It has been demonstrated that long-term space flights have a significantly greater impact on the cardiovascular, skeletal, and nervous systems of astronauts. The structural and functional alterations in the skeletal and muscular systems resulting from exposure to weightlessness can lead to the development of low back pain, significantly impairing the ability of astronauts to perform tasks and respond to emergencies. Both space flight and simulated microgravity have been shown to result in low back pain among astronauts, with the following factors identified as primary contributors to this phenomenon. The occurrence of intervertebral disc (IVD) edema results in the stimulation of type IV mechanoreceptors, which subsequently activate nociceptive afferents. The protrusion of an IVD causes compression of the spinal nerve roots. Furthermore, the elongation of the vertebral column and/or the diminished lumbar curvature of the spine exert traction on the dorsal root nerves. Paravertebral muscle degeneration leads to the inhibition of decreased nociceptive activity of the wide-dynamic range neurons of the spinal dorsal horn. Moreover, endogenous pain descending facilitation triggered by conditioning stimulation can be enhanced via the thalamic mediodorsal nuclei, while endogenous pain descending inhibition triggered by conditioning stimulation can be weakened via the thalamic ventromedial nuclei. Psychological factors may contribute to the development of low back pain. The mechanisms governing the generation, maintenance, and alleviation of low back pain in weightlessness differ from those observed in normal gravitational environments. This presents a significant challenge for space medicine research. Therefore, the elucidation of the occurrence and development mechanism of low back pain in weightlessness is important for the prevention and treatment during space flight. To reduce the incidence of low back pain during long-term missions on the space station, astronauts may choose to wear specialized space clothing that can provide axial physiological loads, designed to stimulate both musculature and skeletal structures, mitigating potential increases in vertebral column length, diminished lumbar curvature, and intervertebral disc edema and/or muscular atrophy. Additionally, assuming a “fetal tuck position” described as the knees to chest position may increase lumbar IVD hydrostatic pressure, subsequently reducing disc volume, rectifying diminished lumbar curvature, and alleviating dorsal root nerve tensions. Moreover, this position may reduce type IV mechanoreceptor facilitation and nerve impulse propagation from the sinuvertebral nerves of the annulus fibrosus. Elongated posterior soft tissues (apophyseal joint capsules and ligaments) with spinal flexion may potentially stimulate type I and II mechanoreceptors. It is also recommended to exercise the paraspinal muscles to prevent and alleviate the decrease in their cross-sectional area and maintain their structure and function. Photobiomodulation has been proved to be an effective means of activating the pain descending inhibition pathway of the central nervous system. In addition, astronauts should be encouraged to participate in mission-related activities and strive to avoid psychological problems caused by the long-term confinement in a small space station. The article presents a concise review of potential causes and targeted treatment strategies for low back pain induced by space flight or simulated microgravity in recent years. Its objective is to further elucidate the mechanisms underlying the occurrence and development of low back pain in weightless environments while providing scientific evidence to inform the development of guidelines for preventing, treating, and rehabilitating low back pain during long-term space flights.

Objective To compare the effects of dexmedetomidine and midazolam on intraoperative blood pressure and postoperative 90-day outcome of endovascular treatment(EVT)in patients with acute anterior circulation large vessel occlusive stroke.Methods Retrospective consecutive patients with acute anterior circulation large vessel occlusion stroke who received EVT within 24 hours of onset,admitted to the Department of Neurology at the Second People's Hospital of Hefei from January 2024 to February 2025 were included.Patients were divided into the dexmedetomidine group and the midazolam group based on the choice of sedative in EVT.Baseline and clinical data were collected from patients,including sex,age,medical history(hypertension,diabetes,atrial fibrillation,stroke history),smoking history,blood pressure at admission(systolic,diastolic,mean arterial pressure),National Institutes of Health stroke scale(NIHSS)score at admission,trial of Org 10172 in acute stroke treatment(TOAST)classification,and site of vascular occlusion(internal carotid artery,M1 segment of the middle cerebral artery).Procedure related parameters,including intravenous thrombolysis before EVT,intraoperative use of tirofiban,modified thrombolysis in cerebral infarction(mTICI)grade,thrombectomy techniques(stent-retriever thrombectomy,aspiration thrombectomy,combined stent-retriever and aspiration thrombectomy,and other salvage measures),number of thrombectomy,time from onset to revascularization,time from puncture to revascularization,blood pressure during EVT(minimum systolic,minimum diastolic,and minimum mean arterial pressure),and blood pressure at the end of EVT(systolic,diastolic,and mean arterial pressure).The primary outcome was good prognosis at 90 days after EVT(modified Rankin scale score of 0-2 at 90 days),while secondary outcome was＞20％decrease in mean arterial pressure during EVT,early neurological improvement(ENI;a decrease on NIHSS score no less than 8 or a reduction of NIHSS score to 0-1 at 24 hours after EVT),and early neurological deterioration(END;an increase of more than 2 points on the NIHSS at 24 hours after procedure).Safety outcomes included any intracranial hemorrhage within 48 hours after EVT,symptomatic intracranial hemorrhage within 48 hours after EVT(sICH;intracranial hemorrhage confirmed by head CT leading to neurological deterioration,with an increase in NIHSS score of at least 4 points,or the presence of potentially fatal intracranial hemorrhage on head CT),pneumonia within 2 weeks after EVT,and the 90-day mortality after EVT.The baseline and clinical data,EVT conditions,primary outcome,secondary outcome,and safety indicators were compared between the two groups.Univariate Logistic regression analysis was used to screen the variables associated with a decrease in mean arterial pressure＞20％during EVT in patients with acute anterior circulation large vessel occlusive stroke.Variables with P＜0.15 and those considered potentially influential based on clinical experience were included in multivariate Logistic regression analysis to identify predictors of a＞20％decrease in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusive stroke.Results A total of 93 patients with acute anterior circulation large vessel occlusive stroke who underwent EVT were included,comprising 51 males and 42 females,aged 34 to 99 years,with an average of(71±13)years old.Among them,63 patients were in the dexmedetomidine group,and 30 patients were in the midazolam group.33 patients showed＞20％decreases in mean arterial pressure during EVT,while 60 patients had ≤20％decreases.(1)Compare with the midazolam group,the proportion of female patients in the dexmedetomidine group was lower(36.5％[23/63]vs.63.3％[19/30],P=0.015),and the age was younger([69±13]years vs.[77±13]years,P=0.005).There were no statistically significant differences in other baseline and clinical data(all P＞0.05).(2)In comparison with the midazolam group,the dexmedetomidine group had a higher proportion of patients with more thrombectomy procedures(1.00[1.00,2.00]times vs.1.00[1.00,1.25]times,P=0.011),END(27.0％[17/63]vs.6.7％[2/30],P=0.023),sICH within 48 hours(19.0％[12/63]vs.3.3％[1/30],P=0.041),and a decrease in mean arterial pressure＞20％during EVT(42.9％[27/63]vs.20.0％[6/30],P=0.031).There were no statistically significant differences in the remaining EVT conditions,primary outcome,secondary outcome,and safety indicators(all P＞0.05).(3)The results of univariate Logistic regression analysis showed that diastolic blood pressure at admission(P=0.002),mean arterial pressure at admission(P=0.009),and dexmedetomidine sedation(P=0.036)were the influencing factors of a decrease＞20％in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusion stroke.(4)The results of multivariate Logistic regression analysis showed that dexmedetomidine sedation(OR,3.271,95％CI 1.057-10.126,P=0.040)and higher diastolic blood pressure on admission(OR,1.105,95％CI 1.006-1.213,P=0.037)were independent predictors of a decrease over 20％in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusive stroke.Conclusions Dexmedetomidine is an independent predictor of an over 20％decrease in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusive stroke,but there is no statistically significant differences in the rate of good neurological function at 90 days and 90-day mortality postoperatively between the two groups.Further prospective randomized controlled studies are needed.

Objective To compare the effects of dexmedetomidine and midazolam on intraoperative blood pressure and postoperative 90-day outcome of endovascular treatment(EVT)in patients with acute anterior circulation large vessel occlusive stroke.Methods Retrospective consecutive patients with acute anterior circulation large vessel occlusion stroke who received EVT within 24 hours of onset,admitted to the Department of Neurology at the Second People's Hospital of Hefei from January 2024 to February 2025 were included.Patients were divided into the dexmedetomidine group and the midazolam group based on the choice of sedative in EVT.Baseline and clinical data were collected from patients,including sex,age,medical history(hypertension,diabetes,atrial fibrillation,stroke history),smoking history,blood pressure at admission(systolic,diastolic,mean arterial pressure),National Institutes of Health stroke scale(NIHSS)score at admission,trial of Org 10172 in acute stroke treatment(TOAST)classification,and site of vascular occlusion(internal carotid artery,M1 segment of the middle cerebral artery).Procedure related parameters,including intravenous thrombolysis before EVT,intraoperative use of tirofiban,modified thrombolysis in cerebral infarction(mTICI)grade,thrombectomy techniques(stent-retriever thrombectomy,aspiration thrombectomy,combined stent-retriever and aspiration thrombectomy,and other salvage measures),number of thrombectomy,time from onset to revascularization,time from puncture to revascularization,blood pressure during EVT(minimum systolic,minimum diastolic,and minimum mean arterial pressure),and blood pressure at the end of EVT(systolic,diastolic,and mean arterial pressure).The primary outcome was good prognosis at 90 days after EVT(modified Rankin scale score of 0-2 at 90 days),while secondary outcome was＞20％decrease in mean arterial pressure during EVT,early neurological improvement(ENI;a decrease on NIHSS score no less than 8 or a reduction of NIHSS score to 0-1 at 24 hours after EVT),and early neurological deterioration(END;an increase of more than 2 points on the NIHSS at 24 hours after procedure).Safety outcomes included any intracranial hemorrhage within 48 hours after EVT,symptomatic intracranial hemorrhage within 48 hours after EVT(sICH;intracranial hemorrhage confirmed by head CT leading to neurological deterioration,with an increase in NIHSS score of at least 4 points,or the presence of potentially fatal intracranial hemorrhage on head CT),pneumonia within 2 weeks after EVT,and the 90-day mortality after EVT.The baseline and clinical data,EVT conditions,primary outcome,secondary outcome,and safety indicators were compared between the two groups.Univariate Logistic regression analysis was used to screen the variables associated with a decrease in mean arterial pressure＞20％during EVT in patients with acute anterior circulation large vessel occlusive stroke.Variables with P＜0.15 and those considered potentially influential based on clinical experience were included in multivariate Logistic regression analysis to identify predictors of a＞20％decrease in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusive stroke.Results A total of 93 patients with acute anterior circulation large vessel occlusive stroke who underwent EVT were included,comprising 51 males and 42 females,aged 34 to 99 years,with an average of(71±13)years old.Among them,63 patients were in the dexmedetomidine group,and 30 patients were in the midazolam group.33 patients showed＞20％decreases in mean arterial pressure during EVT,while 60 patients had ≤20％decreases.(1)Compare with the midazolam group,the proportion of female patients in the dexmedetomidine group was lower(36.5％[23/63]vs.63.3％[19/30],P=0.015),and the age was younger([69±13]years vs.[77±13]years,P=0.005).There were no statistically significant differences in other baseline and clinical data(all P＞0.05).(2)In comparison with the midazolam group,the dexmedetomidine group had a higher proportion of patients with more thrombectomy procedures(1.00[1.00,2.00]times vs.1.00[1.00,1.25]times,P=0.011),END(27.0％[17/63]vs.6.7％[2/30],P=0.023),sICH within 48 hours(19.0％[12/63]vs.3.3％[1/30],P=0.041),and a decrease in mean arterial pressure＞20％during EVT(42.9％[27/63]vs.20.0％[6/30],P=0.031).There were no statistically significant differences in the remaining EVT conditions,primary outcome,secondary outcome,and safety indicators(all P＞0.05).(3)The results of univariate Logistic regression analysis showed that diastolic blood pressure at admission(P=0.002),mean arterial pressure at admission(P=0.009),and dexmedetomidine sedation(P=0.036)were the influencing factors of a decrease＞20％in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusion stroke.(4)The results of multivariate Logistic regression analysis showed that dexmedetomidine sedation(OR,3.271,95％CI 1.057-10.126,P=0.040)and higher diastolic blood pressure on admission(OR,1.105,95％CI 1.006-1.213,P=0.037)were independent predictors of a decrease over 20％in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusive stroke.Conclusions Dexmedetomidine is an independent predictor of an over 20％decrease in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusive stroke,but there is no statistically significant differences in the rate of good neurological function at 90 days and 90-day mortality postoperatively between the two groups.Further prospective randomized controlled studies are needed.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

In recent years,as the survival time of liver transplant recipients continues to increase,serious complications after transplantation,including diabetes,which affects the long-term survival of patients,have attracted more and more attention.Diabetes after liver transplantation can increase the risk of infection and cardiovascular disease,which in turn affects the survival rate of grafts and patients,and therefore,identification and intervention for high-risk populations are of great importance for improving the prognosis of patients.This article reviews the risk factors for diabetes after liver transplantation,in order to deepen the understanding of diabetes after liver transplantation and provide a theoretical basis for disease prevention and treatment.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.

Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of Rehmannia glutinosa by various chromatographic techniques such as silica gel, MCI gel CHP-20, ODS, Toyopearl HW-40C, combined with TLC and semi-preparative HPLC. Their structures were elucidated by modern spectroscopy techniques (NMR, MS, UV, IR), and identified as neomartynoside A (1), osmanthuside B₆ (2), martynoside (3), isomartynoside (4), (E)-p-hydroxycinnamic acid (5), caffeic acid (6), ferulic acid (7), and methyl caffeate (8). Compound 1 is a new phenylethanol glycoside, which was identified as neomartynoside A. Compound 2 was isolated from Rehmannia glutinosa for the first time. In addition, compounds 2, 6 and 7 significantly increased relative glucose consumption, showing potential hypoglycemic activity.