Aim To investigate the effects of the phos-phodiesterase 8(PDE8)inhibitor PF-04957325 on learning and memory,anxiety and depression in Alzhe-imer's disease(AD)mice induced by Okadaic acid(OA),and to explore its mechanism.Methods Twenty-one 2-month-old male C57BL/6J mice were se-lected for the experiment and randomly divided into the control group,AD model group,and PDE8 inhibitor group(0.1 mg·kg-1).AD model was induced by bi-lateral hippocampal localization injection of OA(50 ng on each side)in the model and PDE8 inhibitor groups of mice.Two days after the injection of OA,PDE8 in-hibitor group was given 0.1 mg·kg-1 drug,while the AD model groups and control group were given with the same volume of vehicle for 21 consecutive days.On day 13 of inhibitor administration,behavioral tests re-lated to learning and memory abilities,anxiety and de-pressive behaviors were performed in mice.HE stai-ning was used to observe the morphology of neuronal cells in the DG,CA1,and CA3 regions of the hippo-campus of mice,and Western blot was used to detect the levels of phosphorylated Tau proteins at different sites within the hippocampus of mice as well as the ex-pression of proteins related to the PDE8/cAMP/CREB pathway.Results Compared with the control group,the Y-maze Spontaneous alternation,Recognition index of NOR and Latency of PAT were significantly shorter(P＜0.01),and Entries times、Time in the target quadrant of MWM were reduced(P＜0.05)in the AD model group,which showed a decrease in the ability of learning and memory,whereas the administration of PF-04957325 significantly improved the ability of learning and memory in the AD mice;mice in the AD model group showed a significant decrease in the num-ber of entries into the central area of the OFT and the time spent in the central area(P＜0.05),and a sig-nificant increase in the Immobility time of TST(P＜0.01),suggesting that the mice had anxiety and de-pression,and the administration of PF-04957325 did not improve the anxious behavior of the mice,but im-proved the depressed behavior to a certain extent;the hippocampus of the AD model group mice showed ker-nel solidification in the DG,CA1 and CA3 regions,and neurons were not neatly arranged,and the admin-istration of PF-04957325 could alleviate the damage of hippocampal nerve cells in mice.Compared with the control group,the phosphorylation levels of Tau protein Ser1 99,Ser396 and Ser202 sites in the hippocampus of mice in the AD model group were significantly in-creased(P＜0.01),the expression of PDE8A and PDE8B proteins was significantly increased(P＜0.01),and the expression of p-PKA/PKA and BDNF proteins was decreased(P＜0.05),after administra-tion of PF-04957325,the phosphorylation levels of Tau protein Ser396 and Ser202 sites were significantly re-duced(P＜0.01),PDE8A and PDE8B protein ex-pression was significantly decreased(P＜0.01),and p-PKA/PKA,p-CREB/CREB and BDNF protein ex-pression was significantly increased(P＜0.01).Con-clusion PDE8 inhibitor PF-04957325 can improve learning memory ability,reduce cognitive dysfunction,restore Tau protein function,and attenuate neuronal cell damage in the hippocampus of AD mice with amel-iorative effects.The mechanism of action may be relat-ed to the activation of PDE8/cAMP/CREB pathway and inhibition of Tau protein phosphorylation.

infC gene encodes the translation initiation factor IF3 in bovine Pasteuella multocida,but it whether or not regulation to the virulence and cross-protection in P.multocida is still not well understood.In this study,the infC gene mutant(△infC)derived from bovine P.multocida type A strain CQ2 was constructed using by homologous recombination method.Compared with wild strain,the △infC showed significant increasing in biofilm formation,but the capsule produc-tion,virulence and bacterial loading in organs were significant decreased,and the IL-1β secretion of mouse peritoneal macrophage increased.Along with the infC gene deletion,the expression of genes related to capsule synthesis and LPS synthesis and transport were significantly down-regulated,while that of genes related to biofilm synthesis and outer membrane protein were significantly up-regulated.The inactivated vaccines of wild type and mutant were prepared and mice were immu-nized twice then challenged with wild type strains,respectively.The immuno-protection rate of△in fC inactivated vaccine against bovine P.multocida type A,B and F were 100.0％,83.3％and 0.0％,respectively,and the immuno-protection rate that against rabbit type P.multocida was 33.3％.The results indicated that infC gene could affect the virulence of P.multocida by regula-ting the production of capsule and the expressions of virulence related factors,and the deletion of infC gene conferred a certain cross-protection property of strains.This study provided a certain foundation for the development of P.multocida vaccine.

The elderly are prone to develop severe disease or die after infection with SARS-CoV-2, and inoculation of COVID-19 vaccine is of great significance to reduce the serious case and death. Several COVID-19 vaccines have been administered and demonstrated their safety and effectiveness in the real world. This review summarizes the safety and effectiveness of COVID-19 vaccines in the real-world studies, especially the rare adverse reactions associated with vaccine and protection against severe disease, hospitalization and death in different epidemiological contexts.

Objective To investigate the safety and efficacy of Remimazolam combined with nalbuphine in painless endoscopic mucosal resection(EMR)of colorectal polyps.Methods A total of 100 patients who undergo painless colorectal polyp EMR were randomly divided into nalbuphine combined with remimazolam(NR)and nalbuphine combined with propofol(NP),with 50 patients in each group.The mean arterial pressure,heart rate and oxygen saturation were recorded after entry(T0),1min after administration(T1),1min at the beginning of surgery(T2),3min(T3),5min(T4),and at the end of surgery(T5).The frequency of application of vasoactive drugs,their operation time,consciousness vanishing time,recovery time,the times of supplementary sedation,dosage of incidence of nalbuphine,adverse reactions,The satisfaction of doctors and patients were compared.Results The mean arterial pressure of T1,T2,T3,T4 and T5 in the NR group was higher than that in the NP group(P<0.05),and the heart rate of T1 in the NR group was higher than that in the NP group(P<0.05).The incidence of respiratory depression,hypotension,injection pain,the recovery time and the frequency of application of vasoactive drugs in the NR group was lower than that in the NP group(P<0.05).The satisfaction of doctors in the NR group was higher than that in the NP group(P<0.05).There was no significant difference between the two groups in the operation time,oxygen saturation,the times of supplementary sedation,the dosage of incidence of nalbuphineincidence of dizziness,nausea and vomiting,and other adverse reactions(P>0.05).Conclusion Nalbuphine combined with remimazolam can be used safely in the EMR,has few perioperative adverse effects,and is a good choice for painless EMR.

The 19 th Chinese Symposium of Burns and Wounds was successfully held in Foshan of Guangdong Province from June 20 th to 22 nd in 2024. There were more than 700 delegates attending the academic event. The theme of the congress was expansion, integration and standardization, which could promote academic exchanges, multi-disciplinary fusion, and standardization of clinical treatment of burns and wounds. A total of nearly 200 famous experts and scholars had their speeches on the two-day keynote forum and special academic seminars including critical care, wound repair, scar prevention and treatment, rehabilitation nursing, and disciplinary integration sessions. The congress ended successfully with abundant fruits and friendship.

Objective:To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenstr?m macroglobulinemia (WM) .Methods:Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety.Results:A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion:Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

Objective To analyze the stresses in implanted titanium solid and bone trabecular prosthesis hip replacements.Methods A femur model was built inversely based on Mimics software,and optimized using Geomagic software,and then materialized by SolidWorks software.The osteotomized femur was assembled with the metal femoral stem to form a model,and then the model was imported into ABAQUS for finite element calculation.The upper femur was divided into four regions in different states of integration:medial proximal point(small trochanter region),lateral proximal region(large trochanter region),proximal point of the femoral stem(region around the mid-portion of the styloid process)and distal region(around the end of the styloid process and distal portion).Calculations were carried out over the femoral stresses before and after implantation of titanium solid and trabecular prostheses under gait and stair-climbing loads and the interfacial stresses when the region was unintegrated.The type of deformation at the bone interface was analyzed by means of a stress ellipsoid.Results At the small trochanter region,the stress shielding rates of the trabecular prosthesis under gait and stair climbing loads were reduced by 20.5％and 14.7％compared to the titanium solid prosthesis,respectively.In case of different integration states of the titanium solid prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 10.842 MPa and 12.900 MPa,and the shear stresses reached 7.050 MPa and 6.805 MPa,respectively;in case of different integration states of the trabecular prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 3.858 MPa and 4.389 MPa,and the shear stresses reached 4.156 MPa and 3.854 MPa,respectively.Under the 2 different loads,the inboard shear stress ellipsoid of the interface opened toward the sides and the bone interface showed tensile deformation;the outboard shear stress ellipsoid of the interface opened up and down and had compressive deformation.Conclusion After total hip arthroplasty,the overall performance of the trabecular prosthesis is better than that of the titanium solid prosthesis.The unintegrated edges of the prosthesis-bone interface are susceptible to stress concentrations and distortion which may result in occurrence of failures.[Chinese Medical Equipment Journal,2024,45(3):29-35]

Harmine(HM)is a type of β-Carboline alkaloid abundant in nature and has many biological effects.In recent years.Studies have found that HM had a significant positive effect on Alzheimer's disease(AD)both in vivo and in vitro.Its mechanism may be related to the reduction of abnormal deposition of β-amyloid protein(Aβ),excessive phosphorylation of Tau protein,regulation of the cholinergic system,antioxidant stress,and antineuritis.This article reviews the research progress on the improvement effect and mechanism of HM in AD in order to provide an experimental basis for the clinical application of HM and the development of drugs in the area of AD the prevention and treatment.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To discuss the inhibitory effect of chelerythrine(CHE)on the migration,invasion,and epithelial-mesenchymal transition(EMT)of the human ovarian cancer SKOV3 cells,and to clarify the associated mechanism.Methods:The SKOV3 cells were cultured in vitro and divided into control group and 2.5,5.0,10.0,20.0,and 40.0 μmol·L-1 CHE groups.Methylthiazolydiphenyl-tetrazolium(MTT)assay was used to detect the inhibitory rates of proliferation of the cells in various groups.The SKOV3 cells were cultured in vitro and divided into control group,transforming growth factor-β1(TGF-β1)group,TGF-β1+5 μmol·L-1 CHE group,and TGF-β1+10 μmol·L-1 CHE group.Cell scratch assay was used to detect the migration rates of the cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups;Western blotting method was used to detect the expression levels of E-cadherin,N-cadherin,and Vimentin proteins in the cells in various groups;immunofluorescence staining method was used to detect the fluorescence intensities of E-cadherin and N-cadherin in the cells in various groups.Results:The MTT assay results showed that compared with control group,the inhibitory rates of proliferation of the cells in 5.0,10.0,20.0,and 40.0 μmol·L-1 CHE groups were significantly increased(P<0.05 or P<0.01).The cell scratch assay results showed that compared with control group,the migration rate of the cells in TGF-β1 group was increased(P<0.01);compared with TGF-β1 group,the migration rates of the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly decreased(P<0.01).The Transwell chamber assay results showed that compared with control group,the numbers of migration and invasion cells in TGF-β1 group were significantly increased(P<0.05);compared with TGF-β1 group,the numbers of migration and invasion cells in TGF-β1+5 μmo·l L-1 CHE group and TGF-β1+10 μmo·l L-1 CHE group were significantly decreased(P<0.01).The Western blotting results showed that compared with control group,the expression level of E-cadherin protein in the cells in TGF-β1 group was significantly decreased(P<0.01),while the expression levels of N-cadherin and Vimentin proteins were increased(P<0.05 or P<0.01);compared with TGF-β1 group,the expression levels of E-cadherin protein in the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins were significantly decreased(P<0.01).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of E-cadherin in the cells in TGF-β1 group was decreased,and the fluorescence intensity of N-cadherin was increased;compared with TGF-β1 group,the fluorescence intensities of E-cadherin in the cells in TGF-β 1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased,and the fluorescence intensities of N-cadherin were decreased.Conclusion:CHE can inhibit the proliferation,migration,invasion,and EMT of the human ovarian cancer SKOV3 cells.