High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective This study aimed to explore the effects and mechanisms of chronic intermittent exposure to alcohol on fear,anxiety and depression behavior in post-traumatic stress disorder mice.Methods Thirty-six 8-week-old male C57BL/6J mice were randomly divided into a control group(Control),a traumatic stress disorder(PTSD)group and a chronic intermittent alcohol exposure(PTSD+Alcohol)group.The PTSD mice were prepared via the plantar electric shock method and then chroni-cally exposed to alcohol for 14 days.The fear,anxiety and depression behaviors of each group of mice were observed via a behav-ioral test.Western blotting was used to detect the expression levels of the microglial markers ionized calcium binding adapter molecule 1(IBA1),postsynaptic density protein 95(PSD95),and synaptotagmin Ⅰ(SYT1)in the hippocampal tissue of the mice in each group.Immunofluorescence staining was performed to assess the expression levels of IBA1 and Synaptophysin(SYN)in the hippocampal tissue.An enzyme-linked immunosorbent assay(ELISA)was used to measure the release of tumor necrosis fac-tor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the hippocampal tissue.Results Compared with those in the control group,the ratio of freezing time in the conditioned fear chamber significantly increased,the number of open arm entries decreased,the immobility time in the forced swim test increased in the PTSD group,and the expression of IBA1 protein and TNF-α release increased,with decreased expression of SYN,PSD95 and SYT1(all P＜0.05).Compared with the PTSD group,the PTSD+Alcohol group presented significantly increased freezing time in the conditioned fear chamber,decreased locomotor distance and time spent in the center zone in the open field test,increased IBA1 protein expression,and increased release of TNF-α and IL-1β(all P＜0.05).Conclusion Chronic intermittent alcohol exposure can aggravate fear,anxiety and depression in post-traumatic stress model mice,and the mechanism may be related to the activation of microglia.

OBJECTIVE To study the pharmacokinetics and tissue distribution of cannabidiol（CBD）-cholesterol succinate monoester-g-carboxymethyl chitosan （CCMC） nano-micelles in rats， and to evaluate its anti-inflammatory effect. METHODS CBD- CCMC nano-micelles were prepared by dialysis method and the properties were characterized. SD rats were divided into CBD group and CBD-CCMC nano-micelles group with 6 rats in each group. The rats were given 100 mg/kg CBD and CBD-CCMC nano- micelle by intragastric administration， respectively （based on the CBD load）. Blood was collected from the posterior ophthalmic venous plexus at 0.5， 1， 1.33， 1.5， 1.75， 2， 4， 8， 24， 48 h after administration. The heart， liver， spleen， lung， kidney and muscle tissues of rats were separated at 0.25， 1.5， 10 and 24 h after administration of CBD and CBD-CCMC nano-micelle with the same dose. The drug content in plasma and tissues was determined， the pharmacokinetic parameters were calculated， and the tissue distribution was analyzed. The inflammatory model of Caco-2 cells was induced by lipopolysaccharide， after 24 h of treatment with 5， 10， and 15 µg/mL CBD and CBD-CCMC nanomicelles （based on loaded CBD）， its anti-inflammatory activity was investigated by measuring cell viability， transepithelial electrical resistance （TEER） and inflammatory cytokines IL-1β， IL-8 and TNF-α. RESULTS The prepared CBD- CCMC nano-micelles had a particle size of （230.6±1.8） nm， a polydispersity index of 0.170±0.053， a Zeta potential of （－13.5± 1.2） mV， an encapsulation rate of （86.35±0.56）% and a drug loading of （9.18±0.32）%， respectively； the solubility was 68.240 μg/mL. The pharmacokinetic results showed that the AUC0-48 h， AUC0-∞， half-life time and peak concentration of CBD-CCMC nano- micelle group were significantly increased/extended compared with CBD group （P＜0.05 or P＜0.01）. The results of the tissue distribution study showed that at the same time point， the drug distribution concentration of CBD-CCMC nanomicelles in the rat tissue was higher than that in the CBD group. Research on anti-inflammatory effects shows that compared with CBD of the same mass concentration, CBD-CCMC nano-micelles can significantly increase cell viability （P＜0.05 or P＜0.01）， enhance TEER， and reduce the levels of IL-8， IL-1β and TNF-α in cells （P＜0.01）， and the secretion levels of inflammatory cytokines IL-8， IL-1β and TNF- α were significantly decreased （P＜0.01）. CONCLUSIONS CBD-CCMC nano-micelles can increase the plasma concentration and tissue distribution concentration of CBD， and improve anti-inflammatory activity of CBD.

Clinical microbiology examination technology experiment is an important part of clinical microbiology examination technology teaching. In the experimental teaching of clinical microbiology examination technology, the virtual simulation technology was combined with traditional teaching to give full play to the advantages of the virtual experimental platform. As to experimental projects that couldn't be carried out in traditional teaching and some important experimental projects, students could learn on the virtual experimental platform, and after learning, they would participate in the corresponding assessment. The perfect combination of the two can solve the problem of high experimental cost and limited experimental content in the current experimental class, make up for the shortcomings of traditional teaching, realize the sharing of teaching resources. Besides, it can strengthen the students' experimental operation skills and enhance the interest of learning for cultivation of application-oriented medical talents.

Objective To explore the perioperative outcomes and safety of enhanced recovery after surgery (ERAS) in laparoscopic radical cystectomy (LRC).Methods We retrospectively evaluated outcome of 10 LRC patients on ERAS protocol from May 2017 to October 2017,and 39 LRC patients on conventional recovery after surgery(CRAS) protocol from July 2015 to November 2016.There were (60.9 ±11.4) years and (63.7 ± 12.1) years in ERAS group and CRAS group respectively(P =0.514);(25.5 ±2.7) kg/m2 and (24.4 ± 3.6) kg/m2 with body mass index (P =0.375).Both of the median of charlson comorbidity index (P =0.931) and American Society of Anesthesiologists score (P =0.254) were 2 There was no statistical significance between the two groups for type of urinary diversion and preoperative laboratory studies (P ＞ 0.05).Patients' perioperative outcomes,early (30-day) complications and postoperative readmission rate were compared.Results The ERAS group had less intraoperative crystalloid infusion [(950.0 ± 474.3) ml vs.(1 797.4 ± 448.1) ml,P ＜ 0.001],faster removed gastric tube (0 d vs.4 d,P ＜0.001),and shorter passing flatus time [(1.6 ± 0.8) d vs.(2.9 ± 1.4) d,P =0.006] than the CRAS group;however,no difference was found in terms of intraoperative colliod infusion [(1 110.0 ± 331.5)ml vs.(1 117.9 ± 397.9) ml,P =0.954].No patients from either group required conversion to open surgery.There was no significant difference between the two groups for operative time (P =0.311),estimated blood loss (P =0.073),drain days (P =0.681),postoperative hospital stay (P =0.509),overall blood transfusion (P =1.000),intensive care unit stay (P =1.000) and tumor characteristics (pathological stage,histology,nodes removed,positive nodes,lymph node-positive patients,positive surgical margins).The 30-day postoperative complications were documented in 5 (50％)and 23 (59％)patients in groups ERAS and CRAS (P =0.878),respectively.And the most common complication were minor complications (Clavien-Dindo grade 1 and 2) in both groups (100.0％ vs.86.9％,P =0.729).The 30-day readmission rate was 20.0％ (2 patients) in ERAS group and 10.3％ (4 patients) in CRAS group with no statistical significance(P =0.588).Conclusions Our ERAS protocol expedited bowel function recovery after RC and urinary diversion without increasing in 30-day complications compared with CRAS.The key of implement ERAS pathway is to explore and develop their own protocol conformed to their medical treatment enviroment.

Objective To explore the influence of agricultural mechanization progress on epidemic intensity of hemorrhagic fever with renal syndrome (HFRS) so as to provide reference for prevention and control of HFRS in rural areas.Methods Data of HFRS epidemics and agricultural mechanization progress of Qingdao City and five main epidemic areas of HFRS were collected by retrospective analysis methods.Agricultural mechanization progress,time distribution,incidence rate of HFRS and capture rate of rats were compared,respectively.Risk factors were analyzed by case-control study using simple random sampling method.Cases of case group were selected from HFRS cases of Jiaonan County recovered between 2012 and 2013.The control group was healthy residents with a equal number of the case group.Residential locations,work ways,rodent infestation at work locations and in residential areas and skin injury conditions were surveyed by a household questionnaire survey.Results Agricultural machinery gross power of Qingdao City was developed from 174.76 megawatts of electricity (mwe) in 1985 to 854.00 mwe in 2015.The comprehensive mechanization degree marched from 60.0％ in 1994 to 90.2％ in 2015.HFRS incidence in Qingdao City declined from the first epidemic peak (1986) of 32.97/100 000 to the third peak (2012) of 3.54/100 000.HFRS incidence in Jiaonan,Jiaozhou,Pingdu,Laixi,Jimo cities reduced from the first epidemic peak (1985 or 1986) of 101.25/100 000,86.37/100 000,35.80/100 000,11.55/100 000,8.13/100 000 to the third peak(2012) of 14.68/100 000,4.43/100 000,2.33/100 000,6.02/100 000,3.26/100 000.The platform stage of epidemic peak in autumn and winter shortened from 4 or 5 months to 2 months.The capture rate of rats fluctuated around 2％.The infection risk of small farm implements or handwork was greater than huge mechanization (OR =0.01,P ＜ 0.01).Conclusions Agricultural mechanization changes the agricultural activity patterns to a large extent and lowers the HFRS epidemic by minimizing the risk of infection and shortening the platform stage of epidemic peak.The higher the degree of mechanization,the lower the epidemic intensity.

Objective To investigate the influence of the variations of an epidemic focus on hemorrhagic fever with renal syndrome (HFRS) so as to provide a basis for effective control of HFRS.Methods HFRS epidemic data from the rapid development of urbanization of Huangdao District and the general development of Jiaonan City were collected and analyzed retrospectively from 1979 to 2014.And the HFRS cases,incidences,host animals and Hantavirus surveillances were compared.Results The three epidemic peaks occurred from 1979 to 2014 in Huangdao District and Jiaonan City,they were in the mid-1980s (1983-1987),the late 1990s (1995-1999) and around 2012 (2010-2014),and 954,80,37 and 2 506,614,432 cases were reported,respectively,in Huangdao District and Jiaonan City.The three peak years were 1986,1999 and 2012.And the annual incidences of Huangdao District were 385.73/100 000,15.64/100 000 and 2.51/100 000,respectively.The annual incidences of Jiaonan City were 67.07/100 000,28.68/100 000 and 14.68/100 000,respectively.The three peaks obviously appeared double peaks [the autumn and winter (from Oct.to Dec.) and the spring (from Jan.to Feb.)] in Jiaonan City.And the first peaks in Huangdao District was in the autumn and winter (from Oct.to Dec.) and the spring (from Jan.to Feb.),the second and the third were only in the autumn and winter (from Oct.to Dec.).Eight kinds of host animals were detected in Jiaonan City from 2005 to 2014.They were house mouse [27.53％ (1 108/4 024)],brown rat [25.50％ (1 026/ 4 024)],striped field mouse [14.84％ (597/4 024)],black rat [10.74％ (432/4 024)],hamsters [11.01％ (443/4 024)],shrew [8.72％ (351/4 024)],back grain hamster [1.02％ (41/4 024)] and club rat [0.65％ (26/4 024)].Two kinds of host animals were detected in Huangdao District.They were house mouse [57.14％ (16/28)] and brown rat [42.86％ (12/28)].The capture rates in Jiaonan City were higher than those of Huangdao District.The capture rate in 2012 was 8.04％ (855/10 638) and the capture rates in Huangdao District were all lower than 0.84％.The total detection rate in Jiaonan City was 2.81％ (113/4 024).And there was no positive detection for ten years in Huangdao District.Conclusions HFRS epidemic intensities have receded gradually in Huangdao District and Jiaonan City.The epidemic in Huangdao District obviously presents a low epidemic condition after the first peak.The few kinds and low densities of host animals are resulting in the sustainable condition.The evolution of epidemic patterns of HFRS is related to the change of epidemic sources by the differences in urbanization between the two places.

Objective To investigate the influence of host animals on epidemics of hemorrhagic fever with renal syndrome (HFRS) so as to provide a basis for effective control of HFRS.Methods From the national infectious disease network direct reporting system,the incidence of HFRS cases diagnosed by direct diagnosis of medical institutions in Qingdao was collected from 2011-2015.We captured rats indoor and outdoor by night trapping method quarterly and calculated the capture rates from 2011-2015 in Qingdao areas.The incidence of HFRS in different regions and the change of seasonal growth,the distribution of host animals,the characteristics and distribution of animals,and the seasonal variation of dominant species were analyzed and a database was set up and statistic analysis was conducted by SPSS 13.0.Results The peak incidence rate of HFRS in Qingdao areas occurred in 2012 (3.54/100 000) and presented a decrease trend year by year (x2 =64.15,P ＜ 0.05),but there were different characteristics among the epidemic areas,and lowest in 2015 (1.68/100 000).And the peak presented a two-peak pattern which was mainly an autumn peak and a gentle peak in late spring and early summer.The epidemics were gradually decreased from the rural areas to the urban fringes and then the urban areas.The seasonal variation was disappeared gradually.There was a heavy epidemic intensity in areas with a high capture rate and a complex type of host animals.The epidemic peak was in consistence with the distribution of rats.Capture rates were different among the epidemic areas.The capture rate in Jiaonan was the highest [5.32％(2 886/54 287)] and lowest in Pingdu [1.77％ (258/14 584)].The mean (x2 =820.39,P ＜ 0.05) and annual capture rates (x22011-2015 =32.61,356.24,233.07,129.33,33.42,all P ＜ 0.05) among epidemic areas were different.In the third quarter the accumulated capture rate was the highest [4.69％ (1 187/25 301)].In total 8 kinds of host animals were captured and the dominant species were brown rat [30.27％ (1 235/4 080)],house mouse[29.75％ (1 214/4 080)] and striped field mouse [16.25％ (663/4 080)].Conclusions The epidemic intensity of HFRS is related to the densities and the types of host animals.The gradually decreased epidemic pattern from the rural areas to the urban fringes and then the urban areas may be related to urbanization and improved health behaviors.

Objective To observe the effects of Bushen Huoxue Decoction on clinical symptom, vertigo degree and cognitive function for elderly patients with chronic cerebral circulation insufficiency (CCCI); To explore its possible mechanism. Methods Totally 70 cases were randomly divided into observation group and control group according to the random digits table method, with 35 cases in each group. The two groups were given Western medicine consisting of blood pressure control, glucose control and blood lipid control. Based on this, the control group was given Flunarizine Hydrochloride capsules, 5 mg once a day orally before sleeping. The observation group was given Bushen Huoxue Decoction, one dose a day and taken twice a day. The treatment lasted for 30 days. The TCM symptom score, Chinese version of dizziness handicap inventory (DHI) and Montreal cognitive assessment (MoCA) score were observed. The mean blood flow velocity (Vm) of basilar artery (BA), bilateral vertebral artery (VA), bilateral middle cerebral artery (MCA) and the content of plasma acid phospholipid (AP) were detected, and the clinical efficacy was evaluated. Results The total effective rate of the observation group was 94.3％ (33/35), which was significantly higher than that of 82.9％ (29/35) in the control group, with statistical significance (P<0.05); after treatment, the TCM symptom score, DHI score, and the content of plasma AP were significantly lower than those of pre-treatment in the same group (P<0.05); the MoCA score and the Vm of VA, LBA, RBA, LMCA, RMCV were significantly higher than those of pre-treatment in the same group (P<0.05); the TCM symptom score, DHI score, MoCA score, the Vm of LVA, LMCA, RMCA and the content of plasma AP in the observation group were improved better than those in the control group, with statistical significance (P<0.05). Conclusion Bushen Huoxue Decoction has an obvious therapeutic effects for elderly patients with CCCI, which can improve clinical symptom, vertigo degree and cognitive level, which possible mechanism is related to increasing the cerebral blood flow velocity and reducing the content of plasma AP.