ObjectiveTo combine metabolomics， proteomics， and transcriptomics to analyze the biological characteristics of damp-heat toxin accumulation syndrome and damp-heat accumulation syndrome in acute gout. MethodsBlood samples were collected from 15 patients with damp-heat toxin accumulation syndrome and 15 patients with damp-heat accumulation syndrome in acute gout in clinical practice. Metabolomics technology was applied to detect serum metabolites， and an orthogonal partial sample least squares discriminant analysis model was constructed to screen for metabolites with significant intergroup changes， and enrichment pathway analysis and receiver operating characteristic （ROC） curve analysis were performed. Astral data independence acquisition （DIA） was used to detect serum proteins， perform principal component analysis and screen differential proteins， demonstrate differential ploidy by radargram， apply subcellular localisation to analyse protein sources， and finally apply weighted gene co-expression network analysis （WGCNA） to find key proteins. Transcriptome sequencing technology was also applied to detect whole blood mRNA， screen differential genes and perform WGCNA， and construct machine learning models to screen key genes. ResultsMetabolome differential analysis revealed 62 differential metabolites in positive ion mode and 26 in negative ion mode. These differential metabolites were mainly enriched in the mTOR signaling pathway and FoxO signaling pathway， with trans-3,5-dimethoxy-4-hydroxycinnamaldehyde， guanabenz， 4-aminophenyl-1-thio-beta-d-galactopyranoside showing the highest diagnostic efficacy. The proteome differential analysis found that 55 proteins up-regulated and 20 proteins down-regulated in the samples of damp-heat toxin accumulation syndrome. Notably， myelin basic protein （MBP）， transferrin （TF）， DKFZp686N02209， and apolipoprotein B （APOB） showed the most significant differences in expression. Differential proteins were mainly enriched in pathways related to fat digestion and absorption， lipid and atherosclerosis， and cholesterol metabolism. WGCNA showed the highest correlation between damp-heat toxin accumulation syndrome and the brown module， with proteins in this module primarily enriched in the hypoxia-inducible factor 1 （HIF-1） signaling pathway and lipid and atherosclerosis. Transcriptomic differential analysis identified 252 differentially expressed genes， with WGCNA indicating the highest correlation between damp-heat toxin accumulation syndrome and the midnight blue module. The random forest （RF） model was identified as the optimal machine learning model， predicting apolipoprotein B receptor （APOBR）， far upstream element-binding protein 2 （KHSRP）， POU domain class 2 transcription factor 2 （POU2F2）， EH domain-containing protein 1 （EHD1）， and family with sequence similarity 110A （FAM110A） as key genes. Integrated multi-omics analysis suggested that damp-heat toxin accumulation syndrome in the acute phase of gout is closely associated with lipid metabolism， particularly APOB. ConclusionCompared to damp-heat accumulation syndrome in the acute phase of gout， damp-heat toxin accumulation syndrome is more closely associated with lipid metabolism， particularly APOB， and lipid metabolism disorders contribute to the development of damp-heat toxin accumulation syndrome in patients with acute gout.

BACKGROUND:Several observational studies have found a close relationship between thyroid function levels and sarcopenia,but the causal relationship between thyroid function levels and the onset of sarcopenia is not yet clear. OBJECTIVE:To investigate the causal relationship between thyroid function levels and sarcopenia using a two sample Mendelian randomization method. METHODS:A two sample Mendelian randomization analysis was conducted using genome-wide association study data on thyrotropin,free triiodothyronine,free tetraiodothyronine,subclinical hyperthyroidism,subclinical hypothyroidism,and four related phenotypes of sarcopenia-lefthand grip strength,right hand grip strength,limb lean mass,and gait speed.The inverse-variance weighted method,weighted median method,simple mode method,weighted median estimator method,and MR Egger regression method were used as analysis methods,while heterogeneity test,pleiotropy test,MR-PRESSO,leave-one-out method,funnel plot and other methods were used for sensitivity analysis. RESULTS AND CONCLUSION:Elevated levels of thyroid-stimulating hormone increased left-(β=0.02,SE=0.01,P=0.01)and right-handed grip strength(β=0.02,SE=0.01,P=0.01),an increase in free triiodothyronine decreased left-(β=-0.06,SE=0.02,P=9.5×10-5)and right-handed grip strength(β=-0.07,SE=0.02,P=9.3×10-5),and subclinical hyperthyroidism decreased gait speed(β=-4.4×10-3,SE=1.7×10-3,P=0.01).The sensitivity analysis results were basically consistent with the main analysis results.To conclude,an increase in thyroid-stimulating hormone is a protective factor for sarcopenia,and elevation of free triiodothyronine and subclinical hyperthyroidism may increase the risk of sarcopenia.

OBJECTIVE To explore the effects of isorhamnetin on the development of gastric cancer through up-regulation of solute carrier family 25 member 25 antisense RNA 1（SLC25A25-AS1）. METHODS Using BALB/c nude mice as the subjects， the xenograft tumor model was established by subcutaneously inoculating human gastric cancer MKN28 cells into the axillary region. The effects of low and high doses of isorhamnetin （20 and 40 mg/kg） on the tumor volume and mass in nude mice were investigated. MKN28 cells were selected and divided into control group， isorhamnetin group （70 μmol/L， similarly hereinafter）， isorhamnetin+knocking down negative control group， isorhamnetin+knocking down SLC25A25-AS1 group， isorhamnetin+ overexpression negative control group and isorhamnetin+overexpressing SLC25A25-AS1 group. Effects of knocking down/ overexpressing SLC25A25-AS1 on viability， apoptosis， migration and invasion ability of isorhamnetin-treated cells were detected. After verifying the targeting relationships between microRNA-212-3p （miR-212-3p） and SLC25A25-AS1， as well as phosphatase and tensin homologue deleted on chromosome 10 （PTEN）， the effects of knocking down/overexpressing SLC25A25-AS1 on the expression of miR-212-3p， PTEN mRNA， and PTEN protein in isorhamnetin-treated cells were investigated. RESULTS Compared with the model control group， tumor volume and mass of nude mice in the isorhamnetin low-dose and high-dose groups were reduced significantly， and the isorhamnetin high-dose group was significantly lower than the isorhamnetin low-dose group （P＜0.05）. miR-212-3p had targeting relationships with SLC25A25-AS1 and PTEN. Compared with the control group， the cell viability （intervened for 24， 48 h）， migration number， invasion number and miR-212-3p expression of cells in the isorhamnetin group， isorhamnetin+knocking down negative control group and isorhamnetin+overexpressing negative control group were significantly reduced or decreased or down-regulated， while the apoptosis rate， mRNA and protein expressions of PTEN were significantly increased or up-regulated （P＜0.05）. Compared with isorhamnetin group and isorhamnetin+knocking down negative control group， the cell viability， migration number， invasion number and miR-212-3p expression of cells in the isorhamnetin+knocking down SLC25A25-AS1 group were significantly increased or up- regulated， while the apoptosis rate， mRNA and protein expressions of PTEN were significantly reduced or down-regulated （P＜ 0.05）. Compared with isorhamnetin group and isorhamnetin+overexpressing negative control group， the cell viability， migration number， invasion number and miR-212-3p expression of cells in isorhamnetin+overexpressing SLC25A25-AS1 group were significantly reduced or decreased or down-regulated， while the apoptosis rate， PTEN mRNA and protein expressions were significantly increased or up-regulated （P＜0.05）. CONCLUSIONS Isorhamnetin may inhibit the development of gastric cancer by up-regulating the expression of SLC25A25-AS1， down-regulating miR-212-3p， and up-regulating the expression of PTEN， which is a downstream target of miR-212-3p.

Aortic dissection is a life-threatening cardiovascular disease with devastating complications and high mortality. It requires rapid and accurate diagnosis and a focus on prognosis. Many laboratory tests are routinely performed in patients with aortic dissection including D-dimer, brain natriuretic peptide, cardiac troponin I, C-reactive protein, and procalcitonin. D-dimer shows vital performance in the diagnosis of aortic dissection, and brain natriuretic peptide, cardiac troponin I, C-reactive protein, and procalcitonin exhibits important value in risk stratification and prognostic effect in aortic dissection patients. Our review summarized the clinical utility of these laboratory tests in patients with aortic dissection, aiming to provide advanced and comprehensive evidence for clinicians to better understand these laboratory tests and help their clinical practice.

Objective: To explore the relationship of physical activity (PA) and sedentary behavior (SB) with cardiorespiratory fitness (CRF) among middle schoold students in Tibet, so as to provide empirical references for improving the cardiorespiratory fitness and health levels of adolescents in Tibet. Methods: From August to December 2020, 1 225 junior and senior high school students were selected from 2 middle schools in Lhasa, Tibet Autonomous Region, using the stratified cluster random sampling method. Triaxial accelerometers were used to evaluate PA and SB behaviors, and the 20 meter shuttle run was employed to assess CRF among the middle school students. Isochronous substitution modeling was used to analyze the associations of SB, low intensity physical activity (LPA), and moderate vigorous physical activity (MVPA) with CRF, and the saturation threshold effect in the dose response relationship between MVPA and CRF was analyzed through restricted cubic spline and two stage linear regression. Results: After adjusting for covariates such as gender, body mass index and sleep quality score, isotemporal substitution analysis showed that among junior high school students aged 13-15, replacing 30 minutes of SB ( B =1.73) or LPA ( B =2.38) with MVPA were positively associated with CRF (both P <0.05). Among senior high school students aged 16-18, replacing SB ( B =0.99) or LPA ( B =1.38) with MVPA were also positively associated with CRF (both P <0.05). Restricted cubic spline and two piecewise linear regression analyses indicated that only middle school girls aged 13-18 exhibited a saturation threshold effect between MVPA and CRF (logarithmic likelihood ratio test=0.03), with the optimal CRF improvement observed at 60 minutes of MVPA per day ( B=0.13, P ＜ 0.01). Conclusions Reducing SB and LPA while increasing MVPA can improve CRF in Tibetan middle school students. To maximize CRF improvement, middle school girls should engage in at least 60 minutes of MVPA daily.

Objective　The objective of this research is to construct a technical indicator framework for preventing the of re-establishment of imported malaria at the county level in China, excluding border areas, with the aim of guiding specialist agencies to prevent the re-establishment of imported malaria in a scientific, feasible and comprehensive way. Methods　The preliminary framework was built based on literature review and on-site research. Two rounds of Delphi consultation were carried out. The positive coefficient, degree of concentration, degree of coordination, and authority of the experts were calculated. The weights and the combined weights for the indicators were determined using the analytic hierarchy process and probability method, respectively. Results　Twenty experts were invited in the 1st round of consultation, and twenty-six in the 2nd round. The authority coefficients of the experts for two rounds were 0.955 and 0.968, respectively. The P value of the degree of coordination of two rounds were less than 0.05. The final framework included 5 primary indicators, 19 secondary indicators and 42 tertiary indicators. Primary indicators included government-led, joint control and prevention, surveillance and response, capacity building and organization guarantee, whose weights were 20.2%, 2.4%, 20.1%, 44.7% and 12.5%, respectively. Among the secondary indicators, the highest combined weight was medical institutions (25.0%) of capacity building, and the lowest was cross-sectoral cooperation (0.3%) of joint control and prevention. The three tertiary indicators with higher combined weights were: "1.2.1 There is a comprehensive plan for preventing the re-establishment of imported malaria, and the responsibilities of relevant departments are clearly defined" accounting for 14.9%; "4.1.4 Laboratory personnel in medical institutions possess the ability to conduct microscopic examinations for malaria detection" accounting for 10.6%; and "4.2.1 Specialized malaria surveillance laboratories have been established and are fully equipped with the necessary capabilities to conduct effective surveillance" accounting for 7.6%. Conclusions　 A framework has been created for the prevention of re⁃establishment of imported malaria at the county level in China, excluding border areas. The framework provides an operational, scientific and comprehensive technical guidance for county-level areas from the perspective of the effectiveness of government-led, joint prevention and control, surveillance and response, capacity building and organizational support. The importance of maintaining the capacity to prevent re-establishment of imported malaria and whole-process case management under medical and preventive cooperation in the post-elimination stage was highlighted.

AIM:To investigate the regulatory effects of proanthocyanidins on autophagy and apoptosis in the retinas of guinea pigs with form-deprivation myopia via the AMPK/Wnt/β-catenin pathway.METHODS:Fifty guinea pigs were randomly divided into a normal control group, a myopia model group, and low-dose, medium-dose, and high-dose proanthocyanidins groups(25, 50 and 100 mg/kg). Refractive power and axial length of right eye were measured using a retinoscope and A-scan ultrasound. Retinal pathological changes were observed via HE staining. Immunohistochemistry assessed p-AMPK and p-mTOR expression in the retina. Immunofluorescence detected p62 and LC3 expression. TUNEL staining evaluated retinal cell apoptosis. Western blot examined expression of proteins related to the AMPK/Wnt/β-catenin pathway and autophagy(p62, Beclin1, LC3-II/LC3-I), and apoptosis-related proteins(Bax, Bcl-2, Cleaved-Caspase3, Caspase3)in the retina.RESULTS:Compared with the control group, the myopia model group showed significantly reduced refractive power and significantly increased axial length(both P<0.05); retinal cell arrangement became sparse and retinal thickness thinned. The p-AMPK levels in the retina were significantly reduced, while p-mTOR levels were significantly increased(both P<0.05), indicating suppression of the AMPK-Wnt/β-catenin pathway. The p62 levels were significantly elevated and LC3 levels were significantly reduced(both P<0.05), suggesting inhibition of autophagy. Bax and Cleaved-Caspase3 were significantly increased, while Bcl-2 was significantly decreased, indicating significantly increased apoptosis(both P<0.05). Compared with the myopia model group, all proanthocyanidins dose groups significantly inhibited refractive error reduction and axial length growth(both P<0.05), restored retinal cell alignment and thickness, activated the AMPK/Wnt/β-catenin pathway, significantly increased p-AMPK expression, and suppressed p-mTOR expression(all P<0.05); significantly suppressed p62 expression, increased Beclin1 and LC3-II/LC3-I expression(both P<0.05), and activated retinal autophagy; significantly suppressed Bax and Cleaved-Caspase3 expression, increased Bcl-2 expression(both P<0.05), and inhibited retinal cell apoptosis.CONCLUSION:Proanthocyanidins enhance retinal autophagy by activating the AMPK/Wnt/β-catenin pathway, thereby inhibiting retinal apoptosis and preventing or alleviating the onset of myopia.

OBJECTIVE: To explore the effectiveness of the modified Lemaire procedure in anterior cruciate ligament reconstruction (ACLR) in patients with a highly positive pivot shift test. METHODS: The clinical data of 18 patients with anterior cruciate ligament (ACL) rupture and highly positive pivot shift test between April 2020 and September 2022 were retrospectively analyzed. There were 13 males and 5 females with an average age of 28.3 years (range, 17-41 years). Causes of injury included 11 cases of direct violence injury, including 6 cases of traffic accident injury, 4 cases of sports injury, 1 case of falling injury; 7 cases of indirect violence injury, all sports injury. All patients had complete ACL rupture, including 15 acute injuries and 3 old injuries. The preoperative pivot shift test was grade Ⅱ in 9 cases and grade Ⅲ in 9 cases. All patients were treated with ACLR combined with modified Lemaire procedure. The International Knee Documentation Committee (IKDC) score and Lysholm score were used to evaluate the effectiveness before operation and at 3, 6, 12 months after operation. KT-2000 arthrometer was used to measure the anterior stability of the knee joint, and the difference between the healthy and affected sides was recorded. Pivot shift test was used to evaluate the rotational stability of the knee joint. During the follow-up, X-ray films were taken to observe the bone tunnel and internal fixation, and MRI was used to examine the healing of ACL, anterolateral collateral ligament and fibular collateral ligament grafts. RESULTS: All patients completed the operation successfully without complications such as knee joint infection, vascular and nerve injury. All patients were followed up 12-19 months (mean, 13.2 months). After operation, the rotational stability of the knee joint recovered satisfactorily, and there was no adverse symptom such as knee instability and locking at last follow-up. X-ray film and MRI showed that the bone tunnel was anatomically located and healed well, the internal fixation was in good position, and the reconstructed ACL and iliotibial band were continuous and in good tension. The IKDC score, Lysholm score, and the difference of KT-2000 between the healthy and the affected sides significantly improved at 3, 6, and 12 months after operation ( P<0.05). All the indicators further improved with time after operation, except that there was no significant difference in IKDC score between 3 and 6 months after operation and in the difference of KT-2000 between 3 months and 6, 12 months after operation ( P>0.05), and there were significant differences in other indicators between different time points ( P<0.05). Pivot shift test was negative immediately after operation and at last follow-up. CONCLUSION In ACL injuries with a highly positive pivot shift test, ACLR combined with the modified Lemaire procedure can effectively restore anterolateral knee stability, leading to satisfactory knee stability and function in the early postoperative period.
Humans ; Anterior Cruciate Ligament Reconstruction/methods* ; Male ; Female ; Anterior Cruciate Ligament Injuries/physiopathology* ; Adult ; Adolescent ; Retrospective Studies ; Young Adult ; Anterior Cruciate Ligament/surgery* ; Treatment Outcome ; Joint Instability/surgery* ; Knee Joint/physiopathology* ; Range of Motion, Articular

OBJECTIVE: To explore the effects of two methods of smear layer removal on the surface properties of dentin. METHODS: Sixty extracted sound third molars were collected in this study, and were prepared as uniform dentin specimens with smear layer. All specimens were randomly divided into three groups: Control group, ultrasonic treatment (UT) group and etched treatment (ET) group. Scanning electron microscope (SEM) were used to observe the surface micromorphology of all three groups. Then, the surface elements, mineral phases and functional groups were analyzed by energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD) and flourier transformed infrared spectrometer (FTIR) respectively. The mechanical properties, hydrophilicity and biocompatibility were also further evaluated. RESULTS: It was revealed that dentin tubules of UT and ET groups were exposed, but lots of dentin debris piled up on the surface of the control one which covered up dentin tubules on the surface. The EDX results should that the weaker peak value of calcium and phosphorus in ET group than control and UT groups. Characteristic peaks of hydroxyapatite could be seen by XRD in all of the three groups, but lower distinctive peaks of amide Ⅰ, Ⅱ and Ⅲ bands of collagen of the dentin surface in control group than in ET and UT groups. The microhardness results showed that ET group was lower than control and UT groups, the difference was significant (P < 0.05). Better hydrophilicity of ET group was investigated (P < 0.05) than control group and UT group. Cells could be observed to adhere normally to dentin surface of each group which meant that all of the three groups had good biocompatibility. CONCLUSION Both UT and ET could effectively remove the smear layer on the surface of dentin and had no adverse effect of the dentin micromorphology and biocompatibility. The ultrasonic removal of the smear layer did not influence the mineral structure, hydrophilicity and mechanical properties of dentin surface. Although ET can effectively improve the hydrophilicity of dentin but decreased mechanical properties and the content of calcium and phosphorus.
Dentin/ultrastructure* ; Humans ; Surface Properties ; Smear Layer ; Molar, Third ; Microscopy, Electron, Scanning ; Dental Etching/methods*

Objective:To explore of auditory-vestibular function and inner ear imaging features of patients with Meniere's disease（MD） at different clinical stages. Methods:The clinical data of 110 patients with unilateral MD who were admitted from January 2023 to March 2024 were collected, and all patients were staged according to the results of pure tone hearing threshold test, including 13 patients with stage Ⅰ, 18 cases with stage Ⅱ, 65 cases with stage Ⅲ, and 14 cases with stage Ⅳ. All patients were tested for vestibular function, including caloric tests, vestibular evoked myogenic potentials（VEMPs）, vHIT and sensory integration tests（SOT）. The sites of endolymphatic hydrops were evaluated by intravenous endotogidolinium-based MRI, twenty-seven patients completed electrocochleography. Results:①The disease course time of patients with different stages was different, and the disease course time of stage Ⅰ and Ⅱ was shorter than that of stage Ⅲ and Ⅳpatients（P<0.05）. ②No statistical differences were found in clinical data or vestibular function between normal and abnormal ECochG groups（P>0.05）. ③The results of caloric tests showed that the UW% values of stage Ⅲ（45.5±14.79） and stage Ⅳ （51.57±22.44） were higher than those of stageⅠ（31.2±14.9） and stage Ⅱ（33.5±13.31）, there were statistically significant differences between stage Ⅰ and stage Ⅱ with stage Ⅲ and Ⅳ groups（P<0.05）, the total abnormal rate of cVEMP was 62.72%, there was a statistically significant difference between stageⅠand stage Ⅲ with the stage Ⅳ group（P<0.05）, the total abnormal rate of oVEMP was 71.82%, the difference between stage Ⅰ and stage Ⅳ group was statistically significant（P<0.05）. The total score of SOT comprehensive balance gradually decreased with the increase of clinical stage, and there was a significant difference between the stage Ⅰ and Ⅳ groups（H=26.08, P<0.01）, and there was a statistically significant difference in the rate of vestibular dysfunction of SOT between the two groups（χ²=6.7, P<0.05）. ④Patients with vestibular and cochlear endolymphatic hydrops, and patients with simple cochlear or vestibular had significantly differences in disease course time, clinical stages, UW% value of caloric test, abnormal rate of cVEMP and oVEMP, total SOT balance score, the rate of vestibular abnormality（P<0.01）. Among them, when the vestibular and cochlear endolymphatic hydrops are at the same time, the clinical stage of the patient is mainly stage Ⅲand Ⅳ. Conclusion:Auditory-vestibular and inner ear gadolinium-contrasted MRI examinations in clinical practice provide a supplementary reference for judging vestibular function and the type of endolymphatic hydrops.
Humans ; Meniere Disease/diagnostic imaging* ; Ear, Inner/physiopathology* ; Male ; Magnetic Resonance Imaging ; Female ; Middle Aged ; Vestibule, Labyrinth/diagnostic imaging* ; Adult ; Vestibular Evoked Myogenic Potentials ; Aged ; Audiometry, Pure-Tone ; Caloric Tests ; Vestibular Function Tests