Objective To evaluate the effect of small-dose ketamine on the onset time and course of modified electroconvulsive therapy (MECT) in mentally depressed rats.Methods Sixty SPF adult male SpragueDawley rats,aged 2-3 months,weighing 220-250 g,were randomly divided into 6 groups (n =10 each) using a random number table:normal control group (group C),depression group (group D),ECT group,propofol + ECT group (group PE),ketamine + ECT group (group KE) and ketamine + propofol + ECT group (group KPE).The depression model was established by chronic unpredictable mild stress (CUMS).Mter CUMS,C,D and ECT groups received intraperitoneal normal saline 8 ml/kg,group PE received intraperitoneal propofol 100 ml/kg,group KE received intraperitoneal ketamine 10 ml/kg,and group KPE received intraperitoneal ketamine 10 ml/kg + propofol 80 ml/kg.All the groups received ECT once a day for 7 consecutive days starting from the time point when righting reflex was lost except C and D groups.Open-field test was performed before CUMS,at 1 day after CUMS and at the end of each ECT (T0 8).The total distance and the number of standing on the back legs were recorded.Morris water maze test was performed at 2 days after CUMS and 1 day after the end of therapy,and the escape latency and time of staying at the original platform quadrant were recorded.Results Compared with group C,the total distance was shortened and the number of standing on the back legs was reduced,the escape latency was prolonged,and the time of staying at the original platform quadrant was shortened at T1-8 in D,ECT,PE and KE groups and at T1 5 in KPE group,and no significant was found in KPE group in the total distance,number of standing on the back legs,escape latency,and time of staying at the original platform quadrant at T6-8.Compared with group D,the total distance was prolonged and the number of standing on the back legs was increased at T6-8 in ECT and PE groups and at T4-8 in KE and KPE groups,the escape latency was prolonged,and the time of staying at the original platform quadrant was shortened in ECT group,and the escape latency was shortened,and the time of staying at the original platform quadrant was prolonged in KPE group.Compared with ECT and PE groups,the total distance was prolonged and the number of standing on the back legs was increased at T4-7 in group KE and at T4-8 in group KPE,and the escape latency was shortened,and the time of staying at the original platform quadrant was prolonged in KPE group.Compared with group KE,the total distance was prolonged and the number of standing on the back legs was increased at T6.7,the escape latency was shortened,and the time of staying at the original platform quadrant was prolonged in KPE group.Conclusion Small-dose ketamine can shorten the onset time and course of MECT in mentally depressed rats.

Objective To evaluate the effect of therapeutic hypercapnia preconditioning on lung ischemia-reperfusion (I/R) injury in rats.Methods Forty healthy adult Sprague-Dawley rats of either sex,aged 2 months,weighing 250-300 g,were divided into 5 groups (n=8 each) using a random number table:sham operation group (group S),grouP I/R and preconditioning with therapeutic hypercapnia of different level groups (group THP1-3).Lung I/R injury was induced by clamping the left hilum of lung for 45 min followed by 120 min of reperfusion.In THP1-3 groups,the respiratory parameters were adjusted at 5 min of stability after isolating the left hilum of lung to make PETCO2 reach 55-65,65-75 and 75-85 mmHg respetively and maintained at this level for 5 min,normal ventilation was then used to make PETCO2 restore the normal level,continuously repeating for 3 circles,and then the left hilum of lung was blocked for 45 min followed by 120 min of reperfusion.The bronchoalveolar lavage fluid (BALF) was collected at the end of reperfusion for determination of the total protein (TP) concentration using Coomassie brilliant blue staining.Lung tissues were obtained at the end of reperfusion for examination of pathological changes after haematoxylin and eosin staining (under a light microscope) and for determination of wet/dry weight ratio (W/D ratio),malondialdehyde (MDA) content,superoxide dismutase (SOD) activity,interleukin-8 (IL-8) and IL-10 contents (by enzyme-linked immunosorbent assay),tumor necrosis factor-alpha (TNF-α) expression (by immunohistochemistry) and expression of TNF-α mRNA (by real-time polymerase chain reaction).Results Compared with group S,the TP concentration in BALF,W/D ratio and contents of MDA,IL-8 and IL-10 in lung tissues were significantly increased,the SOD activity was decreased,the expression of TNF-α mRNA was up-regulated (P＜0.05),strong positive expression of TNF-α was found,and the pathological changes of lung tissues were aggravated in group I/R.Compared with group I/R,the TP concentration in BALF,W/D ratio and contents of MDA and IL-8 in lung tissues were significantly decreased,the SOD activity was increased,the expression of TNF-α mRNA was down-regulated (P＜0.05),no significant change was found in IL-10 content (P＞0.05),the staining range and intensity of TNF-α were decreased,and the pathological changes of lung tissues were significantly attenuated in THP1-3 groups.Conclusion Therapeutic hypercapnia preconditioning can reduce lung I/R injury in rats,and the mechanism is related to inhibiting inflammatory responses and oxidative stress responses.

Objective: To investigate the incidence of adverse events following immunization (AEFI) of human papillomavirus (HPV) vaccines in Hangzhou City from 2017 to 2021, so as to provide insights into safety monitoring and evaluation for HPV vaccines. Methods: The AEFI caused by immunization of bivalent (HPV2), quadrivalent (HPV4) and nonavalent HPV vaccines (HPV9) reported in Hangzhou City from 2017 to 2021 were captured from the AEFI Surveillance Module of Chinese Disease Control and Prevention Information System, and HPV vaccination data were captured from the Zhejiang Municipal Immunization Information Management System. The incidence, temporal distributions and clinical symptoms of AEFI were analyzed. Results: Totally 922 310 doses of HPV vaccines were immunized in Hangzhou City from 2017 to 2021, and 232 cases with AEFI were reported, with an overall incidence rate of 25.15/105 doses. The reported incidence rates of AEFI caused by HPV2, HPV4 and HPV9 vaccination were 31.13/105 doses, 25.93/105 doses and 22.01/105 doses, respectively. General reactions and abnormal reactions were predominant AEFI, and the reported incidence rates of general reactions and abnormal reactions were 21.58/105 doses and 2.60/105 dose, respectively. AEFI predominantly occurred 0 to 1 day post-immunization (165 cases, 71.12%), and the main clinical symptoms included local swelling of injection sites, hard tubercle and fever, with reported incidence rates of 10.30/105 doses, 5.96/105 doses and 6.18/105 doses, respectively. Conclusions Low incidence of AEFI was reported following HPV vaccination in Hangzhou City from 2017 to 2021, and all AEFI were mild. The safety of HPV2, HPV4 and HPV9 remains high.

Objective To evaluate the effects of exendin-4 on glial brillary acidic protein (GFAP ) and interleukin-1β(IL-1β) expression in hippocampi of aged rats .Methods Forty-eight healthy male Sprague-Dawley rats ,aged 22-24 weeks ,weighing 500-700 g ,were randomly divided into 4 groups (n=12 each) using a random number table:control group (group C ) ,exendin-4 group (group E ) ,operation group (group O ) and exendin-4 plus operation group (group OE) .The rats were anesthetized with intraperitoneal fentanyl and droperidol .Groups C and E did not receive anesthesia or splenectomy .In O and OE groups ,splenectomy was carried out .In E and OE groups , exendin-4 5 μg/kg was injected intraperitoneally at 30 min before skin incision and 12 h after operation .C and O groups received the equal volume of normal saline instead of exendin-4 .Learning and memory function was assessed using Morris water maze test (escape latency (EL) and total swimming distance (TSD) at 1 day before operation (T0 ) .The fasting blood glucose was measured after anesthesia (T1 ) ,at the end of operation (T2 ) and on postoperative day 1 (T3 ) .The rats were sacrificed after assessment of the cognitive function at T 3 and the hippocampi were removed for determination of the expression of GFAP (by immuno-histochemistry ) and IL-1β(by Western blot ) .Results There was no significant difference in the EL and TSD at T0 between the four groups ( P>0.05) .Compared with group C ,the EL and TSD were significantly prolonged at T3 and fasting blood glucose was increased at T2 ,3 ,and the expression of IL-1βand GFAP was up-regulated at T3 in O and OE groups ( P<0.05) .Compared with group O ,the EL and TSD were significantly prolonged at T3 and fasting blood glucose was decreased at T2 ,3 ,and the expression of IL-1βand GFAP was down-regulated at T3 in group OE ( P<0.05) . Conclusion Exendin-4 can improve the postoperative cognitive function of aged rats by inhibiting inflammatory responses in hippocampi and maintaining stable perioperative blood glucose .

OBJECTIVETo investigate the effects of polygala on leaning and memory and the expression of Microtubule associated protein on manganese poisoned mice.

METHODS60 female Kunming mice were randomly and equally divided into 5 group. They are normal control group (CG), manganese poisoned group (MG), manganese poisoned with polygala high dose group (MHG), manganese poisoned with polygala middle dose group (MMG), manganese poisoned with polygala low dose group (MLG). The model of manganese poisoned mice was prepared of the way of intraperitoneal injection of manganese chloride (MnCl2 15 mg/kg), the spatial learning and memory ability was tested by Morris water maze, the Doublecortin (DCX) was tested by the way of immunofluorescent staining in the SVZ and SGZ.

RESULTIn the navigation test, compared with MG, the escape latency of MHG, MMG and MLG were significantly decreased (P < 0.05), in space exploration experiments, MHG, MMG, MLG compared with MG, the number increased significantly across platforms (P < 0.05). compared with MG, the DCX expression of MHG, MMG and MLG were significantly increased (P < 0.05).

CONCLUTIONThe leaning and memory ability of manganese poisoned mice can be improved by the polygala, and the mechanism may be related to promote the expression of DCX and neurogenesis in the brain.

Animals ; Female ; Manganese Poisoning ; drug therapy ; Maze Learning ; drug effects ; Memory ; drug effects ; Mice ; Microtubule-Associated Proteins ; drug effects ; Neurogenesis ; drug effects ; Neuropeptides ; drug effects ; Plant Extracts ; pharmacology ; Polygala ; chemistry

Objective To evaluate the value of endoscopic ultrasonography( EUS) alone for early liver cirrhosis and the diagnostic efficacy of EUS combined with liver histopathology ( LH) and liver stiffness measurement ( LSM) for early liver cirrhosis. Methods Data of 226 patients with chronic liver lesions who underwent endoscopy and EUS at Tianjin Second People's Hospital were collected to assess esophageal and gastric varices. Liver fibrosis was assessed by LH and LSM was determined by Fibroscan. Models of EUS-LSM, EUS-LH, LSM-LH, ELL ( EUS, LSM and LH) were constructed to predict early liver cirrhosis. The ROC curve and AUROC were used to evaluate the efficacy of different models in the diagnosis of early liver cirrhosis. Results A total of 149 patients were diagnosed as chronic liver disease and 77 patients were diagnosed as early liver cirrhosis ( Child-Pugh A grade) by clinical evaluation. Ratio of varices found by EUS was significantly higher than that by endoscopy [ 68. 8％ ( 53/77) VS 32. 5％ ( 25/77) , P<0. 05] . The cut-off value was 8. 65 kPa by LSM to predict early liver cirrhosis. Pseudolobules were confirmed by LH in 42 ( 54. 5％) patients in the early liver cirrhosis group. The AUROC of ELL was 0. 919 ( 95％CI: 0. 875-0. 951),sensitivity=0. 792,specificity=0. 913,PPV=0. 824,NPV=0. 895,+LR=9. 08,-LR=0. 23, accuracy=0. 872, and ELL was superior to EUS ( P<0. 0001) , LSM ( P<0. 0001) , LH ( P<0. 0001) , EUS-LSM (P<0. 0001), EUS-LH (P=0. 0134) and LSM-LH (P=0. 0022) in the diagnosis of early liver cirrhosis. Conclusion EUS is superior to endoscopy in detecting the varices for early liver cirrhosis. Combination of EUS with LSM and LH can improve diagnostic efficacy for early liver cirrhosis.

BACKGROUND:Platelet-rich fibrin(PRF)has many advantages,such as simple preparation,low production cost,and high safety,and has been widely used in the study of bone defect repair in oral and maxillofacial surgery,but there are problems such as too fast degradation rate and short release time of growth factors. OBJECTIVE:PRF was loaded into gelatin methacryloyl(GelMA)hydrogel and its osteogenic properties were analyzed by in vivo and in vitro experiments. METHODS:(1)New Zealand white rabbit venous blood was extracted to prepare PRF.GelMA hydrogels containing 0,0.05,0.075,and 0.1 g PRF were prepared,respectively,and were recorded as GelMA,GelMA/PRF-0.05,GelMA/PRF-0.075,and GelMA/PRF-0.1,respectively,to characterize the micromorphology and in vitro slow-release properties of the hydrogels.(2)Four kinds of hydrogels were co-cultured with MC3T3-E1 cells,respectively,and the cell proliferation activity was detected with the single cultured cells as the control.After osteogenic induction,alkaline phosphatase activity,mineralization ability,mRNA and protein expression levels of osteogenic genes(osteocalcin,osteopontin,RUNX2),ERK1/2-p38 MAPK pathway protein mRNA and protein expression levels were detected.(3)Fifteen New Zealand white rabbits were taken.Four full-layer bone defects of 8 mm diameter were prepared in the skull of each rabbit,one of which was implanted without any material(blank control group),and the other three were implanted with GelMA hydrogel,PRF,and GelMA/PRF-0.1 hydrogel,respectively.The bone defect was detected by Micro-CT and bone morphology was observed at 4,8,and 12 weeks after operation. RESULTS AND CONCLUSION:(1)Scanning electron microscopy observed that all the hydrogels of the four groups had honeycomb pore structure,and the pore size of the hydrogels decreased slightly with the increase of PRF content,but there was no significant difference between the groups.The three groups of GelMA/PRF hydrogel could release transforming growth factor β1 and insulin-like growth factor 1 at a certain rate,and the cumulative release of transforming growth factor β1 and insulin-like growth factor 1 increased significantly with the extension of time.(2)CCK-8 assay and live/dead staining showed that GelMA/PRF hydrogel could promote the proliferation of MC3T3-E1 cells.The results of alkaline phosphatase staining,alizarin red staining,and osteogenic gene detection showed that GelMA/PRF hydrogel could promote the osteogenic differentiation of MC3T3-E1 cells,and inhibit the expression of ERK1/2-p38 MAPK pathway protein,and showed a PRF content dependence.(3)Micro-CT scan showed that the bone mineral density and bone volume fraction in the bone defect of GelMA/PRF-0.1 hydrogel group were higher than those in the other three groups(P<0.05).Hematoxylin-eosin staining showed that compared with the other three groups,GelMA/PRF-0.1 hydrogel group had faster and more mature new bone formation at the bone defect.(4)These findings indicate that GelMA/PRF hydrogel has good osteogenic activity both in vivo and in vitro,which may be related to inhibiting the expression of ERK1/2-p38 MAPK pathway protein.

Extracorporeal membrane oxygenation (ECMO) is an important treatment for extracorporeal cardiopulmonary life support for clinically critical patients. Currently, ECMO tubing is commonly fixed by tie-wraps or tourniquets, which have shortcomings such as easy loosening and potential damage to the tubing. Improper fixation of the catheter can lead to a series of adverse events, such as accidental disconnection of the tubing, rupture of the tubing, tubing folding, and air ingress into the tubing. In order to overcome the above problems, the research team of Zhongda Hospital, Southeast University invented a device for ECMO line fixation and obtained a national utility model patent of China (patent number: ZL 2019 2 2282849.3). The tool is mainly composed of several devices, including a line fixation clamp, a clip fixation device, and a base plate, which is uniquely designed and easy to operate. During ECMO therapy, this device ensures effective stabilization of the ECMO tubing, preventing unexpected incidents due to catheter loosening and facilitating the observation of ECMO catheter insertion markings. Pipeline can be effectively fixed to avoid the occurrence of accidents due to the loosening of the catheter, and at the same time, it is convenient to observe the placement scale of the ECMO catheter. The novelty and uniqueness of the fixation device materials also effectively prevent the occurrence of pressure injuries during its use.

Objective To evaluate the impact of ultra-high-molecular-weight polyethylene(UHMWPE)-Ribbond fi-bers,when combined with different restorative materials,on fracture resistance and marginal adaptation of isolated pri-mary molar defects,to provide a reference for clinical practice.Methods This study was approved by the Ethics Re-view Committee.A total of 72 extracted primary molars with complete crowns were collected,and 66 primary molars were randomly assigned as experimental groups for the fracture resistance and microleakage tests.The molars were di-vided into six groups(n=11)based on the type of restorative materials and the application of Ribbond fibers:Group A1,3M Filtek Z250+Ribbond;Group A2,3M Filtek Z250;Group B1,Beautifil Ⅱ LS+Ribbond;Group B2,Beautifil Ⅱ LS;Group C1,3M Filtek Bulk Fill+Ribbond;and Group C2,3M Filtek Bulk Fill.Groups A1,B1 and C1 received the fiber-reinforcing technique,whereas Groups A2,B2 and C2 received the direct restorative technique;the remainings were in Group D(blank control group),which did not receive treatment for the fracture resistance test.The fracture re-sistance test was divided into six experimental groups and one blank control group(n=6).Primary molar teeth in each experimental group were prepared with Class Ⅱ cavities and filled.The fracture load of all samples was detected,and the fracture mode was analyzed after thermal cycling.The microleakage test was divided into six experimental groups,with five in each group.Class Ⅰ cavities with a diameter of 3 mm and depth of 2.5 mm were prepared within the mesial and distal marginal ridges on the occlusal surface and filled for primary molars in each group.Marginal microleakage was assessed after thermal cycling.Results The fracture resistance test results showed that the fracture resistance in groups that received the fiber-reinforcing technique was greater than that in groups that received the direct restorative technique:Group A1>Group A2,Group B1>Group B2,Group C1>Group C2(P<0.05).The application of Ribbond fibers increased fracture resistance to all tested restorative materials by 37.08％to 39.34％.The proportion of tooth frac-ture decreased significantly in groups A1,C1 compared with A2,C2,with a significant increase in the occurrence rate of"Repairable"(P<0.05).The fracture resistance in Group A1 was significantly greater than that in Group B1 and Group C1(P<0.05).The marginal microleakage test results showed that the microleakage depth in groups that received the fiber-reinforcing technique was smaller than that in groups that received the direct restorative technique:Group A1

Deconvolution of potential drug targets of the central nervous system (CNS) is particularly challenging because of the complicated structure and function of the brain. Here, a spatiotemporally resolved metabolomics and isotope tracing strategy was proposed and demonstrated to be powerful for deconvoluting and localizing potential targets of CNS drugs by using ambient mass spectrometry imaging. This strategy can map various substances including exogenous drugs, isotopically labeled metabolites, and various types of endogenous metabolites in the brain tissue sections to illustrate their microregional distribution pattern in the brain and locate drug action-related metabolic nodes and pathways. The strategy revealed that the sedative-hypnotic drug candidate YZG-331 was prominently distributed in the pineal gland and entered the thalamus and hypothalamus in relatively small amounts, and can increase glutamate decarboxylase activity to elevate γ-aminobutyric acid (GABA) levels in the hypothalamus, agonize organic cation transporter 3 to release extracellular histamine into peripheral circulation. These findings emphasize the promising capability of spatiotemporally resolved metabolomics and isotope tracing to help elucidate the multiple targets and the mechanisms of action of CNS drugs.