1B1 group(red irradiation 20 minutes + lipid hydrocolloidal silver sulfate dressing),A1B2 group(red light irradiation 20 minutes + calcium alginate fiber dressing),A2B1 group(red light irradiation 30 minutes + lipid hydrocolloidal silver sulfate dressing),and A2B2 group(red light irradiation 30 minutes + calcium alginate fiber dressing);change dressing,irradiate once,and change dressing every 24 hours.After 14 days of continuous treatment,wound healing rate,bacterial colony number,inflammatory response,histomorphology and angiogenesis were detected in each group. RESULTS AND CONCLUSION:(1)With the extension of treatment time,the wound healing rate of rats in the four groups was increased,and the wound healing rate of rats in the A2B2 group at 3,7,and 14 days after treatment was higher than that in the other three groups(P<0.05).(2)The wound bacterial culture results on day 7 after treatment demonstrated that the number of bacterial colonies in the A2B2 group was lower than that in the other three groups(P<0.05).Western blot assay exhibited that with the extension of treatment time,the protein expressions of tumor necrosis factor α and interleukin-6 in wound tissue of rats in the four groups were decreased,while the protein expressions of interleukin-10 were increased.The protein expressions of tumor necrosis factor α and interleukin-6 in the A2B2 group were lower than those in the other three groups(P<0.05).The protein expression of interleukin-10 in the A2B2 group was higher than that of the other three groups(P<0.05).(3)The wound hematoxylin-eosin staining on day 14 after treatment demonstrated that a large number of collagen fibers in the A2B2 group were parallel distributed and the most closely connected,which was significantly better than the other three groups.(4)The results of immunofluorescence staining indicated that the fluorescence intensity expression of CD31 in the A2B2 group was higher than that in the A1B1,A1B2 and A2B1 groups(P<0.05).q-PCR detection at 3,7,and 14 days after treatment exhibited that the mRNA expressions of vascular endothelial growth factor a and vascular endothelial growth factor receptor 2 in the A2B2 group were higher than those in the other three groups(P<0.05).Western blot assay at 3,7 and 14 days after treatment revealed that the protein expressions of vascular endothelial growth factor a and vascular endothelial growth factor receptor 2 in the A2B2 group were higher than those in the other three groups(P<0.05).(5)These findings confirm that 30 minutes of red light irradiation combined with silver alginate fiber dressing has better results in treatment of chronic non-healing wounds.

Clinical efficacy of tirellizumab combined with chemotherapy in the treatment of advanced non-small cell lung cancer / 中国基层医药

Objective:To investigate the efficacy of tirellizumab combined with chemotherapy in the treatment of advanced non-small cell lung cancer and its effect on immune function and quality of life in patients.Methods:In this retrospective case-control study, we analyzed the clinical data of 104 patients with advanced (stages III and IV) non-small cell lung cancer who received treatment at Zhoushan Hospital between May 2021 and June 2022. These patients were divided into two groups: group A ( n = 52) and group B ( n = 52), based on the treatment methods utilized. Patients in group A received chemotherapy with gemcitabine plus cisplatin or pemetrexed plus cisplatin. Meanwhile, patients in group B were treated with tirellizumab combined with chemotherapy regimens of gemcitabine plus cisplatin or pemetrexed plus cisplatin, with 21 days as a treatment cycle. Both groups of patients received three cycles of treatment. The short-term efficacy was compared between the two groups. Additionally, serum levels of tumor markers, immune function indexes, quality of life score, and incidence of adverse reactions were compared between the two groups before and after treatment. Results:The short-term response rate in group B was significantly higher than that in group A [51.92% (27/52) vs. 32.69% (17/52), Z = 4.11, P < 0.001]. When compared with pretreatment levels, serum levels of tumor markers and the percentage of CD8 + cells decreased in both groups after treatment. Notably, the serum levels of tumor markers and the percentage of CD8 + cells were significantly lower in group B compared with group A (all P < 0.05). Moreover, after treatment, the percentage of CD4 + cells, the ratio of CD4 +/CD8 + cells, functional subscale, symptom subscale, and total score increased significantly compared with pretreatment levels (all P < 0.05) and were significantly higher in group B compared with those in group A (all P < 0.05). The incidence of adverse events in group B was significantly higher than that in group A [44.23% (23/52) vs. 21.15% (11/52), χ2 = 6.29, P = 0.012]. Conclusion:Tirelizumab combined with chemotherapy is effective for advanced non-small-cell lung cancer. The combined therapy can lower serum levels of tumor markers, restore immune function, and improve overall quality of life.

Status of clinical and MRI researches of area postrema syndrome / 中国医学影像技术

Area postrema syndrome(APS)is characterized by intractable hiccup,nausea and vomiting,which could occur in various central nervous system diseases and remain as one of the focuses in the field of neurology in recent years.The status of clinical and MRI researches of APS were reviewed in this article.

Pay Attention to the Application of PET Imaging in the Early Diagnosis of Cognitive Dysfunction in Parkinson's Disease / 中国医学影像学杂志

Parkinson's disease(PD)is the second largest neurodegenerative disease,secondary to Alzheimer's disease,which seriously endangers people's life and health,and brings huge burden to society and family.Cognitive dysfunction in PD mainly includes mild cognitive impairment and dementia.With the development of different PET targeting tracers,PET imaging technology has become an important molecular imaging tool for assessment of cognitive dysfunction in PD patients,which is of great value for early diagnosis of PD with cognitive dysfunction.

Progress on Cerebral Glucose Metabolism Patterns of PET Imaging in Parkinson's Disease / 中国医学影像学杂志

Parkinson's disease(PD)is a common neurodegenerative disease,which seriously affects the quality of life of patients.The early and accurate diagnosis of PD is still a major medical problem.Positron computed tomography(PET)can be used to monitor noninvasively the pathophysiological changes in the early stage of PD in vivo,which has good clinical application value.18F-FDG PET cerebral glucose metabolism imaging is the most convenient and widely used detection method.At present,a variety of specific cerebral metabolic patterns of PD have been found,which have good guidance for the early diagnosis,differential diagnosis,disease monitoring and curative efficacy judgment of PD.Therefore,this paper focuses on the review of the 18F-FDG PET cerebral glucose metabolism model related to PD,aiming to enable a better application of this technique to the diagnosis of PD.

Stroke incidence of the household population inShanghai's Qingpu District in 2017 - 2022 / 公共卫生与预防医学

Objective To understand the characteristics and temporal trends of stroke incidence in the household population of Shanghai's Qingpu District and to provide a basis for the development of comprehensive prevention and control strategies. Methods The stroke case database for Qingpu District from 2017-2022 was obtained from the Shanghai Stroke and Acute Myocardial Infarction Registry and Reporting Information System. The average age of onset, incidence rate, standardised incidence rate, and constitutive ratio were calculated. Independent samples t-tests were used for comparisons between groups, 2-tests and 2-trend tests for comparisons of rates, and the Joinpoint regression model for calculating the annual percentage change (APC) to analyse the temporal trend of rates. Results Between 2017 and 2022, the average age of stroke onset in the household population of Shanghai's Qingpu District was 73.69±11.60 years. The average annual incidence rate was 556.62/100 000, with an average annual standardised incidence rate of 333.76/100000. There was an increasing trend in the incidence and standardised incidence of stroke in males (APC=7.06%, t=3.44, P=0.03, APC=5.32%, t=3.04, P=0.04). The incidence of stroke increases with age, with cases mainly concentrated in those aged 65 years and above, accounting for 79.47%. Ischemic stroke dominates the stroke typology, accounting for 91.08% of cases, while the incidence of hemorrhagic stroke shows an increasing trend (APC=4.64%, t=4.59, P=0.01). Conclusion The occurrence of stroke in the general population of Shanghai’s Qingpu District is concerning. The study indicates that males, individuals aged 65 years and above, and ischaemic stroke are significant factors that require attention for stroke prevention and control.

The regulatory mechanism of physiological sleep-wake / 中国药理学通报

This paper explains the mechanism of the mutual switching between physiological sleep and wakefulness from the aspects of the sleep circadian system and the sleep homeostasis system. In the circadian rhythm system, with the suprachiasmatic nucleus as the core, the anatomical connections between the suprachiasmatic nucleusand various systems that affect sleep are summarized, starting from the suprachiasmatic nucleus, passing through the four pathways of the melatonin system, namely, subventricular area of the hypothalamus, the ventrolateral nucleus of the preoptic area, orexin neurons, and melatonin, then the related mechanisms of their regulation of sleep and wakefulness are expounded. In the sleep homeostasis system, with adenosine and prostaglandin D2 as targets, the role of hypnogen in sleep arousal mechanisms in regulation is also expounded.

Clinical Analysis of Infants with Acute Lymphoblastic Leukemia (18 cases) / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features and outcomes of infants (<1 year old) with acute lymphoblastic leukemia (IALL).@*METHODS@#The clinical manifestations, laboratory examination results, treatment and prognosis of 18 infants diagnosed with ALL at our department between January 1, 2014 and August 31, 2022 were retrospectively analyzed.@*RESULTS@#Among the 18 cases of IALL, there were 10 males and 8 females. The median age of patients was 6.5 months old (3 months-11 months old). The median white blood cell count (WBC) was 33.63×109/L ［(3.92-470)×109/L］ at initial diagnosis, including 2 patients with WBC≥300×109/L. Flow cytometric immunophenotyping showed a B-lineage infant ALL in all the 18 patients. Eight of the 18 children had abnormal chromosome karyotype analysis. Fusion gene detection showed 12 KMT2A-rearrangement of 18 patients. 15 patients underwent leukemia related mutation gene screening, among which KRAS, NRAS and FLT3 were the most common mutation genes. 4 patients underwent allogeneic hematopoietic stem cell transplantation and two survived. 14 patients received chemotherapy only and ten survived. The 3-year OS rate was (65.5±11.5)%, while the EFS rate was (46.9±12.3)%.@*CONCLUSION@#B-cell ALL and KMT2A rearrangement are prevalent in IALL. The therapeutic effect of IALL with standard childhood ALL protocal is similer to international infant specific protocal.

The application of silent MR angiography in the imaging of brain arteriovenous malformation in children / 中华放射学杂志

Objective:To explore the application value of silent MR angiography (MRA) in imaging of brain arteriovenous malformation (BAVM) in children.Methods:A total of 20 children with BAVM confirmed by digital subtraction angiography (DSA) were retrospectively collected. All children were imaged by silent MRA and time-of-flight MRA (TOF MRA) in the same examination. The image quality of feeding artery, nidus and drainage vein of BAVM was evaluated using the four-point method. Wilcoxon rank-sum test was utilized to compare the image quality scores between silent MRA and TOF MRA. Weighted Kappa statistics used to evaluate the inter-modality agreement of silent MRA and TOF MRA with DSA in displaying of angioarchitecture characteristics and determination of Spetzler-Martin grading.Results:Among the 20 BAVMs, significant differences in image quality scores of the nidus (2.75±0.55 versus 2.20±0.70) and drainage vein (2.60±0.68 versus 2.20±0.77) were observed between silent MRA and TOF MRA ( Z=-3.05, P=0.002; Z=-2.13, P=0.033, respectively). The agreement between silent MRA and DSA was excellent in nidus size grading, deep venous drainage, associated aneurysm and SM grading (Kappa 0.91, 1.00, 0.83 and 0.93, respectively); The agreement between TOF MRA and DSA was fair to moderate (Kappa 0.46, 0.59, 0.35 and 0.47, respectively). Conclusions:Silent MRA showes better image quality compared to TOF MRA and improves the evaluation of angioarchitecture characteristics and Spetzler-Martin grading of BAVMs in children.

Correlation analysis for the lateral condylar tibial plateau fracture and complete medial collateral ligament rupture / 中华骨科杂志

Objective:To investigate the relationship between the CT images of a lateral condylar tibial plateau fractures and complete medial collateral ligament (MCL) injury.Methods:Data of 59 patients with lateral condylar fracture of tibial plateau complicated with MCL injury admitted to Tianjin Hospital from January 2020 to November 2021 were collected, including 32 males and 27 females, aged 42.4±12.3 years (range, 19-65 years), there were 26 cases of extension injury and 33 cases of flexion injury. The patients were separated into two groups: those with partial MCL injury and those with total rupture based on preoperative MR examination and intraoperative valgus stress test following fracture fixation. According to the ABC fracture classification of lateral condyle tibial plateau proposed by Sun et al., the fracture locations were determined on CT images, and the lateral plateau collapse depth (LPD) was measured. The relationship between LPD and MCL complete rupture was analyzed by receiver operating characteristic (ROC) curve.Results:Among 59 patients with lateral condylar tibial plateau fracture and MCL injury, 42 had partial injuries and 17 had complete ruptures. According to the ABC fracture classification, there were 26 cases of extension injury (involving area A), 21 cases of AB type, and 5 cases of ABC type; and 33 cases of flexion type injury, 19 cases of B type, 12 cases of BC type, and 2 cases of C type. All the 17 cases of MCL complete fracture occurred in extension injury, including type AB (14 cases) and type ABC (3 cases). The difference between the mean LPDs of the MCL full rupture group and the partial injury group was not statistically significant ( t=0.11, P=0.567), and the mean LPDs of both groups were 11.7±5.3 mm (range, 4.3-28.1 mm) and 11.5±4.8 mm (range, 3.8-23.6 mm), respectively. The area under the curve (AUC) of the ROC curve analysis was 0.504, and there was no statistical correlation between lateral platform collapse depth and MCL injury. Among the 26 patients with extensional injury area, MCL was completely ruptures in 17 cases and partially injury in 9 cases, LPD was 11.7±5.3 mm (range, 4.3-28.1 mm) and 6.6±1.8 mm (range, 3.8-9.4 mm), respectively, and the difference was statistically significant ( t=3.57, P=0.009). The best predictive cut-off value of LPD was 7.25 mm, the sensitivity was 88.2%, the specificity was 77.8%, and the AUC was 0.868. Conclusion:When the lateral condyle fracture of the tibial plateau is located in the extensional injury area (involving the A area in the ABC fracture classification) and the LPD measured on the CT image is greater than 7.25 mm, the complete rupture of the MCL should be considered. Clinical MCL repair is required after the fracture fixation surgery for improved surgical outcomes.

Interpretation of presynaptic dopaminergic PET imaging results / 中华核医学与分子影像杂志

Presynaptic dopaminergic PET imaging is a useful method for the diagnosis of parkinsonism. Based on the expert consensus on operation and clinical application of dopamine transporter brain PET imaging technology published in 2020, this paper further recommends the relevant elements of result interpretation of presynaptic dopaminergic PET imaging.

Assessment of myocardial viability in ischemic heart disease by integrated PET/MR / 中华核医学与分子影像杂志

Objective:To evaluate the value of integrated PET/MR in assessing myocardial viability in ischemic heart disease.Methods:A total of 39 patients (28 males, 11 females; age (60.1±12.0) years) diagnosed with ischemic heart disease in Xuanwu Hospital, Capital Medical University were retrospectively enrolled from September 2020 to December 2021. All patients underwent cardiac 13N-NH 3·H 2O and 18F-FDG PET/MR examinations. Late gadolinium enhancement (LGE) sequence was included in MRI scan. PET and MRI images were analyzed and myocardial viability of each myocardial segment was evaluated according to the American Heart Association (AHA) 17 segment method. The extent of left ventricular infarcted myocardium was measured based on PET and MRI images. Weighted Kappa test was used to evaluate the agreement of PET and MRI in assessing myocardial viability. The extent of infarcted myocardium measured by PET and MRI was compared by paired- t test, and Pearson correlation analysis was used to assess the correlation between them. Results:There was a moderate agreement between PET and MRI in assessing myocardial viability ( Kappa=0.532, P<0.001), with the agreement rate of 69.83%(463/663). There was no significant difference but strong correlation between the extents of infarcted myocardium measured by PET and MRI ((23.89±14.23)% vs (23.55±11.90)%; t=-0.24, P=0.809; r=0.79, P<0.001). In segments with normal perfusion and metabolism on PET, 22.52% (100/444) showed abnormal enhancement on MRI. On the other hand, 39.89% (73/183) of the segments classified as non-viable on MRI showed normal or viable on PET. Conclusion:Integrated PET/MR is able to take full advantage of the complementary nature of PET and MRI, achieving the comprehensive and accurate evaluation of myocardial viability.

Mechanism study of impaired homocysteine transsulfuration metabolism in sepsis / 中国小儿急救医学

Objective:To investigate the clinical significance and possible mechanisms of elevated homocysteine(Hcy) levels in peripheral blood of children with sepsis.Methods:The clinical data of 51 children with sepsis (sepsis group) admitted to PICU at Xuzhou Children′s Hospital from January 2019 to December 2019 were analyzed, and the levels of Hcy in plasma were compared with 50 non-septic children (common infection group) and 50 healthy children (healthy control group) during the same period.The possible mechanism of metabolic disorders about Hcy was analyzed by detecting the levels of the key rate-limiting enzymes cystathionine-β-synthase(CBS) and cystathionine-γ-lyase(CSE), which were in the downstream of metabolism in septic mouse model induced by lipopolysaccharide.Results:The level of Hcy in plasma was (12.62±5.46)μmol/L in sepsis group, which was significantly higher than those in common infection group[(9.42±2.28) μmol/L] and healthy control group[(8.14±1.60) μmol/L]( P<0.05). The level of Hcy in plasma of 12 children with acute kidney injury in sepsis group was significantly higher than that of 39 children without acute kidney injury in sepsis group[(16.48±5.87)μmol/L vs.(11.62±4.74) μmol/L, P<0.05]. The level of Hcy in plasma of six children with acute liver failure in sepsis group was significant higher than that of 45 children without acute liver failure in sepsis group[(18.35±7.10) μmol/L vs.(11.84±4.78) μmol/L, P<0.05]. The level of Hcy in serum significantly increased in septic mouse models ( P<0.01). The transcription and protein expression levels of key rate-limiting Hcy transcription enzymes CBS and CSE in liver and kidney tissues of septic mouse were significantly down-regulated ( P<0.05). Conclusion:The level of Hcy in peripheral blood of children with sepsis increases, which is more obviously in children with acute kidney injury or acute liver injury.When patients developed sepsis, the expression of CBS and CSE will be restrained, leading to disorders related to transsulfuration metabolism and elevated level of Hcy in peripheral blood.

Correlation between cardiac dysfunction and cognitive impairment in patients with ischemic heart disease / 中华老年心脑血管病杂志

Objective To investigate the correlation between left ventricular dysfunction and cogni-tive impairment in patients with ischemic heart disease(IHD),and explore the potential patho-genesis of cognitive impairment in IHD patients.Methods Fifty IHD patients who underwent hybrid cardiac PET/MR in our hospital from September 2020 to December 2022 were retrospec-tively enrolled in this study.According to their Montreal cognitive assessment(MoCA)scores,they were categorized into a cognitively normal group(21 cases,MoCA score ≥26)and a cogni-tively declining group(29 cases,MoCA score＜26).All patients received 13N-NH3·H2O myocar-dial perfusion imaging and 18F-FDG cardiac PET/MR to evaluate cardiac function and obtain car-diac imaging parameters.Spearman correlation analysis was applied to analyze the correlation between cardiac PET/MR parameters and MoCA scores.General linear model analysis was applied to analyze the correlation between MoCA scores and cardiac PET/MR parameters after adjusting for co variates.Results Compared with the cognitively normal group,the patients in the cognitively declining group had significantly lower stroke volume[56.95(47.51,77.64)ml vs 82.66(73.88,92.92)ml,P=0.001],stroke volume index[34.07(28.93,43.20)ml/m2 vs 44.28(38.06,49.49)ml/m2,P=0.008],cardiac output[3.92(3.18,5.34)L/min vs 5.13(4.58,5.67)L/min,P=0.007],and cardiac index[(2.42±0.68)L/(min·m2)vs(2.78±0.39)L/(min·m2),P=0.021].Spearman correlation analysis revealed that MoCA score was positively correlated with stroke volume(r=0.497,P=0.001),stroke volume index(r=0.365,P=0.009)and cardiac output(r=0.361,P=0.010).After adjusting for sex,age,education level and vascular risk factors,MoCA score re-mained positively correlated with stroke volume(r=0.497,P=0.003).Conclusion Systemic hy-poperfusion in IHD patients may be one of the mechanisms leading to cognitive impairment.

Imaging study of elderly first-ever ischemic stroke patients with asymptomatic coronary artery disease / 中华老年心脑血管病杂志

Objective To explore imaging predictors in elderly patients with first-ever ischemic stroke combined with asymptomatic coronary artery disease(ACAD).Methods A total of 241 non-cardioembolic ischemic stroke patients within 14 d of symptom onset admitted to the neuro-logical department of our hospital from September 2019 to November 2021 were consecutively en-rolled.Based on the diagnosis,they were divided into an ACAD group(103 cases)and a non-ACAD group(138 cases).All patients underwent routine brain MRI and hybrid coronary and cer-vicocephalic CT angiography.Logistic regression analysis was used to identify factors influencing the presence of ACAD in these patients.Results The ACAD group had significantly larger ratios of males,smoking,silent brain infarcts(SBI,both single and multiple),positive stenosis in in-tracranial arteries,numbers of positive stenotic segments in intracranial and extracranial arteries,and total number of positive stenotic segments in head and neck arteries when compared with the non-ACAD group(P＜0.05,P＜0.01).Multivariate logistic regression analysis revealed that both single and multiple SBI were independent risk factors for ACAD(OR=4.474,95％CI:2.057-9.731,P=0.001;OR=8.071,95％CI:3.945-16.513,P=0.001).Conclusion SBI is an independ-ent predictive factor for ACAD in elderly patients with first-ever ischemic stroke,and it has better predictive value than cerebral white matter hyperintensities and intracranial/extracranial arterial stenosis for ACAD.

Drug-coated balloons for the treatment of ostial left anterior descending or ostial left circumflex artery lesions: a patient-level propensity score-matched analysis / 老年心脏病学杂志（英文版）

BACKGROUND@#Controversy exists as to the optimal treatment approach for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. Drug-coated balloons (DCB) may overcome some of the limitations of drug-eluting stents (DES). Therefore, we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions, and compared it with the conventional DES-only strategy.@*METHODS@#We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment. They were categorized into two groups based on their treatment approach: the DCB group and the DES group. The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies, whereas the DES group utilized crossover or precise stenting techniques. Two-year target lesion revascularization was the primary endpoint, while the rates of major adverse cardiovascular events, cardiac death, target vessel myocardial infarction, and vessel thrombosis were the secondary endpoints. Using propensity score matching, we assembled a cohort with comparable baseline characteristics. To ensure result analysis reliability, we conducted sensitivity analyses, including interaction, and stratified analyses.@*RESULTS@#Among the 397 eligible patients, 6.25% of patients who were planned to undergo DCB underwent DES. A total of 108 patients in each group had comparable propensity scores and were included in the analysis. Two-year target lesion revascularization occurred in 5 patients (4.90%) and 16 patients (16.33%) in the DCB group and the DES group, respectively (odds ratio = 0.264, 95% CI: 0.093-0.752, P = 0.008). Compared with the DES group, the DCB group demonstrated a lower major adverse cardiovascular events rate (7.84% vs. 19.39%, P = 0.017). However, differences with regard to cardiac death, non-periprocedural target vessel myocardial infarction, and definite or probable vessel thrombosis between the groups were non-significant.@*CONCLUSIONS@#The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx. Nevertheless, a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.

Reproducible Abnormalities and Diagnostic Generalizability of White Matter in Alzheimer's Disease / 神经科学通报·英文版

Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.

Activation of PXR causes drug interactions with Paxlovid in transgenic mice

Paxlovid is a nirmatrelvir (NMV) and ritonavir (RTV) co-packaged medication used for the treatment of coronavirus disease 2019 (COVID-19). The active component of Paxlovid is NMV and RTV is a pharmacokinetic booster. Our work aimed to investigate the drug/herb-drug interactions associated with Paxlovid and provide mechanism-based guidance for the clinical use of Paxlovid. By using recombinant human cytochrome P450s (CYPs), we confirmed that CYP3A4 and 3A5 are the major enzymes responsible for NMV metabolism. The role of CYP3A in Paxlovid metabolism were further verified in Cyp3a-null mice, which showed that the deficiency of CYP3A significantly suppressed the metabolism of NMV and RTV. Pregnane X receptor (PXR) is a ligand-dependent transcription factor that upregulates CYP3A4/5 expression. We next explored the impact of drug- and herb-mediated PXR activation on Paxlovid metabolism in a transgenic mouse model expressing human PXR and CYP3A4/5. We found that PXR activation increased CYP3A4/5 expression, accelerated NMV metabolism, and reduced the systemic exposure of NMV. In summary, our work demonstrated that PXR activation can cause drug interactions with Paxlovid, suggesting that PXR-activating drugs and herbs should be used cautiously in COVID-19 patients receiving Paxlovid.

Early Enteral Nutrition and Sepsis-Associated Acute Kidney Injury: A Propensity Score Matched Cohort Study Based on the MIMIC-III Database

Purpose@#We aimed to analyze the optimal timing of enteral nutrition (EN) in the treatment of sepsis and its effect on sepsis-associated acute kidney injury (SA-AKI.) Materials and Methods: The MIMIC-III database was employed to identify patients with sepsis who had received EN. With AKI as the primary outcome variable, receiver operating characteristic (ROC) curves were utilized to calculate the optimal cut-off time of early EN (EEN). Propensity score matching (PSM) was employed to control confounding effects. Logistic regressions and propensity score-based inverse probability of treatment weighting were utilized to assess the robustness of our findings. Comparisons within the EEN group were performed. @*Results@#2364 patients were included in our study. With 53 hours after intensive care units (ICU) admission as the cut-off time of EEN according to the ROC curve, 1212 patients were assigned to the EEN group and the other 1152 to the delayed EN group. The risk of SA-AKI was reduced in the EEN group (odds ratio 0.319, 95% confidence interval 0.245–0.413, p<0.001). The EEN patients received fewer volumes (mL) of intravenous fluid (IVF) during their ICU stay (3750 mL vs. 5513.23 mL, p<0.001). The mediating effect of IVF was significant (p<0.001 for the average causal mediation effect). No significant differences were found within the EEN group (0–48 hours vs. 48–53 hours), except that patients initiating EN within 48 hours spent fewer days in ICU and hospital. @*Conclusion@#EEN is associated with decreased risk of SA-AKI, and this beneficial effect may be proportionally mediated by IVF volume.

Surgical treatment of retrograde type A aortic dissection after thoracic endovascular aortic repair for Stanford type B aortic dissection / 中国胸心血管外科临床杂志

@#Objective     To analyze the etiologies, surgical treatment and outcomes of retrograde type A aortic dissection (RTAD) after thoracic endovascular aortic repair (TEVAR) for Stanford type B aortic dissection. Methods     The clinical data of patients with RTAD after TEVAR for Stanford type B aortic dissection receiving operations in Changhai Hospital from March 2014 to August 2018 were analyzed. All patients were followed-up by clinic interview or telephone. Results     A total of 16 patients were enrolled, including 13 males and 3 females with a mean age of 49.1±12.2 years. The main symptoms of RTAD were chest pain in 12 patients, headache in 1 patient, conscious disturbance in 1 patient, and asymptomatic in 2 patients. All the 16 patients received total arch replacement with the frozen elephant trunk technique. Bentall procedure was used in 2 patients, aortic root plasticity in 10 patients and aortic valve replacement in 1 patient. The primary tear in 10 patients was located in the area which were anchored by bare mental stent, and in the other 6 patients it was located in the anterior part of ascending aorta. The mean cardiopulmonary bypass time was 152.2±29.4 min, aortic cross-clamping time was 93.6±27.8 min and selective cerebral perfusion time was 29.8±8.3 min. There was no death in hospital or within postoperative 30 days. The follow-up period was 32-85 (57.4±18.3) months. No death occurred during the follow-up period. One patient underwent TEVAR again 3 years after this operation and had an uneventful survival. Conclusion     Total arch replacement with the frozen elephant trunk technique is a suitable strategy for the management of RTAD after TEVAR for Stanford type B aortic dissection.