OBJECTIVE To explore the effects of ADRB1 Arg389Gly polymorphisms on the efficacy of bisoprolol， thus providing some information for individualized drug therapy. METHODS A systematic search was conducted in PubMed， Embase， Cochrane Library， CBM， CNKI， and Wanfang Data to retrieve and find out all relevant literature about bisoprolol and ADRB1 Arg389Gly polymorphism from the inception to May 2023. The retrieved literature was screened and selected according to the inclusive and exclusive criteria， thereafter quality assessment was conducted. RevMan 5.4 software was utilized to perform the meta- analysis for the outcome index. RESULTS Overall 7 literature with 1 339 cases were included. Among them， 4 studies provided the changes in systolic blood pressure （SBP）， diastolic blood pressure （DBP） （ΔSBP and ΔDBP）； 4 involving the change （ΔLVEF） of left ventricular ejection fraction （LVEF）. Results of the study showed that there was no statistical significance in the improvement of blood pressure between wild-type group （AA） and mutation group （AG+GG） of ADRB1 Arg389Gly treated with bisoprolol {ΔSBP [SMD＝0.17，95%CI （－0.97，1.31）， P＝0.77]， ΔDBP [SMD＝－0.01，95%CI （－0.65，0.62）， P＝0.97]}； there was no statistical significance in the improvement of ΔLVEF [SMD＝－0.61， 95%CI （－2.74，1.53）， P＝0.58] between 2 groups. CONCLUSIONS ADRB1 Arg389Gly gene polymorphism has no significant influence on the improvement of SBP， DBP， and LVEF in cardiovascular patients who use bisoprolol.

BACKGROUND:The application of orthodontic force triggers autophagy in the periodontal tissue via diverse signaling pathways,augmenting or attenuating the activity of relevant cell types such as periodontal ligament cells,osteocytes,osteoclasts,and osteoblasts,thus facilitating the process of periodontal remodeling. OBJECTIVE:To review the research progress in orthodontic force mediated autophagy in periodontal tissue and its impact on orthodontic tooth movement. METHODS:The PubMed,Web of Science,China Biology Medicine disc and CNKI were searched for literature published from 2010 to 2023 to summarize the progress in orthodontics-related autophagy.And 76 papers were finally included in the analysis and discussion. RESULTS AND CONCLUSION:Orthodontic force can trigger a series of biochemical signal changes through periodontal mechanical receptors and aseptic inflammation they cause,leading to autophagy in periodontal tissue.Subsequently,autophagy generates corresponding feedback through cascaded amplified signaling pathways such as Phosphoinositide 3-kinase/protein kinase B,Hippo,and mitogen-activated protein kinase pathways,promoting periodontal tissue remodeling and ultimately achieving tooth movement and stability.Orthodontic force-induced autophagy can differentially regulate bone resorption on the tooth pressure side and bone formation on the tension side.Related targets have good prospects in the clinical application of orthodontic treatment.Orthodontics and autophagy have complex mechanisms.However,existing research has only focused on exploring the role of autophagy in orthodontic tooth movement.Further exploration is needed to investigate the mutual regulatory effects between autophagy and orthodontic tooth movement,as well as the interactions between upstream mechanical receptors and signaling pathways involved in related pathways.

Abstract Dry eye disease is a chronic ocular surface inflammatory disease caused by abnormal tear quality or quantity and decreased tear film stability due to various reasons, and often accompanied by ocular discomfort such as itching, dryness, foreign body sensation, and visual dysfunction, which can seriously affect the patient′s quality of life and visual quality if not intervened in time. With the change of social lifestyles, the increase of environmental pollution and the trend of population aging, dry eye disease has become the most common ocular surface disease besides refractive error. Currently, dry eye disease is widely recognized as a non-infectious immune-related inflammatory disease, but the signaling pathways involved in dry eye disease are poorly understood. Whether dry eye disease is caused by excessive tear evaporation, insufficient tear production, or mucin deficiency, the ocular surface tissues(cornea/conjunctiva) inevitably undergo pathological processes such as aberrant proliferation, squamous epithelial hyperplasia, initiation of corneal damage repair mechanisms, and reduction in the number of conjunctival goblet cells, whereas the Wnt/β-catenin pathway is known to have a wide range of biological functions and plays an important role in cell proliferation, differentiation, and stemness maintenance. Therefore, this review describes the pathogenesis and potential experimental therapeutic options of the Wnt/β-catenin signaling pathway in dry eye disease from this perspective, aiming to provide new targets for the treatment of dry eye disease and achieve the goal of controlling the disease progression from the root.

Objective The purpose of this study was to investigate the differences in the anti cyclic fatigue perfor-mance of Woride KS(WKS),Proteper Gold(PTG),and Hyflex CM(HCM)nickel titanium instruments with different tip diameters in curved root canal models,and to provide reference for the targeted selection of suitable nickel titanium in-struments in clinical preparation of curved root canals.Methods Three kinds of new nickel titanium files with 20#and 25#(0.20 mm and 0.25 mm)tip diameters were selected,including WKS(20/0.06),WKS(25/0.06),PTG(20/0.07),PTG(25/0.08),HCM(20/0.06),and HCM(25/0.06),each with 20 files.According to the recommended speed and torque of the motor,the anti cycle fatigue performance of the nickel titanium file was tested in 30° and 60° stainless steel root canal models.The time from rotation to fatigue fracture(TTF)of the nickel titanium file was recorded with a camera and timer,and the fragment length(FL)was measured and recorded with a Vernier scale.Results Com-parison of TTF of the same type of file.① WKS:the TTF of files with the same tip diameter in a 30° curved root canal was longer than 60°(P＜0.05);The TTF of 25# nickel titanium files in the same angle curved root canal was longer than that of 20# nickel titanium files(P＜0.05).②PTG:the 20# nickel titanium files had a TTF longer than 60° in a 30° curved root canal(P＜0.05),while the 25# nickel titanium files had no statistically significant difference in TTF be-tween the 30° curved root canal and 60° curved root canal(P＞0.05);In a 30° curved root canal,the TTF of 20# nickel titanium files was longer than that of 25# nickel titanium files(P＜0.05).In a 60° curved root canal,there were no sta-tistically significant difference between the TTF of 20# nickel titanium files and 25# nickel titanium files(P＞0.05).③HCM:the TTF of files with the same tip diameter in a 30° curved root canal was longer than 60°(P＜0.05);The TTF of 20# nickel titanium files in the same angle curved root canal is longer than that of 25# nickel titanium filea.Compari-son of TTF of different files:in a 30° curved root canal,there was no statistically significant difference in TTF among the three types of 20# nickel titanium files(P＞0.05).The TTF of 25# WKS was longer than that of other files(P＜0.05);In a 60 ° curved root canal,the TTF of 20# HCM was longer than other files with the same tip diameter(P＜0.05),and the TTF of 25# WKS was longer than HCM with the same tip diameter(P＜0.05).The FL of 20# PTG,25#PTG,and 20# HCM in the 30° curved root canal model is significantly longer than that of 60°(P＜0.05),while there is no statistical difference in FL among 20# WKS,25# WKS,and 25# HCM in the 30° and 60° curved root canal models.Conclusion The anti cyclic fatigue performance of WKS is significantly superior to PTG and HCM in a 30° curved root canal.In a 60° curved root canal,20# HCM had a significant advantage in terms of anti cyclic fatigue performance compared to other files,while only 25# WKS had a significant advantage in anti cyclic fatigue performance compared to HCM.

Sphincter of Oddi dysfunction (SOD) refers to the abnormal physiological function of sphincter of Oddi, which causes a series of syndromes in biliary tract, pancreas and liver. At present, the related research of SOD is becoming a hot spot, but its pathogenesis is not clear. This article will review the domestic and international literatures on SOD, review the advantages and disadvantages of experimental animals such as rabbits, dogs and guinea pigs, and analyze the characteristics of drugs and surgical modeling, so as to provide references for future related model establishment.

Objective:To study the changes in the sphincter of Oddi pressure in rabbits after bilateral vagus nerve trunk severance and the therapeutic effect of Qingre Lidan Decoction, to provide a new way for the treatment of sphincter of Oddi dysfunction.Methods:Twenty-four 1.5~2.0 kg New Zealand Large White rabbits of either gender were randomly selected and divided into the control group, the model group, and the treatment group. In the control group, only pyloroplasty was performed; in the model group and the treatment group, pyloroplasty plus bilateral vagus nerve trunk dissection at the level of the diaphragm were performed, and in the treatment group, one month of gavage treatment with Qingre Lidan Decoction was carried out 7 days after the operation. Multi-channel bio-signal acquisition system was used to record the pressure changes of the sphincter of Oddi in rabbits of each group; ELISA was used to detect the changes of inflammatory factors IL-6 and tumor necrosis factor TNF-α in the serum of rabbits.Results:The pressure of the sphincter of Oddi in the model group was significantly higher than those in the control group [low-pressure area: (51.95±0.35) mmHg (1 mmHg=0.133 kPa) vs (21.60±1.13) mmHg ( P<0.05) ; High pressure area: (60.75±0.49) mmHg vs (20.70±0.85) mmHg ( P<0.05)], the pressure of sphincter of Oddi in the treatment group of Qingre Lidan Decoction was lower than that of the model group [low-pressure area: (22.70±1.13) mmHg vs (51.95±0.35) mmHg ( P<0.05); high-pressure area: (32.15±0.49) mmHg vs (60.75±0.49) mmHg ( P<0.05)]. Serum IL-6 and TNF-αwere significantly elevated in the model group compared to the control group; IL-6 and TNF-α levels were decreased in the treatment group compared to the model group, and the differences were statistically significant ( P<0.05). Conclusion:Bilateral vagus nerve trunk severance leads to Oddi sphincter dysfunction, and treatment with Qingre Lidan Decoction could improve Oddi sphincter dysfunction.

ObjectiveTo explore the effect of Baitouweng Tang （BTWT） on the apoptosis of human colorectal cancer HCT116 cells and decipher the underlying mechanism based on the Hedgehog （Hh） signaling pathway. MethodHCT116 cells were treated with BTWT （25， 50， 100， 200， 500， 750， and 1 000 mg·L^-1） for 24 h， and then the cell proliferation was detected by methyl thiazolyl tetrazolium （MTT） colorimetry. Five groups were designed for the treatment of HCT116 cells， including a blank control group， BTWT groups （125， 250， and 500 mg·L^-1）， and a positive control （5-fluorouracil， 5-FU， 40 mmol·L^-1） group. The cell morphology was observed under an inverted microscope. The migration of the cells was detected by scratch test， and the apoptosis by Hoechest 33324/propidium iodide （PI） staining and flow cytometry. Western blot was employed to determine the protein levels of sonic hedgehog （SHh）， GLI family zinc finger protein 1 （Gli1）， smoothened （Smo）， suppressor of fused （SuFu）， cellular-myelocytomatosis viral oncogene （c-Myc）， and the apoptosis-related proteins B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）. The quantitative real-time reverse transcription PCR （Real-time PCR） was employed to determine the mRNA levels of Bax， Bcl-2， SHh， Gli1， Smo， SuFu， and c-Myc. ResultCompared with the blank control group， BTWT changed the cell morphology （making the cell become round with dense nucleus）， inhibited the proliferation of HCT116 cells in a dose-dependent manner， decreased the ability of migration （P<0.05， P<0.01）， and increased apoptotic cells. Compared with the blank control group， BTWT （500 mg·L^-1） treatment for 24 h up-regulated the protein and mRNA levels of Bax （P<0.05， P<0.01） and down-regulated the protein and mRNA levels of Bcl-2 in HCT116 cells （P<0.05， P<0.01）. Moreover， the treatment down-regulated the mRNA and protein levels of SHh， Gli1， Smo， and c-Myc （P<0.05， P<0.01） and up-regulated the mRNA and protein levels of SuFu （P<0.05， P<0.01）. ConclusionBTWT inhibited the proliferation and migration and induced the apoptosis of colorectal cancer HCT116 cells by down-regulating the Hh signaling pathway.

ObjectiveTo observe the effect of augmented reality training based on enriched environment on walking dysfunction after stroke. MethodsFrom January, 2021 to June, 2022, 36 stroke patients in the Affiliated Suzhou Hospital of Nanjing University Medical School were randomly divided into control group (n = 18) and experimental group (n = 18). Both groups received conventional rehabilitation treatment. The control group was supplemented with conventional walking training, and the experimental group was supplemented with augmented reality training based on enriched environment, for four weeks. They were assessed with Berg Balance Scale (BBS), Timed Up and Go Test (TUGT), 10-meter walk test (10MWT) and Barthel Index (BI) before and after treatment, and the gait parameter was compared. ResultsNo adverse event occurred during treatment. After treatment, the BBS score, TUGT time, 10MWT speed, BI, gait speed, gait frequency and the proportion of single-leg support on the affected side significantly improved in both groups (|t| > 5.161, P < 0.001). All the above indexes were better in the experimental group than in the control group (|t| > 2.106, P < 0.05), except for BI (t = 1.099, P = 0.282). ConclusionAugmented reality training based on enriched environment could improve the walking function of paitents after stroke, which is better than conventional walking training.

Sinapic acid (SA) is a phenolic acid that is widely distributed in fruits and vegetables, which has various bioactivities, such as antidiabetic, anticancer and anti-inflammatory functions. Over-activated microglial is involved in the development progress of neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. The objective of this study was to investigate the effect of SA in microglia neuroinflammation models. Our results demonstrated that SA inhibited secretion of the nitric oxide (NO) and interleukin (IL)-6, reduced the expression of inducible nitric oxide synthase (iNOS) and enhanced the release of IL-10 in a dose-dependent manner. Besides, our further investigation revealed that SA attenuated the phosphorylation of AKT and MAPK cascades in LPS-induced microglia. Consistently, oral administration of SA in mouse regulated the production of inflammationrelated cytokines and also suppressed the phosphorylation of MAPK cascades and AKT in the mouse cerebral cortex. These results suggested that SA may be a possible therapy candidate for anti-inflammatory activity by targeting the AKT/MAPK signaling pathway.

Objective: To explore the biomechanical characteristics of short implants with different diameters in mandibular molars with severe jaw absorption, and to provide theoretical basis for the application of short implants in mandibular molar area. Methods: CBCT data of patient were imported into Mimics and 3-Matic, and the finite element model of mandibular second molar repaired with short implant with diameter of 5.5 mm or 6.5 mm and length of 7 mm was established. The data were imported into three-dimensional finite element analysis software Marc Mentat, and high or low density bone was set up. An axial or buccal load of 150 N was applied to simulate clinical situation. A total of 8 models were established. Cortical bone stress, cancellous bone strain and implant displacement were calculated and analyzed. Results: The cortical bone stress was concentrated in the neck of implant, and the cancellous bone strain was mainly distributed in the apical area of implant. The maximum values of cortical bone stress, cancellous bone strain and implant displacement were higher in buccal loading model than those in axial loading model, and they were higher in low density bone model than those in high density bone model under the same conditions. When the 5.5 mm diameter implant was loaded in buccal direction and the surrounding bone density was low, the maximum strain of cancellous bone was greater than the upper limit of physiological absorption of bone tissue 3 000 μstrain. Conclusion The application of short implants in mandibular molars with insufficient vertical bone mass is a feasible restoration scheme. But for patients with low bone mineral density, large diameter short implants can be appropriately selected, and the occlusal area and the cusp inclination can be appropriately reduced, so as to reduce the lateral force and obtain the stability and success of the implant in the short and long term.