Objective:To observe any effect of cooling on the amplitude of vibration-induced sensory nerve action potentials (SNAPs) in human digits.Methods:The middle fingers of 15 healthy adults were either cooled to about 22℃ using an ice pack or kept at about 32℃. A vibrator was applied to the joint connecting the middle finger and the palm vibrating with an amplitude of 2mm at a frequency of 60Hz. The amplitudes of middle finger SNAPs before, during and right after the vibration were recorded.Results:The SNAP amplitude at a given temperature was lower during vibration than before it, but it immediately returned to the pre-vibration level after the vibration ceased. The middle finger SNAP amplitudes at 22℃ were significantly higher than those at 32℃ throughout. The decrease in amplitude at 32℃ (61.7±15.1%) was significantly greater than that at 22℃ (24.1±7.0%).Conclusions:Cooling significantly reduces the effect of vibration on the amplitude of digital SNAPs. That suggests a way to protect the sensory nerves in hand-arm vibration syndrome.

Objective This study aimed to investigate the temporal and spatial changes in the expression of perios-tin during periodontal inflammation in mice.Methods A periodontitis model was constructed using silk thread ligation.Mice were randomly divided into five groups in-cluding control group,4-day ligation group,7-day liga-tion group,14-day ligation group,and self-healing group(thread removal for 14 days after 14-day ligation).Mi-cro-CT and histological staining were performed to char-acterize the dynamic changes in the mouse periodontal tissue in each group.RNAscope and immunohistochemical staining were used to analyze the pattern of changes in peri-ostin at various stages of periodontitis.The cell experiment was divided into three groups:control group,lipopolysac-charide(LPS)stimulation group(treated with LPS for 12 h),and LPS stimulation removal group(treated with LPS for 3 h followed by incubation with medium for 9 h).Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression of periostin,transforming growth factor-β1(TGF-β1),and matrix metalloproteinase 2(MMP2).Results Significant alveolar bone resorption was observed 7 days after ligation.With increasing duration of ligation,the damage to the mouse periodontal tissue was aggravated,which manifested as increased osteoclasts,widen-ing of the periodontal membrane space,and decreased alveolar bone height.Some degree of periodontal tissue repair was observed in the self-healing group.Periostin expression decreased at 4 and 7 days compared with the control group and increased at 14 days compared with 4 and 7 days.A significant recovery was found in the self-healing group.The qRT-PCR results showed that the expression of periostin and TGF-β1 in the LPS stimulation group decreased compared with that in the control group but significantly recovered in the LPS removal group.Conclusion Periostin expression in the PDL of mice showed a downward and upward trend with inflammation progression.The significant recovery of periostin expression after removing inflammatory stimuli may be related to TGF-β1,which is crucial to maintain the in-tegrity of the PDL.

Food toxicology plays a crucial role in supporting scientific and technical aspects of food safety risk assessment.However,traditional methods relying on animal testing are becoming increas-ingly inadequate for identifying and evaluating emerging foods and unknown risks.There is a strong push worldwide towards the development of new approach methodologies(NAMs)based on non-animal testing methods.Policies and regulations related to NAMs are being standardized gradually in the European Union,the United States,and China.Some progress has also been made in applying these methodologies in food toxicology research in China.For instance,within the"Food Toxicology Program"at the National Center for Food Safety Risk Assessment,high-content and high-throughput in vitro hazard identification models employing model organisms like human macrophages,hepatocytes,adipocytes,embryonic stem cells,and zebrafish,as well as Toxicological Thresholds of Concern and quantitative in vitro to in vivo extrapolation based on physiologically-based toxicokinetic models have been estab-lished and applied.Nonetheless,new toxicological hazard identification technologies still face challenges such as inadequate elucidation of toxic mechanisms,insufficient collaborative research efforts,and inef-ficient translation of these findings into practical applications.

Objective This study was performed to develop and assess a genetically engineered mouse model for visualizing in vivo fluorescence of glioma cells,mural cells,and blood vessels using two-photon microscopy.Methods PDGFRβ-Cre+/-:Rosa26-tdTomato+/-genetically engineered mice underwent skull clearance and were injected with GL261-CFP.This was performed to study the dynamic alterations in blood vessels and mural cells during the progression and invasion of glioma using two-photon microscopy.Results PDGFRβ-Cre+/-:Rosa26-tdTomato+/-mice were successfully bred and subjected to hematoxylin-eosin section analysis of functional organ tissues.The mice exhibited no discernible differences from C57BL/6 mice in terms of appearance and morphology.Cre recombinase activity was fully induced following tamoxifen treatment on day 7.Subsequent GL261-CFP inoculation demonstrated the dynamic progression of glioma proliferation and invasion,as well as vascular abnormalities and increased mural cell detachment within the tumor.Conclusions Genetically engineered mice expressing fluorescent mural cells were successfully bred.Blood vessels labeled with fluorescein isothiocyanate-dextran and blue fluorescent tumor cells were utilized.Glass discs and fixed rings were employed to replace the skulls of the mice.This allowed for the tracking of morphological and structural changes in blood vessels and vascular supporting cells following the development of brain tumors in vivo over an extended period.This model offers a valuable tool for studying brain diseases through pathological visualization.

Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm.The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress.Sinensetin(Sin)is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities.Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms.We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells(PDLCs)under inflammatory conditions.Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo.By molecular docking,we identified Bach1 as a strong binding target of Sin,and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays.Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter,subsequently upregulating the expression of the key antioxidant factor HO-1.Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects.Additionally,we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1,thereby inducing HO-1 expression and inhibiting oxidative stress.Overall,Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.

Objective:To seek a correlation between short-chain fatty acids (SCFAs) and skill in the activities of daily living (ADL) after an ischemic stroke.Methods:Ninety ischemic stroke survivors were assessed using the Barthel Index (BI). Fecal samples were collected and analyzed for the concentration of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid using gas chromatography. Spearman correlation analysis was conducted to identify SCFAs that correlated with the total BI score. Linear regressions were evaluated to explore the correlation between the total BI score and SCFAs.Results:The concentrations of propionic and butyric acids in the feces were found to correlate significantly with the total BI scores. Data including propionic acid and butyric acid levels, age, gender, body mass index, disease duration, any history of hypertension or diabetes, and other SCFAs were included in the regression models. Propionic and butyric acid levels were found to be potentially useful predictors of total BI scores.Conclusions:The concentration of propionic and butyric acids in the feces after an ischemic stroke can predict the survivor′s total BI score. Those concentrations could therefore be useful for predicting ADL ability.

Objective:To explore any effect of blood flow restriction during exercise on knee proprioception and motor coordination after anterior cruciate ligament (ACL) reconstruction.Methods:Thirty patients recovering from ACL reconstruction were randomly divided into an experimental group and a control group, each of 15. Both groups were given routine rehabilitation training, while the experimental group was additionally provided with 45 minutes of training with blood flow restriction, 3 times a week for 8 weeks. The blood flow restriction training involved constant pressure in the groin while the patient performed knee flexion and extension resistance training, squats, alternate knee flexion and extension and ergometer cycling. Before and after the intervention, both groups′ knee function, proprioception and lower limb motor coordination were evaluated using the Lysholm knee scale, the Humac isokinetic measurement system and surface electromyography.Results:Before the experiment there were no significant differences between the two groups in any of the measurements. After the intervention, both groups′ average Lysholm score had improved significantly, and errors in reproducing a knee angle had decreased significantly. Significantly better improvement was observed in the observation group than in the control group. That group′s average coordinated contraction rate on the affected side in extension and flexion was also significantly better than the control group′s ave-rage. Indeed, there were no significant differences in the contraction rates between the healthy and affected sides.Conclusions:Training with restricted blood flow can significantly improve knee function, proprioception and motor coordination after anterior cruciate ligament reconstruction.

AIM:To explore the effect of microRNA-184(miR-184)on compensatory lung growth(CLG)af-ter lobectomy in multiple primary lung cancer(MPLC)and its mechanism.METHODS:(1)Lung tissue samples(n= 16)from MPLC patients and patients with good recovery after lobectomy(CLG)were collected,and the expression of miR-184 was measured by RT-qPCR.(2)Human alveolar epithelial cells were divided into NC-mimic group,miR-184 mimic group,OE-NC group,tissue inhibitor of metalloproteinase-2(TIMP-2)overexpression(OE-TIMP-2)group,and miR-184 mimic+OE-TIMP-2 group according to the transfection(n=3).The expression of miR-184,TIMP-2 mRNA and matrix metalloproteinase-14(MMP-14)mRNA was measured by RT-qPCR,and the protein expression of TIMP-2 and MMP-14 was determined by Western blot.The proliferation of the cells was measured by CCK-8 and colony formation assays.(3)C57BL/6J mice were divided into pneumonectomy(PNX)group and PNX+miR-184 mimic group(n=5).The flexiVent system was used to measure the vital capacity and lung compliance of the mice.Lung volume was measured by water dis-placement method,and lung tissue changes were observed by HE staining.RESULTS:The expression of miR-184 was significantly higher in the patients with better recovery after lobectomy(P＜0.01).Overexpression of miR-184 promoted the proliferation of human alveolar epithelial cells and the recovery of lung function in mice after PNX.In terms of mecha-nism,miR-184 showed targeted binding with TIMP-2,and overexpression of miR-184 promoted the expression of MMP-14 by inhibiting TIMP-2,thereby promoting the proliferation of human alveolar epithelial cells and the recovery of mouse lung function after PNX.CONCLUSION:miR-184 promotes CLG after PNX through the TIMP-2/MMP-14 axis.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To observe any effect of supplementing head-eye movement with repeated transcranial magnetic stimulation (rTMS) on the lower limb movement and balance of hemiplegic stroke survivors.Methods:Forty stroke survivors with hemiplegia were divided at random into a control group and an observation group, each of 20. Both groups received conventional medication and head-eye movement rehabilitation training, while the observation group was additionally provided with rTMS daily for 20 days. The head-eye movement training involved one minute for each movement, twice a day, five days a week for 4 weeks. Before and after the treatments, both groups were assessed using the Fugl-Meyer Assessment Scale for the Lower Extremities (FMA-LE), the Berg Balance Scale (BBS), timed up and go tests (TUGs), and the Modified Barthel Index (MBI).Results:The treatment improved both groups′ average FMA-LE, BBS and MBI scores significantly, and significantly shortened their average TUG times. The observation group showed significantly greater improvement than the control group, on average.Conclusion:Combining rTMS with head-eye movement can significantly improve the lower limb movement and balance of hemiplegic stroke survivors.