BACKGROUND:LncRNA-TNFRSF13C,an important factor in B cell development and function,is expressed in periodontal tissues of patients with periodontitis,but the specific mechanism is still unclear. OBJECTIVE:To investigate the mechanism of lncRNA-TNFRSF13C regulating miR-1246 on hypoxia-inducible factor 1α in periodontal cells. METHODS:Human periodontal ligament cells(hPDLCs)were treated with lipopolysaccharide and divided into group A(hPDLCs cell lines without transfection),group B(hPDLCs cell lines transfected with TNFRSF13C NC-siRNA),group C(hPDLCs cell lines transfected with TNFRSF13C-siRNA),group D(hPDLCs cell line transfected with miR-1246 mimics),group E(hPDLCs cell line transfected with miR-1246 siRNA),group F(hPDLCs cell line transfected with TNFRSF13C-siRNA+miR-1246 mimics),and group G(hPDLCs cell line transfected with TNFRSF13C-siRNA+miR-1246 siRNA).The relative expression of lncRNA-TNFRSF13C and miR-1246 in each group was detected by qRT-PCR.Cell counting kit-8 assay was used to detect cell viability.Apoptosis was detected by flow cytometry.Expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins was detected by western blot.The correlation between lncRNA-TNFRSF13C and miR-1246 was analyzed by Pearson,and the targeting relationship was analyzed by dual-luciferase reporter assay. RESULTS AND CONCLUSION:There was no significant difference in human periodontal ligament cell activity,apoptosis rate and protein indexes between groups A and B(P>0.05).Compared with group B,hPDLCS cell activity in group C was increased,and apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins were decreased(P<0.05).Compared with group C,hPDLCS cell activity in group D was decreased,and apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins were increased(P<0.05).Compared with group D,the cell activity of group E was increased(P<0.05).The cell activity in group F was lower than that in group E,and the apoptosis rate was reduced in both groups E and F(P<0.05).Compared with group F,the cell activity of group G was increased,and the apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor were decreased(P<0.05).LncRNA-TNFRSF13C was positively correlated with miR-1246(P<0.05).Compared with the TNFRSF13C-siRNA group,the fluorescence activity of miR-1246-wt in the TNFRSF13C-NC group was reduced(P>0.05);compared with the miR-1246-NC group,the fluorescence activities of hypoxia-inducible factor 1α-wt and vascular endothelial growth factor-wt in the miR-1246 mimics group were increased(P<0.05).To conclude,down-regulation of lncRNA-TNFRSF13C can promote the activity of periodontal cells treated with lipopolysaccharide,reduce apoptosis,and inhibit hypoxia-inducible factor 1α and vascular endothelial growth factor.The mechanism is related to the regulation of miR-1246 activity.

BACKGROUND:The absence of blood vessels in tendon tissue makes tendon repair challenging.Therefore,improving tendon healing and raising the efficacy of stem cell and other therapeutic cell transplantation after tendon damage have become hotspots for research in both clinical and scientific contexts. OBJECTIVE:The stem cells and gelatin microcarrier scaffold were joined to form tissue engineered stem cells.Human umbilical cord mesenchymal stem cells cultured in gelatin microcarriers were used to investigate the therapeutic impact and mode of action on tendinopathy healing in rats in vitro and In vivo. METHODS:(1)In vitro cell experiments:After seeding human umbilical cord mesenchymal stem cells with three-dimensional gelatin microcarriers,the cell vitality and survival were assessed.Human umbilical cord mesenchymal stem cells conventionally cultured were cultured as controls.(2)In vivo experiment:Adult SD rats were randomly assigned to normal group,tendinopathy group,2D group(tendinopathy+conventional culture of human umbilical cord mesenchymal stem cells),and 3D group(tendinopathy+gelatin microcarrier three-dimensional culture of human umbilical cord mesenchymal stem cells),with 6 rats in each group.Four weeks after therapy,animal behavior tests and histopathologic morphology of the Achilles tendon was examined. RESULTS AND CONCLUSION:(1)In vitro cell experiments:the seeded human umbilical cord mesenchymal stem cells on gelatin microcarriers showed high viability and as time went on,the stem cell proliferation level grew.Compared with the control group,3D stem cell culture preserved cell viability.(2)In vivo experiment:Following a 4-week treatment,the 3D stem cell culture group showed a significant improvement in both functional recovery of the lower limbs and histopathological scores when compared to the tendinopathy group.The 2D stem cell culture group also showed improvement in tendinopathy injury,but its effect is not as much as the 3D stem cell culture group.(3)The outcomes demonstrate that human umbilical cord mesenchymal stem cells cultured with three-dimensional gelatin microcarrier can promote the repair and regeneration of tendon injury tissue,and the repair effect is better than that of conventional human umbilical cord mesenchymal stem cells.

BACKGROUND:Lijin manipulation can promote skeletal muscle repair and treat skeletal muscle injury.However,the formation of fibrosis and scar tissue hyperplasia are closely related to the quality of skeletal muscle repair.To study the regulatory effect of Lijin manipulation on the formation of fibrosis and scar tissue hyperplasia is helpful to explain the related mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury. OBJECTIVE:To explore the mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury in rabbits,thereby providing a scientific basis for clinical treatment. METHODS:Forty-five healthy adult Japanese large-ear white rabbits were randomly divided into blank group,model group and Lijin group,with 15 rats in each group.Gastrocnemius strike modeling was performed in both model group and Lijin group.The Lijin group began to intervene with tendon manipulation on the 3rd day after modeling,once a day,and 15 minutes at a time.Five animals in each group were killed on the 7th,14th and 21st days after modeling.The morphology and inflammatory cell count of gastrocnemius were observed by hematoxylin-eosin staining,the collagen fiber amount was observed by Masson staining,the expression of interleukin-6 and interleukin-10 in gastrocnemius was detected by ELISA.The protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin,alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen were detected by western blot and RT-PCR,respectively,and the expression of type Ⅰ collagen protein was detected by immunohistochemistry. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and Masson staining showed that compared with the model group,inflammatory cell infiltration and collagen fiber content decreased in the Lijin group(P<0.01),and the muscle fibers gradually healed.ELISA results showed that compared with the model group,the expression of interleukin-6 in the Lijin group continued to decrease(P<0.05),and the expression of interleukin-10 increased on the 7th day after modeling(P<0.05)and then showed a decreasing trend(P<0.05).Western blot and RT-PCR results showed that compared with the model group,the protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin in the Lijin group were significantly increased on the 14th day after modeling(P<0.05),but decreased on the 21st day(P<0.05);the protein and mRNA expressions of alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen in the Lijin group were significantly decreased compared with those in the model group(P<0.05).Immunohistochemical results showed that the expression of type Ⅰ collagen in the Lijin group was significantly lower than that in the model group(P<0.05).To conclude,Lijin manipulation could improve the repair quality of skeletal muscle injury by inhibiting inflammation,promoting the proliferation and differentiation of muscle satellite cells,and reducing fibrosis.

BACKGROUND:Traditional surgery for lumbar disc herniation involves extensive excision of tissue surrounding the nerve for decompression and removal of protruding lumbar intervertebral discs,which poses various risks and complications such as nerve damage causing paralysis,lumbar instability,herniation recurrence,intervertebral space infection,and adjacent vertebral diseases. OBJECTIVE:To propose the symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous technique for lumbar spine symmetrically decompression,showing the induced resorption of herniated nucleus pulpous phenomenon and early clinical efficacy,and then analyze its decompression mechanism. METHODS:214 patients with lumbar disc herniation at Department of Orthopedics,First Affiliated Hospital of Zhengzhou University from March 2021 to May 2023 were enrolled in this study.Among them,81 patients received conservative treatment as the control group,and 133 patients received symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous treatment as the trial group.Before surgery,immediately after surgery(7-14 days),and early after surgery(over 1 year),MRI images were used to measure the volume changes of lumbar disc herniation.CT images were used to measure the posterior displacement distance of the lumbar spinous process ligament complex,as well as the width and height of the lateral recess.Japanese Orthopaedic Association scores were used to evaluate the patient's neurological function recovery. RESULTS AND CONCLUSION:(1)Control group:81 patients with lumbar disc herniation were treated conservatively,with a total of 171 herniated lumbar discs.The average follow-up time was(22.7±23.1)months.The first and second MRI measurements of 171 herniated lumbar discs showed herniated lumbar disc volumes of(551.6±257.9)mm3 and(792.2±330.4)mm3,respectively,with an average volume increase rate of(53.2±44.4)%,showing statistically significant differences(P<0.001).Out of 171 herniated lumbar discs,4 experienced natural shrinkage,with an absorption ratio of 2.3%(4/171)and an absorption rate of(24.5±9.9)%.(2)Trial group:133 patients with lumbar disc herniation had a total of 285 herniated lumbar discs.(1)Immediately after surgery:All patients were followed up immediately after surgery.229 out of 285 herniated lumbar discs experienced retraction,with an absorption ratio of 80.3%(229/285)and an average absorption rate of(21.5±20.9)%,with significant and complete absorption accounting for 6.5%.There were a total of 70 herniated lumbar discs in the upper lumbar spine,with an absorption ratio of 85.7%(60/70),an average absorption rate of(23.1±19.5)%,and a maximum absorption rate of 86.6%.There were 215 herniated lumbar discs in the lower lumbar spine,with an absorption ratio of 78.6%(169/215),an average absorption rate of(21.0±21.3)%,and a maximum absorption rate of 83.2%.Significant and complete absorption of the upper and lower lumbar vertebrae accounted for 5.7%and 6.5%,respectively,with no statistically significant difference(P>0.05).The average distance of posterior displacement of the spinous process ligament complex immediately after surgery was(5.2±2.8)mm.There were no significant differences in the width and height of the left and right lateral recess before and immediately after surgery(P>0.05).The Japanese Orthopaedic Association score immediately after surgery increased from(10.1±3.4)before surgery to(17.0±4.8),and the immediate effective rate after surgery reached 95.6%.(2)Early postoperative period:Among them,46 patients completed the early postoperative follow-up.There were 101 herniated lumbar discs,with an absorption ratio of 94%(95/101)and an average absorption rate of(36.9±23.7)%.Significant and complete absorption accounted for 30.6%,with a maximum absorption rate of 100%.Out of 101 herniated lumbar discs,3 remained unchanged in volume,with a volume invariance rate of 2.97%(3/101).Out of 101 herniated lumbar discs,3 had an increased volume of herniated lumbar discs,with an increase ratio of 2.97%(3/101)and an increase rate of(18.5±18.4)%.The Japanese Orthopaedic Association score increased from preoperative(9.3±5.1)to(23.5±4.0),with an excellent and good rate of 93.4%.(3)The early postoperative lumbar disc herniation absorption ratios of the control group and trial group were 2.3%and 85.9%,respectively,with statistically significant differences(P<0.001).(4)Complications:There were two cases of incision exudation and delayed healing in the trial group.After conservative treatment such as dressing change,no nerve injury or death occurred in the incision healing,and no cases underwent a second surgery.(5)It is concluded that symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous is a new method for treating lumbar disc herniation that can avoid extensive excision of the"ring"nerve and achieve satisfactory early clinical efficacy.It does not damage the lumbar facet joints or alter the basic anatomical structure of the lateral recess,fully preserves the herniated lumbar discs,and can induce significant or even complete induced resorption of herniated nucleus pulpous.Symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous provides a new basis and method for the clinical treatment of lumbar disc herniation.

As a long-standing art form， drama can purify the soul and deepen people’s perception of the world. The use of drama in medical humanities education has demonstrated its unique and significant teaching effects. This paper explored and analyzed the drama module settings and interdisciplinary module constructions in the curriculum of renowned medical schools in Britain and America， revealing the effectiveness of their explorations in four aspects， including improving self-efficacy， enhancing teamwork awareness， improving doctor-patient communication skills， and promoting mental health. Based on the actual needs of current scenario-simulation teaching in China， suggestions were proposed to integrate drama elements into medical humanities in China from four aspects， encompassing emphasizing the cultivation of comprehensive humanistic literacy， carrying out interdisciplinary projects centered on drama， improving the drama curriculum evaluation system， and promoting the Sinicization of drama elements. The aim is to promote the integration of drama art and medical education， with a view to cultivating medical talents with comprehensive humanistic literacy.

OBJECTIVE To establish management index system for rational drug use of key monitoring drugs， and provide reference for the management of key monitoring drugs in the hospitals. METHODS First， the management index system for rational drug use of key monitoring drugs was drafted by collecting the evidence from related medical literature. Next， using a modified Delphi method， twenty experienced experts from the fields of pharmacy， medical practice， healthcare insurance， and finance were selected to participate in two rounds of questionnaire consultations. Based on the expert enthusiasm coefficient， authority coefficient， degree of opinion concentration， and degree of coordination， the final indicators were determined to establish a management index system for rational drug use of key monitored drugs in medical institutions. RESULTS The expert enthusiasm coefficients reached 100% in both rounds of consultation. In first-level， second-level and third-level indicators， the authority coefficients of experts were 0.89， 0.86 and 0.87， and coordination coefficients of the experts in importance score were 0.300 （P＜ 0.05）， 0.125 （P＜0.05） and 0.139 （P＜0.05）， respectively. The average score for the importance of all indicators reached over 3.5， in which the full score ratio ranged from 35% to 100%. Except that the variation coefficient of a third-level indicator “number of specifications purchased for key monitored drugs” was 0.26， the variation coefficients of rest indicators were less than or equal to 0.25. Based on the results of expert consultation， final version of the management index system established in this study， including two first-level indicators （drug procurement and use， and rational drug use）， five second-level indicators （such as the accessibility， cost-effectiveness） and twenty third-level indicators （such as the number of specifications purchased for key monitored drugs， the increase in the cost of key monitored drugs）. CONCLUSIONS The management index system established in this study possesses high reliability and strong operability， and may provide a reference for the management of key monitoring drugs in the hospitals.

OBJECTIVE To investigate the effects of ertugliflozin on pharmacokinetic of sorafenib and donafenib in rats and explore the mechanism. METHODS Twenty-four male SD rats were randomly divided into four groups， with 6 rats in each group. Groups A and B were respectively gavaged with 0.5% sodium carboxymethyl cellulose solution and ertugliflozin （1.5 mg/kg） for 7 consecutive days， and both were given sorafenib （100 mg/kg） on the 7th day. Groups C and D were administered intragastrically in the same way as those in Groups A and B， respectively， for the first 7 days； after the drug administration on the 7th day， all rats in Groups C and D were further gavaged with donafenib （40 mg/kg）. Blood samples were collected at different time points before and after administration of sorafenib or donafenib， the concentrations of sorafenib in plasma of rats in groups A and B and donafenib in groups C and D were determined by UPLC-MS/MS method. The pharmacokinetic parameters were calculated by DAS 2.1.1 software. Six additional rats were randomly divided into blank control group and ertugliflozin group， with three rats in each group. Blank control group was given 0.5% sodium carboxymethyl cellulose intragastrically， while rats in ertugliflozin group were given ertugliflozin （1.5 mg/kg） once a day for 7 consecutive days. After the last administration， the mRNA expression levels of uridine diphosphate glucuronosyl transferase 1A7 （UGT1A7）， breast cancer resistance protein （BCRP）， and P-glycoprotein （P-gp） in the liver and small intestine tissues of the rats were detected. RESULTS Compared with group A， the AUC0-t， AUC0-∞， cmax， tmax， MRT0-t and MRT0-∞ of sorafenib in group B were decreased significantly， while CL and V were increased significantly. Compared with group C， the AUC0-t， AUC0-∞ ， tmax， cmax and MRT0-t of Δ donafenib in group D were decreased significantly， while V and CL were increased significantly （P＜0.05）. mRNA expression of UGT1A7， P-gp and BCRP in the liver tissue and small intestine of rats were not significantly affected after intragastric administration of ertugliflozin for 7 consecutive days. CONCLUSIONS Ertugliflozin can affect the pharmacokinetics of sorafenib and donafenib in rats and decrease the plasma exposure of them significantly. However， its mechanism of action may not be through the regulation of related metabolic enzymes and transporters. When using drugs in combination clinically， one should be vigilant about the potential for disease progression due to poor therapeutic effects.

Based on the "Qi-blood-meridians" system， it is proposed that recurrence after radiofrequency ablation （RFA） for arrhythmia originates from damage to the heart and injury to the meridians caused by thermal burns. Disorder of qi movement， blood obstruction and heat constraint are the prerequisites for recurrence， while internal consumption of deficient qi， yin damage and scarce blood are key factors in frequent episodes. Latent pathogen of both phlegm and stasis， along with condensation of pathogenic yin， is the main cause of disease progression. Accordingly， self-made Tong Xin Beverage （通心饮） with 18 herbs is used throughout the postoperative intervention process to nourish the heart， unblock the meridians， restore vessels in balance of yin and yang. Self-made Qingxin Dingji Decoction （清心定悸汤） can be used to promote qi movement， diffuse stagnation， relieve heat and activate blood circulation so as to facilitate early recovery. Self-made Peiben Yangxin Decoction （培本养心汤） can boost qi and nourish yin， harmonize the ying （营） level and nourish blood， thereby improving long-term prognosis. In addition， Shiwei Wendan Decoction combined （十味温胆汤） with Taoren Honghua Decoction （桃仁红花煎） resolves phlegm， dissipates masses， removes stasis， and softens hardness， which can be used to prevent disease aggravation. These approaches aim to provide ideas and references for clinical practice.

Major depressive disorder (MDD) is a prevalent psychiatric condition characterized by high rates of prevalence and recurrence. Repetitive transcranial magnetic stimulation (rTMS) has been widely utilized in the acute phase treatment of MDD and has shown potential in maintenance therapy. However, the factors influencing the efficacy of rTMS during the acute phase and the sustainability of its long-term therapeutic effects remain incompletely understood. Additionally, a consensus on the optimal maintenance treatment protocol has yet to be established. This article reviews recent evidence on the application of rTMS in both acute and maintenance treatment of MDD, aiming to summarize current research progress and provide insights for the further promotion and application of rTMS in clinical practice.

Lipocalin-2 (LCN2), a member of the human lipocalin family, has been demonstrated to be closely associated with diabetes, cardiovascular diseases, and renal disorders. Recent studies have indicated that LCN2 plays a significant regulatory role in the pathogenesis and progression of various neurological diseases by mediating pathways such as inflammation, oxidative stress, and ferroptosis. This article reviews the research advancements on the mechanism of LCN2 in neurological disorders, including cerebrovascular diseases, cognitive impairment disorders, Parkinson's disease, depression, and anxiety disorders, aiming to enhance clinical understanding.