BACKGROUND:Currently,miR-196b-5p has been found to play a role in cell proliferation,migration and inhibition of scar hyperplasia,but there is a lack of relevant studies on whether it plays a role in the process of wound healing.OBJECTIVE:To investigate the effect of miR-196b-5p in adipose stem cell-derived exosomes on burn wound healing.METHODS:The models of deep second degree skin burn in SD rats were established and randomly divided into four groups:blank control group,exosome group,agomiR-196b-5p group,and exosome+antagomiR-196b-5p group,with 10 rats in each group.PBS,adipose-derived stem cell-derived exosomes,miR-196b-5p agonist,and miR-196b-5p inhibitor were injected around the wound according to different groups.Wound healing was observed immediately after injury and on days 7,14,and 21 after injury.On day 7 after surgery,hematoxylin-eosin staining was used to observe the expression of inflammation in the wound surface.On day 14 after suregery,Masson staining was used to observe the expression of collagen and immunohistochemical staining was used to observe the expression of CD31 in the wound surface.On day 7 after surgery,western blot assay was performed to detect the expression of α-smooth muscle actin and type Ⅰ collagen in the wound surface.RESULTS AND CONCLUSION:(1)The wound healing was faster in the agomiR-196b-5p group,while it was slower in the blank control group and the exosome+antagomiR-196b-5p group.(2)Compared with the blank control group and the exosome+antagomiR-196b-5p group,the wound infiltration of inflammatory cells was less in the exosome group and the agomiR-196b-5p group,and the expression of CD31 was significantly increased(P＜0.01).(3)Compared with the blank control group and the exosome+antagomiR-196b-5p group,the expression levels of α-smooth muscle actin and type Ⅰ collagen were increased in the exosome group and the agomiR-196b-5p group(P＜0.05).These findings indicate that miR-196b-5p in adipose stem cell-derived exosomes can promote burn wound healing in rats.

BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

BACKGROUND:Orthodontic treatment to move the mandibular second molar in place of the missing first molar is a good method for preserving natural teeth.However,molars often exhibit mesial tipping when using clear aligners.The impact of attachments and overcorrection on the molar mesialization with clear aligners is unclear.OBJECTIVE:To investigate the effects of attachments and overcorrection on displacement and biomechanics of the mandibular second molar mesialization.METHODS:A finite element model with the left mandibular first molar missing was constructed using a volunteer's cone-beam CT and intraoral scan data.The experiment was divided into four groups based on the position of attachments on the left mandibular second molar:without attachment,buccal attachment,lingual attachment,and buccal-lingual attachment,with overcorrection degrees(0°,1°,2°,3°,and 4°)for each group,totaling 20 models.The calculation and analysis of the displacement trends and stress were performed using Abaqus software.RESULTS AND CONCLUSION:(1)Mesial tipping and intrusion of the molar,distal tipping of the canines and permolars,and linguaing of the incisors occurred during molar mesialization.(2)The displacement of molars increased when attachments were used,with the maximum displacement occurring when buccal-lingual attachments were applied.Molars tended to tip towards the side without attachments when attachments were designed unilaterally.However,the inclination of molars did not decrease when attachments were used.(3)Molars exhibited reduced mesial tipping and intrusion,approaching overall movement,and the stress of periodontal ligament was relieved and more evenly distributed during overcorrection treatment,and this effect became more pronounced with increased degrees of overcorrection.(4)Attachments can enhance the effectiveness of overcorrection,with the best performance observed when buccal-lingual attachments are used.Using attachments and overcorrection together helps control molar mesial tipping and intrusion,but overall molar movement is not achieved.

OBJECTIVE:Elevated blood pressure increases the risk of cardiovascular diseases.Isometric exercise training has been shown to significantly reduce resting blood pressure,but the factors influencing its effectiveness remain unclear,and specific application guidelines are yet to be established.This study aims to evaluate the impact of isometric exercise training on resting blood pressure through meta-analysis,explore its moderating factors,and provide evidence-based recommendations based on its dose-response relationship.METHODS:Following the PRISMA guidelines,a systematic search was conducted in PubMed,Embase,Cochrane Library,Scopus,and Web of Science databases using keywords"Isometric exercise training,""Systolic blood pressure,"and"Diastolic blood pressure,"covering literature up to September 2024.Randomized controlled trials involving isometric exercise training and resting blood pressure were included.Three independent researchers performed literature screening and data extraction,assessing bias risk and quality grades using the Risk of Bias 2.0 tool and GRADE framework.Main effect pooling,publication bias assessment,subgroup,and regression analysis were conducted using R software(version 4.3.4).RESULTS:A total of 28 articles(comprising 32 randomized controlled trials)involving 977 participants were included.(1)Meta-analysis results indicated that isometric exercise training significantly reduced resting systolic blood pressure(MD=-8.01,95％CI=-9.22 to-6.80,P＜0.01,I2=18.20％,low evidence grade)and diastolic blood pressure(MD=-3.46,95％CI=-4.64 to-2.28,P＜0.01,I2=0％,moderate evidence grade)compared to no exercise.(2)Subgroup analysis results revealed significant influences of gender,health status,exercise modality,frequency,intensity,duration,sets per session,rest duration,and baseline blood pressure on the main effects for both systolic(P＜0.01)and diastolic blood pressure(P＜0.05).(3)Regression analysis results did not show any significant influencing factors,but body mass index(β=-4.11,P=0.091)showed a significant negative trend on the main effect for systolic blood pressure.(4)No significant publication bias was observed in the meta-analysis results(P＞0.05).CONCLUSION:(1)Isometric exercise training significantly lowers systolic(low evidence grade)and diastolic(moderate evidence grade)blood pressure with clinically meaningful thresholds.(2)Participant characteristics(gender,health status,baseline blood pressure,and body mass index)and isometric exercise training protocols(modality,frequency,intensity,duration,cycle,sets per session,and rest duration)influence its antihypertensive effects.(3)The article recommends the optimal blood pressure management prescription:three sessions per week,with four sets per session,each set lasting 2 minutes with a 2-minute rest,at an intensity of 95％HRpeak using isometric wall squat exercises;the intervention period can be adjusted around a 6-week node.Future high-quality research is urgently needed to further validate and support these conclusions.

BACKGROUND:The titanium alloy bone trabecular bone socket cup prosthesis printed by 3D technology has superior biological characteristics,which helps to promote osteogenic differentiation of stem cells.The Kidney Tonifying and Blood Activating Decoction has the functions of tonifying the kidneys,strengthening tendons,promoting blood circulation,and relieving pain.However,the application of the combination of the two in elderly hip arthroplasty is rarely reported.OBJECTIVE:To evaluate the application value and safety of 3D printed titanium alloy bone trabecular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction in elderly hip arthroplasty.METHODS:A total of 200 elderly patients who received hip arthroplasty in Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to January 2024 were selected and randomly divided into control group(n=100)and trial group(n=100).The control group underwent Pinnaele cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction,while the trial group underwent 3D printed titanium alloy bone trabecular cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction.The medication was taken continuously for 1 week before hip arthroplasty and for 4 weeks after arthroplasty.The differences in pain,swelling,hemorheology,inflammatory factors,bone metabolism,intra-articular stress,and hip abduction muscle strength were compared between the two groups to evaluate the clinical efficacy and safety of the two treatment options.RESULTS AND CONCLUSION:(1)Four weeks after surgery,the pain visual analog scale score,limb swelling,whole blood viscosity,and plasma viscosity of the trial group were lower than those of the control group(P＜0.05).The interleukin-6 level of the trial group was lower than that of the control group,and the interleukin-10 level was higher than that of the control group(P＜0.05).The levels of type Ⅰ collagen carboxyl terminal peptide β specific sequence and tartrate-resistant acid phosphatase 5b in the trial group were lower than those in the control group,while the levels of osteocalcin,bone-specific phosphatase and typeⅠ procollagen amino-terminal propeptide were higher than those in the control group(P＜0.05).The intra-articular stress and hip abduction muscle strength in the trial group were higher than that of the control group(P＜0.05).(2)Three months after surgery,the excellent and good treatment rate in the trial group was higher than that in the control group,and the incidence of safety evaluation events such as postoperative incision hematoma and infection was lower than that in the control group(P＜0.05).(3)It suggests that 3D printed titanium alloy trabecular acetabular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction can improve the blood rheology of elderly patients with hip arthroplasty,inhibit inflammatory response,reduce postoperative pain and swelling,and enhance bone metabolism,thereby promoting postoperative hip joint function recovery,and reducing the incidence of adverse events,with high safety.

BACKGROUND:Currently,miR-196b-5p has been found to play a role in cell proliferation,migration and inhibition of scar hyperplasia,but there is a lack of relevant studies on whether it plays a role in the process of wound healing.OBJECTIVE:To investigate the effect of miR-196b-5p in adipose stem cell-derived exosomes on burn wound healing.METHODS:The models of deep second degree skin burn in SD rats were established and randomly divided into four groups:blank control group,exosome group,agomiR-196b-5p group,and exosome+antagomiR-196b-5p group,with 10 rats in each group.PBS,adipose-derived stem cell-derived exosomes,miR-196b-5p agonist,and miR-196b-5p inhibitor were injected around the wound according to different groups.Wound healing was observed immediately after injury and on days 7,14,and 21 after injury.On day 7 after surgery,hematoxylin-eosin staining was used to observe the expression of inflammation in the wound surface.On day 14 after suregery,Masson staining was used to observe the expression of collagen and immunohistochemical staining was used to observe the expression of CD31 in the wound surface.On day 7 after surgery,western blot assay was performed to detect the expression of α-smooth muscle actin and type Ⅰ collagen in the wound surface.RESULTS AND CONCLUSION:(1)The wound healing was faster in the agomiR-196b-5p group,while it was slower in the blank control group and the exosome+antagomiR-196b-5p group.(2)Compared with the blank control group and the exosome+antagomiR-196b-5p group,the wound infiltration of inflammatory cells was less in the exosome group and the agomiR-196b-5p group,and the expression of CD31 was significantly increased(P＜0.01).(3)Compared with the blank control group and the exosome+antagomiR-196b-5p group,the expression levels of α-smooth muscle actin and type Ⅰ collagen were increased in the exosome group and the agomiR-196b-5p group(P＜0.05).These findings indicate that miR-196b-5p in adipose stem cell-derived exosomes can promote burn wound healing in rats.

BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

BACKGROUND:Orthodontic treatment to move the mandibular second molar in place of the missing first molar is a good method for preserving natural teeth.However,molars often exhibit mesial tipping when using clear aligners.The impact of attachments and overcorrection on the molar mesialization with clear aligners is unclear.OBJECTIVE:To investigate the effects of attachments and overcorrection on displacement and biomechanics of the mandibular second molar mesialization.METHODS:A finite element model with the left mandibular first molar missing was constructed using a volunteer's cone-beam CT and intraoral scan data.The experiment was divided into four groups based on the position of attachments on the left mandibular second molar:without attachment,buccal attachment,lingual attachment,and buccal-lingual attachment,with overcorrection degrees(0°,1°,2°,3°,and 4°)for each group,totaling 20 models.The calculation and analysis of the displacement trends and stress were performed using Abaqus software.RESULTS AND CONCLUSION:(1)Mesial tipping and intrusion of the molar,distal tipping of the canines and permolars,and linguaing of the incisors occurred during molar mesialization.(2)The displacement of molars increased when attachments were used,with the maximum displacement occurring when buccal-lingual attachments were applied.Molars tended to tip towards the side without attachments when attachments were designed unilaterally.However,the inclination of molars did not decrease when attachments were used.(3)Molars exhibited reduced mesial tipping and intrusion,approaching overall movement,and the stress of periodontal ligament was relieved and more evenly distributed during overcorrection treatment,and this effect became more pronounced with increased degrees of overcorrection.(4)Attachments can enhance the effectiveness of overcorrection,with the best performance observed when buccal-lingual attachments are used.Using attachments and overcorrection together helps control molar mesial tipping and intrusion,but overall molar movement is not achieved.

OBJECTIVE:Elevated blood pressure increases the risk of cardiovascular diseases.Isometric exercise training has been shown to significantly reduce resting blood pressure,but the factors influencing its effectiveness remain unclear,and specific application guidelines are yet to be established.This study aims to evaluate the impact of isometric exercise training on resting blood pressure through meta-analysis,explore its moderating factors,and provide evidence-based recommendations based on its dose-response relationship.METHODS:Following the PRISMA guidelines,a systematic search was conducted in PubMed,Embase,Cochrane Library,Scopus,and Web of Science databases using keywords"Isometric exercise training,""Systolic blood pressure,"and"Diastolic blood pressure,"covering literature up to September 2024.Randomized controlled trials involving isometric exercise training and resting blood pressure were included.Three independent researchers performed literature screening and data extraction,assessing bias risk and quality grades using the Risk of Bias 2.0 tool and GRADE framework.Main effect pooling,publication bias assessment,subgroup,and regression analysis were conducted using R software(version 4.3.4).RESULTS:A total of 28 articles(comprising 32 randomized controlled trials)involving 977 participants were included.(1)Meta-analysis results indicated that isometric exercise training significantly reduced resting systolic blood pressure(MD=-8.01,95％CI=-9.22 to-6.80,P＜0.01,I2=18.20％,low evidence grade)and diastolic blood pressure(MD=-3.46,95％CI=-4.64 to-2.28,P＜0.01,I2=0％,moderate evidence grade)compared to no exercise.(2)Subgroup analysis results revealed significant influences of gender,health status,exercise modality,frequency,intensity,duration,sets per session,rest duration,and baseline blood pressure on the main effects for both systolic(P＜0.01)and diastolic blood pressure(P＜0.05).(3)Regression analysis results did not show any significant influencing factors,but body mass index(β=-4.11,P=0.091)showed a significant negative trend on the main effect for systolic blood pressure.(4)No significant publication bias was observed in the meta-analysis results(P＞0.05).CONCLUSION:(1)Isometric exercise training significantly lowers systolic(low evidence grade)and diastolic(moderate evidence grade)blood pressure with clinically meaningful thresholds.(2)Participant characteristics(gender,health status,baseline blood pressure,and body mass index)and isometric exercise training protocols(modality,frequency,intensity,duration,cycle,sets per session,and rest duration)influence its antihypertensive effects.(3)The article recommends the optimal blood pressure management prescription:three sessions per week,with four sets per session,each set lasting 2 minutes with a 2-minute rest,at an intensity of 95％HRpeak using isometric wall squat exercises;the intervention period can be adjusted around a 6-week node.Future high-quality research is urgently needed to further validate and support these conclusions.

BACKGROUND:The titanium alloy bone trabecular bone socket cup prosthesis printed by 3D technology has superior biological characteristics,which helps to promote osteogenic differentiation of stem cells.The Kidney Tonifying and Blood Activating Decoction has the functions of tonifying the kidneys,strengthening tendons,promoting blood circulation,and relieving pain.However,the application of the combination of the two in elderly hip arthroplasty is rarely reported.OBJECTIVE:To evaluate the application value and safety of 3D printed titanium alloy bone trabecular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction in elderly hip arthroplasty.METHODS:A total of 200 elderly patients who received hip arthroplasty in Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to January 2024 were selected and randomly divided into control group(n=100)and trial group(n=100).The control group underwent Pinnaele cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction,while the trial group underwent 3D printed titanium alloy bone trabecular cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction.The medication was taken continuously for 1 week before hip arthroplasty and for 4 weeks after arthroplasty.The differences in pain,swelling,hemorheology,inflammatory factors,bone metabolism,intra-articular stress,and hip abduction muscle strength were compared between the two groups to evaluate the clinical efficacy and safety of the two treatment options.RESULTS AND CONCLUSION:(1)Four weeks after surgery,the pain visual analog scale score,limb swelling,whole blood viscosity,and plasma viscosity of the trial group were lower than those of the control group(P＜0.05).The interleukin-6 level of the trial group was lower than that of the control group,and the interleukin-10 level was higher than that of the control group(P＜0.05).The levels of type Ⅰ collagen carboxyl terminal peptide β specific sequence and tartrate-resistant acid phosphatase 5b in the trial group were lower than those in the control group,while the levels of osteocalcin,bone-specific phosphatase and typeⅠ procollagen amino-terminal propeptide were higher than those in the control group(P＜0.05).The intra-articular stress and hip abduction muscle strength in the trial group were higher than that of the control group(P＜0.05).(2)Three months after surgery,the excellent and good treatment rate in the trial group was higher than that in the control group,and the incidence of safety evaluation events such as postoperative incision hematoma and infection was lower than that in the control group(P＜0.05).(3)It suggests that 3D printed titanium alloy trabecular acetabular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction can improve the blood rheology of elderly patients with hip arthroplasty,inhibit inflammatory response,reduce postoperative pain and swelling,and enhance bone metabolism,thereby promoting postoperative hip joint function recovery,and reducing the incidence of adverse events,with high safety.