Objective:To observe the effectiveness of combining mirror therapy with pneumatic flexible glove training in treating hand dysfunction after a stroke. Its effect on cerebral cortex activation was documented using near-infrared functional imaging of the brain.Methods:A total of 84 stroke survivors with hand dysfunction were randomly divided into a Mirror Group, a Glove Group and a Combined Group, each of 28. In addition to standard rehabilitation training, the Glove Group received 20 minutes of training with a pneumatic soft glove, 5 days per week for 6 consecutive weeks. The Mirror Group received mirror therapy (MT). The Combined Group was given both simultaneously. Before and after the treatment, everyone′s upper limb functioning was evaluated (using the Fugl-Meyer Upper Limb Assessment (FMA-U)), along with their hand motor skills (using the Arm Action Test (ARAT)) and their ability in daily living activities (using the Barthel Index (BI)). Functional near-infrared spectroscopy (fNIRS) was employed to measure any changes in oxygenated hemoglobin (HBO) concentration at 730nm and 850nm wavelengths.Results:The FMA-U, ATAT and BI scores in both the proximal and distal regions of all three groups showed significant improvement after the treatments compared to pre-treatment levels. The combined group demonstrated significantly better distal FMA-U and ARAT scores after the treatment (12.25±8.80 and 20.93±15.68 respectively), outperforming both the glove and mirror groups. The infrared spectroscopy revealed that bilateral SM1 activation, affected-side somatosensory association cortex (SAC) and supplementary motor cortex excitability in both the mirror and combined groups were significantly better than among the glove group after the experiment.Conclusions:Combined with pneumatic flexible glove training, mirror therapy can not only significantly improve the hand function of stroke survivors, but also activate the relevant brain regions of both hemispheres through bilateral motor patterns combined with multisensory stimulation, promoting the balance between hemispheres.

ObjectiveTo reveal the active substances and mechanisms of modified Qing'e formula （MQEF） in delaying skin photoaging by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS），network pharmacology， and cell experiments. MethodsUPLC-Q-TOF-MS and a literature review were employed to analyze the transdermally absorbed components in mice after the topical application of MQEF. The potential targets of MQEF in treating skin photoaging were retrieved from databases.The compound-potential target network and protein-protein interaction network were constructed to screen the key components and core targets. A photoaging cell model was established by irradiating HaCaT cells with medium-wave ultraviolet B （UVB）. The safe doses of bakuchiol （BAK） and salvianolic acid B （SAB） for treating HaCaT cells and the effects of BAK and SAB on the viability of cells exposed to UVB irradiation were determined by the cell counting kit-8 （CCK-8） method.The reactive oxygen species （ROS） fluorescent probe was used to measure the ROS production in the cells treated with BAK and SAB.The expression levels of genes related to oxidative stress，inflammation，collagen metabolism，and circadian rhythm clock were measured by Real-time PCR. ResultsA total of 24 transdermally absorbed components of MQEF were identified，which acted on 367 potential targets，and 417 targets related to skin photoaging were screened out，among which 47 common targets were predicted as the targets of MQEF in treating skin photoaging. MQEF exerted the anti-photoaging effect via key components such as BAK and SAB，which acted on core proteins such as serine/threonine kinase 1 （Akt1） and mitogen-activated protein kinase 3 （MAPK3） and intervened in core pathways such as the tumor necrosis factor （TNF） and phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathways.Compared with the model group，the administration of BAK and SAB increased the survival rate of HaCaT cells （P<0.01），down-regulated the mRNA levels of cyclooxygenase-2 （COX-2），interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），matrix metalloproteinase-1 （MMP-1），and matrix metalloproteinase-9 （MMP-9） （P<0.01），and up-regulated the mRNA levels of heme oxygenase-1 （HO-1） and NAD（P）H quinone dehydrogenase 1 （NQO-1） （P<0.05，P<0.01） in photoaged HaCaT cells.In addition，it eliminated excess ROS production induced by UVB and up-regulated the mRNA levels of brain and muscle ARNT-like 1 （BMAL1） and circadian locomotor output cycles kaput （CLOCK） associated with circadian clock （P<0.05，P<0.01）. ConclusionMQEF delays skin photoaging through the coordinated effects of various components，multiple targets，and diverse pathways.The key components BAK and SAB in MQEF exhibit anti-photoaging properties，which involve inhibiting oxidative stress，preventing collagen degradation，mitigating inflammation，and maintaining normal skin circadian rhythms by regulating clock gene expression.

Purpose Discover new prostate cancer-related single nucleotide variants.Methods Tissue wax blocks from 21 prostate cancer patients who underwent radical surgery and had relatively complete clinical data were collected for somatic mutation detection to analyze new mutated genes associated with prostate cancer.The levels of cor-responding proteins in the urine of prostate cancer patients were tested according to the results of the selected genes.Results All 21 prostate cancer patients showed obvious somatic mutations,and the mutation types were dominated by C＞T and G＞A.The number of somatic mutations was 521,of which 27 genes had high mutation proportions(≥2 ca-ses),including ZSWIM6(5/21),FOXA1(4/21),SPTA1(2/21),FAM47C(2/21),FLG2(2/21),PRSS3(2/21),TP53(2/21),FLG(2/21),UBR4(2/21),and the mutations occurring in ZSWIM6 were all deletion muta-tions,and the mutations occurring in FOXA1 were missense mutations,deletion mutations,and deletion insertion mu-tations.The urinary levels of UPF1,SPTA1,and IDH1 proteins of the 10 prostate cancer patients were significantly different than those of the healthy controls.Correlation analysis showed that FOXA1 was positively correlated with UBR4(r=0.669,P=0.001),SPTA1 was positively correlated with FLG2(r=1.000,P＜0.001),FAM47C was positively correlated with PRSS3(r=1.000,P＜0.001),and there was a significant positive correlation between TP53 and FLG(r=1.000,P＜0.001).ZSWIM6 and FOXA1 were not correlated with biochemical recurrence.SP-TA1 mutation affected progression-free survival(PFS)[(66.0±0)months vs(30.0±7.8)months,P=0.008].FAM47C was positively correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].ZNF676 was correlated with PFS[(66.0±0)months vs(26.0±5.0)months,P=0.008].FLG2 was correlated with PFS[(66.0±0)months vs(30.0±7.8)months,P=0.008].PRSS3 was correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].Conclusion All 21 prostate cancer patients harbored somatic mutations,including ZSWIM6(5/21)and FOXA1(4/21)mutations.SPTA1,FAM47C,ZNF676,FLG2,and PRSS3 may be associated with prognosis.

Purpose Discover new prostate cancer-related single nucleotide variants.Methods Tissue wax blocks from 21 prostate cancer patients who underwent radical surgery and had relatively complete clinical data were collected for somatic mutation detection to analyze new mutated genes associated with prostate cancer.The levels of cor-responding proteins in the urine of prostate cancer patients were tested according to the results of the selected genes.Results All 21 prostate cancer patients showed obvious somatic mutations,and the mutation types were dominated by C＞T and G＞A.The number of somatic mutations was 521,of which 27 genes had high mutation proportions(≥2 ca-ses),including ZSWIM6(5/21),FOXA1(4/21),SPTA1(2/21),FAM47C(2/21),FLG2(2/21),PRSS3(2/21),TP53(2/21),FLG(2/21),UBR4(2/21),and the mutations occurring in ZSWIM6 were all deletion muta-tions,and the mutations occurring in FOXA1 were missense mutations,deletion mutations,and deletion insertion mu-tations.The urinary levels of UPF1,SPTA1,and IDH1 proteins of the 10 prostate cancer patients were significantly different than those of the healthy controls.Correlation analysis showed that FOXA1 was positively correlated with UBR4(r=0.669,P=0.001),SPTA1 was positively correlated with FLG2(r=1.000,P＜0.001),FAM47C was positively correlated with PRSS3(r=1.000,P＜0.001),and there was a significant positive correlation between TP53 and FLG(r=1.000,P＜0.001).ZSWIM6 and FOXA1 were not correlated with biochemical recurrence.SP-TA1 mutation affected progression-free survival(PFS)[(66.0±0)months vs(30.0±7.8)months,P=0.008].FAM47C was positively correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].ZNF676 was correlated with PFS[(66.0±0)months vs(26.0±5.0)months,P=0.008].FLG2 was correlated with PFS[(66.0±0)months vs(30.0±7.8)months,P=0.008].PRSS3 was correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].Conclusion All 21 prostate cancer patients harbored somatic mutations,including ZSWIM6(5/21)and FOXA1(4/21)mutations.SPTA1,FAM47C,ZNF676,FLG2,and PRSS3 may be associated with prognosis.

Objective:To observe the effectiveness of combining mirror therapy with pneumatic flexible glove training in treating hand dysfunction after a stroke. Its effect on cerebral cortex activation was documented using near-infrared functional imaging of the brain.Methods:A total of 84 stroke survivors with hand dysfunction were randomly divided into a Mirror Group, a Glove Group and a Combined Group, each of 28. In addition to standard rehabilitation training, the Glove Group received 20 minutes of training with a pneumatic soft glove, 5 days per week for 6 consecutive weeks. The Mirror Group received mirror therapy (MT). The Combined Group was given both simultaneously. Before and after the treatment, everyone′s upper limb functioning was evaluated (using the Fugl-Meyer Upper Limb Assessment (FMA-U)), along with their hand motor skills (using the Arm Action Test (ARAT)) and their ability in daily living activities (using the Barthel Index (BI)). Functional near-infrared spectroscopy (fNIRS) was employed to measure any changes in oxygenated hemoglobin (HBO) concentration at 730nm and 850nm wavelengths.Results:The FMA-U, ATAT and BI scores in both the proximal and distal regions of all three groups showed significant improvement after the treatments compared to pre-treatment levels. The combined group demonstrated significantly better distal FMA-U and ARAT scores after the treatment (12.25±8.80 and 20.93±15.68 respectively), outperforming both the glove and mirror groups. The infrared spectroscopy revealed that bilateral SM1 activation, affected-side somatosensory association cortex (SAC) and supplementary motor cortex excitability in both the mirror and combined groups were significantly better than among the glove group after the experiment.Conclusions:Combined with pneumatic flexible glove training, mirror therapy can not only significantly improve the hand function of stroke survivors, but also activate the relevant brain regions of both hemispheres through bilateral motor patterns combined with multisensory stimulation, promoting the balance between hemispheres.

Objective:To investigate the predictive role of relative diffusion-weighted imaging (DWI) signal intensity (DWI-rSI) in outcome in patients with anterior circulation large vessel occlusion cardioembolic stroke and successful recanalization after endovascular therapy (EVT).Methods:Patients with anterior circulation large vessel occlusion stroke due to cardioembolic embolism underwent EVT and successful recanalization at the Affiliated Hospital of Yangzhou University from March 2017 to March 2023 were retrospectively included. According to the modified Rankin Scale score 3 months after procedure, the patients were divided into a good outcome group (0-2 points) and a poor outcome group (3-6 points). Multivariate logistic regression analysis was used to identify independent predictive factors for poor outcome. Results:A total of 59 patients were enrolled, including 29 males (49.2%), median age of 74 years (interquartile range, 68-80 years). The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 15 (12-21), and the median DWI Alberta Stroke Program Early CT Score (ASPECTS) was 8 (5-9). Thirty-two patients (54.2%) had good outcome, and 27 (45.8%) had poor outcome. Among them, 9 patients (15.3%) died (6 died from cerebral herniation after malignant brain edema, 2 died from complications, and 1 died from severe intracranial hemorrhage after procedure). Twenty-one patients (35.6%) experienced hemorrhagic transformation, including 12 (20.3%) with symptomatic intracranial hemorrhage. There were significant differences in baseline systolic blood pressure, NIHSS score, DWI-ASPECTS, DWI-rSI, and incidence of symptomatic intracranial hemorrhage between the good outcome group and the poor outcome group (all P<0.05). Multivariate logistic regression analysis showed that baseline systolic blood pressure (odds ratio 0.977, 95% confidence interval 0.919-0.991; P=0.015) and DWI-rSI (odds ratio 11.809, 95% confidence interval 1.932-72.170; P=0.008) were the independent predictors for poor outcome. Conclusion:DWI-rSI can predict the outcome of patients with anterior circulation large vessel occlusion cardioembolic stroke and successful recanalization after EVT.

High-altitude regions,characterized by their elevated altitude,are subject to a complex set of environmental conditions including intense ultraviolet radiation,low oxygen levels,low temperatures,and low humidity.These distinctive environmental features lead to unique dietary patterns,lifestyles,and physiological adaptations.Notably,individuals who have just moved into high-altitude areas and those who live there on a long-term basis undergo specific adaptive adjustments in glucose metabolism.Typically,newcomers experience transient elevations in blood glucose levels,which gradually decline after prolonged residence at high altitudes to levels even lower than those found at low altitudes.In general,current findings of observational studies generally suggest a decreased risk of diabetes mellitus among populations inhabiting high-altitude regions.However,the glucose metabolism varies among populations from different high-altitude regions across the world,which indicates that the reshaping of glucose metabolism induced by high altitudes is a complicated phenomenon.This article provides an overview of the impact of various components of high-altitude environment,characteristic lifestyle factors,and socioeconomic development levels on glucose metabolism and the related diseases and the potential mechanisms involved.The aim is to offer valuable insights for researchers investigating glucose metabolism in high-altitude settings.

BACKGROUND:The key to preventing the recurrence of intrauterine adhesions is to reconstruct the endometrium with normal function.The latest breakthrough in the treatment of recurrent intrauterine adhesions in and outside China is the use of degradable materials to prepare hydrogels to prevent the recurrence of adhesions. OBJECTIVE:To review the research advance in hydrogel-promoted endometrial repair in intrauterine adhesions. METHODS:PubMed,Web of Science,China National Knowledge Infrastructure(CNKI),and WanFang databases were searched systematically,with the keywords"intrauterine adhesions,endometrial injury,endometrium regeneration,hydrogel"in Chinese and English.Relevant articles published in each database from January 1990 to March 2023 were collected. RESULTS AND CONCLUSION:In recent years,research on hydrogel-promoted endometrial repair in uterine adhesions in and outside China has made some progress and plays an important role in the prevention and treatment of intrauterine adhesions and the promotion of endometrial repair:(1)As an important carrier in tissue engineering,hydrogel itself has excellent biocompatibility,biodegradability and three-dimensional network structure,which can be better applied in the treatment of intrauterine adhesions.(2)The hydrogel-based carrier system can promote the proliferation and differentiation of endometrial epithelial cells by transporting drugs/biologics/stem cells,and restore normal uterine morphology to prevent adhesion recurrence.(3)Hyaluronic acid hydrogels can not only meet good biocompatibility,but also promote the proliferation and differentiation of endometrial epithelial cells,and will be hydrolyzed by corresponding enzymes in utero,without affecting the normal metabolism of the body.They are currently commonly used uterine anti-adhesion agents in the clinic and are also the most commonly used hydrogel carriers in tissue engineering research.(4)Poloxamer hydrogel with excellent temperature-sensitive properties can rapidly gelate into the body,quickly form a physical barrier,and can play a slow-release effect on carrying substances and provide a platform for cell growth/adhesion.(5)There are broad prospects for the preparation of therapeutic hydrogels using materials with different characteristics,such as temperature-sensitive hydrogels,pH-responsive hydrogels and photosensitive hydrogels,but there are still many problems to be solved,such as the safety of the hydrogel system,whether the degradation products cause immune reactions,and whether they have an impact on the normal body's menstrual period.A large number of animal experiments and clinical trials are needed to verify its safety and efficacy,and continuously improve the treatment strategy.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is an unmet clinical challenge due to the rapid increased occurrence but lacking approved drugs. Autophagy-related protein 16-like 1 (ATG16L1) plays an important role in the process of autophagy, which is indispensable for proper biogenesis of the autophagosome, but its role in modulating macrophage-related inflammation and metabolism during MASH has not been documented. Here, we aimed to elucidate the role of ATG16L1 in the progression of MASH. Methods: Expression analysis was performed with liver samples from human and mice. MASH models were induced in myeloid-specific Atg16l1-deficient and myeloid-specific Atg16l1-overexpressed mice by high-fat and high-cholesterol diet or methionine- and choline-deficient diet to explore the function and mechanism of macrophage ATG16L1 in MASH. Results: Macrophage-specific Atg16l1 knockout exacerbated MASH and inhibited energy expenditure, whereas macrophage-specific Atg16l1 transgenic overexpression attenuated MASH and promotes energy expenditure. Mechanistically, Atg16l1 knockout inhibited macrophage lipophagy, thereby suppressing macrophage β-oxidation and decreasing the production of 4-hydroxynonenal, which further inhibited stimulator of interferon genes(STING) carbonylation. STING palmitoylation was enhanced, STING trafficking from the endoplasmic reticulum to the Golgi was promoted, and downstream STING signaling was activated, promoting proinflammatory and profibrotic cytokines secretion, resulting in hepatic steatosis and hepatic stellate cells activation. Moreover, Atg16l1-deficiency enhanced macrophage phagosome ability but inhibited lysosome formation, engulfing mtDNA released by pyroptotic hepatocytes. Increased mtDNA promoted cGAS/STING signaling activation. Moreover, pharmacological promotion of ATG16L1 substantially blocked MASH progression. Conclusions ATG16L1 suppresses MASH progression by maintaining macrophage lipophagy, restraining liver inflammation, and may be a promising therapeutic target for MASH management.