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 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.

Objective To observe the value of MRI texture features combined with apparent diffusion coefficient(ADC)for differentiating uterine sarcoma(US)and cellular uterine leiomyoma(CUL).Methods Pelvic MRI data of 27 US patients(US group)and 34 CUL patients(CUL group)were retrospectively analyzed.The texture features of lesions were extracted from T2WI and diffusion weighted imaging(DWI),the ADC value were measured,and the average ADC value(ADCmean),the minimum ADC value(ADCmin)and standard ADC value(ADCst)were recorded.Then logistic regression(LR)models were constructed based on ADC value,optimal texture features alone and their combination,respectively,including LRADC,LRtexture and LRADC+texture models.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each model for differentiating US and CUL.Results The ADCmean,ADCmin and ADCst in US group were all lower than those in CUL group(all P＜0.05).A total of 3 750 texture features were extracted from pelvic T2WI and DWI,5 optimal features were finally obtained,and the constructed LRADC+texture model and LRtexture model had similar efficacy of differentiating US and CUL(AUC=0.921,0.887;P＞0.05),which were both higher than that of LRADC model(AUC=0.696;both P＜0.05).The calibration curve of LRADC+texture model was basically consistent with the ideal curve,which had better clinical benefits than LRADC and LRtexture models.Conclusion MRI texture features combined with ADC value could improve efficacy for differentiating US and CUL.

Objective:To explore the current situation of nursing human caring in hospital wards and analyze its influencing factors, so as to facilitate the development of nursing human caring practice.Methods:From July to November 2022, a total of 107 hospitals were surveyed through stratified convenience sampling method, and 4 072 ward nursing managers were recruited to finish the general information questionnaire and the ward nursing human caring status questionnaire. The general information included the region, class and type of the hospital, etc. The ward nursing human caring status questionnaire included 38 items in 5 dimensions of nursing human caring system and process, humanistic quality and training of nursing staff, humanistic environment and facilities, human caring procedures and measures, and human caring quality evaluation and improvement, with a full score of 190 points. Descriptive statistics were used to analyze the general data, independent samples t-test, ANOVA and correlation analysis were used to analyze the factors influencing the current status of nursing human caring in the ward, while multiple linear regression analysis was used to conduct a multivariate analysis. Results:The score of nursing human caring in hospital wards was 156.91±27.78. Whether the hospital had carried out nursing human caring pilot(demonstration) wards, whether the ward had previously been a hospital nursing human caring pilot(demonstration) nursing unit, the type of ward, and whether nursing managers had participated in human caring training were the influencing factors of the implication of nursing humanistic caring in wards( P<0.05). Conclusions:The practice of nursing human caring in hospital wards is at a good level, but needs to be further strengthened. Nursing managers should take systematically strategies to promote the development of nursing human caring practice.

Objective To assess the feasibility and efficacy of multi-modality three dimensional imaging reconstructive technology in diagnosing the urethral stricture.Methods Totally,121 male patients,suffered with urethral strictures,were enrolled in this study between January 2012 and June 2017.Their age ranged from 17 to 63 years old.The etiology included pelvic fracture in 71 cases,straddle injury in 16 cases,iatrogenic injury in 25 cases,infection in 9 cases.All patients accepted the routine antegrade and retrograde urethrography.The slim CT scan and 3D image reconstruction were performed in patients with posterior urethral stricture.The 3D ultrasound detection and image reconstruction were used in patients with anterior urethral strictures.The fly-through mode was used in each 3D image in order to simulate the process of endoscopic examination.The length of stricture was compared between that in traditional urethrography and in 3D dimensional image,based on the results from anastomotic procedure and substitution.Result Among patients,71 cases were diagnosed as posterior urethral stricture and 50 cases were diagnosed as anterior urethral stricture.In those patients with posterior urethral stricture,no statistical significant difference of stricture length was noticed between traditional urethrography and 3 D dimensional image [(2.30 ± 1.60)cm vs.(2.18 ± 1.55)cm,P =0.91)].In patients who complained about the urine leakage from anus,higher detective rate of fistula could be seen in the CT 3D image than that in traditional endoscopic examination (87.9％ vs.77.6％).To patients with anterior urethral strictures,no statistical significant difference of stricture length was noticed between traditional urethrography and 3D dimensional image [Penile:(2.13 ±0.34) cm vs.(2.24 ± 0.31) cm,P =0.13;Bulbar:(1.98 ± 0.47) cm vs.(2.13 ± 0.32) cm,P =0.23)].However,the advantage of 3D image could be shown in detecting the lesion of navicular fossa and periurethral pathologic fibrosis.In the fly-through mode,the effect of 3D CT image seems to be superior to that in the 3D ultrasound image,which could show more smooth urethral wall and longer urethral segment.The limitation of those 3D image reconstructive technology was that long time consuming was needed during the 3D image reconstruction.Conclusion Our study showed that the multi-modality three dimensional imaging reconstructive technology can improve the sensitivity and specify in diagnosing the urethral stricture.After some modification,it will become the alternative method in diagnosing the urethral stricture.

Objective To analyze the clinical effect of tongue traction massage in the improvement of speech deficit in acute stage of ischemic stroke. Methods A total of 60 cases of acute ischemic stroke aphasia patients from June 2015 to June 2016 were selected and divided into experimental group (30 cases)and control group(30 cases)by random digits table method,the control group was treated with drug therapy, experimental group was treated with drug plus tongue traction massage therapy. The curative effect of tongue body massage and traction safety was compared between two groups. Results After 2 courses of treatment, there was no significant change in vital signs in the experimental group, the total effective rate was 90.00%(27/30), and the total effective rate of the control group was 70.00% (21/30), there was significant difference between two groups(Z=-2.05,P<0.05). Conclusions In the treatment of acute ischemic stroke aphasia,the tongue traction massage,good clinical effect,can effectively improve the patient′s speech function,simple operation,safety,compliance is good,worthy of promotion.

OBJECTIVE: To explore different doses of sodium(s)-2-(dithiocarboxylato((2R,3R,4R,5R,6R)-2,3,4,5,6-pentahydroxyhexyl) amino)-4-(methylthio) butanoate(GMDTC) for removing cadmium. METHODS: Thirty-five male New Zealand rabbits were randomly divided into blank control group,GMDTC high dose control group,model control group,ethylene diamine tetraacetic acid(EDTA) control group and GMDTC low,medium and high dose groups,five rabbits in each group. The blank control group and GMDTC high dose control group were given 0. 90% normal saline solution intravenously; model control group,EDTA control group and GMDTC low,medium and high dose group were given 2 μmol/kg of cadmium chloride(CdCl_2) and 40 μmol/kg of β-mercaptoethanol mixed solution intravenously,5. 0mL/kg body weight(bw),once a day for five days. On the forty-one day of the experiment(the fist day of GMDTC treatment),the control group and the model control group were injected 0. 90% normal saline solution 250 mL via ear vein,the EDTA control group was given EDTA solution at the dose of 93. 5 mg/kg bw with 250 mL 0. 90% normal saline solution,also via ear vein; the GMDTC high dose control group,and the GMDTC low,medium and high dose groups were given 250 mL GMDTC solution at the concentration of 108.0,12.0,36.0 and 108. 0 mg/kg bw with 0. 90% normal saline by intravenous infusion,once a day,6 times a week for four consecutive weeks. The urine β_2-microglobulin(MG),renal cadmium,blood cadmium,and urinary cadmium before and after the treatment were detected. RESULTS: The body weight of New Zealand rabbits increased with the increasing feed time(P < 0. 01). The levels of β_2-MG before treatment increased in model control group,EDTA control group,GMDTC low,medium and high dose groups than that in the blank control group(P < 0. 01). The levels of renal cadmium after treatment in GMDTC medium and high dose groups decreased compared with those in the blank control group and EDTA control group respectively(P < 0. 05). The blood cadmium after treatment in EDTA control group,GMDTC low,medium and high dose groups were decreased compared with those before treatment in the same group respectively(P < 0. 05),meanwhile decreased than the blood cadmium after treatment in the model control group respectively(P < 0. 05). The blood cadmium after treatment had not a statistically significant difference among the EDTA control group,GMDTC medium and high dose groups(P < 0. 05). At all the time points(1,6,8,13,15,20,22 and 28 days after treatment),the urinary cadmium after treatment in EDTA control group and the three GMDTC dose groups increased compared to the model control group at the same time(P < 0. 05). The urinary cadmium after treatment increased with GMDTC dose increased at the other six time points,expect on 20 and 22 days after treatment(P < 0. 05). The blood cadmium removal rates after treatment were 70. 06%,74. 86% and 78. 05% and the renal cadmium removal rates were 14. 27%,27. 95% and 61. 24% in GMDTC low,medium and high dose groups,respectively. CONCLUSION: The intravenous infusion of GMDTC at the dose of 108. 0 mg/kg bw effectively removed cadmium in cadmium poisoning rabbit. This dose had no obvious toxic effect and was equivalent to human dose of 36. 0mg/kg bw which meets the requirement of new drug property.

SUMMARY Thehumanembryonicstemcells(hESCs)serveasaself-renewable,genetically-healthy, pluripotent and single source of all body cells,tissues and organs.Therefore,it is considered as the good standard for all human stem cells by US,Europe and international authorities.In this study,the standard and healthy human mesenchymal progenitors,ligament tissues,cardiomyocytes,keratinocytes,primary neurons,fibroblasts,and salivary serous cells were differentiated from hESCs.The human cellular health-safety of NaF,retinoic acid,5-fluorouracil,dexamethasone,penicillin G,adriamycin,lead ace-tate PbAc,bisphenol A-biglycidyl methacrylate (Bis-GMA)were evaluated selectively on the standar-dized platforms of hESCs,hESCs-derived cardiomyocytes,keratinocytes,primary neurons,and fibro-blasts.The evaluations were compared with those on the currently most adopted cellular platforms.Parti-cularly,the sensitivity difference of PM2.5 toxicity on standardized and healthy hESCs derived fibroblasts, currently adopted immortalized human bronchial epithelial cells Beas-2B and human umbilical vein endo-thelial cells (HUVECs)were evaluated.The results showed that the standardized hESCs cellular plat-forms provided more sensitivity and accuracy for human cellular health-safety evaluation.