Objective To investigate the effect of dexmedetomidine(Dex)on the rat model of perioperative stroke and its mechanism.Methods One hundred male rats were randomly divided into sham group,middle cerebral artery occlusion(MCAO)group,low dose Dex[Dex-L,0.5 μg/(kg·h)]group,medium dose Dex[Dex-M,2 μg/(kg·h)]group,high dose Dex[Dex-H,10 μg/(kg·h)]group,20 rats in each group.A rat model of perioperative stroke was established by middle cerebral artery occlusion.Dex was injected intravenously at different doses during ischemia.After 24 h,the neurological function of the rats was evaluated.Then,the rats were sacrificed and the peripheral blood and whole brain tissue were collected,ischemic core area tissue was separated from some brain tissues and the cerebral infarction area was observed by TTC staining.The inflammatory cytokine contents in serum and ischemic core area were measured by ELISA.In addition,the expressions of formyl peptide receptor 1(FPR1),transmembrane protein 119(TMEM119),CD31 and VE-cadherin proteins were assayed by immunofluorescence,and the expressions of FPR1,nuclear factor-κB(NF-κB)and NLRP3 proteins by Western blotting in the ischemic core area.Results Compared with sham group,the proportion of cerebral infarction area and neurological scores in the MCAO group were significantly increased,and the contents of interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α in the serum and the ischemic core area were significantly increased,the expressions of FPR1,TMEM119,p-NF-κB,NLRP3,CD31 and VE-cadherin in the ischemic core were significantly increased(P<0.001),and there was obvious co-expression of FPR1 and TMEM119.Compared with MCAO group,the proportion of cerebral infarction area and neurological scores in the Dex-M and Dex-H groups were significantly decreased,and the contents of IL-1β,IL-6 and TNF-α in serum and brain ischemic core area were significantly decreased,the expressions of FPR1,TMEM119,p-NF-κB,NLRP3,CD31 and VE-cadherin in the ischemic core were significantly decreased(P<0.001).Conclusions Dex can significantly alleviate perioperative stroke injury.The mechanism may be due to inhibiting the expression of FPR1 protein,activation of microglia cells and cerebral collateral circulation angiogenesis.

OBJECTIVE: To observe the effects of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture therapy on the expression of hypoxia-inducible factor 1α (HIF-1α) and Nod-like receptor protein 3 (NLRP3) in cerebral ischemia-reperfusion rats, and to explore the mechanism of acupuncture against cerebral ischemia-reperfusion injury. METHODS: Seventy-two male SD rats were randomly divided into a sham-operation group, a model group, an acupuncture group and a non-point acupuncture group, with 18 rats in each one. Using modified Longa thread embolization method, the rat model of acute focal cerebral ischemia was prepared; and after 2 h ischemia, the reperfusion was performed to prepared the model of cerebral ischemia-reperfusion. Immediately after reperfusion, Xingnao Kaiqiao acupuncture method was applied to bilateral "Neiguan" (PC 6) and "Shuigou" (GV 26) in the acupuncture group, while in the non-point acupuncture group, acupuncture was delivered at non-points and all of the needles were retained for 30 min in these two groups. The samples were collected 24 h after reperfusion in the rats of each group. Zea-Longa neurological deficit score was used to evaluate the degree of cerebral neurological impairment, TTC staining was adopted to observe the volume percentage of cerebral infarction, HE staining was provided to observe the morphological changes of brain, and Western blot was applied for detecting the expression of HIF-1α and NLRP3 proteins in the cerebral cortex on the right side. RESULTS: Compared with the sham-operation group, neurological deficit score and volume percentage of cerebral infarction were increased in the model group (P<0.01), and HIF-1α and NLRP3 protein expression was elevated (P<0.01). Compared with the model group, neurological deficit score and volume percentage of cerebral infarction were decreased (P<0.01), and HIF-1α and NLRP3 protein expression was lower (P<0.01) in the acupuncture group. There was no significant difference in above indexes in the non-point acupuncture group compared with the model group (P>0.05). Compared with the sham-operation group, the brain tissue of the rats in the model group and the non-point acupuncture group was loose and edema, and the nuclei were shriveled. The brain tissue morphology in the acupuncture group was similar to that of the sham-operation group. CONCLUSION Acupuncture can alleviate cerebral ischemia-reperfusion injury, and its mechanism may be related to the regulation of HIF-1α/NLRP3 signaling pathway to attenuate inflammatory response.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Acupuncture Therapy ; Reperfusion Injury/therapy* ; Brain Ischemia/therapy* ; Cerebral Infarction/therapy* ; NLR Proteins

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
Humans ; Polymyxin B/adverse effects* ; Retrospective Studies ; Gram-Negative Bacterial Infections/complications* ; Fever/drug therapy* ; Sepsis/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/complications*

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVE: To compare the clinical effect of electroacupuncture at Siguan points and flunarizine hydrochloride capsule on migraine of liver yang hyperactivity. METHODS: A total of 110 patients with migraine of liver yang hyperactivity were randomly divided into an electroacupuncture group (55 cases, 2 cases dropped off) and a western medication group (55 cases, 2 cases dropped off). In the electroacupuncture group, electroacupuncture was applied at Siguan points (Hegu [LI 4] and Taichong [LR 3]), with disperse-dense wave of 2 Hz/100 Hz in frequency and current intensity of 0.1-1 mA, 30 min each time, once a day, 5 times per week for 4 weeks. Flunarizine hydrochloride capsule was given orally in the western medication group, 10 mg a day for 4 weeks. The visual analogue scale (VAS) score and the migraine attack days were observed before and after treatment, during follow-up of 1, 3 and 6 months, and the migraine symptom score was observed before and after treatment in the two groups. RESULTS: After treatment, during follow-up of 1, 3 and 6 months, the VAS scores and the migraine attack days in the two groups were decreased compared with before treatment (Ｐ<0.05), and above indexes in the electroacupuncture group were lower than the western medication group (Ｐ<0.05). After treatment, the migraine symptom scores in the two groups were decreased (Ｐ<0.05), the change in the electroacupuncture group was greater than the western medication group (Ｐ<0.05). CONCLUSION Electroacupuncture at Siguan points could effectively reduce headache intensity and migraine attack days, relieve migraine symptoms in patients with migraine of liver yang hyperactivity, and the efficacy is superior to oral flunarizine hydrochloride capsules.
Acupuncture Points ; Electroacupuncture ; Flunarizine/therapeutic use* ; Humans ; Liver ; Migraine Disorders/therapy*

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Aim To study the antiviral anrl antipyretic mechanism of Phillvrin in vitro and in vivo.Methods By respiratory virus infection cell model, SI index and antiviral activity of forsythia glycosides virus activity in vitro were detected.A mouse model of influenza virus infection was established, and hemagglutination titer, lung index, lung histopathology pathology were detec¬ted.Hemagglutination titer, lung index, lung histopa¬thology pathology were observed and in vivo anti-influ¬enza virus and pneumonia effects were investigated.Dry yeast induced rat fever model was established, temperature and plasma and hypothalamus thermoregu¬lation and inflammation of the related factors were test¬ed , and its antipyretic mechanism was investigated.By AutoDock Vina software for molecular docking, the docking results were plotted with PyMol software.Re¬sults Phillyrin had certain inhibitory effects on H3N2, RSV, E71 , ADV-3, HSV-1 and HSV-2 (SI >2).Phillyrin could reduce hemagglutination titer of infected lung tissue, decrease lung index, and alleviate lung lesions, especially interstitial pneumonia.Phill- vrin could also significantly reduce the body tempera¬ture of rats with fever, and its antipyretic mechanism might he related to the decrease of PGE2 and IL-ip levels in plasma and hypothalamus of rats.Molecular docking results showed that the binding energies of Phillyrin with a-MSH, IL-lp, PEG2, A VP, cAMP and other proteins were all less than - 5 kcal • mol 1.Conclusions Phillyrin has obvious antiviral, antipy-retic and improvement of pulmonary inflammatory le¬sions, and it is speculated that it can play an anti-in¬fluenza effect through "treating both symptoms and root causes".

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Antibodies, Monoclonal/therapeutic use* ; Antibodies, Monoclonal, Humanized ; China ; Double-Blind Method ; Humans ; Psoriasis/drug therapy* ; Severity of Illness Index ; Treatment Outcome

: ]Objective:To investigate the efficacy and safety of induction regimens containing arsenite, allo-transretinoic acid (ATRA) and anthracyclines of different doses as induction chemotherapy for acute promyelocytic leukemia (APL). METHODS: The clinical data of 129 consecutive hospitalized newly diagnosed APL patients from January 2011 to December 2017 were collected and retrospectively analyzed. Sixty-six patients received arsenite, ATRA and anthracyclines of low doses (low dose group), while other 63 patients received arsenite, ATRA and anthracyclines of standard doses (standard dose group), the efficacy and safety were compared and analyzed in 2 groups. RESULTS: There were no statistically significant differences in terms of age, sex, routine blood indexes,LDH level, bone marrow promyelocyte count,prognostic stratification between patients in two groups (P>0.05). During the treatment, WBC count peak and its time point were not significantly different between two groups (P>0.05). Both induction regimens showed good efficacy, the PML-RARα gene conversion rate from positive into negative, the 2-year overall survival rate and disease-free survival rate in the low-dose group were similar to those in the standard dose group(P＞0.05). The recovery time of neutrophils and platelets in the low-dose group was 0 d and 11 d, respectively, which were statistically  significantly shorter than those in the standard dose group (3 d,15 d) (both P=0.000). The median value of platelet and erythrocyte transfusion in the low-dose group was 6.9 U and 4.2 U, respectively, which were statistically significantly lower than that in the standard dose group (8.4 U,6.8 U) (P=0.037，0.000). And the inpatient time in the low and the standard dose groups were 30.98 and 30.71 days, respectively (P=0.770). CONCLUSION For newly diagnosed patients with APL, the efficacy was similar between induction therapy containing arsenite,ATRA and low dose anthracyclines and the induction therapy containing arsenite, ATRA and standard dose anthracyclines, however, the former appears even safer.
Anthracyclines ; Antineoplastic Combined Chemotherapy Protocols ; Humans ; Leukemia, Promyelocytic, Acute ; Remission Induction ; Retrospective Studies ; Treatment Outcome ; Tretinoin

Exosomes and long non-coding RNAs (lncRNAs) are emerging as important elements contributing to a more comprehensive understanding of cancer development and progression. The discovery of lncRNAs in exosomes further indicates their bona fide biological functional roles in cancer development and drug resistance. In this review, we describe the biogenesis of exosomes and summarize the function of exosomal lncRNAs in the field of cancer research. These findings strikingly advance current knowledge of exosomal lncRNAs and suggest that they may be promising diagnostic biomarkers and therapeutic targets for cancer.
Exosomes ; physiology ; Humans ; Neoplasms ; diagnosis ; genetics ; therapy ; RNA, Long Noncoding ; physiology