Objective:To investigate the protective effects of oleanic acid (OA) on cerebral ischemia-reperfusion (I/R) injury in rats and the role of JAK2/STAT3 signaling pathway.Methods:Seventy-two adult male SD rats were randomly divided into sham-operation group, model group (I/R), OA group (I/R+OA), and inhibitor group (I/R+OA+FLLL32). The left middle cerebral artery I/R model was constructed by the thread occlusion method. After modeling, OA and JAK2/STAT3 inhibitor FLLL32 were administered via intraperitoneal injection and lateral ventricular injection, respectively, for a total of 7 days. Neurological deficits were evaluated by behavioral methods, infarct volume was detected by 2,3, 5-triphenyltetrazolium chloride staining, the expressions of Bcl-2, Bax, JAK2, STAT3, p-JAK2 and p-STAT3 in ischemic brain tissue were analyzed by Western blotting, and the percentage of caspase-3 positive cells in ischemic brain area was detected by immunofluorescence staining.Results:Compared with sham-operation group, the model group showed significant neurological deficits and cerebral infarction lesions. The expressions of Bax and caspase-3, as well as the phosphorylation levels of JAK2 and STAT3 proteins, were significantly decreased, while the expression of Bcl-2 was significantly up-regulated. Compared with model group, neurological deficits and infarct volume were significantly reduced in OA and inhibitor groups, the expression of Bax, the phosphorylation levels of JAK2 and STAT3, and the percentage of caspase-3 positive cell were significantly decreased, while the expression of Bcl-2 was significantly up-regulated.Conclusion:OA may reduce neuronal apoptosis by inhibiting the activation of the JAK2/STAT3 signaling pathway, and then alleviate I/R injury.

Cyperi Rhizoma is a common Chinese medicine in clinical practice， which has a long history of processing. In order to sort out the process of its processing， starting with the angle of processing excipients， the historical evolution and developmental venation of Cyperi Rhizoma processing were analyzed and summarized by consulting relevant literature of ancient medical records and modern codes. After combing the ancient and modern literature， it was found that there were many processing methods of Cyperi Rhizoma， the processing methods without auxiliary materials included frying， boiling， steaming and so on， and the adding auxiliary materials included vinegar， ginger， salt， multiple excipients， etc. However， with the evolution of history， some characteristic excipients have gradually disappeared， while vinegar-processed products are mainly used in modern times. Meanwhile， processing methods of Cyperi Rhizoma are well documented in various processing standards， the phenomenon of multiple methods adopted in one place and different methods in different places exists， which lacks unified quality standards and leads to uneven quality of Cyperi Rhizoma decoction pieces， which may even affect the safety and effectiveness of its clinical medication. Based on this， the problems existing in the processing research of Cyperi Rhizoma were analyzed in this paper， and made an outlook on the inheritance of the ancient processing methods and the quality standard improvement of the decoction pieces， in order to provide important literature evidence and theoretical support for the study of processing process and mechanism of Cyperi Rhizoma.

ObjectiveTo investigate the relative content changes of differential metabolites and reducing sugars during the processing process of Rehmanniae Radix Praeparata （RRP） processed with Amomi Fructus （AF） and Citri Reticulatae Pericarpium （CRP）， and to lay the foundation for revealing the processing principle of this characteristic variety. MethodThe samples of the 0-54 h processing process of RRP processed with AF and CRP were taken as the research object， and their secondary metabolites were detected by ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）. The 0.1% formic acid aqueous solution （A）-acetonitrile （B） was used as the mobile phase for gradient elution （0-1 min， 1%-3%B； 1-10 min， 3%-9%B； 10-15 min， 9%-12%B； 15-22 min， 12%-18%B； 22-31 min， 18%-24%B； 31-35 min， 24%-100%B； 35-36 min， 100%-5%B； 36-40 min， 5%-1%B； 40-45 min， 1%B）， column temperature was 40 ℃， injection volume was 3 μL， flow rate was 0.3 mL·min^-1. Electrospray ionization （ESI） was used to scan and collect MS data in the negative ion mode， the scanning range was m/z 50-1 250. Data analysis was carried out using PeakView 1.2 software， and the chemical composition of RRP processed with AF and CRP was identified by combining the literature information and chemical composition databases. The MS data were normalized by MarkerView 1.2， and then the multivariate statistical analysis was applied to screen the differential metabolites， and the changes of the relative contents of the differential metabolites with different processing times was analyzed， finally， correlation analysis was performed between the differential metabolites， the change of the reducing sugar content was combined to determine the most suitable processing time of RRP processed with AF and CRP. ResultA total of 121 compounds were identified from RRP processed with AF and CRP at different processing times， and 12 differential metabolites were screened out by multivariate statistical analysis， including catalpol， hesperidin， isoacteoside， acteoside， narirutin， echinacoside， isomartynoside， decaffeoylacteoside， 6-O-E-feruloylajugol， dihydroxy-7-O-neohesperidin， jionoside D， and rehmapicroside. With the prolongation of processing time， the relative contents of these 12 differential metabolites and reducing sugars changed slightly at 52-54 h. ConclusionUPLC-Q-TOF-MS can comprehensively and accurately identify the chemical constituents of RRP processed with AF and CRP at different processing times， and the suitable processing time of 52-54 h is determined according to the content changes of different metabolites and reducing sugars， which provides a basis for revealing the scientific connotation of the processing principle of this variety.

Objective:To investigate the protective effect of lipopolysaccharide (LPS) preconditioning on cerebral ischemia reperfusion in rats.Methods:One hundred and twenty adult male SD rats were randomly divided into sham operation group, model group, low-dose LPS group (0.05 mg/kg), medium-dose LPS group (0.15 mg/kg), and high-dose LPS group (0.45 mg/kg). LPS was injected intraperitoneally for preconditioning, once a day for 7 consecutive days. Twenty-four hours after the last injection, the left middle cerebral artery occlusion model was induced by suture-occluded method. The model was reperfused 1.5 h after ischemia. At 24 h after reperfusion, the neurological deficit was evaluated by neurobehavioral score. The volume of cerebral infarction was measured by triphenyltetrazolium chloride staining. The serum levels of proinflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay. The expression of Toll-like receptor 4 (TLR4), matrix metalloproteinase (MMP) -2 and MMP-9 in ischemic brain tissue was detected by Western blot analysis.Results:Compared with the sham operation group, blood-brain barrier permeability was increased in the model group, serum IL-1β, IL-6 and TNF-α were up-regulated, and the expression of TLR4, MMP-2 and MMP-9 proteins in ischemic brain tissue was up-regulated. Compared with the model group, the neurological impairment of each LPS intervention group was significantly reduced, the volume of cerebral infarction was significantly reduced, the permeability of blood-brain barrier was significantly reduced, the serum IL-1β, IL-6 and TNF-α were down-regulated, and the expression of TLR4, MMP-2 and MMP-9 protein in ischemic brain tissue was down-regulated, especially in the medium-dose group and the high-dose group.Conclusions:LPS preconditioning can induce the formation of ischemic tolerance, inhibit the activation of TLR4-MMP-2/MMP-9 signal pathway, reduce the damage and inflammation of blood-brain barrier structure, and thus play a neuroprotective role in rats with cerebral ischemia reperfusion.

Objective:To retrieve, evaluate, and integrate the best evidence for the prevention of central venous catheter-associated thrombosis in children, so as to provide a basis for clinical nursing programs for children with catheter-associated thrombosis.Methods:UpToDate, British Medical Journal Best Practice, Joanna Briggs Institute Evidence Synthesis, the Cochrane Library, CINAHL, Guideline International Network, National Guideline Clearinghouse, ACP Journal Club, PubMed, China Medlive Guidelines Network, China Biomedical Database, WanFang Data, China National Knowledge Infrastructure were retrieved by computer. The retrieval time limit was from June 30, 2011 to June 30, 2021. Four researchers independently screened the article, and extracted and summarized the article that met the quality standards.Results:A total of 10 articles were included, including four guidelines, three expert consensus articles, two evidence summaries, and one systematic review. A total of 24 pieces of evidence were summarized in five aspects of children's central venous catheter training, risk factor assessment, central venous catheter placement, catheter maintenance and thrombosis prevention.Conclusions:The best evidence for the prevention of central venous catheter-associated thrombosis in children is comprehensive and extensive, instructive and actionable, and can provide a basis for the clinical nursing program of catheter-associated thrombosis prevention in children. Medical and nursing staff can further refine evidence-based nursing practice programs according to the characteristics of children of different ages from the above five aspects, standardize the process of central venous catheter placement and maintenance, and provide children with drug or non-drug prevention.

Objective:To evaluate the effect of Xuebijing injection on the improvement of pneumonia severity index (PSI) and prognosis in patients with severe coronavirus disease 2019 (COVID-19).Methods:A multicenter prospective cohort study was designed. Adult patients with COVID-19 admitted to the intensive care unit (ICU) of 28 designated COVID-19 hospitals in 15 provinces and cities of China from January to March 2020 were enrolled. All patients were treated according to the standard treatment plan of COVID-19 issued by the National Health Commission of the People's Republic of China. They were divided into Xuebijing group and standard treatment group according to whether they received Xuebijing injection or not. In the standard treatment group, routine medical care measures such as antiviral, respiratory support, circulatory support and symptomatic treatment were taken. In the Xuebijing group, on the basis of standard treatment, Xuebijing was used within 12 hours of admission to the ICU, 100 mL each time, twice daily. The minimum duration of Xuebijing administration was 1 day. The improvement rate of PSI risk rating on the 8th day and clinical outcome on the 28th day were recorded.Results:A total of 276 COVID-19 patients were screened continuously, and the data of 144 severe patients who met PSI risk rating Ⅲ-Ⅴ were analyzed. Seventy-two cases were involved each in standard treatment group and Xuebijing group. The average age of the standard treatment group and Xuebijing group were (65.7±7.9) years old and (63.5±10.9) years old, and male accounted for 75.0% (54/72) and 70.8% (51/72), respectively. There were no significant differences in general conditions, comorbidities, PSI risk rating and score, sequential organ failure assessment (SOFA) score, oxygenation index (PaO 2/FiO 2), respiratory support mode and other baseline indicators between the two groups. Compared with the standard treatment group, the improvement rate of PSI risk rating in Xuebijing group on the 8th day after admission was significantly improved [56.9% (41/72) vs. 20.8% (15/72), between-group difference and 95% confidence interval (95% CI) was 36.1% (21.3% to 50.9%), P < 0.01], PSI score, SOFA score and PaO 2/FiO 2 were significantly improved [PSI score: 83.7±34.8 vs. 108.2±25.6, between-group difference (95% CI) was -24.5 (-34.9 to -14.1); SOFA score: 2.0 (1.0, 4.0) vs. 7.0 (4.0, 10.0), between-group difference (95% CI) was -3.5 (-5.0 to -2.0); PaO 2/FiO 2 (mmHg, 1 mmHg = 0.133 kPa): 289.4±111.6 vs. 188.5±98.1, between-group difference (95% CI) was 100.9 (65.3 to 136.5); all P < 0.01]. The 28-day discharge rate of Xuebijing group was 44.5% higher than that of standard treatment group [66.7% (48/72) vs. 22.2% (16/72), P < 0.01], and the 28-day survival rate was 9.8% [91.7% (66/72) vs. 81.9% (59/72), P < 0.01]. There was no significant difference in the combination of antiviral drugs, antibiotics, anticoagulants and vasopressor drugs between the two groups. There was no significant difference in the incidence of adverse events between the Xuebijing group and standard treatment group [41.7% (30/72) vs. 43.1% (31/72), P > 0.05], and no serious adverse events and adverse reactions of Xuebijing were reported. Conclusion:Standard treatment combined with Xuebijing injection can significantly improve the PSI risk score and clinical prognosis of patients with severe COVID-19 without increasing drug safety risk.

Adaptation, Psychological ; Adolescent ; COVID-19 ; Child ; China ; Cross-Sectional Studies ; Female ; Humans ; Male ; SARS-CoV-2

Objective　To investigate the role of miR-132 in oxygen-glucose-deprivation （OGD） induced ischemic injury model using primary cortical neurons.Methods　Cultured primary cortical neurons were exposed to oxygen-glucose-deprivation （OGD）for 2 h followed by 24 h reperfusion.The cells were randomly divided into sham operation group (Sham),OGD group,lentivirus control group (LV-control),miR-132 low expression group (LV-anti-miR-132),and miR-132 overexpression group (LV-miR-132).CCK-8,real-time PCR,and Western blot were used to study the effects and mechanisms of miR-132 on primary cortical neurons injured by OGD.Results　The expression levels of miR-132 were significantly reduced in the OGD-induced ischemic injury model (P<0.05).The reduced expression of miR-132 aggravated OGD injury and significantly reduced cell viability in OGD-induced primary cortical neuron ischemic injury.On the contrary,the increased expression levels of miR-132 reduced OGD injury and increased cell survival.Western blot results showed that overexpression of miR-132 upregulated the levels of synapsin-1 and PSD95.Conclusion　Overexpression of miR-132 can improve OGD-induced ischemic injury and increase the survival of primary cortical neurons by upregulating the synapsin-1 and PSD95.

Objective To evaluate the cognitive function and its correlative factors in centenarians.Methods Forty-nine subjects in Zhongxiang city were included in this mass screening.Questionnaire was utilized to collect basic data,including age,gender,ability of daily life,depression,life habits,body mass index,and history of chronic diseases on all the subjects.And the mini-mental state examination(MMSE)was adopted to evaluate cognitive function of old people.T test and chi-square test were used to compare the difference in effectiveness of multiple different factors on cognitive function,while binary logistic regression analysis was used to assess the effects of multiple different factors on cognitive function.Results The mean score of the ability of different dimensions of cognitive function was (7.10 ± 2.71) in direction,(1.94 ±± 0.80) in memory,(0.61 ± 1.07) in attention and computation,(1.92 ± 0.86) in recall,and (4.73 ± 2.14) in speech,respectively,with total score of cognitive function of(16.30±6.02) in forty-nine centenarians.Normal cognitive function was found in 25 cases,and decreased cognitive function was found in 24 cases.Single factor logistic analysis indicated that body mass index(t=-3.399,P=0.001)and self-rating depression scale(t=-5.731,P＜0.001) were lower in patients with normal cognitive function than in patients with declined cognitive function.And smoking patients were associated with higher rates of normal cognitive function than the non-smoking patients(87.5％ vs.43.9％,x2 =5.091,P=0.028),and patients with normal hearing were associated with higher rate of normal cognitive function than patients with hearing loss(70.3 ％ vs.27.3 ％,x2 =9.01,P=0.030).Multivariate logistic analysis indicated that depression index(β=-14.40,P=0.001) and body mass index(β=-0.424,P=0.015) were independent effective factors for cognitive function.Conclusions Improvement of the condition of depression and controlling the body mass index are hopeful for recovering or postponing their cognitive impairment in centenarians.

BACKGROUND: The symptoms of allergic rhinitis (AR) greatly affect the quality of life (QoL) in the patients with AR. The correlations of nasal response to leukotriene D4 (LTD4) and histamine nasal provocation with health related QoL in AR are not clear. OBJECTIVE: To evaluate the correlations of nasal response to LTD4 and histamine nasal challenge with QoL in AR. METHODS: Patients randomly underwent LTD4 and histamine nasal challenge tests, completed the rhinoconjunctivitis quality of life questionnaire (RQoLQ), and rating the symptom severity score (total symptom score 4, TSS4) in the previous week. The correlations between nasal challenge tests induced nasal responses and QoL in RQoLQ were analyzed. RESULTS: A total of 25 eligible AR patients enrolled and finished both LTD4 and histamine nasal challenge and completed the questionnaire of RQoLQ. Histamine nasal challenge induced sneezing, increased nasal resistant were correlated with most of the dimensions (general, practical, nasal, eye problems, and quality of sleep, p < 0.05), while LTD4 nasal challenge induced sneeze, increased nasal resistant only correlated with nasal and ocular problems. On the contrary, the severity of the sneeze assessed by TSS4, was not correlated with QoL, while the severity of rhinorrhea, congestion, and nasal pruritus were correlated with nasal and practical problems, and nasal congestion was also correlated with ocular problems (r = 0.60, p = 0.01). CONCLUSION: LTD4 and histamine nasal challenge induced nasal responses were correlated with different clinical symptoms severity and QoL, which can be used as a good diagnosis and evaluation methods for the management of AR.
Diagnosis ; Estrogens, Conjugated (USP) ; Histamine ; Humans ; Leukotriene D4 ; Pruritus ; Quality of Life ; Rhinitis, Allergic ; Sneezing