ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription （ZSHXP） ameliorates cognitive dysfunction in rats with vascular dementia （VD） induced by the bilateral common carotid artery ligation （2-VO model rats） through regulating the glucose-regulated protein 78 （GRP78）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley （SD） rats were randomly divided into six groups： Sham group， Model group， donepezil hydrochloride group （0.45 mg·kg^-1）， and ZSHXP groups at low （8.90 g·kg^-1）， medium （17.80 g·kg^-1）， and high （35.60 g·kg^-1） doses，with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats， and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin （HE） and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy （TEM） was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen （NeuN） with GRP78 and βⅢ Tubulin with gasdermin D （GSDMD） in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress （ERS）-related proteins including GRP78， PERK， ATF4， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， C/EBP homologous protein （CHOP）， NOD-like receptor protein 3 （NLRP3）， Caspase-1 and GSDMD. ResultsCompared with the sham operation group， the model group showed a significantly prolonged escape latency （P<0.01）， a significant decrease in the number of platform crossings and the residence time in the target quadrant （P<0.01）， and a markedly reduced recognition index （P<0.01）. Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity， deformed and shrunken cell bodies， and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously， accompanied by abnormal dilation and swelling， and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78， p-PERK/PERK， ATF4， CHOP， NLRP3， GSDMD and Caspase-1 in the model group were significantly elevated （P<0.01）. Compared with the model group， the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency （P<0.01） and an increased number of platform crossings （P<0.05， P<0.01）. The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups （P<0.05， P<0.01）， with a significantly improved recognition index （P<0.01）. In the donepezil hydrochloride group and all ZSHXP groups， the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group， the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group， the protein expressions of GRP78， ATF4 and CHOP were increased （P<0.01）， while the expression of p-PERK/PERK was decreased （P<0.05）. In the ZSHXP low-dose group， the expressions of GRP78， p-PERK/PERK and CHOP were elevated （P<0.05， P<0.01）. The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK， ATF4 and CHOP （P<0.01）， and the high-dose group had a markedly reduced GRP78 protein expression （P<0.01）. In the donepezil hydrochloride group， the Caspase-1 protein expression was increased （P<0.01） and the NLRP3 protein expression was decreased （P<0.01）. In the ZSHXP low-dose group， the GSDMD expression was elevated （P<0.01） while the NLRP3 protein expression was reduced （P<0.01）. After treatment with medium and high doses of ZSHXP， the protein expression levels of NLRP3， GSDMD and Caspase-1 were significantly decreased （P<0.01）. ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway， which ameliorates ERS and inhibits neuronal pyroptosis.

ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription （ZSHXP） ameliorates cognitive dysfunction in rats with vascular dementia （VD） induced by the bilateral common carotid artery ligation （2-VO model rats） through regulating the glucose-regulated protein 78 （GRP78）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley （SD） rats were randomly divided into six groups： Sham group， Model group， donepezil hydrochloride group （0.45 mg·kg^-1）， and ZSHXP groups at low （8.90 g·kg^-1）， medium （17.80 g·kg^-1）， and high （35.60 g·kg^-1） doses，with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats， and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin （HE） and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy （TEM） was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen （NeuN） with GRP78 and βⅢ Tubulin with gasdermin D （GSDMD） in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress （ERS）-related proteins including GRP78， PERK， ATF4， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， C/EBP homologous protein （CHOP）， NOD-like receptor protein 3 （NLRP3）， Caspase-1 and GSDMD. ResultsCompared with the sham operation group， the model group showed a significantly prolonged escape latency （P<0.01）， a significant decrease in the number of platform crossings and the residence time in the target quadrant （P<0.01）， and a markedly reduced recognition index （P<0.01）. Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity， deformed and shrunken cell bodies， and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously， accompanied by abnormal dilation and swelling， and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78， p-PERK/PERK， ATF4， CHOP， NLRP3， GSDMD and Caspase-1 in the model group were significantly elevated （P<0.01）. Compared with the model group， the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency （P<0.01） and an increased number of platform crossings （P<0.05， P<0.01）. The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups （P<0.05， P<0.01）， with a significantly improved recognition index （P<0.01）. In the donepezil hydrochloride group and all ZSHXP groups， the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group， the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group， the protein expressions of GRP78， ATF4 and CHOP were increased （P<0.01）， while the expression of p-PERK/PERK was decreased （P<0.05）. In the ZSHXP low-dose group， the expressions of GRP78， p-PERK/PERK and CHOP were elevated （P<0.05， P<0.01）. The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK， ATF4 and CHOP （P<0.01）， and the high-dose group had a markedly reduced GRP78 protein expression （P<0.01）. In the donepezil hydrochloride group， the Caspase-1 protein expression was increased （P<0.01） and the NLRP3 protein expression was decreased （P<0.01）. In the ZSHXP low-dose group， the GSDMD expression was elevated （P<0.01） while the NLRP3 protein expression was reduced （P<0.01）. After treatment with medium and high doses of ZSHXP， the protein expression levels of NLRP3， GSDMD and Caspase-1 were significantly decreased （P<0.01）. ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway， which ameliorates ERS and inhibits neuronal pyroptosis.

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

Objective To observe the effects of Baishile Capsules on neonatal neuronal activity and synaptic plasticity in hippocampus of depression model rats;To explore its mechanism of antidepressant.Methods Totally 32 SD rats were randomly divided into blank group,model group,fluoxetine group(5.4 mg/kg)and Baishile Capsules group(2.88 g/kg),with 8 rats in each group.The depression rat model was established by chronic unpredictable mild stress and single cage feeding,and drugs were administered at the same time as modeling for 21 consecutive days.Forced swimming test and open field test were used to evaluate the depressive-like behavior of rats,Golgi staining was used to observe the synaptic morphology of hippocampal neurons,and immunofluorescence was used to detect the positive expressions of BrdU/GABA-B,BrdU/c-fos,BrdU/GAP-43,BrdU/MAP-2 and CXCR4 in hippocampal tissue.Results Compared with the blank group,the immobility time of forced swimming experiment in the model group increased,and the horizontal and vertical time of open field experiment decreased significantly(P<0.01);the hippocampal neurons dendrites and dendritic spines atrophied,the density decreased,the branches became shorter,synaptic structure becomes blurred,and the longest and total lengths of synaptic branches significantly decreased(P<0.01);the positive expressions of GABA-B,c-fos,GAP-43 and MAP-2 proteins in hippocampal neonatal neurons decreased(P<0.05,P<0.01),and the expression of CXCR4 in hippocampal tissue decreased significantly(P<0.01).Compared with the model group,the immobility time of the forced swimming experiment in fluoxetine group and Baishile Capsules group significantly reduced,and the horizontal and vertical activity time of the open field experiment significantly increased(P<0.01);the number of dendritic spines in hippocampal neurons increased,synaptic damage improved,and the length of the longest and total branches of synapses significantly increased(P<0.01);the positive expressions of GABA-B,c-fos,GAP-43 and MAP-2 in hippocampal neonatal neurons significantly increased(P<0.05,P<0.01),and the positive expression of CXCR4 in hippocampal tissue significantly increased(P<0.01).Conclusion Baishile Capsules can regulate hippocampal synaptic plasticity and nerve regeneration by improving the activity and function of hippocampal neonatal neurons in depression model rats,exerting antidepressant effects.

Objective To investigate washing patterns in human simulated body fluids(SBF)by combining high doses of vancomycin,manuperenan and single compound with bone cement.The antibacterial effect of five common bacteria in orthopaedic infections were observed.Methods Vancomycin 2g and meropenem 3g were combined or alone mixed with ordinary bone cement 20g in aseptic operation.Six copies of antibiotic bone cement pellets were made,immersed in SBF,replaced with SBF buffer every 48 hours,sampled every 24 hours 2 μl drops in methicillin-resistant staphylococcus aureus(MRSA),petries of staphylococcus aureus,pseudomonas aeruginosa,E.coli,and extended-spectrum beta-lactamase(ESBL)-positive E.coli were observed for 24 hours and measured the size of the bactericidal rings of the washing fluid at each time point.The antibacterial effect of different ratios of antibiotic bone cement on 5 common orthopedic infections were compared.Results Compound antibiotic group had a better bactericidal effect,and the drug continues to be given for about 30 days.Wancomycin alone could not cover E.coli,ESBL positive E.coli,pseudomonas aeruginosa,and melopicillin alone had only a partial mild bactericidal effect on MRSA around 3 to 6 days after use.The effect on staphylococcus aureus and pseudomonas aeruginosa lasted only about 15 days.Conclusion The combined antibiotic bone cement has a more comprehensive,longer duration and better bactericidal effect than the alone antibiotic bone cement.

OBJECTIVE To study the prevention and control strategies for carbapenem-resistant Acinetobacter bau-mannii(CRAB)infection through inves-tigating an outbreak of CRAB infection in an intensive care unit(ICU),and provide a scientific basis for the prevention and control of such hospital-acquired infections.METHODS Epide-miological investigations were conducted on patients with CRAB infection in the ICU of a hospital from Jul.7 to Jul.29,2023,and microbial sampling,identification and drug sensitivity testing were conducted on suspected con-taminated environments and items.Targeted prevention and control measures were taken to control the outbreak.RESULTS Within a short period,8 patients in this hospital developed CRAB hospital-acquired infection,among whom,the drug resistance profiles of CRAB isolated from the specimens of 7 patients in bed A4,A14,B18,B19,B20,B21 and B22 were consistent.Through environmental hygiene monitoring,CRAB isolated from patient clothing,isolation gowns and medical staff uniforms matched the drug resistance profiles of the seven patient iso-lates.After taking targeted measures,no new CRAB infection cases occurred in Oct.,and CRAB was no longer i-solated from the environment and medical fabrics.CONCLUSIONS The suspected outbreak of CRAB infection may be related to the inadequate management and contamination of medical fabrics.Therefore,in addition to strictly implementing the routine prevention and control measures for multidrug-resistant bacteria,it is also crucial to strengthen the standardized management of medical fabrics for the prevention and control of hospital-acquired in-fections and outbreaks.

Objective To investigate the predictive value of geriatric nutritional risk index(GNRI)combined with CHA2DS2-VASc-60 score for short-term prognosis of elderly multimorbid patients with atrial fibrillation.Methods A total of 220 elderly multimorbid patients with non-valvular atrial fibrillation admitted to our hospital from May 2020 to December 2022 were recruited.Clinical data were collected,and GNRI and CHA2DS2-VASc-60 score were calculated.With 98 as a cut-off value of GNRI,the patients were divided into normal nutritional group(109 cases)and nutritional risk group(GNRI ≤ 98,111 cases).Clinical characteristics were compared between the two groups.Multivariate logistic regression analysis was used to identify the influencing factors for compound events in elderly multimorbid patients with atrial fibrillation.Variance inflation factor was adopted for collinearity diagnosis.ROC curve was plotted to evaluate the prognostic value of GNRI,CHA2DS2-VASc-60 score and their combination.Results Compared with the normal nutritional group,the nutritional risk group had significantly advanced age,higher CHA2DS2-VASc-60 score,and larger proportion of concomitant chronic heart failure(P＜0.05).Age(OR=1.228,95％CI:1.112～1.357),GNRI(OR=0.693,95％CI:0.494～0.997)and CHA2DS2-VASc-60 score(OR=1.488,95％CI:1.008～2.194)were influencing factors for the occurrence of complex events(P＜0.05,P＜0.01).The AUC value of GNRI,CHA2DS2-VASc-60 score,and their combination in predicting complex events at the end of 6 months was 0.665(95％CI:0.539～0.791),0.689(95％CI:0.578～0.801),and 0.749(95％CI:0.653～0.844),respectively(P＜0.05).Conclusion Age,GNRI,and CHA2DS2-VASc-60 score are influencing factors for the occurrence of complex events in elderly multimorbid patients with atrial fibrillation.The combination of GNRI and CHA2DS2-VASc-60 score has predictive value for the short-term prognosis of the patients.

Objective:To explore any myogenic effect of extracorporeal shock wave therapy (ESWT) on shoulder joint contracture.Methods:Sixty-eight patients with shoulder contracture were enrolled and randomly divided into a conventional therapy group ( n=34) and an ESWT group ( n=34) for this clinical trial. The conventional therapy group received standard rehabilitation treatment, while the ESWT group received additional extracorporeal shock wave therapy. In addition, 24 Sprague-Dawley rats were randomly assigned to a blank control group, a model group, a natural recovery group, or an ESWT animal group, each of 6. All of the groups except the blank control group had contracture modeled using plaster cast immobilization of the left shoulder joint. After successful modeling, the natural recovery group was routinely raised for two weeks, while the ESWT animal group received two weeks of extracorporeal shock wave intervention. In both the clinical and animal experiments, ESWT was administered twice weekly (every Tuesday and Friday) for two consecutive weeks. Before and after the treatment, the patient groups were assessed using a visual analog scale (VAS) for pain, shoulder range of motion (ROM), and the root mean square (RMS) values of the surface electromyographs of the peri-shoulder muscles. Shoulder ROM was assessed in all four of the rat groups after the ESWT treatment, and histological analysis of the supraspinatus muscle was performed. Results:After the treatment, both patient groups showed significant improvements in their average VAS scores, active and passive shoulder ROM, and RMS values. On average, the ESWT group demonstrated significantly greater improvements than the conventional therapy group in active forward flexion, passive forward flexion, active abduction, passive abduction, and the RMS values of the deltoid, biceps brachii, and triceps brachii muscles. After the treatment the left shoulder abduction angle had been reduced significantly in the model group (to 96.00±2.37)°, the natural recovery group (103.00±4.05)° and the ESWT animal group (121.33±4.89)° compared to the blank control group (154.50±2.35)°. Both the natural recovery group and the ESWT animal group had significantly greater shoulder abduction angles than the model group, and the ESWT animal group also demonstrated a significantly larger abduction angle than the natural recovery group. After the treatment, significant differences between the model group and the blank control group were observed in the cross-sectional area of left supraspinatus muscle fibers and the proportion of collagen. The ESWT animal group too exhibited significantly improved muscle fiber cross-sectional area and collagen proportion compared to the natural recovery group.Conclusions:Shoulder joint contracture is accompanied by significant myopathic changes (muscle atrophy and fibrosis). ESWT effectively ameliorates these problems while enhancing muscle strength and functional recovery.

Objective:To explore the diagnostic value of transcranial magnetic stimulation (TMS), transsacral magnetic root stimulation combined with sacral reflexes, external anal sphincter electromyography and pudendal nerve somatosensory evoked potentials in the assessment of neurogenic lower urinary tract dysfunction (NLUTD).Methods:Twenty-one NLUTD patients (1 with a supra-pontine lesion, 5 with a spinal cord injury, 5 with a cauda equina injury, and 10 with pelvic floor disorders) were enrolled. Needle electromyography (EMG) was used to record TMS-induced and transsacral magnetic stimulation-induced motor evoked potentials (tc-MEPs and ts-MEPs, respectively) related to the external anal sphincter (EAS). The dorsal nerve of the penis or clitoris was stimulated electrically to record the latency of the sacral reflex related to the EAS. Central motor conduction time (CMCT) and the tc/ts-MEP latency ratio were calculated to distinguish central from peripheral lesions.Results:In the one patient with a supra-pontine lesion, although the tc-MEP and ts-MEP latencies were within normal limits, the CMCT was prolonged (28.2ms) and the tc/ts-MEP ratio was large (7.4). Among the five patients with a spinal cord injury, one exhibited prolonged tc-MEP latency (50.6ms) and CMCT (47.8ms), along with a large tc/ts-MEP ratio (18.1). In the five patients with cauda equina injury and the ten with NLUTD secondary to pelvic floor disorders, CMCT was within the normal range [averaging (22.9±4.9ms) and (24.2±3.5ms), respectively], but the ts-MEP latency was prolonged [(7.1±2.1ms) and (8.6±3.7ms), respectively], and the tc/ts-MEP ratio was small [(4.4±0.9) and (4.3±1.5), respectively]. The tc/ts-MEP ratio demonstrated the best rate of abnormality detection (93.8%), with an area under the curve of 0.99, indicating good sensitivity.Conclusions:The tc/ts-MEP ratio can be useful for distinguishing central and peripheral lesions. A markedly increased tc/ts-MEP ratio may suggest central nervous system injury, whereas a decreased ratio may indicate peripheral nervous system injury.

ObjectiveTo investigate the mechanism by which 2，3，5，4'-tetrahydroxyldiphenylethylene-2-O-glucoside （THSG） mitigates cerebral ischemia/reperfusion （CI/R） injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham， model， SAS （40 mg·kg^-1）， and low-， medium- and high-dose （10， 20， 40 mg·kg^-1， respectively） THSG groups， with 10 rats in each group. The middle cerebral artery occlusion/reperfusion （MCAO/R） model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring， and cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 （CCK-8） assay， and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 （PINK1） and leucine zipper/EF-hand-containing transmembrane protein 1 （LETM1） in neurons. Transmission electron microscopy （TEM） was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 （TOMM20）， autophagy-associated protein p62， microtubule-associated protein light chain 3 （LC3）， cysteinyl aspartate-specific proteinase-9 （Caspase-9）， B-cell lymphoma 2-associated protein X （Bax）， and cytochrome C （Cyt C）. ResultsCompared with the sham group， the model group exhibited increased infarct volume （P<0.01） and neurological deficit scores （P<0.01）， neuronal structure was disrupted with reduced Nissl bodies. （P<0.01）， mitochondrial swelling/fragmentation， decreased PINK1/LETM1 co-localization （P<0.01）， upregulated protein levels of LC3Ⅱ/LC3Ⅰ， TOMM20， Caspase-9， Bax， and Cyt C （P<0.01）， downregulated protein level of p62 （P<0.05）， weakened PC12 viability （P<0.01）， and elevated mitochondrial calcium level （P<0.01）. Compared with the model group， THSG and SAS groups showed reduced infarct volumes （P<0.05，P<0.01） and neurological deficit scores （P<0.05，P<0.01）， mitigated mitochondrial damage， and increased PINK1/LETM1 co-localization （P<0.01）. Medium/high-dose THSG and SAS alleviated the neurological damage， increased Nissl bodies （P<0.05，P<0.01）， downregulated the protein levels of p62， TOMM20， Caspase-9， Bax， and Cyt C （P<0.05，P<0.01）， and elevated the LC3Ⅱ/LC3Ⅰ level （P<0.05，P<0.01）. High-dose THSG enhanced PC12 cell viability （P<0.01）， increased PINK1/LETM1 co-localization （P<0.01）， and reduced mitochondrial calcium （P<0.01）. ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway， reducing the mitochondrial calcium overload， and promoting mitophagy.