Autophagy is a metabolic pathway that widely presents in eukaryotic cells through the lysosomal mechanism to degrade its components. Autophagy regulates cell death not only by activating classic autophagosomal-lysosomal pathway, but also by influencing the occurrence and development of apoptosis and necrosis. Currently, the effect of autophagy in neuronal injury after acute cerebral ischemia/hypoxia and its specific mechanisms remain unclear. Studies have demonstrated that the autophagy after ischemia/hypoxia has a neuroprotective effect, such as maintaining neuronal homeostasis and reducing neuronal death; but other studies have also suggested that autophagy may aggravate neuronal injury after ischemia/hypoxia by activating multiple pathways, and even induce neuronal death.

[Objective] To refer a geographical distribution rule of alpha-L-fucosidase (AFU) reference values for the health adults in China via exploring its spatial distribution trend and its correlation with geographical factors.[Methods] A total of 6564 samples of AFU reference values from 66 administrative units in the years 2004-2015 were collected,male and female of which were 3701 cases (56.4％) and 2863 cases (46.3％).A research concerning AFU reference values in whole country were calculated using methods of information content and ridge regression.[Results] AFU reference values for Chinese healthy adults were influenced by geographical factors and presented autocorrelation,and it showed eastern and northern areas were highery than western and southern areas.[Conclusions] AFU reference values have a spatial variation and the regional disparities should be considered in practice.

Objective To establish sepsis-associated encephalopathy (SAE) animal models by using neurobiology score,electroencephalography (EEG),somatosensory evoked potentials in order to provide evidence for early clinical diagnosis of SAE.Methods A total of 30 rats were weighted,numbered,and monitored with EEG electrodes 10 days before modeling.Ten days later,rats were weighted,numbered,and divided randomly (random number) into groups.Rat models of sepsis were made by cecal ligation and puncture (CLP).The changes of their neurological behaviors were observed and EEG was used to monitor at 4,6,8,12 and 24 hours after CLP.The changes of EEG waveform and somatosensory evoked potentials were analyzed and recorded.Rat models of sepsis were divided into sepsis + non-SAE group and SAE group based on the presence or absence of EEG or somatosensory evoked potentials changes ~thin 24 hours.Rats were sacrificed 24 hours later,and histopathological changes of brain tissue were observed under electronic microscopy.Thus,the feasibility of establishing early SAE animal model by monitoring the changes of neurological behaviors,EEG and somatosensory evoked potentials was evaluated.Results SAE could be early diagnosed by using neurobiology score,reduced α wave and markedly increased δ wave on EEG,reduced amplitudes of evoked potentials P1,and significantly prolonged latency of S-P1 and NI-P1.In survived septic rats,6 had changes on neurological behaviors,EEG and somatosensory evoked potentials,and thus were diagnosed as SAE.The incidence of SAE was 46％.Conclusions SAE can be diagnosed in early stage by using neurobiology score,EEG and somatosensory evoked potentials,confirming the SAE rat models to be successfully established.

Objective To investigate the role of neuroglobin ( NGB) in oxygen-glucose deprivation and reoxygenation ( OGD/R ) induced mitochondrial depolarization and reactive oxygen species ( ROS ) production in a human neuroblastoma cell line (SH-SY5Y).Methods SH-SY5Y cells were transfected with lentivirus to establish a stable cell line of NGB knockdown ( KD).After treated with OGD/R, cells were collected at different time points to analyze NGB mRNA and protein levels.Furthermore, cells were stained with JC-1 and DCFH-DA to evaluate mitochondrial depolarization and ROS production by inverted fluorescence microscope.Also, to determine the neurotoxicity , we measured the lactate dehydrogenase ( LDH) level in the cell culture medium.Results After the treatment of OGD/R, the NGB mRNA and protein started to elevate and peak at 4 h and 8 h (2.04 ±0.35 fold,1.69 ±0.18 fold).Compared with the vector group , NGB KD group had much more mitochondrial depolarization [ JC-1 red/green ( 1.10 ±0.10 ) vs (1.46 ±0.11),P<0.05] and ROS production [DCFH-DA fluorescence (36.30 ±5.32) vs (16.26 ± 2.97),P<0.05].Furthermore, NGB KD groups had a higher level of LDH release [(63.42 ±6.14)%vs (49.65 ±5.09 )%, P <0.05 ].Conclusions NGB plays an important role in the homeostasis of mitochondria.Knockdown of NGB results in increased mitochondrial depolarization , ROS production and neurotoxicity under hypoxia circumstances.

Objective: To investigate the clinical significance of transcranial Doppler (TCD) in early diagnosis of sepsis-associated encephalopathy(SAE). Methods: Septic patients admitted to the intensive care unit(ICU) were recruited at Xiangya Hospital, Central South University from July 2015 to March 2016. Clinical data and TCD parameters during 24 hours after admission were collected. All patients were screened for delirium using the confusion assessment method for the intensive care unit (CAM-ICU) twice a day. The gold standard of the diagnosis of SAE was positive CAM-ICU evaluation. Patients were divided into SAE group and the non-SAE group. TCD data including systolic velocity (Vs), diastolic velocity (Vd), mean velocity (Vm), pulsatility index (PI) and resistant index (RI) were analyzed to determine the optimal diagnostic cut-off value. Results: A total of 43 patients were enrolled including 12 in SAE group and 31 in non-SAE group. Vm and Vd were lower in SAE group [Vm: (53.50±12.22) cm/s vs. (61.68±9.63) cm/s, P<0.05; Vd: (33.42±10.87) cm/s vs. (43.16±7.84) cm/s, P<0.01] but PI and RI were significant higher in SAE group[PI:(1.16±0.2) vs. (0.90±0.15), P<0.01;RI:(0.65±0.08) vs. (0.56±0.06), P<0.01] than in non-SAE group. The cut-off values of Vs, Vm, Vd, PI and RI for the diagnosis of SAE were 112cm/s, 55.50cm/s, 34.50cm/s, 1.16, 0.65, respectively, with the relevant sensitivities of 19.4%, 83.9%, 93.5%, 58.3%, 58.3% and the specificities of 100.0%, 50.0%, 58.3%, 96.8%, 96.8%, respectively. The diagnostic AUC of Vd, PI and RI were 0.741, 0.808 and 0.808 respectively. Conclusions The parameter changes of TCD suggest that the pathogenesis of SAE is related to cerebral hypoperfusion, TCD is a helpful method for the early diagnosis of SAE.

Objective To investigate the characteristics of lung ultrasound images in critical care postoperative patients using BLUE-plus protocol . Methods Two hundred and twenty-two patients who were performed lung ultrasound measurements according to the BLUE-plus protocol within 24 hours admitted to the Department of critical care were included in this study . Data was collected and retrospectively analyzed to compare the proportion of different lung ultrasound signs at different speculate regions ,and to compare the lung ultrasound characteristics of patients undergo different surgeries . Results Excluding A lines ,the most common abnormal lung ultrasound signs at the diaphragmatic points were B7 lines (13 .06％ ) ,and the most common abnormal lung ultrasound signs at the posterior blue points were C signs (28 .60％ ) . The rate of C signs was significantly higher in post spinal cord surgery patients than those in other groups ( P =0 .032) . The rate of B3 lines was significantly higher at bilateral PLAPS points in oxygenation index 100-200 group compared with that in oxygenation index>300 group ( P =0 .011) . The rate of C signs was significantly higher at the left posterior blue point in oxygenation index 200-300 group , and at bilateral posterior blue point in oxygenation index 100-200 and <100 groups compared with those in oxygenation index >300 group ( P =0 .011 , P <0 .001 and P =0 .002) . The rate of pleural effusion was significantly higher at the right posterior blue point in oxygenation index 200 -300 group ,and at bilateral posterior blue point in oxygenation index 100 -200 group compared with those in oxygenation index >300 group ( P = 0 .001 , P < 0 .001 ) . Conclusions Screen with the BLUE-plus protocol can help to find abnormal signs including B3 lines ,B7 lines ,C signs and pleural effusion ,therefore instructs individualized treatment for postoperative patients . Pulmonary edema ,lung consolidation and pleural effusion are three main reasons responsible for hypoxemia in postoperative patients . Intensivists should avoid fluid overload , strengthen airway management ,postural therapy and encourage early mobility in postoperative patients .

Objective To analyze the characteristics of alcohol-related brain damage according to 18F-fluorodeoxy-glucose (18F-FDG) position emission tomography-computer tomography (PET-CT).Methods Excessive alcohol consumption patients accepted 18F-FDG PET-CT in our hospital from August 2016 to November 2018 were chosen as excessive alcohol consumption group and non-drinking patients accepted 18F-FDG PET-CT in our hospital at the same time were chosen as non-drinking group according to 1:4 ratio.The 18F-FDG PET-CT imaging data were analyzed;the characteristics of abnormal changed rate of CT sequences after stratification by age and the relations of alcohol consumption with abnormal CT sequences and PET sequences were compared between the two groups.Results A total of 52 patients with excessive alcohol consumption and 200 non-drinking patients were chosen.Among patients aged 45-59 years,the abnormal changed rate of CT sequences in the excessive alcohol consumption group was significantly higher than that in the non-drinking group (P＜0.05).In the CT sequences,33 patients in the 2 groups presented abnormalities,mainly including cerebral atrophy and lacunar infarction.In the PET sequences,62 patients in the two groups presented abnormalities,mainly manifesting as reduced metabolism level of bilateral frontal and parietal lobes.Among the 52 patients from excessive alcohol consumption group,those with abnormal CT sequences were older,had longer drinking history and had higher total drinking amount than those with normal CT sequences,and the differences were statistically significant (P＜0.05).As compared with those in patients with normal PET sequences,those with abnormal PET sequences had higher weekly and total alcohol consumption,and longer drinking history,and the differences were statistically significant (P＜0.05).Conclusion Excessive alcohol consumption is an important risk factor for structural damages in middle-aged men,which can cause a decrease of glucose metabolism level in the frontal and parietal lobes.

BACKGROUNDAcute kidney injury (AKI) is a common complication of sepsis, which is associated with higher risks of adverse outcomes. Recently, kidney disease: improving global outcomes (KDIGO) recommended a new guideline for AKI, including a little modification on the AKI staging criteria.

METHODSThis retrospective study included 211 septic patients admitted to the intensive care unit (ICU) at Xiangya Hospital, Central South University from January 2008 to January 2011. AKI was diagnosed and classified according to the KDIGO or acute kidney injury network (AKIN) criteria. Differences between the AKI and non-AKI groups for baseline characteristics, laboratory examinations, etiology, outcomes, as well as the risk factors for AKI and 28-day mortality were analyzed. The reliability of the KDIGO criteria was also evaluated by comparing it with the AKIN criteria.

RESULTSThe overall incidence of AKI in septic patients was 47.9%, and the 28-day mortality was 32.7%. The incidence of AKI was significantly higher in patients with more severe sepsis. Indicators of hepatic and respiratory function were significantly worse in the AKI group. Furthermore, a higher proportion of patients were infected with Enterobacter cloacae in the AKI group. The independent risk factors for AKI were shock, the number of organ failures, blood urea nitrogen (BUN) levels, and the use of vasopressors. The independent risk factors for mortality were BUN and creatine kinase-MB (CK-MB) levels. Both the KDIGO criteria and the AKIN criteria were significantly associated with 28-day mortality.

CONCLUSIONSThe incidence and 28-day mortality of AKI were very high in ICU septic patients. Greater attention should be paid to AKI-induced hepatic and respiratory dysfunction in clinical practice. Patients with an intra-abdominal source of infection were more likely to develop AKI. KDIGO criteria are reliable in AKI staging.

Acute Kidney Injury ; epidemiology ; etiology ; Adult ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Sepsis ; complications ; epidemiology

Objective:To explore the correlation between different types of microcirculation alterations and the prognosis in patients with septic shock.Methods:This research employed a prospective observational study methodology for selecting subjects with septic shock. Side-stream dark field(SDF) was used to monitor the sublingual microcirculation to determine the total vascular density (TVD), perfused vessel density (PVD), the proportion of perfused vessels (PPV), and the microvascular flow index (MFI), heterogeneity index (HI) indicators. At the bedside, patients with microcirculation disorders were divided into four types: stasis, dilution, heterogeneity, and hyperdynamic. The 30-day survival status after enrollment and hemodynamics parameters were recorded.Results:A total of 64 patients with septic shock were selected in the study, including 18 cases of stasis type, 11 of dilution type, 18 of heterogeneous type, and 17 of hyperdynamic type. There were statistical differences in the mean arterial pressure (MAP) [stasis:(77±9) mmHg (1 mmHg=0.133 kPa), dilution:(80±11) mmHg, heterogeneity: (78±12) mmHg, hyperdynamic:(88±12) mmHg], TVD [ stasis:(10.84±3.01) mm/mm 2, dilution:(9.64±1.72) mm/mm 2, heterogeneity:(11.39±2.18) mm/mm 2, hyperdynamic: (11.87±2.67) mm/mm 2 ], PVD [stasis:(5.93±1.94) mm/mm 2, dilution:(6.86±1.48) mm/mm 2, heterogeneity: (8.31±1.78) mm/mm 2, hyperdynamic:(9.68±2.46) mm/mm 2], PPV [stasis:52.45 (46.25, 63.33)%, dilution:73.70 (61.50, 75.20)%, heterogeneity: 71.25 (67.95, 77.00)%, hyperdynamic:80.70 (77.25, 86.45)%], MFI(stasis:1.34±0.45, dilution: 1.70±0.38, heterogeneity:1.82±0.28, hyperdynamic:2.25±0.33), and HI [stasis:0.68 (0.51, 1.87), dilution: 0.57 (0.49, 0.64), heterogeneity:0.70 (0.59, 0.91), hyperdynamic: 0.40 (0.37, 0.52)] of the four types of microcirculation alterations. The cumulative survival rates in stasis, dilution, heterogeneity and hyperdynamic types at 30 day were 7/18, 4/11, 10/18 and 14/17, respectively, which in stasis and dilution types was significantly lower than that of hyperdynamic type (χ2=7.221, P=0.007;χ 2=6.764, P=0.009). Multivariate Cox regression analysis showed the type of microcirculation alterations (stasis: RR=4.551, 95 %CI 1.228-16.864, P=0.023; dilution: RR=4.086, 95 %CI 1.011-16.503, P=0.048), acute physiology and chronic health evaluation Ⅱ ( RR=1.077, 95 %CI 1.006-1.153, P=0.032) were independent prognostic risk factors. Conclusions:Microcirculation alterations are common in patients with septic shock, and it is hard to predict the types of microcirculation alterations with hemodynamics parameters. The prognosis of patients with septic shock is related to the types of microcirculation alterations, suggesting that routine monitoring of microcirculation might be helpful to guide hemodynamic therapy.

Objective:To systematically review the profile of lymph node dissection (LND) for patients with intrahepatic cholangiocarcinoma (ICC) in China.Methods:Using the key words "intrahepatic cholangiocarcinoma" "intrahepatic cholangiocellular carcinoma" "lymph node dissection" "lymphadenec-tomy" "lymph node metastasis", the databases including China Zhiwang, Wanfang, Weipu, Sinomed, PubMed, Embase, Web of Science, Scopus, Cochrane Library were systematically searched. Cohort studies or randomized controlled clinical trials with intraoperative LND documentation and with analysis on the clinicopathologic characteristics or prognostic influences on patients with ICC were included into this meta-analysis from the date of database creation to April 20, 2022. The risk of bias in non-randomized controlled trials was evaluated using the Newcastle-Ottawa scale. A meta-analysis of preoperative imaging lymph node enlargement rates, LND rates, and pathological lymph node metastasis rates were performed using R software.Results:Thirty-three relevant studies that met the systematic evaluation criteria were included, all of which were retrospective cohort studies. All these publications were of medium to high quality. Patients’ enrollment ranged from 1993 to 2020. Patients were enrolled from 20 provinces/autonomous regions/municipalities with a total of 39 medical centers and 4 278 patients. The meta-analysis indicated that the LND rate, preoperative imaging lymph node enlargement rate, pathological lymph node metastasis rate were 47.8%(95% CI: 41.3%-54.3%), 18.5%(95% CI: 7.5%-29.6%) and 51.2%(95% CI: 43.8%-58.6%), respectively. Subgroup analysis showed the LND rate was 36.0%(95% CI: 27.0%-45.0%) in studies with a median year of enrollment before 2010, 48.3% (95% CI: 38.1%-58.6%) in studies from 2010 to 2017, and 53.3%(95% CI: 43.3%-63.2%) in studies after 2017. The LND rates were statistically different in the studies in the different periods of patient enrollment ( P=0.032). Conclusion:The meta-analysis indicated that the overall LND rate for ICC in China was not high but showed an increasing tendency.