BACKGROUND:Currently,there are many modeling methods for pelvic organ prolapse animal models,and the commonly used methods are vaginal balloon dilatation,oophorectomy and the combination of the two.There is no study comparing the three modeling methods in detail.OBJECTIVE:To construct and validate a rat animal model of pelvic organ prolapse using three different methods and to identify the advantages and disadvantages of various models.METHODS:Seventy-two 8-week SPF-grade female Sprague-Dawley rats were selected and randomly divided into four groups,namely,vaginal balloon dilatation group,ovariectomy group,ovariectomy combined with vaginal balloon dilatation group(the combined group),and the sham-operated group(no ovariectomy and no vaginal dilatation).The vaginal wall tissues of rats were collected at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining,EVG staining and immunohistochemical staining of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 detection,and the pelvic floor muscle tissues were taken at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining and EVG staining.RESULTS AND CONCLUSION:(1)Hematoxylin-eosi staining showed that there was no significant difference in the decrease of vaginal epithelial layer thickness in the vaginal balloon dilatation group compared with the sham-operated group,(P＞0.05),while the thickness of the vaginal epithelial layer was significantly reduced in the ovariectomy group and the ovariectomy combined with vaginal balloon dilation group(P＜0.001),and the reduction was more significant in the ovariectomy combined with vaginal balloon dilation group,remained stable at 8 weeks after surgery and lasted until 12 weeks.(2)The changes in the content of collagen fibers and elastic fibers in the vaginal wall stained by Masson and EVG staining were the same as the changes in the thickness of the vaginal epithelial layer stained by hematoxylin-eosin,and there were no changes in collagen fibers and elastic fibers in the pelvic floor muscle tissues of the treatment groups.(3)At 4,8 and 12 weeks after treatment,there was no significant difference in the expression levels of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 in the vaginal wall tissue of the balloon dilation group compared with the control group(P＞0.05),whereas the expression levels of α-smooth muscle actin and Vimentin were significantly decreased in the ovariectomy group and ovariectomy combined with vaginal balloon dilation group(P＜0.01)and the expression of matrix metalloproteinase 9 showed a significant increase(P＜0.01),with a more pronounced increase in the ovariectomy combined with vaginal balloon dilation group,and the increase reached a stable state at 8 weeks after surgery and could persist up to 12 weeks.To conclude,vaginal balloon dilatation could not maintain the degeneration of pelvic organ prolapse formed by the vaginal wall for a long period,and both ovariectomy and the combined method can be used.Ovariectomy combined with vaginal balloon dilatation can significantly accelerate and aggravate the formation of typical histological features of pelvic organ prolapse in vaginal wall tissues,effectively shorten the experimental period,and improve the efficiency.These effects reach a stable state at 8 weeks after surgery and can be sustained up to 12 weeks,which is practical and convenient for the study of pelvic organ prolapse animal models.

BACKGROUND:Maxillofacial bone three-dimensional(3D)printing technology has been widely used in clinical diagnosis and treatment,but the data source before performing maxillofacial bone 3D printing mainly comes from the CT scanning data.The lens,thyroid and other parts of the human body are extremely sensitive to X-rays;therefore,it is particularly important to effectively reduce the dose of CT radiation when acquiring the data source.OBJECTIVE:To explore the feasibility of low-dose CT technology in optimizing radiation dose for maxillofacial bone 3D printing.METHODS:The medical records of 65 patients who underwent maxillofacial bone 3D printing in the Department of Stomatology at the General Hospital of Northern Theater Command from March 2021 to December 2023 were retrospectively collected and categorized into a conventional CT-dose 3D printing group(conventional CT-dose,120 kVp,automated tube current modulation,n=32)and a low-CT-dose 3D printing group(low-CT-dose group,80 kVp,automated tube current modulation,n=33).The effective dose of radiation was calculated and compared between the two groups.A Likert scale was used to evaluate the quality of 3D printing in the two groups,and the measurement bias and consistency between evaluators were measured using the Bland-Altman method.RESULTS AND CONCLUSION:(1)There was no significant difference in the general demographic characteristics(age,height,weight,body mass,sex,and body mass index)between the two groups(all P＞0.05).(2)The effective dose value of the low CT-dose 3D printing group was(0.3±0.1)mSv,which was about 62.5％lower than that in the conventional CT-dose 3D printing group[(0.8±0.1)mSv].(3)There was no significant difference in the subjective scoring of 3D printing quality between the two groups(all P＞0.05).The subjective consistency among evaluators was good,with Kappa values of 0.85,0.80,and 0.76.The scatter points in the Bland-Altman for both protocols were uniformly distributed within the standard deviation line,indicating good consistency between the two groups.To conclude,low-dose CT technology can be effectively applied in maxillofacial bone 3D printing,reducing radiation dose without affecting the quality of 3D printing.

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:Clinical studies suggest that both bone quality and excessive crown-to-implant ratio are factors that affect the success rate of implant surgery,but there is no consensus on how large the crown-to-implant ratio under each bone quality will affect the prognosis of implant repair.OBJECTIVE:To analyze the stress and strain of bone tissue around implant restorations with different crown-to-implant ratios under different bone types after stress loading using three-dimensional finite element method.Combined with the Frost bone mechanics regulation system theory,the physiological limits of bone strain were observed for each bone type within a certain range of crown to implant ratios.METHODS:Cone beam CT data were selected from a patient to establish solid bone block models with four different bone types(class Ⅰ bone:cortical bone thickness 3 mm+dense cancellous bone,class Ⅱ bone:cortical bone thickness 2 mm+relatively dense cancellous bone,class Ⅲ bone:cortical bone thickness 1 mm+relatively low-density cancellous bone,class Ⅳ bone:cortical bone thickness 1 mm+low-density cancellous bone).Implant restorations with five different crown-to-implant ratios(1,1.5,2,2.5,and 3)were created on each bone block model,for a total of 20 models.Vertical and oblique forces were applied to the dental crown to observe the von Mises stress values,strains,and displacement of the cortical and cancellous bones,as well as the degree of implant displacement.RESULTS AND CONCLUSION:(1)In the class Ⅰ bone model,when the crown-to-implant ratio reached 3 under oblique loading,the cortical bone strain exceeded the physiological limit.In the class Ⅱ bone model,under oblique loading,when the crown-to-implant ratio reached 2.5,the cortical bone strain exceeded the physiological limit.In the class Ⅲ bone model,under oblique loading,cortical bone exceeded the physiological limit when the crown-to-implant ratio reached 2.5,while cancellous bone reached the critical physiological limit at 1.In the class Ⅳ bone model,under oblique loading,when the crown-to-implant ratio reached 1.5,2,2.5,and 3,the cortical bone strain exceeded the physiological limit.In the class Ⅳ bone model,all five crown-to-implant ratios of cancellous bone exceeded physiological limits.(2)Under vertical load,the cancellous bone strain exceeded the physiological limit when the crown-root ratio reached 1,2,2.5,and 3 in the class Ⅲ bone model,and when the cancellous bone strain of the five crown-root ratios in the class Ⅳ bone model exceeded the physiological limit.(3)Under oblique or vertical load,the implant displacement of the 20 groups of models did not exceed 100 μm.(4)From the perspective of biomechanics,when patients with insufficient bone height choose implant restoration,the crown-root ratio that class Ⅰ bone can tolerate is up to 2.5 times,the crown-root ratio that class Ⅱ bone can tolerate is up to 2 times,and the crown-root ratio that class Ⅲ and class Ⅳ bones can tolerate is up to 1 times due to excessive strain of cancellous bone;but the crown-root ratio that cortical bone in class Ⅲ bone can tolerate is up to 2 times.Whether class Ⅲ bone can tolerate implant restoration with a high crown-root ratio and whether cancellous bone can tolerate higher strains needs further study.

BACKGROUND:Studies have shown that disorders of mineral metabolism may be responsible for premature aging and that the kl/FGF23 axis plays an important role in mineral metabolism.OBJECTIVE:To explore the effect of long-term endurance exercise on the kl/FGF23 axis in naturally aging mice,and to observe the impact of long-term endurance exercise on calcium and phosphorus metabolism,so as to provide a reference for the influence of long-term endurance exercise on natural aging.METHODS:Twenty-two 5-week-old SPF male balb/c mice were randomly divided into three groups:young and quiet control group,natural aging quiet group and natural aging exercise group.Mice in the young and quiet control group were then killed immediately.Mice in the natural aging quiet group were raised normally until 60 weeks of age.Mice in the natural aging exercise group were subjected to adaptive exercise for 1 week,followed by the maximum running speed test.The official exercise speed was set at 70％of the maximum running speed,and exercise was performed on Mondays,Wednesdays,and Fridays for 50 minutes each.Maximum running speed was retested at 8-week intervals to adjust the official exercise speed until the age of 60 weeks.(3)Enzyme-linked immunoassay was used to measure the levels of femoral fibroblast growth factor 23,renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2D3.RESULTS AND CONCLUSION:(1)Compared with the young and quiet control group,serum calcium and phosphorus levels in natural aging quiet group had no significant changes(P＞0.05),but bone calcium and phosphorus levels were significantly reduced(P＜0.01).Compared with the natural aging quiet group,the serum phosphorus level was significantly reduced(P＜0.05),the serum calcium level did not change(P＞0.05),and bone calcium and phosphorus levels were significantly increased in the natural aging exercise group(P＜0.05).(2)Compared with the young and quiet control group,the level of fibroblast growth factor 23 in the femur of the natural aging quiet group was significantly increased(P＜0.05).Compared with the natural aging quiet group,the level of fibroblast growth factor 23 in the femur of the natural aging exercise group was reduced,but it was not statistically significant(P＞0.05).(3)Compared with the young and quiet control group,the renal Klotho protein expression,the renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2 D3 levels in the natural aging quiet group were significantly decreased(P＜0.05,P＜0.01).Compared with the natural aging quiet group,the levels of the above-mentioned indicators were significantly increased in the natural aging exercise group(P＜0.05,P＜0.01).To conclude,long-term endurance exercise can regulate Klotho protein and fibroblast growth factor 23 through the kl/FGF23 axis,thereby affecting the expression of 1α-hydroxylase and the level of 1,25(OH)2D3,and further regulating the body's calcium and phosphorus metabolism,especially phosphate metabolism.This indicates that long-term endurance exercise can delay the natural aging of the body through the kl/FGF23 axis.

ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang （WDD） on mice with ischemic heart disease （IHD） presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group， WDD low-dose group （WDD-L）， WDD medium-dose group （WDD-M）， WDD high-dose group （WDD-H）， and atorvastatin calcium tablet group， with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91， 17.81， 35.62 g·kg^-1， and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg^-1， twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration， the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin （HE） staining. Serum N-terminal pro-B-type natriuretic peptide （pro-BNP） content was measured by enzyme-linked immunosorbent assay （ELISA）. Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL） were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group， model serum group， WDD-L drug-containing serum group， WDD-M drug-containing serum group， and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group， the model group showed a significantly increased cardiac index （P0.01）， significantly decreased fractional shortening （FS） （P0.01）， and significantly increased left ventricular end-diastolic internal diameter （LVDD） and left ventricular end-systolic internal diameter （LVDS） （P0.01）. Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated （P0.01）， and whole-blood viscosity （BV） at high， medium， and low shear rates was significantly increased （P0.01）. Compared with the model group， the WDD groups showed significantly reduced cardiac index （P0.05， P0.01）， significantly increased FS （P0.05， P0.01）， significantly decreased LVDD and LVDS （P0.01）， markedly improved cardiomyocyte morphology， significantly reduced inflammatory infiltration， significantly decreased serum pro-BNP levels （P0.01）， and significantly decreased BV at high， medium， and low shear rates （P0.01）， with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group， TC， TG， and LDL levels were significantly increased in the model group （P0.05， P0.01）， while HDL levels were significantly decreased （P0.05）. After WDD-H treatment， TC， TG， and LDL levels were significantly reduced and HDL levels were significantly increased in mice （P0.05， P0.01）. Compared with the sham-operation group， classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group （P0.01）， whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased （P0.01）. After WDD administration， all circulating monocyte subsets in blood and bone marrow were significantly alleviated （P0.05， P0.01）， with the WDD-M group showing the optimal effect. In vitro， compared with the blank group， CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group （P0.01）， and CD36 expression was significantly upregulated on RAW264.7 cells （P0.01）. Compared with the model serum group， all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation （P0.01）. WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines （P0.05， P0.01）， with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.

ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang （WDD） on mice with ischemic heart disease （IHD） presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group， WDD low-dose group （WDD-L）， WDD medium-dose group （WDD-M）， WDD high-dose group （WDD-H）， and atorvastatin calcium tablet group， with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91， 17.81， 35.62 g·kg^-1， and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg^-1， twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration， the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin （HE） staining. Serum N-terminal pro-B-type natriuretic peptide （pro-BNP） content was measured by enzyme-linked immunosorbent assay （ELISA）. Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL） were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group， model serum group， WDD-L drug-containing serum group， WDD-M drug-containing serum group， and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group， the model group showed a significantly increased cardiac index （P<0.01）， significantly decreased fractional shortening （FS） （P<0.01）， and significantly increased left ventricular end-diastolic internal diameter （LVDD） and left ventricular end-systolic internal diameter （LVDS） （P<0.01）. Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated （P<0.01）， and whole-blood viscosity （BV） at high， medium， and low shear rates was significantly increased （P<0.01）. Compared with the model group， the WDD groups showed significantly reduced cardiac index （P<0.05， P<0.01）， significantly increased FS （P<0.05， P<0.01）， significantly decreased LVDD and LVDS （P<0.01）， markedly improved cardiomyocyte morphology， significantly reduced inflammatory infiltration， significantly decreased serum pro-BNP levels （P<0.01）， and significantly decreased BV at high， medium， and low shear rates （P<0.01）， with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group， TC， TG， and LDL levels were significantly increased in the model group （P<0.05， P<0.01）， while HDL levels were significantly decreased （P<0.05）. After WDD-H treatment， TC， TG， and LDL levels were significantly reduced and HDL levels were significantly increased in mice （P<0.05， P<0.01）. Compared with the sham-operation group， classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group （P<0.01）， whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased （P<0.01）. After WDD administration， all circulating monocyte subsets in blood and bone marrow were significantly alleviated （P<0.05， P<0.01）， with the WDD-M group showing the optimal effect. In vitro， compared with the blank group， CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group （P<0.01）， and CD36 expression was significantly upregulated on RAW264.7 cells （P<0.01）. Compared with the model serum group， all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation （P<0.01）. WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines （P<0.05， P<0.01）， with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.

Adverse drug reactions （ADRs） refer to harmful or unintended reactions unrelated to the intended purpose of medication administration， which can lead to various issues such as accelerated disease progression and prolonged hospitalization. Traditional ADRs monitoring systems （such as spontaneous reporting systems） suffer from limitations such as low reporting rates and inconsistent data quality， which hinder the early prevention and control of ADRs. With the rapid development of information technology， machine learning has emerged as a powerful tool for management and decision-making of ADRs by leveraging its strengths in feature extraction and dynamic temporal pattern analysis. By reviewing relevant literature at home and abroad in recent years， this paper summarizes the progress in the application of machine learning for ADRs prediction. It is found that machine learning has gradually been applied to the early warning and risk prediction of ADRs in target organs such as the kidneys， liver， heart and bone marrow （such as acute kidney injury， drug-induced liver injury， and so on）. Although machine learning demonstrates significant application potential in the field of ADRs prediction， it still faces limitations such as inadequate quality control of clinical data， lack of standardized criteria for model performance evaluation， insufficient model interpretability and difficulties in clinical translation. In the future， the development trend of machine learning in the field of ADRs prediction should follow a “technology-validation-integration” pathway to systematically promote the practical implementation of models.

Objective: To explore the latent profiles of psychological help seeking intentions among adolescents in Wuhan, and to investigate their association with non suicidal self injury (NSSI), in order to provide a theoretical basis for constructing an early intervention system for adolescents NSSI. Methods: From October to December 2022, a convenient sampling method was used to select 3 975 students from grades 7 to 12 in Wuhan. A self administered questionnaire assessed psychological help seeking intentions, followed by a post survey interview using the Ottawa Self injury Inventory to evaluate NSSI behaviors. Latent profile analysis(LPA) was used to explore the potential categories of help seeking intentions in adolescents. Multinomial Logistic regression was used to analyze factors associated with the latent profiles of help seeking intentions and multiple Logistic regression was used to analyze the association between latent profiles of help seeking intentions and NSSI. Results: Based on latent profile analysis, four latent profiles of help seeking intentions in adolescents were identified, namely overall low, moderate, and high help seeking group, as well as family/friendfocused help seeking group, accouting for 14.1%, 20.9%, 43.1% and 21.8%, respectively. Multinomial Logistic regression analysis showed that compared to senior high school students, junior high school students were more willing to seek help from family and friends ( OR =1.56); compared to males, females were more likely to exhibit moderate help seeking intentions( OR =1.37); students with extroverted or balanced personalities were more likely to exhibit high level help seeking intentions( OR =1.50, 1.49); students with average or good family economic status, better parental relationships, and adequate mental health knowledge were more likely to exhibit moderate and high level help seeking intentions( OR =1.59, 2.02; 1.80, 2.64; 1.44, 1.55; 1.34, 1.58) (all P <0.05). Students with moderate or severe family dysfunction were less likely to seek help from family and friends or to exhibit moderate and high level help seeking intentions( OR =0.51, 0.60, 0.25; 0.22, 0.27, 0.06, all P <0.01). Students whose parents exhibited stigma towards mental illness were less likely to show high level help seeking intentions( OR= 0.78 , P <0.05). Multivariable Logistic regression analysis results indicated that compared to the overall low help seeking intentions group, reduced risk of NSSI was observed among students in the overall moderate and overall high groups, as well as in the family/friend focused help seeking group( OR =0.73, 0.60, 0.70, all P <0.05). Conclusions Active psychological help seeking intentions can reduce NSSI behaviors in adolescents. Interventions should focus on improving family support environment to enhance adolescents intentions to seek psychological help.