Objective:To observe any effect of dynamic instability training on the balance and posture control of persons with chronic ankle instability (CAI).Methods:Thirty persons with CAI were divided at random into a control group and an observation group, each of 15. Both groups received routine rehabilitation interventions (including ankle strength training, kinesio taping, and vibration training), while the observation group additionally underwent 20 minutes of dynamic instability training daily, 5 days a week for 4 consecutive weeks. Before and after the treatment, everyone′s balance was evaluated using the Berg balance scale (BBS) and the star moving balance test (SEBT). Surface electromyography (sEMG) was used to collect electromyograms of the affected peroneus longus, tibialis anterior, rectus femoris and medialis femoris muscles of both groups within 100ms before and after landing in the jump-landing test. The intensity of muscle activation was thus analyzed.Results:After the treatment there was significant improvement in the average BBS scores, anterior medial SEBT, medial SEBT and posterior medial SEBT results of both groups. On average, all three SEBT results [(80.27±4.06)cm, (90.27±4.06)cm and (97.73±3.47)cm respectively] were significantly better in the observation group than in the control group. The standardized integrated electromyographs of the peroneus longus, tibialis anterior, rectus femoris and medialis femoris muscles on the affected sides showed significant improvement compared with before the treatment, but there too the observation group′s results were significantly better than those of the control group.Conclusions:Combining dynamic instability training with conventional rehabilitation can further improve the balance and postural control of persons with chronic ankle instability.

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Objective:To establish an evaluation index system for the emergency capability of occupational poisoning incidents in Tianjin, providing a reference basis for evaluating the emergency capability level of occupational poisoning incidents in Tianjin.Methods:In February 2023, the Delphi method was applied to conduct expert consultation and establish the framework of the emergency response capability evaluation index system for occupational poisoning incidents in Tianjin. The positive coefficient, authority coefficient and coordination coefficient of experts were calculated. The weights of indicators at all levels were determined by using the Analytic Hierarchy Process (AHP) and the proportional allocation method, and the internal consistency reliability of the evaluation index system was tested by using the Cronbach's α wefficient.Results:Regarding the evaluation index system for the emergency capability of occupational poisoning incidents in Tianjin, the expert positive coefficient in both rounds of consultation was 100.00% (33/33), the expert authority coefficients were 0.80 and 0.74 respectively, the expert coordination coefficients were 0.59 and 0.62 respectively ( P<0.001), and the Cronbach's α coefficient of all indicators was 0.998. The evaluation index system of emergency capability for occupational poisoning incidents in Tianjin was finally determined, including 7 first-level indicators, 30 second-level indicators and 135 third-level indicators. Conclusion:The evaluation index system of emergency capability for occupational poisoning incidents in Tianjin constructed based on the Delphi method shows that the expert consultation is active, representative and authoritative. The indicator system covers the emergency response capability to occupational poisoning incidents and has high internal consistency, providing a reliable and quantifiable reference for improving the emergency response level of occupational poisoning incidents in Tianjin.

Objective:To establish an evaluation index system for the emergency capability of occupational poisoning incidents in Tianjin, providing a reference basis for evaluating the emergency capability level of occupational poisoning incidents in Tianjin.Methods:In February 2023, the Delphi method was applied to conduct expert consultation and establish the framework of the emergency response capability evaluation index system for occupational poisoning incidents in Tianjin. The positive coefficient, authority coefficient and coordination coefficient of experts were calculated. The weights of indicators at all levels were determined by using the Analytic Hierarchy Process (AHP) and the proportional allocation method, and the internal consistency reliability of the evaluation index system was tested by using the Cronbach's α wefficient.Results:Regarding the evaluation index system for the emergency capability of occupational poisoning incidents in Tianjin, the expert positive coefficient in both rounds of consultation was 100.00% (33/33), the expert authority coefficients were 0.80 and 0.74 respectively, the expert coordination coefficients were 0.59 and 0.62 respectively ( P<0.001), and the Cronbach's α coefficient of all indicators was 0.998. The evaluation index system of emergency capability for occupational poisoning incidents in Tianjin was finally determined, including 7 first-level indicators, 30 second-level indicators and 135 third-level indicators. Conclusion:The evaluation index system of emergency capability for occupational poisoning incidents in Tianjin constructed based on the Delphi method shows that the expert consultation is active, representative and authoritative. The indicator system covers the emergency response capability to occupational poisoning incidents and has high internal consistency, providing a reliable and quantifiable reference for improving the emergency response level of occupational poisoning incidents in Tianjin.

Objective:To observe any effect of dynamic instability training on the balance and posture control of persons with chronic ankle instability (CAI).Methods:Thirty persons with CAI were divided at random into a control group and an observation group, each of 15. Both groups received routine rehabilitation interventions (including ankle strength training, kinesio taping, and vibration training), while the observation group additionally underwent 20 minutes of dynamic instability training daily, 5 days a week for 4 consecutive weeks. Before and after the treatment, everyone′s balance was evaluated using the Berg balance scale (BBS) and the star moving balance test (SEBT). Surface electromyography (sEMG) was used to collect electromyograms of the affected peroneus longus, tibialis anterior, rectus femoris and medialis femoris muscles of both groups within 100ms before and after landing in the jump-landing test. The intensity of muscle activation was thus analyzed.Results:After the treatment there was significant improvement in the average BBS scores, anterior medial SEBT, medial SEBT and posterior medial SEBT results of both groups. On average, all three SEBT results [(80.27±4.06)cm, (90.27±4.06)cm and (97.73±3.47)cm respectively] were significantly better in the observation group than in the control group. The standardized integrated electromyographs of the peroneus longus, tibialis anterior, rectus femoris and medialis femoris muscles on the affected sides showed significant improvement compared with before the treatment, but there too the observation group′s results were significantly better than those of the control group.Conclusions:Combining dynamic instability training with conventional rehabilitation can further improve the balance and postural control of persons with chronic ankle instability.

Objective To investigate the expression of Midkine(MDK)in cholangiocarcinoma(CCA)and its value in predicting the prognosis of CCA,as well as the potential mechanism of the effect of MDK on the progression of CCA.Methods The data of CCA samples were obtained from TCGA database to analyze the difference in the expression of MDK between cancer tissue and paracancerous tissue and its association with clinical features,and the data collected from GEO database and 11 CCA patients who underwent surgical resection in The Fifth Medical Center of Chinese PLA General Hospital from June 2018 to September 2021 were used for validation.STRING and Cytoscape were used to construct a protein-protein interaction network,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were used to investigate the biological functions and tumor-related pathways involving MDK-related genes.In addition,TIMER and TISIDB databases were used to analyze the correlation between MDK expression and immune cell infiltration in CCA tissue.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the Fisher's exact test was used for comparison of categorical data between two groups.The Kaplan-Meier method was used to plot survival curves,and the Log-rank test was used for comparison between groups.The Spearman correlation analysis was used to investigate the correlation between two variables.Results The expression level of MDK in cancer tissue and paracancerous tissue of CCA patients was compared based on TCGA database,and the results of the non-paired and paired analyses showed that the expression level of MDK in CCA tumor tissue was significantly higher than that in paracancerous tissue(P<0.001).Transcriptome sequencing was performed for the tumor tissue and its corresponding paracancerous tissue from 11 CCA patients,and the results showed that the expression level of MDK in CCA tumor tissue was significantly higher than that in corresponding paracancerous tissue(P<0.01).High expression of MDK was associated with lymph node metastasis(P=0.045)and vascular invasion(P=0.044).Survival analysis showed that compared with the CCA patients with low MDK expression,the CCA patients with high MDK expression had significantly shorter overall survival time(χ2=5.30,P=0.028)and disease-specific survival time(χ2=6.25,P=0.019).The GO and KEGG enrichment analyses showed that the 30 MDK-related genes were closely associated with ubiquitin-mediated proteolysis and affected the prognosis of CCA patients.The TIMER analysis showed that the expression level of MDK was positively correlated with the infiltration of B cells(r=0.356,P=0.035 6)and dendritic cells(r=0.409,P=0.014 7)in tumor microenvironment of CCA;the TISIDB analysis showed that the expression level of MDK was positively correlated with CXCL16(r=0.465,P=0.004 67)and was negatively correlated with CXCL12(r=-0.389,P=0.019 7)and CXCR5(r=-0.393,P=0.018 5),and it was also negatively correlated with the immune checkpoint regulators VTCN1(r=-0.393,P=0.018 3),LTA(r=-0.380,P=0.022 7),and PVR(r=-0.350,P=0.037 3).Conclusion High expression of MDK is associated with poor prognosis in CCA patients,and MDK has the potential of being used as a molecular marker for predicting the prognosis of CCA.MDK may promote the development and progression of CCA by regulating ubiquitin-mediated proteolysis and the infiltration of B cells and dendritic cells.

Objective To analyze the applicability of different risk assessment methods in assessing laboratory benzenes exposure. Methods The work positions exposed to benzenes (benzene, toluene, xylenes) of a chemical catalyst research and development company were selected as the research subjects. An occupational health field survey was conducted, and the benzenes exposure levels of the lab personnel were measured. Qualitative assessment method, comprehensive index method, quantitative assessment method, and occupational hazards classification method were used to evaluate the occupational health risk on benzenes exposure in the laboratory personnel. The applicability of different assessment methods was compared. Results The occupational health engineering protection measures and management system of the company need to be further implemented. The benzene exposure level of benzene hydrogenation laboratory personnel exceeded the national standard, with the exposure concentration of time weighted average (C_TWA) of 5.00 mg/m³ and short term exposure concentration (C_STE) of 10.50 mg/m³. The C_TWA and C_STE of toluene and xylenes exposure were both lower than the minimum quantitative concentrations. The results of different risk assessment methods varied. The qualitative assessment method indicated higher level of occupational health risk of benzenes, while the comprehensive index and hazard classification methods indicated consistent result on lower level of benzenes. For occupational health risk of benzene, the standardized risk ratio (RR) levels corresponding to the qualitative and quantitative assessment methods were both extremely high risk. The RR levels of benzene exposure assessment using the comprehensive index method and the occupational hazards classification method were high, while the corresponding RR levels of exposure to toluene and xylenes were both low. Conclusion Attention should be paid on the health risks of benzene exposure to benzene hydrogenation laboratory personnel. When benzene exposure level is below the national occupational exposure limit, occupational hazards classification method is not recommended for health risk assessment for benzenes. The comprehensive index method is preferable when more comprehensive occupational health information is available, as it provides a more objective and comprehensive evaluation on occupational health risks of benzenes.

AIM:To investigate the impact of honokiol(HKL),an activator of silent information regulator 3(SIRT3),on postoperative cognitive dysfunction(POCD)in mice,and to explore the potential mechanisms.METHODS:Ten-month-old male C57/BL6 mice were randomly divided into control(Con)group,surgical(Sur)group and Sur+HKL group(n=10).The mice in Sur+HKL group were intraperitoneally injected with HKL for 7 d before modeling.The mice in Sur and Sur+HKL groups underwent tibial fracture open reduction and internal fixation to establish the POCD model.The assessment of cognitive function was conducted using the open-field test(OFT),novel object recognition test(NORT),Morris water maze test(MWMT),and Y-maze test(YMT).Nissl staining was employed to assess the morphology,struc-ture and vitality of hippocampal and cortical neurons in mice.The protein expression of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),acyl coenzyme A synthetase long-chain family member 4(ACSL4),SIRT3 and nuclear factor E2-related factor 2(NRF2)in the mouse hippocampus was detected by Western blot,while im-munofluorescence staining was utilized to determine GPX4 level in mouse neurons.RESULTS:No statistically signifi-cant differences were observed among the groups in terms of total distance moved and central zone exploration during the OFT(P>0.05).However,the results from the NORT and YMT indicated that the mice in Sur group exhibited significant-ly lower recognition indexes,reduced alternation rates(P<0.01),and decreased percentages of entries and crossing time into the new arm after side arm blockade(P<0.01),when compared with Con group.Furthermore,the mice in Sur group demonstrated a slower decrease in latency during the learning period of MWMT,while significantly lower latency,fewer crossing number and lower percentage of time in the target quadrant were observed during the testing period of MWMT(P<0.01).The above indicators were obviously enhanced in Sur+HKL group compared with Sur group(P<0.01).The results of Nissl staining indicated lighter neuronal staining in the hippocampal CA1 region and medial prefrontal cortex in Sur group,accompanied by a significant reduction in the number of Nissl-stained positive neurons(P<0.01).Notably,HKL pretreatment demonstrated a significant improvement in neuronal vitality.Analysis of Western blot revealed that compared with Con group,the expression of SIRT3,GPX4,SLC7A11 and NRF2 in Sur group was significantly reduced,while the expression of ACSL4 was significantly increased(P<0.05).However,these alterations were reversed after treatment with HKL(P<0.05).Immunofluorescence staining of hippocampal neurons corroborated the findings from Western blot analy-sis,demonstrating a notable decrease in GPX4 expression in hippocampal neurons of Sur group,which was significantly restored after HKL pretreatment(P<0.01).CONCLUSION:Treatment with HKL attenuates POCD in mice,potentially through its inhibitory effect on hippocampal neuronal ferroptosis.

Objective To investigate the effect of subchronic inhalation of toluene diisocyanate (TDI) on oxidative stress damage in rat lung tissue. Methods SPF-grade Sprague-Dawley male rats were randomly divided into 4 groups,the rats were placed in a HOPE-MED 8050A movable poison cabinet in a cage.To observe the ultrastructural and histopathology changes of lung tissue in rats.The levels of reduced glutathione (GSH), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in lung tissue were detected. The ultrastructural and histopathological changes were examined. The expression levels of HO-1 mRNA and protein were detected by Real-time PCR and Western Blot, respectively. Results The body mass, lung tissue mass, and lung organ coefficient of rats in each dose group were lower than those in the control group (P<0.05), and the body mass of rats in each group increased with the increase of exposure time (P<0.05); The results of lung histopathological examination showed that after TDI exposure,in the high-dose group, pulmonary alveolar wall hyperemia and edema were observed in the lung tissue of rats, alveolar wall thickening was observed, alveolar septa widening, and a large number of red blood cells were seen in the alveolar cavity. The results of ultrastructural examination of lung tissue showed that after TDI exposure, while in the high-dose group, the number of alveolar cells decreased, with unclear cell boundaries and irregular morphology. The levels of MDA in the lung tissue of rats exposed to TDI at various doses were higher than those in the control group (P<0.05), while the levels of GSH, GSH-Px, SOD, and CAT were lower than those in the control group (P<0.05); There was no significant difference in HO-1 gene and protein levels among rats in each group (P>0.05). Conclusion Subchronic inhalation of TDI can cause changes in the pathology and ultrastructure of rat lung tissue, leading to abnormal levels of metabolic enzymes in lung function, thereby inducing oxidative stress damage to the lungs. However, but HO-1 is involved in oxidative stress damage in the lungs induced by TDI.