OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

Objective: To investigate the correlation between social jetlag and psychological behavior in upper primary school students,so as to provide reference for sleep health promotion in primary school students. Methods: From April to June 2024, a survey was conducted among 4 341 fourth and fifth grade students from 9 public primary schools in a district in Beijing. Sleep patterns were assessed using a self designed questionnaire, while psychological behavior was evaluated using the Strengths and Difficulties Questionnaire (SDQ)(parent version). A generalized estimating equation (GEE) model was used to examine the association between different levels of social jetlag and psychological behavior problem scores in primary school students. Results: The proportions of students with social jetlag of <1.0, 1.0-<2.0, and ≥2.0 h were 57.6%, 30.6%, and 11.8%, respectively. The GEE model analysis found that after adjusting for covariates, compared with primary school students with social jetlag of <1.0 h, those with 1.0 -<2.0 and ≥2.0 h had higher scores for internalizing behavior problems [ β (95% CI ) =0.23(0.05-0.41)，0.28(0.02-0.54), P < 0.01]. Primary school students with ≥2.0 h of social jetlag had higher scores for externalizing behavior problems [ β (95% CI )=0.42 (0.13-0.71)， P <0.01]. Among boys and primary school students with an average nighttime sleep duration of ≥9 h, comparied with social jetlag of <1.0 h,those with sucial jetlag 1.0-<2.0 h had higher scores on internalizing and externalizing behavior problems[ β (95% CI )=0.32(0.07-0.56),0.51 (0.11-0.90), 0.26 (0.06-0.46)，0.58 (0.25-0.91), P <0.05]. Conclusions Greater social jetlag may be a risk factor for internalizing and externalizing behavior problems in upper primary school students. Reducing social jetlag may help decrease the occurrence of psychological behavior problems in primary school students.

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:Individuals with chronic ankle instability are prone to inversion ankle sprains during landing.Moderately increasing the foot toe-out angle during landing may reduce the occurrence of inversion ankle sprains,but no studies have directly demonstrated this effect. OBJECTIVE:To explore the effect of increased toe-out angle during landing on the peak inversion angle,peak angular velocity,and the time to peak inversion among individuals with and without chronic ankle instability. METHODS:A total of 60 participants were recruited for this study,including 30 individuals with chronic ankle instability and 30 without chronic ankle instability.The study utilized a simulated sprain apparatus for drop-landing tests,featuring a platform that could tilt forward by 24° and inward by 15°,thus simulating the foot position during an ankle inversion sprain.Participants were required to perform drop-landing tests under two landing conditions:natural landing and toe-out landing,with the latter involving a greater foot toe-out angle,over 150%more than the former.Kinematic data of participants were recorded using a 12-camera three-dimensional motion capture system.Data analysis was conducted using two-way repeated measures analysis of variance and Spearman correlation analysis. RESULTS AND CONCLUSION:(1)Significant main effects of condition were found for peak inversion angle during drop-landing(P<0.001,η2 p=0.270),peak inversion velocity(P=0.015,η2 p=0.098),and peak inversion time(P<0.001,η2 p=0.260);a significant main effect of group was found for peak inversion velocity(P=0.029,η2 p=0.080).(2)There were significant negative correlations between the foot toe-out angle at landing and the peak ankle inversion angle(P=0.021,r=-0.310;P=0.042,r=-0.278)as well as the peak inversion time(P=0.018,r=-0.312;P=0.021,r=-0.309)in both chronic ankle instability and non-chronic ankle instability groups.Moreover,a significant negative correlation was also found between the foot toe-out angle and peak inversion velocity in the chronic ankle instability group(P=0.021,r=-0.312).(3)It is indicated that increasing the foot toe-out angle at landing can reduce the peak inversion angle,peak inversion velocity,and the peak inversion time during landing in patients with chronic ankle instability and non-chronic ankle instability,thereby decreasing the risk of ankle inversion sprains.

BACKGROUND:A large number of articles have reported the effect and mechanism of platelet-rich plasma and hydrogel in the treatment of spinal cord injury,but few articles have summarized their treatment strategies for spinal cord injury. OBJECTIVE:To summarize the pathological process of spinal cord injury and the strategies of repairing spinal cord injury with platelet-rich plasma and hydrogel alone and in combination. METHODS:PubMed and CNKI databases were searched for articles published from inception to March 2024 by computer.The Chinese search terms were"spinal cord injury,platelet-rich plasma,hydrogel."The English search terms were"spinal cord injury,spinal cord,platelet-rich plasma,hydrogel,angiogenesis,neuralgia,combination therapy."Articles were screened according to inclusion and exclusion criteria,and 128 articles were finally included for review and analysis. RESULTS AND CONCLUSION:(1)The classification of platelet-rich plasma is complex and diverse,and the effects of platelet-rich plasma in the repair treatment of spinal cord injury are various,but they all show certain positive effects,that is,they can promote axon regeneration,stimulate angiogenesis,and treat neuropathic pain and so on.(2)The effect of platelet-rich plasma is mainly due to the growth factors contained in platelet-rich plasma.(3)There are many types of hydrogels,which mainly play the role of filling,simulating extracellular matrix,carrying drugs and biological products,and carrying cells as scaffolds in the repair treatment of spinal cord injury.(4)Compared with single therapy,combination therapy of platelet-rich plasma and hydrogel can promote nerve regeneration and spinal cord function recovery more effectively.

BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

ObjectiveTo investigate the association and translational mechanism between the hepatotoxicity of Xianling Gubao （XLGB） and its treatment of osteoporosis based on a zebrafish model. MethodsZebrafish were randomly selected four days after fertilization （4 dpf） and exposed to different concentrations of XLGB （0.7，0.35 mg·L^-1） for 96 h. At the endpoint of the exposure， the mortality rates of zebrafish in the treatment groups of different concentrations were counted， and the "dose-toxicity" curves were plotted. The 10% sublethal concentration （LC₁₀） was calculated. The liver area， acridine orange staining， and pathological tissue sections of transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP）］ were used as indicators to confirm the hepatic damage caused by the sublethal concentration of XLGB. By using the prednisolone （PNSL）-induced osteoporosis model of zebrafish， the anti-osteoporosis activity of XLGB was evaluated by using the area of skull stained by alizarin red and the cumulative optical density value as indicators. Then， the toxicity difference of XLGB on the liver of zebrafish in healthy and osteoporotic states was compared， and the mechanism of the translational action of the toxicity of XLGB was predicted based on network pharmacology and real-time polymerase chain reaction（Real-time PCR）. ResultsThe LC₁₀ of XLGB on zebrafish （8 dpf） was 0.7 mg·L^-1. Compared with the blank group， the sublethal concentration （LC₁₀=0.7 mg·L^-1， 1/2 LC₁₀=0.35 mg·L^-1） of XLGB induced an increase in the number of apoptosis of hepatocytes in a dose-dependent manner， and the tissue arrangement of the liver was disordered and loose. The vacuoles were obvious， and the fluorescence area of the liver was significantly reduced （P<0.01）. Compared with the blank group， the mineralized area and cumulative optical density value of zebrafish skull in the PNSL model group were significantly reduced （P<0.01）， and those in the 0.7，0.35 mg·L^-1 XLGB treatment group were significantly increased compared with the model group （P<0.01）. Most importantly， 0.7 mg·L^-1 XLGB had no significant effect on the liver of zebrafish in the osteoporosis disease model compared with the blank group. The results of network pharmacology and real-time PCR experiments showed that the toxic transformation of XLGB might be related to the differences in the expression levels of key targets， such as tumor protein 53 （TP53）， cysteine aspartic acid specific protease-3（Caspase-3）， interleukin（IL）-6， and alkaline phosphatase（ALP） in different organismal states. ConclusionUnder certain conditions， XLGB has hepatotoxicity in normal zebrafish， but under osteoporotic conditions， XLGB not only exerts significant anti-osteoporosis activity but also alleviates hepatotoxicity significantly， which provides a reference for the safe clinical use of XLGB and real evidence for the theories of traditional Chinese medicine of attacking poison with poison and of treating disease with corresponding drugs without damage to the body.

Precancerous lesions of gastric cancer （PLGC） are a group of pathological changes caused by abnormalities in the structure， morphology， and differentiation of gastric mucosal epithelial cells. Since the early symptoms are hidden and non-specific， PLGC is not easy to be diagnosed and it has often developed into intermediate or advanced gastric cancer once being diagnosed and missed the best time for treatment. Accordingly， the incidence of this disease is increasing year by year， which lifts a heavy burden on the patients. The pathogenesis of PLGC is complex， involving inflammatory microenvironment， bile reflux， glycolysis， autophagy， and apoptosis. Currently， PLGC is mainly treated with anti-inflammatory and endoscopic therapies， which are difficult to curb the development of PLGC. Therefore， seeking a safe and effective therapy is an important topic of modern research. Traditional Chinese medicine （TCM）， characterized by treatment based on syndrome differentiation and a holistic view， exerts effects via multiple pathways， mechanisms， and targets. Recent studies have confirmed that TCM can regulate the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）， Wnt/β-catenin， Sonic Hedgehog， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， hypoxia-inducible factor-1α （HIF-1α）， neurogenic locus notch homolog protein （Notch）， nuclear factor E₂-related factor 2 （Nrf2） and other signaling pathways. By targeting these pathways， TCM can inhibit aerobic glycolysis， reduce oxidative stress， repair the inflammatory microenvironment， regulate cellular autophagy， and promote vascular normalization， thereby delaying or reversing PLGC. However， few researchers have systematically summarized the TCM regulation of PLGC-associated pathways. By reviewing the relevant articles at home and abroad， this paper summarized the roles of the above signaling pathways in the development of PLGC and the research progress in the regulation of signaling pathways by TCM in the treatment of PLGC， with a view to providing a new theoretical basis for the clinical research on PLGC and the drug development for this disease.

AIM:To analyze the association between mobile phone addiction and high myopia among college students.METHODS:We conducted a cross-sectional questionnaire survey in December 2022 on all students of a university in Shaanxi Province, and the questionnaire included socio-demographic characteristics, mobile phone addiction, high myopia, and lifestyle. Binary Logistic regression model was used to analyze the association between mobile phone addiction and high myopia among college students.RESULTS:A total of 19 952 college students were included. The prevalence of high myopia was 7.31%. The rate of mobile phone addiction was 25.68%, and the mobile phone addiction score was 37.59±13.38. The incidence of high myopia among college students with mobile phone addiction was higher than non-mobile phone addiction(P<0.001). After adjusting for socio-demographic characteristics and lifestyle, the risk of high myopia among college students with mobile phone addiction was 1.274 times(95%CI:1.131-1.434)higher than non-mobile phone addiction. For each point increase of total mobile phone addiction score, withdrawal symptoms score, salience score, social comfort score, and mood changes score, the risk of high myopia among college students increased by 0.9%(95%CI:1.005-1.013), 2.0%(95%CI:1.010-1.030), 2.6%(95%CI:1.010-1.043), 4.8%(95%CI:1.030-1.066), and 3.3%(95%CI:1.014-1.052), respectively.CONCLUSION:Mobile phone addiction is significantly associated with the increased risk of high myopia among college students, and early intervention of mobile phone use may reduce the risk of high myopia among college students.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.