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.

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.

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.

Nucleic acid-based molecular diagnostic methods are considered the gold standard for detecting infectious pathogens.However,when applied to portable or on-site rapid diagnostics,they still face various limitations and challenges,such as poor specificity,cumbersome operation,and portability difficulties.The CRISPR(Clustered regularly interspaced short palindromic repeats)/CRISPR-associated protein(Cas)-fluorescence detection method holds the potential to significantly enhance the specificity and signal-to-noise ratio of nucleic acid detection.In this study,we developed a portable grayscale reader detection system based on loop-mediated isothermal amplification(LAMP)-CRISPR/Cas.On one hand,in the presence of CRISPR RNA(crRNA),the CRISPR/Cas12a system was employed to achieve precise fluorescent detection of self-designed LAMP amplification reactions for influenza A and influenza B viruses.This further validated the high selectivity and versatility of the CRISPR/Cas system.On the other hand,the accompanying independently developed portable grayscale reader allowed for low-cost collection of fluorescence signals and high-reliability visual interpretation.At the end of the detection process,it directly provided positive or negative results.Practical sample analyses using this detection system have verified its reliability and utility,demonstrating that this system can achieve highly sensitive and highly specific portable analysis of influenza viruses.

Objective To investigate the influence of modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy on the efficacy,survival status and serum cytokeratin 19 fragment(CYFRA21-1)and neuron-specific enolase(NSE)levels in patients with advanced non-small cell lung cancer(NSCLC).Methods Forty patients with advanced NSCLC of lung-stomach yin deficiency with intense heat-toxin type were randomly divided into a control group and a study group,with 20 patients in each group.The patients in the control group were given Camrelizumab immunotherapy plus chemotherapy,and the patients in the study group were given modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy,with 21 days as a course of treatment and for a total of 4 courses of treatment.The changes of serum NSE and CYFRA21-1 levels in the two groups before and after treatment were observed,and the clinical efficacy,survival status and the incidence of toxic and side effects were compared between the two groups.Results(1)After 4 courses of treatment,the total effective rate of the study group was 70.00%(14/20),which was significantly higher than that of the control group(9/20,45.00%),but the intergroup comparison(tested by chi-square test)showed that the difference was not statistically significant(P＞0.05).(2)After 2 years of follow-up,the overall survival(OS),time to progression(TTP),and progression-free survival(PFS)of the patients in the study group were significantly prolonged compared with those in the control group(P＜0.01).(3)After treatment,the serum NSE and CYFRA21-1 levels of the patients in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of serum NSE and CYFRA21-1 levels in the study group was significantly superior to that in the control group(P＜0.01).(4)The incidence of toxic and side effects in the study group was 25.00%(5/20),which was significantly lower than that of 65.00%(13/20)in the control group,and the intergroup comparison showed that the difference was statistically significant(P＜0.05).Conclusion Modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy has satisfactory therapeutic effect on patients with advanced NSCLC,which can reduce the toxic and side effects of chemotherapy,lower the level of serum tumor markers,and prolong the survival period and time to progression(TTP)of the patients.

Skeletal muscle injury is a common disease in clinical practice,and an in-depth understanding of its repair mechanisms is crucial for the development of effective therapeutic strategies.This paper focuses on the key role of TGF-β in skeletal muscle injury repair,introduces the diversity of its family members and signaling pathways,explores the expression and regulation part of TGF-β after skeletal muscle injury,analyzes its early expression dynamics and regulatory factors,and thoroughly investigates the effects of TGF-β on skeletal muscle repair,revealing its inflammatory regulation,cellular activation and proliferation as well as fibrosis.Key role.Special attention was paid to its mechanism of action in muscle regeneration and its regulatory mechanism at the cellular level.In addition,the potential clinical applications of TGF-β in the repair of skeletal muscle injury were discussed,and the development and application of it as a therapeutic target and modulator were explored.However,controversies and shortcomings still exist in the current study,such as the dual roles of TGF-β and the impact of individual differences on treatment.Future research directions should include digging deeper into the details of signaling pathways and biomarker discovery.By overcoming these challenges,the potential clinical application of TGF-β in skeletal muscle injury repair is expected to usher in new breakthroughs and provide patients with more individualized and effective treatment strategies.

BACKGROUND:The treatment of distal tibial fractures with soft tissue injury has always been challenging,and the new retrograde tibial nailing is a new choice.Up to now,there were few reports on the biomechanical properties between the new retrograde tibial nailing,anterograde intramedullary nailing and supercutaneous locking plate. OBJECTIVE:To explore the biomechanical stability of new retrograde tibial nailing,antegrade intramedullary nailing and supercutaneous locking plate in the treatment of distal tibial fractures with soft tissue injury using finite element analysis so as to offer a scientific foundation for clinical application. METHODS:The finite element model of transverse distal tibia fracture was established by relevant software utilizing the CT data of the tibia from a 42-year-old healthy male.Retrograde tibial nailing,antegrade intramedullary nailing and supercutaneous locking plate finite element models were assembled under the principle of fracture fixation.Finally,meshing,applying loads,and data processing were accomplished with the ANSYS 2019 software.Moreover,the stress distribution and displacement of the tibia and internal fixation of each model were compared. RESULTS AND CONCLUSION:(1)The displacement of fracture end in the three groups increased with the increase of load.In all mode loads,the average displacement of the fracture end was the least in the retrograde tibial nailing group,followed by the supercutaneous locking plate group,and the highest in the antegrade intramedullary nailing group.At 800 N vertical load,the displacement difference of the fracture end was statistically significant(P<0.05).There was no statistical significance in other load modes.(2)Under different loads,the tibial stress in the three groups was the highest in the middle of the tibia,and gradually decreased to the proximal and distal ends.The stress distribution of the tibial shaft was the highest in the retrograde tibial nailing group,followed by the supercutaneous locking plate group,and the least in the antegrade intramedullary nailing group.(3)Under different loads,the stress of the tibial stress raiser in the three groups was significantly higher in the supercutaneous locking plate group than in the other two groups,with statistical significance(P<0.05).(4)Under different loads,the stress of the fixators in the three groups was the largest in the supercutaneous locking plate group,followed by the retrograde tibial nailing group,and the minimum in the antegrade intramedullary nailing group.There were significant differences in the stress of fixator stress raiser among the three groups under different loading modes(P<0.05).(5)It is indicated that all three fixation methods have the good anti-rotation ability and axial stability.Retrograde tibial nail shows better biomechanical stability.

BACKGROUND:The treatment of distal tibial comminuted fractures with soft tissue injury has always been challenging.The new retrograde tibial nailing and supercutaneous locking plate are important treatment methods,but their strain and stress shielding at the fracture end during different periods of fracture healing and different load conditions have not been reported. OBJECTIVE:To explore the biomechanical stability of retrograde tibial nailing and supercutaneous locking plate in different periods of fracture healing by finite element analysis to offer a scientific foundation for clinical application and rehabilitation exercise. METHODS:The finite element model of distal tibial comminuted fracture was established by utilizing the CT data of the tibia from a 40-year-old healthy male.Retrograde tibial nailing,supercutaneous locking plate,and callus models were assembled in accordance with the principle of fracture fixation.The finite element analysis was performed using ANSYS software to compare the displacement of the fracture end,the stress shielding of the tibia,the stress of the callus,and the stress distribution of the tibia and the fixation device during different periods of fracture healing. RESULTS AND CONCLUSION:(1)The relative displacement of the tibial fracture decreased gradually with the healing of the fracture,and the displacement decreased significantly after 3 months.At 0 and 1 months after operation,the vertical displacement and total displacement of the supercutaneous locking plate group were higher than those in the retrograde intramedullary nail group.The Z-axis displacement(horizontal medial and lateral displacement)of the two fixation methods was more obvious than the X-axis and Y-axis,and the Z-axis displacement of supercutaneous locking plate group was the most obvious.The maximum Z-axis displacement of the two fixation methods was located on the outside of the tibia,and the minimum displacement was located on the inside of the tibia.(2)The stress shielding rate at different periods of fracture healing gradually decreased with time.The stress shielding rate of the retrograde intramedullary nail was higher than that of the supercutaneous locking plate at different stages of fracture healing.After 3 months,the stress shielding rate of the supercutaneous locking plate was reduced to about 4%,and the stress shielding rate of the retrograde intramedullary nail was reduced to about 40%.(3)The stress of the stress concentration site of the callus in the two fixation methods increased with the increase of the load,and the stress of the callus in the supercutaneous locking plate group was always greater than that in the retrograde intramedullary nail group.The maximum stress distribution of the callus was approximately equally distributed among the two modes of fixation,both in the lateral portion of the tibia.(4)As the fracture healed,the maximum stress of the tibia in the two groups decreased gradually,and the stress in the supercutaneous locking plate group was always greater than that in the retrograde intramedullary nail group.The average stress of the maximum stress area of the tibia in the supercutaneous locking plate group under 1 500 N load was 285 MPa,while that in the retrograde intramedullary nail group was 26 MPa.(5)As the fracture healed,the stress of the fixation device in the two groups decreased gradually,and the stress in the supercutaneous locking plate group was significantly higher than that in the retrograde intramedullary nail group.After 3 months,the stress of the two fixation devices decreased significantly.(6)It is indicated that in the early stage of fracture healing,the strain on the fracture end in the retrograde intramedullary nail group is small,and the maximum stress of the tibia is moderate,allowing early loaded.The fractured ends in the supercutaneous locking plate group had too large strain and too large maximum stress of the tibia,which needed to be partially loaded under protection and could not be fully loaded.In the middle and late stages of fracture healing,the tibial retrograde intramedullary nail and the supercutaneous locking plate could be completely loaded,and the stress shielding rate of the supercutaneous locking plate was significantly lower than the tibial retrograde intramedullary nail.

AIM: To explore the neuro-ophthalmological characteristics of acute macular neuroretinopathy(AMN)after SARS-CoV-2 infection.METHODS: A total of 8 patients(14 eyes), including 6 females and 2 males, who were diagnosed with AMN in the neuro-ophthalmology department of Xi'an No.1 Hospital(The First Affiliated Hospital of Northwest University)from December 27, 2022 to February 1, 2023 were included in the study. All patients had a history of SARS-CoV-2 infection before the disease, and the results of best corrected visual acuity(BCVA), non-contact indirect intraocular pressure measurement, fundus color photography, near infrared(IR), spectral-domain optical coherence tomography(SD-OCT), OCT angiography(OCTA), fundus fluorescein angiography(FFA), indocyanine green angiography(ICGA), visual field, visual evoked potential(VEP), and electroretinogram(ERG)were collected. Furthermore, the neuro-opthalmology characteristics of the included patients were analyzed and summarized.RESULTS: The included 8 patients aged from 20 to 43, with an average age of(30±6.63)years old. The patients had a history of SARS-CoV-2 infection 3 to 11(mean 5±3.51)d before the disease, and 6 out of 8 patients developed visual symptoms within 5 d of infection with SARS-CoV-2, with manifestated with decreased vision or visual scotoma. The visual acuity varied from 0.08 to 1.0, with visual field defect characterized by central, paracentral or peripheral scotoma. VEP showed prolongation latency of P100 or P2, and ERG revealed impaired function of retinal photoreceptor cell. In the early stage of the disease, the size and shape of early visual acuity, visual field, and extraretinal lesions in patients with AMN associated with SARS-CoV-2 infection may not match, and the lower the visual acuity, the later the VEP peaks.CONCLUSION: The neuro-ophthalmic features of SARS-CoV-2 infection-associated AMN require the attention of clinicians. In addition to multi-mode fundus imaging, clinicians should use a variety of methods to comprehensively evaluate visual function and prognosis of patients.

Objective To explore the role of TMAO from gut microbiota in non-alcoholic fatty liver disease(NAFLD),we detected the serum level of TMAO and its precursor metabolites in NAFLD,as well as the expression level of Eubacterium rectum,Bacteroidetes multiforme,Lactobacillus and bifidobacterium in the intestinal flora.Methods We collected 118 subjects and divided into NAFLD group(86 cases)and healthy control group(32 cases)randomly.We also detected the serum level of TMAO and its precursor metabolites in subjects by high performance liquid chromatography tandem mass spectrometry detection(LC-MS),and the expression of target bacterial DNA was detected by qRT-PCR.Results Serum TMAO,TMA and choline levels were significantly increased in NAFLD(P<0.05),and liver fat content was positively correlated with TMAO(P<0.05).The expression level of Lactobacillus and Eubacterium rectum in NAFLD group were increased(P<0.05);the expression level of Bifidobacterium and Bacteroides multiform were decreased(P<0.05).The serum TMAO level was positively correlated with Eubacterium rectum(r=0.280,P<0.05),and negatively correlated with Bifidobacterium(r=-0.332,P<0.05).Conclusion The level of TMAO in serum shows a positive correlation with NAFLD.The structure of intestinal flora in individuals with NAFLD is altered and linked to TMAO.This suggests that the intestinal flora may have a significant impact on the development of NAFLD through TMAO.