Objective : To investigate the effect of environmental enrichment on cognitive impairment and hippo- campus GAP-43 changes induced by exposure to obstructive sleep apnea-hypopnea syndrome ( OSAHS) during the period of late pregnancy in mice，and to explore relative inflammatory pathway mechanism． Methods : The experi- mental group of C57BL/6J pregnant mice were exposed to an intermittent hypoxic environment for 7 consecutive days starting from gestational day 15．The corresponding offspring were then placed in an enriched environment from postnatal day 21 to 2 months of age (designated as OSAHS + EE group) or in a normal environment (designat- ed as OSAHS group) ．Pregnant mice in the control group were maintained in a normal oxygen environment，and their corresponding offspring were placed in an enriched environment (designated as Control + EE group) or a nor- mal environment (designated as Control group) at the same ages．The spatial learning and memory ability of the mice was assessed by Morris water maze at the age of 2 months．The mRNA levels of NF-kB，NLRP3 and GAP-43 in the hippocampus were detected by real-time fluorescence quantitative PCR , and the protein levels of NLRP3 and GAP-43 in the hippocampus were detected by Western blot． Results: Compared with Control group，the swimming distance increased (P＜0. 01) ，and the percentage of swimming distance in target quadrant decreased (P＜0. 01) in OSAHS group．The level of NF - κB mRNA，NLRP3 mRNA and protein in the hippocampus was increased，and the level of GAP-43 mRNA and protein was decreased (P＜0. 01) ．Compared with the Control group，there were no significant differences in swimming distance，percentage of swimming distance，NF-κB mRNA，NLRP3 mRNA and protein content in the OSAHS + EE group． Conclusion OSAHS during pregnancy impairs the learning and memory ability of offspring mice and reduces the level of GAP-43 protein．The mechanism may be related to the in- crease of NF-κB / NLRP3 level，and environmental enrichment can improve the damage．

In order to the phage therapy for Clostridium perfringens(Cp),Cp was used as the host bacterium to screen specific phages from sewage collected from a large-scale beef cattle farm in a region of Shandong Province.Transmission electron microscopy was utilized to observe the mor-phological structure of the phages.Their characteristics were analyzed through the optimal multi-plicity of infection(MOI),host range,one-step growth curve,and antibacterial experiments.The re-sults showed that one phage was successfully isolated from 18 sewage samples.The plaque was transparent without a halo,exhibiting a broad host range and no lytic reaction with other tested bacteria.The optimal MOI was 0.1,and the phage entered the burst phase in 30 min.The phage maintained high titers at pH3-13 and remained active after treatment at 60℃ for 60 min,demon-strating good stability.Mice were infected with CP and treated with bacteriophage.Animal experi-ments showed that the isolated bacteriophage had a significant inhibitory effect on CP.The results indicated that the isolated phage,designated vB-CpP-Bp7,was a virulent phage with excellent lytic capability,acid-base stability,and thermal stability,laying a foundation for further application of this phage in phage therapy.

In order to the phage therapy for Clostridium perfringens(Cp),Cp was used as the host bacterium to screen specific phages from sewage collected from a large-scale beef cattle farm in a region of Shandong Province.Transmission electron microscopy was utilized to observe the mor-phological structure of the phages.Their characteristics were analyzed through the optimal multi-plicity of infection(MOI),host range,one-step growth curve,and antibacterial experiments.The re-sults showed that one phage was successfully isolated from 18 sewage samples.The plaque was transparent without a halo,exhibiting a broad host range and no lytic reaction with other tested bacteria.The optimal MOI was 0.1,and the phage entered the burst phase in 30 min.The phage maintained high titers at pH3-13 and remained active after treatment at 60℃ for 60 min,demon-strating good stability.Mice were infected with CP and treated with bacteriophage.Animal experi-ments showed that the isolated bacteriophage had a significant inhibitory effect on CP.The results indicated that the isolated phage,designated vB-CpP-Bp7,was a virulent phage with excellent lytic capability,acid-base stability,and thermal stability,laying a foundation for further application of this phage in phage therapy.

Gastric ulcer is a common digestive system disease,and the long-term use of non-steroidal anti-inflammatory drugs(NSAIDs)is the second most important cause.NSAID-induced gastric ulcer animal models are key experimental tools for studying the pathogenesis,corresponding treatment method,and effective mechanisms of NSAID-induced gastrointestinal injury.However,there are currently a lack of reviews on NSAID-induced gastric ulcer animal models.This review summarizes and compares the relevant literature on animal research into indomethacin-and aspirin-induced gastric ulcers in the past 10 years,including the selection of experimental animals,drug solvents,and specific modeling method.The limitations of current models,such as the cumbersome modeling method,incomplete modeling details,inadequate models for clinical use,and lack of comparative drug research,are discussed.Feasible solutions are proposed with the aim of providing an effective reference for research in this field.

[Objective]To explore the intervention effect of β-sitosterol,an effective monomer component of Eucommia ulmoides,on postmenopausal osteoporosis in mice and its potential mechanism.[Methods]Twenty-four female C57BL/6J mice of 12 weeks old were randomly divided into sham operation group,model group and β-sitosterol intervention group,with 8 mice in each group.The model of postmenopausal osteoporosis was established by bilateral ovariectomy.Mice in sham group and model group were given 0.9％sodium chloride solution and β-sitosterol intervention group was given β-sitosterol.Eight weeks after operation,all the mice were sacrificed and samples were collected.Micro-computed tomography(Micro-CT)was used to observe the protective effect of the β-sitosterol intervention on postmenopausal bone loss and trabecular bone breakage.Hematoxylin-eosin(HE)staining was used to analyze the bone histomorphology of the distal femur.The tartrate-resistant acid phosphatase(TRAP)staining and the alkaline phosphatase(ALP)staining were used to evaluate bone resorption and bone formation respectively.Then the expression level of β-catenin in each group was detected by immunohistochemistry.[Results]Micro-CT scanning showed that β-sitosterol could reduce bone loss and bone microstructure destruction in postmenopausal mice.HE staining also confirmed that β-sitosterol could effectively maintain the number and morphology of trabecular bone and inhibit abnormal fat accumulation caused by estrogen deficiency.TRAP staining also showed that β-sitosterol treatment did not affect osteoclast formation,while immunohistochemical results showed that β-sitosterol could significantly promote the expression of osteogenic marker ALP.Moreover,β-sitosterol can increase the expression of β-catenin in the distal femur to promote bone formation.[Conclusion]β-sitosterol treatment could enhance osteogenic differentiation and promote bone formation to relieve postmenopausal osteoporosis by upregulating β-catenin expression in vivo.

Objective To explore the relationship between haptoglobin gene polymorphism and disease se-verity and susceptibility in senile vascular dementia patients.Methods A total of 80 patients with senile vas-cular dementia admitted to the hospital from February 2018 to February 2023 were selected as the vascular de-mentia group,and 80 stroke patients with non-vascular dementia admitted to the hospital during the same pe-riod were selected as the control group.The genotype distribution and allele frequency of haptoglobin gene were measured using polymerase chain reaction with sequence-specific primers,and their relationship with the severity and susceptibility of vascular dementia patients was analyzed.Results The proportion of history of hyperlipidemia and diabetes mellitus and the levels of total cholesterol and triglyceride in vascular dementia group were higher than those in control group,the differences were statistically significant(P＜0.05).The distribution of genotypes was in Hardy-Weinberg equilibrium(P＞0.05).The frequency of haptoglobin 2-2 genotype and haptoglobin 2 allele in vascular dementia group were higher than those in control group,and the differences were statistically significant(P＜0.05).There were significant differences in the scores of mini-mental state examination and hachinski ischaemic score among patients with vascular dementia with different haptoglobin genotypes(P＜0.05).Multivariate Logistic regression analysis showed that the carrier of hapto-globin 2-2 genotype and the carrier of haptoglobin 2 allele were independent risk factors for vascular dementia(P＜0.05).Conclusion Haptoglobin 2-2 genotype and haptoglobin 2 allele distribution frequency are associ-ated with the occurrence of vascular dementia after stroke,and those with high frequency of haptoglobin 2-2 genotype and haptoglobin 2 allele distribution suffer a severe disease,which can provide reference for early i-dentification and assessment of vascular dementia.

Peri-implantitis, characterized by inflammation of tissues around implants and gradual loss of supporting bone tissue, has become one of the main causes for implant failure. Thoroughly removing the plaque biofilm on the implant surface is the first principle in the treatment of peri-implantitis. For this reason, various decontamination methods have been proposed, which can be divided into 2 categories: Removing biofilm and killing microorganisms according to the effect of plaque biofilm on the implant surface. However, at present, there is no decontamination method that can completely remove the plaque biofilm on the implant surface, and it lacks of clinical recommended guidelines. To understand the advantages and disadvantages, effectiveness and safety for different implant surface decontamination methods is of great significance to guide the clinical selection for peri-implantitis treatment.
Bone and Bones ; Decontamination ; Dental Implants ; Humans ; Inflammation ; Peri-Implantitis/therapy* ; Prostheses and Implants

Objective:To evaluate the clinical value of intraoperative transesophageal echocardiography (TEE) in monitoring left ventricular assist device (LVAD) implantation.Methods:Between March 2019 and November 2021, 23 consecutive patients from TEDA International Cardiovascular Hospital, including 21 cases with dilated cardiomyopathy, 1 case with myocardial noncompaction and 1 case with ischemic cardiomyopathy, underwent HeartCon blood pump, a type of third generation LVAD implantation for severe heart failure. TEE was preformed in all cases before and after cardiopulmonary bypass. The dimensions of left-sided and right-sided cardiac chamber, ventricular function, de-airing, interventricular septal position, inlet cannulae position and the function of device were observed and recorded during LVAD implantation. Paired t test was used for statistical analysis of left-sided and right-sided heart parameters in pre- and post-operative measurements. Results:The left heart was dilated significantly and coexistent with right heart enlargement in some degree before LVAD implantation in total 23 cases. More than moderate mitral regurgitation (MR) in 16 cases and less than moderate MR in 7 cases were present. Mild or trace aortic regurgitation (AR) existed in 13 cases. More than moderate tricuspid regurgitation (TR) in 4 cases and less than moderate TR in 16 cases were observed. Left atrial appendage thrombosis was detected in 2 cases. After LVAD implantation, TEE revealed that the left ventricular end-diastolic diameter reduced significantly (42 mm/m 2 vs 32.8 mm/m 2, P<0.05) and left ventricular ejection fraction increased accordingly (22.2% vs 34.0%, P<0.05). There were no significant differences in right ventricular diameter and fractional area change between pre- and post-operative findings(all P>0.05). The ratio of left ventricular inner diameter to right ventricular inner diameter (2.09 vs 1.69, P<0.05) decreased in total 23 cases after LVAD implantation.Interventricular septal position became neutral position instead of pre-oprative rightward position. The severity of MR decreased in varying degrees in total 23 cases after LVAD implantation. All patients underwent tricuspid valvuloplasty with residual mild regurgitation in 8 cases. Conclusions:HeartCon blood pump can effectively unload the left ventricle with sufficient cardiac output in patients with severe congestive heart failure. TEE plays a major role in the clinical decision making during LVAD implantation, which can evaluate pre-operative cardiac abnormalities, intra-operative air embolism, inlet cannulae position, cannulas patency and cardiac function, especially blood volume status and the balance between double ventricles, which is critical for optimal functioning of the device.

Objective: To prepare and in vitro evaluate the self-microemulsifying drug delivery system (SMEDDS) of adefovir dipivoxil (ADV).Methods: The optimized formula was screened by solubility, compatibility, ternary phase diagram and orthogonal design with the self-emulsifying time and particle size of microemulsion as the indices.The property of self-emulsification and the dissolution in vitro of ADV-SMEDDS were also determined.Results: The optimized SMEDDS was composed of Cremophor EL35 (37.5%), Transcutol HP (37.5%) and PECEOL (25%), and the drug loading was 3%.The ADV-SMEDDS formed stable microemulsion after the dilution by 50-fold amount of water in 24 s, the average particle size was (26.30±0.46) nm, the zeta potential was (-8.96±0.57) mV, and the dissolution was more than 85% in 5 min.Conclusion: The optimized formula of ADV-SMEDDS has significantly enhanced solubility and dissolution of adefovir dipivoxil in vitro.

Objective: To investigate echocardiography characteristics and clinical significance in patients with diastolic mitral regurgitation. Methods: A total of 15 patients with diastolic mitral regurgitation were studied including 1 patient with large volume of aortic regurgitation, 6 with atrial ifbrillation (AF), 2 with atrial lfutter, 1 with II° type I atrio-ventricular block (A-V block), 1 with II° type II A-V block and 4 with III° A-V block. The characteristics of mitral regurgitation were observed, the heart rates, left ventricular size were measured and left ventricular function was detected in all patients. Results: There was 1 large volume aortic regurgitation patient with diastolic mitral regurgitation occurred in slow iflling phase with less volume, it was less than positive velocity; 1 AF patient occurred in mid and late diastolic phase with less volume, it was obviously less than positive velocity; the rest 8 patients all occurred in mid and late diastolic phase, the velocity reached or surpassed to positive velocity. All 15 patients had slow heart rate, increased left heart, decreased left ventricular ejection fraction, tissue Doppler imaging showed that the early diastolic peak slowed down in mitral ring. There were 93% (14/15) patients having obvious systolic regurgitation. Conclusion: The time phase, quantity and velocity of diastolic mitral regurgitation have various characteristics, most of them associated with systolic regurgitation combining abnormal cardiac structure and function. Echocardiography provides important information for clinical treatment.