ObjectiveTo collate and compare the characteristics and differences in the methods for constructing animal models of different subtypes of gastroesophageal reflux disease （GERD） based on literature， providing a reference for researchers in this field regarding animal model construction. MethodsExperimental studies related to GERD including reflux esophagitis （RE）， nonerosive reflux disease （NERD） and Barrett's esophagus （BE） model construction from January 1， 2014 to January 27， 2024， were retrieved from databases such as CNKI， Wanfang， VIP， Web of Science， and Pubmed. Information on animal strains， genders， modeling methods including disease-syndrome combination models， modeling cycles were extracted； for studies with model evaluation， the methods of model evaluation were also extracted； then analyzing all those information. ResultsA total of 182 articles were included. SD rats were most frequently selected when inducing animal models of RE （88/148， 59.46%） and NERD （9/14， 64.29%）. For BE， C57BL/6 mice were most commonly used （11/20， 55.00%）. Male animals （RE： 111/135， 82.22%； NERD： 11/14， 78.57%； BE： 10/12， 83.33%） were the most common gender among the three subtypes. The key to constructing RE animal models lies in structural damage to the esophageal mucosal layer， gastric content reflux， or mixed reflux， among which forestomach ligation + incomplete pylorus ligation （42/158， 26.58%） was the most common modeling method； the key to constructing NERD animal models lies in micro-inflammation of the esophageal mucosa， visceral hypersensitivity， and emotional problems， and intraperitoneal injection of a mixed suspension of ovalbumin and aluminum hydroxide combined with acid perfusion in the lower esophagus （8/14， 57.14%） was the most common modeling method； the key to constructing BE animal models lies in long-term inflammatory stimulation of the esophageal mucosa and bile acid reflux， and constructing interleukin 2-interleukin 1β transgenic mice （7/25， 28.00%） was the most common modeling method. Adverse psychological stress was the most common method for inducing liver depression. ConclusionsThe construction key principles and methodologies for RE， NERD， and BE animal models exhibit significant differences. Researchers should select appropriate models based on subtype characteristics （e.g.， RE focusing on structural damage， NERD emphasizing visceral hypersensitivity）. Current studies show insufficient exploration of traditional Chinese medicine disease-syndrome combination models. Future research needs to optimize syndrome modeling approaches （e.g.， composite etiology simulation） and establish integrated Chinese-Western medicine evaluation systems to better support mechanistic investigations of traditional Chinese medicine.

Objective To investigate the molecular mechanism of ALKBH5 reducing sepsis-induced myocardial dysfunction(SIMD).Methods The expression levels of ALKBH5 and TRAF1 in the blood of 50 SIMD patients and 50 healthy individuals were detected using reverse transcription fluorescence quantitative polymerase chain reaction(RT-qPCR),and the correlation between their expression levels was analyzed by person analysis;In vitro experiments,H9C2 myocardial cells were divided into 7 groups according to over expression of TARF1 and knockdown ALKBH5.The molecular mechanism of ALKBH5 targeting TRAF1 to regulate lipopolysaccharide(LPS)induced myocardial cell damage was studied through experiments such as CCK8,ELISA,and Western blot;In the in vivo experiment of rats,LPS induced rats were divided into 6 groups according to over expression of TARF1 and knockdown ALKBH5.Experimental methods such as colorimetry,ELISA,Western blot,HE staining,and immuno-histochemistry were used to study the mechanism of ALKBH5 targeting TRAF1 through NF-κB pathway in reduc-ing myocardial cell damage.Results The expression levels of ALKBH5 and TRAF 1 were downregulated in SIMD,and the Pearson analysis showed a positive correlation between them(P<0.001);In vitro experiments showed that overexpression of TRAF1 promotes cell proliferation,inhibits the expression of inflammatory factors and proteins involved in the NF-κB pathway,and knockdown ALKBH5 obtain the opposite resulst;In vivo experi-ments in rats showed that knockdown ALKBH5 promotes injury in cardiomyocytes,expression of inflammatory factors and NF-κB-related pathway proteins,and nuclear translocation of NF-κB p65 protein,but the overexpression of TRAF 1 yielded the opposite results.Conclusion ALKBH5 increases the stability of TRAF1 by reducing its meth-ylation,thereby inhibiting NF-κB pathway,thereby reducing SIMD.

Small ubiquitin-related modifier(SUMOylation)is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload.However,the function of SUMOylation after myocardial infarction(MI)and the molecular details of heart cell responses to SUMO1 deficiency have not been determined.In this study,we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI.However,SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury.Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells.Among cardiomyocytes,SUMO1 deletion increased the Nppa+Nppb+Ankrd1+cardiomyocyte subcluster pro-portion after MI.In addition,the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice.Importantly,SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes.Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium.Mice preinjected with cardiomyocyte-specific AAV-SUMO1,but not the endothelial cell-specific form,and exhibited ameliorated cardiac remodeling following MI.Collectively,our results identified the role of SUMO1 in cardiomyocytes,fibroblasts,and endothelial cells after Ml.These findings provide new insights into SUMO1 involvement in the patho-genesis of MI and reveal novel therapeutic targets.

Antibodies, Neutralizing ; Antibodies, Viral/isolation & purification* ; B-Lymphocytes/virology* ; COVID-19/virology* ; Humans ; Immunity/genetics* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Single-Cell Analysis

Objective:To explore the application value of microsurgical tethered cord release in children with tethered cord syndrome under perioperative electro-neurophysiology monitoring.Methods:Ninety-six patients with tethered cord syndrome accepted tethered cord release in our hospital from January 2015 to December 2019 were chosen in our study; perioperative electro-neurophysiology monitoring was performed to evaluate whether there was neurological impairment. The surgical results, neuroelectrophysiological monitoring results, and follow-up results were retrospectively analyzed.Results:In these 96 patients, symptoms disappeared in 45 patients, improved in 34, not improved in 10, worsened in 3, and tethered again in 4 patients, with a total effective rate of 82.6%. No death was noted. Preoperative neuroelectrophysiological monitoring showed abnormal sensory and motor functions of lower limbs in 40 patients, and postoperative monitoring showed abnormal sensory and motor functions of lower limbs in 6 patients. Follow up was performed for an average of 13 months; symptoms improved in 79 patients, stabilized in 10 patients, and aggravated in 7 patients.Conclusion:In children with tethered cord syndrome, tethered cord release should be performed as soon as possible regardless of early neurological injury; perioperative electro-neurophysiology monitoring can protect spinal cord function, prevent nerve function injury, improve the surgical safety and improve the prognosis of these children.

Objective:To explore the value of Automated Breast Volume Scanner (ABVS) in evaluating the response of neoadjuvant chemotherapy(NACT) for different molecular subtypes of breast cancer.Methods:Based on immunohistochemical technique, breast cancer was divided into three molecular subtypes according to the negative or positive results of estrogen receptor (ER), progesterone receptor (PR) and proto oncogene human epidermal growth factor receptor 2 (HER2), namely luminal group [ER(+ ) or PR(+ ), and HER2(-/+ )], triple-negative group [ER(-), PR(-) and HER2(-)], HER2 group [ER(-), PR(-)and HER2(+ )]. ABVS was used to analyze the changes of tumor size related parameters in 78 breast cancer patients with three subtypes during NACT.Results:After NACT, the size , area and volume of primary lesion diminished obviously ( P<0.05). 19 cases achieved complete response and 40 cases achieved partial response according to response evaluation criteria in solid tumors (RECIST). After the end of the second cycle of NACT, the primary tumor shrank significantly in HER2 group, and luminal and tri-negative groups were significantly reduced after the end of the third cycle. Conclusions:ABVS has a good value in evaluating the efficacy for different molecular substypes of NACT in breast cancer.

In recent years, due to the irregular and abused use of glucocorticoid in clinical treatment, the incidence of steroid induced avascular necrosis of femoral head (SANFH) is gradually increasing. TCM for the prevention and treatment of SANFH has received much attention from many scholars. However, due to the lack of the scientific explanation of molecular biology level for its pharmacodynamics mechanism, it is difficult to achieve the purpose of standardized treatment. The discovery of OPG/RANK/RANKL signaling pathway has opened up new shortcuts for the prevention and treatment of bone metabolic diseases. OPG/RANK/RANKL signaling pathway is associated with the pathogenesis of spleen deficiency and phlegm - blood stasis caused by phlegm-blood stasis due to paralysis of SANFH. The treatment efficacy based on the phlegm theory can eventually axial control of the system through the micro-information to express. This article discussed the relevance between the phlegm in the treatment of SANFH and molecular biology mechanism of OPG/RANK/RANKL signal regulation mechanism, and combined the system of bone metabolism regulation mechanism to discuss TCM differentiation of SANFH, with a purpose to provide references for clinical and further study.

Objective To develop novel polyetheretherketone(PEEK) based nanocomposites which possess the favorable antibacterial property,and to investigate the oral microbial adhesion and biofilm formation on the surfaces of PEEK,nano-fluorohydroxyapatite(n-FHA)-PEEK and nano-hydroxyaptite (n-HA)-PEEK.Methods The bacterial adhesion and biofilm formation on the surfaces of n-FHA-PEEK,n-HA-PEEK were investigated via microbial viability assay kit and laser scanning confocal microscope (LSCM),respectively,with pure PEEK as control group.Results No significantly statistical difference were found in the bacterial adhesion amounts on the surfaces of n-FHA-PEEK,n-HA-PEEK and PEEK at 1 h and 4 h.However,the number of bacteria on the n-FHA-PEEK surface decreased dramatically at 2 h(0.496±0.008) compared with n-HA-PEEK groups(0.543± 0.015,P＜0.01).Although the biofilms formation on surfaces observed by LSCM had similar morphology and thickness at 3,7,14 d,that on the n-FHA-PEEK surface showed the highest dead-to-live bacteria ratio among the three materials at 14 d.Conclusions The combination of n-HA,especially for the n-FHA could inhibit the bacteria adhesion and accelerate the bacterial death,eventually may have an influence on the structure of biofilms and reduce the risk of periimplantitis.Therefore,n-FHA-PEEK nanocomposites presented a good prospect for clinical applications as dental implant materials.

OBJECTIVETo observe the impact of concurrent administration of recombinant human p53 adenovirus (Ad-p53) with EGFR inhibitor gefitinib on breast cancer MDA-MB-468 cells.

METHODSMDA-MB-468 cells were treated with Ad-p53 and/or gefitinib. The effect of Ad-p53 and gefitinib on the growth of MDA-MB-468 cells was evaluated by MTT assay. Cell apoptosis was detected by flow cytometry. Western blot analysis was used to detect the alteration of p53,EGFR, phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and apoptosis-related proteins. Ad-p53 combined with gefitinib was used in vivo to explore their effect on tumor xenograft in nude mice. Immunohistochemistry was used to detect the p53 expression in vivo.

RESULTSThe MTT assay showed a stronger inhibitory effect of gefitinib on MDA-MB-468 cells infected with Ad-p53 than on the control cells. Cell apoptosis assay revealed that the apoptosis rates of MDA-MB-468 cells in vehicle-treated group, Ad-p53 group, gefitinib group, and combination group were 8.5%, 17.4%, 20.5% and 32.6%, respectively. The apoptosis rate of MDA-MB-468 cells in the combination group was higher than that in other groups (P < 0.05, for all) . Western blot analysis revealed that the expression of p53 was significantly up-regulated in the presence of Ad-p53. The combination of Ad-p53 and gefitinib significantly down-regulated p-Akt (S473)(P < 0.01) and up-regulated caspase-9 and cleaved caspase-3 (P < 0.01 for both). Tumor inhibition rates (TIR) in the Ad-p53, gefitinib, and combination groups were 35.7%, 28.7% and 74.4%, respectively. Ad-p53 and gefitinib combination therapy significantly reduced the tumor burden in nude mice (P < 0.05 for all).Immunohistochemistry showed that after intratumoral administration of Ad-p53, wild-type p53 was increased (P < 0.01). p53 expressions in the vehicle-treated, Ad-p53, gefitinib and combination groups were 45.2%, 80.1%, 50.7% and 90.6%, respectively.

CONCLUSIONSWild-type p53 may reverse the sensitivity of MDA-MB-468 cells to gefitinib through down-regulation of the PI3K/Akt pathway. The apoptotic activity induced by this combination treatment might be regulated through caspase cascade.

Adenoviridae ; Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; Breast Neoplasms ; Caspase 3 ; Caspase 9 ; Cell Line, Tumor ; Down-Regulation ; Genes, p53 ; Humans ; Mice ; Mice, Nude ; Phosphatidylinositol 3-Kinases ; Quinazolines ; pharmacology

Objective:To evaluate the influence of cervical collar height on the compressive strength of CAD/CAMzirconia-ceramic restoration.Methods:Zirconia cores were manufactured and divided into 5 groups (n =1 0)based on the cervical collar height(mm):0.0(A),1 .0(B),1 .5(C),2.0(D)and 2.5(E).After veneered with porcelain,all the samples were cemented on the metal tooth analog and then mounted in an universal test machine.The force was applied at a crosshead speed of 1 mm/min until catastrophic fail-ure occurred.Fracture loads and failure modes were recorded.Results:Mean of the fracture strength values(kN)in group A,B,C, D and E were 0.95 ±0.39,1 .29 ±0.50,1 .54 ±0.28,2.04 ±0.1 9 and 2.27 ±0.53 respectively(among groups,P <0.05).Two types of fracture modes were observed:chipping of the veneering porcelain and fracture of the veneering porcelain together with the framework.Conclusion:Zirconia coping design with 1 .5 mm cervical collar height may increase the compressive strength of CAD/CAMzirconia-ceramic restoration.