OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.

OBJECTIVE To investigate the intervention effect and its potential mechanism of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission in a vascular dementia （VaD） model rats. METHODS VaD rat model was established by bilateral common carotid artery ligation. The experimental animals were randomly divided into sham operation group （SHAM）， model group （MOD），Yifei xuanfei jiangzhuo formula low-dose group （YFXF-L）， Yifei xuanfei jiangzhuo formula high-dose group （YFXF-H）， and Donepezil hydrochloride group （positive control）， with 9 animals in each group. After 30 days of intervention， the spatial learning memory ability was assessed by Morris water maze experiment； HE staining was used to observe histopathological changes in CA1 area of hippocampus； ELISA was used to detect the levels of serum inflammatory factors [interleukin-1β （IL-1β） and IL-4]； Western blot was used to detect the expressions of heat shock protein 90 （HSP90）/mixed lineage kinase domain-like protein （MLKL）/dynamin-related protein 1 （Drp1） pathway-related proteins， mitochondrial fusion proteins （MFN1， MFN2）， and adenosine triphosphate synthase 5A （ATP5A） in hippocampal tissues. The immunohistochemistry was used to detect the level of phosphorylated MLKL （p-MLKL）； real-time fluorescence quantitative PCR was adopted to detect mRNA expressions ofHSP90， MFN1， MFN2 and ATP5A. RESULTS Compared with SHAM group， the escape latency of rats in the MOD group was significantly prolonged， the number of crossing the platform was significantly reduced， and the hippocampal tissues showed typical neuronal damage characteristics， the positive expression level of p-MLKL and the serum level of IL-1β significantly increased， while the serum level of IL-4 significantly decreased， the protein and mRNA expression of HSP90， as well as the protein expressions of p-MLKL/MLKL and p-Drp1（Ser616）/Drp1 were all significantly increased in hippocampal tissue， the protein and mRNA expressions of MFN1， MFN2 and ATP5A， and protein expression of p-Drp1（Ser637）/Drp1 were all significantly decreased （P＜0.05）. After the intervention of Yifei xuanfei jiangzhuo formula， above indicators in each treatment group were all significantly reversed （P＜0.05）. CONCLUSIONS Yifei xuanfei jiangzhuo formula may alleviate neuronal damage and neuroinflammatory responses in VaD rats by regulating the HSP90/MLKL/Drp1 signaling pathway， inhibiting mitochondrial fission， thereby maintaining mitochondrial dynamic balance and improving mitochondrial function.

OBJECTIVE To investigate the mechanism of Yifei xuanfei jiangzhuo formula （YFXF） against vascular dementia （VD）. METHODS The differentially expressed genes of YFXF （YDEGs） were obtained by network pharmacology. High-risk genes were screened from YDEGs by using the nomogram model. The optimal machine learning models in generalized linear， support vector machine， extreme gradient boosting and random forest models were screened based on high-risk genes. VD model rats were established by bilateral common carotid artery occlusion， and were randomly divided into model group and YFXF group （12.18 g/kg， by the total amount of crude drugs）， and sham operation group was established additionally， with 6 rats in each group. The effects of YFXF on behavior （using escape latency and times of crossing platform as indexes）， histopathologic changes of cerebral cortex， and the expression of proteins related to the secreted phosphoprotein 1 （SPP1）/phosphoinositide 3-kinase （PI3K）/protein kinase B （aka Akt） signaling pathway and the mRNA expression of SPP1 in cerebral cortex of VD rats were evaluated. RESULTS A total of 6 YDEGs were obtained， among which SPP1， CCL2， HMOX1 and HSPB1 may be high-risk genes of VD. The generalized linear model based on high-risk genes had the highest prediction accuracy （area under the curve of 0.954）. Compared with the model group， YFXF could significantly shorten the escape latency of VD rats， significantly increase the times of crossing platform （P＜0.05）； improve the pathological damage of cerebral cortex， such as neuronal shrinkage and neuronal necrosis； significantly reduce the expressions of SPP1 protein and mRNA （P＜0.05）， while significantly increase the phosphorylation levels of PI3K and Akt （P＜0.05）. CONCLUSIONS VD high-risk genes SPP1， CCL2， HMOX1 and HSPB1 may be the important targets of YFXF. YFXF may play an anti-VD role by down-regulating the protein and mRNA expressions of SPP1 and activating PI3K/Akt signaling pathway.

Objective:To explore the relationship between the hypertensive snowbirds′ length of migratory stay and their blood pressure control and blood pressure levels.Methods:This study was a cross-sectional study. A population of snowbirds with hypertension was recruited between October and November 2022, and a structured questionnaire was used to collect their self-measured blood pressure and length of stay in Hainan Province. The blood pressure control status is determined based on self-measured blood pressure. According to the self-measured blood pressure to determine whether the blood pressure was well controlled. The associations between snowbirds′ length of stay and their blood pressure control as well as their self-measured blood pressure were analyzed using restricted cubic splines.Results:A total of 362 research subjects were included, 169(46.7%) of whom were male, and their age was (69.7±7.0) years old. The participants′ self-measured systolic blood pressure and diastolic blood pressure were (129.1±16.2) mmHg (1 mmHg=0.133 kPa) and (78.9±10.1) mmHg, respectively. Overall, 174 (48.1%) participants attained adequate blood pressure control. The median length of stay in Wuzhishan City was 7(6, 7) months. There was an inverted U-shaped association between snowbirds′ length of stay and blood pressure control (overall: P=0.023; nonlinearity: P=0.014), where participants with a length of stay of 7 months had the highest rate of blood pressure control. There is a U-shaped curve relationship between length of stay and systolic blood pressure (overall: P=0.001; nonlinearity: P=0.033), and a linear negative correlation with diastolic blood pressure ( β=-1.19, P=0.003). Conclusions:Compared with hypertensive snowbirds with too long or too short lengths of stay, snowbirds who stayed in Wuzhishan City for seven months have better blood pressure control, and systolic blood pressure is also lower.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Logistic Models ; Phenotype ; Risk Factors

Objective:To investigate the relationship of pks gene islands with virulence genes, capsular serotypes and biofilm formation in Klebsiella pneumoniae ( Kp). Methods:A total of 113 Kp clinical isolates were collected in the First Affiliated Hospital of Fujian Medical University and divided into two groups based on the presence of pks gene islands: pks+ and pks- groups. The hypermucoviscous (HM) phenotype was detected by string test. Five virulence genes ( peg-344, rmpA, rmpA2, iucA, iroB) and six common capsular serotypes (K1, K2, K5, K20, K54, K57) were detected by polymerase chain reaction (PCR). The biofilm formation ability was measured by crystal violet staining. Results:Among the 113 Kp isolates, 46 were pks+ strains and 67 were pks- strains. The detection rate of HM phenotype was higher in the pks+ group than in the pks- group [87.0% (40/46) vs 43.3% (29/67)]. The detection rates of virulence genes ( peg-344, rmpA, rmpA2, iucA, iroB) and K1 serotype in the pks+ group were also higher than those in the pks- group ( P<0.05). The biofilm formation ability of the pks+ strains was higher than the pks- strains ( P<0.05). Conclusions:Kp strains carrying pks gene islands were likely to display a HM phenotype and mainly belonged to the K1 serotype. Most of the pks+Kp strains carried the virulence genes of peg-344, rmpA, rmpA2, iucA and iroB, and had a greater ability to form biofilms.

Based on the International Federation of Nursing Anesthetists (IFNA) education and training base, our hospital has built a training base for anesthesia specialized nurses in Nanjing from the following aspects: the application for training base of anesthesia specialized nurses, the qualification and examination of students' and teachers' qualification, the settings of training curriculum, the examination contents and methods, and the evaluation of post-training effect. This article summarizes the construction experience of this base, therefore, providing support and standard for the training of anesthesia specialized nurses.

Objective:To provide a promising and optimal laboratory susceptibility-testing method for the clinical usage of antibiotic (polymyxin), four susceptibility-testing methods were performed and the broth microdilution (BMD) was chosen as the gold standard.Methods:A total number of eighty-eight nonduplicate clinical Enterobacteriaceae specimes were collected from January to December of 2019 in the First Affiliated Hospital, Fujian Medical University. Among the clinical specimens, of which six strains were positive for mcr-1. The minimal inhibitory concentration (MIC) of polymyxin of the clinical specimens were examined by the following methods: (1) broth microdilution, (2) colistin broth disk elution, (3) Vitek-2?, (4)BD PhoenixTM,(5)commercial broth microdilution. With BMD as reference, essential agreement (EA), categorical agreement(CA), very major error(VME) and major error (ME) of polymyxins for different methods were analyzed. The Kappa-consistency testing, paired Chi-square testing and the Spearman-rank correlation testing were used to analyze the consistency between the four antimicrobial susceptibility testing methods and the gold standard.Results:Taking broth microdilution as reference, the EA of colistin broth disk elution, Vitek-2?, BD PhoenixTM, commercial broth microdilution were 94.32% (83/88), 92.05% (81/88), 90.90% (80/88), and 96.59%(85/88), respectively. The CA of all the four methods were 100% (88/88). No VME and ME were recorded for four methods. Moreover, the consistency between four susceptibility testing methods and the gold standard is acceptable (Kappa values=1, P<0.001, McNemar test P=1 and r>0.5, P<0.05). Conclusions:In the present work, four susceptibility testing methods all met the standards recommended jointly by the Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing, of which the performance of the commercial broth microdilution and CBDE fared relatively well. Thus, these four methods could be routinely used in clinical microbiology laboratory of our hospital for colistin and polymyxin B susceptibility testing.

Objective    To provide recommendations for the management of intensive care unit patients without novel coronavirus disease 2019 (COVID-19). Methods    We set up a focus group urgently and identified five key clinical issues through discussion. Total 23 databases or websites including PubMed, National Guideline Clearing-House, Chinese Center for Disease Control and Prevention and so on were searched from construction of the library until February 28, 2020. After group discussion and collecting information, we used GRADE system to classify the evidence and give recommendations. Then we apply the recommendations to manage pediatric intensive care unit in the department of  critical care medicine in our hospital. Results    We searched 13 321 articles and finally identified 21 liteteratures. We discussed twice, and five recommendations were proposed: (1) Patients should wear medical surgical masks; (2) Family members are not allowed to visit the ward and video visitation are used; (3) It doesn’t need to increase the frequency of environmental disinfection; (4) We should provide proper health education about the disease to non-medical staff (workers, cleaners); (5) Medical staff do not need wear protective clothing. We used these recommendations in intensive care unit management for 35 days and there was no novel coronavirus infection in patients, medical staff or non-medical staff. Conclusion    The use of evidence-based medicine for emergency recommendation is helpful for the scientific and efficient management of wards, and is also suitable for the management of general intensive care units in emergent public health events.