Objective To explore the sleep quality and mental fatigue level in elderly patients with cerebrovascular small disease(CSVD).Methods A total of 222 patients aged over 65 years old hospitalized due to chronic diseases in Department of Neurology of the Affiliated Jiangning Hospi-tal of Nanjing Medical University from August 2022 to June 2024 were recruited prospectively and continuously.According to the CSVD score,they were divided into a CSVD group(CSVD score≥1,148 cases)and a non-CSVD group(CSVD score=0,74 cases).All the patients were evaluated by sleep quality,fatigue and neuropsychological scale when they were fully cooperated and in good condition.Subsequently,the patients in the CSVD group were further assigned into a good sleep subgroup(117 cases)and a poor sleep subgroup(31 patients).Results The CSVD group had significantly higher total score of Pittsburgh sleep quality index(PSQI),sleep quality score,sleep disturbance score,total score of self-rating fatigue,and mental fatigue score than the non-CSVD group(P＜0.01).The sleep quality score,sleep disturbance score,and mental fatigue score were risk factors for CSVD(P＜0.05).The mental fatigue score was significantly higher in the CSVD patients with poor sleep than those with good sleep(4.13±1.15 vs 2.50±1.92,P＜0.01).Conclusion Elderly CSVD patients were more likely to have decreased sleep quality and mental fatigue,and among them,those with poor sleep quality are prone to having mental fatigue than those with good sleep.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.

This study explored the effects and underlying mechanism of Raf kinase inhibitory protein(RKIP)on apoptosis in mast cells sensitized by Echinococcus granulosus cyst fluid.Bone marrow-derived mast cells(BMMCs)were isolated and cultured from RKIP knockout(KO)and wild-type(WT)C57BL/6 mice.Cells were divided into control and sensitized groups.The sensitized group was incubated for 24 h in RPMI1640 medium containing 10%serum from mice infected with E.granulosus,then activated for 3 h or 6 h with E.granulosus cyst fluid.The control group was incubated for 24 h in RPMI1640 medium,and then received an equal vol-ume of PBS.Cells and supernatants were collected for analysis.Flow cytometry was used to detect the expression of CD117 and FcεRⅠα on BMMCs.The levels of β-hexosaminidase,IL-4,and TNF-α in the supernatant were quantified with ELISA.Western blot analy-sis was used to assess expression changes in RKIP,apoptosis-related proteins,and pathway proteins in BMMC before and after sensi-tization.Flow cytometry analysis revealed that after 4 weeks of induction,the CD117 and FcεRⅠα double-positivity rates on both WT and KO BMMC exceeded 90%.ELISA indicated that the E.granulosus cyst fluid resulted in significantly greater β-hexosaminidase re-lease(F=16.88,P<0.05),and levels of IL-4(F=16.51,P<0.05)and TNF-α(F=9.78,P<0.05)in the KO sensitized group than the WT sensitized group.With respect to the WT control group,the WT sensitized group showed significantly down-regulated pro-tein expression levels of RKIP(F=8.20,P<0.05)and Bcl-2(F=101.40,P<0.01)after 3 h,but significantly up-regulated levels of p-PI3K(F=8.04,P<0.05),p-Akt(F=32.52,P<0.01),p-P65(F=13.29,P<0.05),and cleaved-caspase-3(F=46.34,P<0.01).With respect to the WT sensitized group,the KO sensitized group showed significantly up-regulated protein expression of p-PI3K(F=8.45,P<0.05),p-Akt(F=8.58,P<0.05),p-P65(F=11.02,P<0.05),and Bcl-2(F=84.50,P<0.001)after 3 h,but significantly down-regulated expression of cleaved-caspase-3(F=15.66,P<0.05).In conclusion,RKIP may inhibit the PI3K/Akt/NF-κB pathway,thereby inducing apoptosis in mast cells sensitized by E.granulosus cyst fluid.This process may help ease aller-gic reactions caused by mast cells in echinococcosis,thus offering a promising new approach for preventing and treating such reactions.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

OBJECTIVE: To assess the value of combined detection strategies using multiple technologies for the genetic testing and prenatal diagnosis for pedigrees affected with Duchenne muscular dystrophy (DMD) for optimizing genetic counseling and reproductive guidance. METHODS: This study has involved 142 subjects from 65 suspected DMD families who had visited the First Affiliated Hospital of Chongqing Medical University from January 2018 to December 2023. A combination of multiple ligation-dependent probe amplification (MLPA), quantitative fluorescence PCR, and next-generation sequencing (NGS) was used. After confirming the genetic diagnosis of the probands, prenatal diagnosis was provided for carrier mothers. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2021-264). RESULTS: Among the 142 subjects tested, 73 cases of large deletions/duplications and 15 cases of small variants of the DMD gene were detected. The hotspot regions for the variants were exons 45 to 55. A total of 41 variant types were identified, of which 3 were previously unreported. In 19 families with suspected patients, 7 exonic deletions, 2 exonic duplications, and 3 small variants were identified. Prenatal diagnosis was performed on 48 fetuses from 46 families, revealing 16 affected male fetuses (including 12 with deletion variants, 2 with duplication variants, and 2 with small variants). Seven carrier females were identified among the 16 female fetuses (including 6 with deletions and 1 with duplication). Among the couples with an affected fetus, 16 had opted to terminate the pregnancy, while the parents of 32 fetuses had chosen to continue with the pregnancy. In families undergoing prenatal diagnosis, 53 (79.1%) pregnant women and their family members were found to carry mutations of the DMD gene. CONCLUSION The combined detection strategy of MLPA, qPCR, and NGS can encompass large deletions/duplications and small variants of the DMD gene, providing timely and accurate prenatal diagnosis for families affected by DMD. In conjunction with genetic counseling, this can effectively reduce the risk of producing affected offspring, which is crucial for the prevention and control of this disease.
Humans ; Muscular Dystrophy, Duchenne/diagnosis* ; Prenatal Diagnosis/methods* ; Female ; Male ; Pregnancy ; Pedigree ; Genetic Testing/methods* ; Dystrophin/genetics* ; Adult ; Genetic Counseling ; High-Throughput Nucleotide Sequencing/methods* ; Exons

Objective To establish and evaluate a mouse model of acute myocardial infarction(AMI)with coronary heart disease(CHD)that integrates syndrome differentiation with disease diagnosis,based on the"deficiency-stagnation-toxicity"pathogenesis.Methods Forty-eight ICR mice were randomly divided into four groups using a random number table:sham-operated,normal diet,high-choline,and trimethylamine N-oxide(TMAO).From weeks 1 to 8,each group received corresponding dietary and water interventions.From the 9th week,the normal diet,high-choline,and TMAO groups underwent coronary artery ligation(left anterior descending artery,LAD).In contrast,the sham-operated group only had suture placement without ligation,maintaining the same dietary and water interventions.Data on general signs,body weight,food and water intake,urine and feces,auricle and paw conditions,and behavioral patterns were collected and compared macroscopically and microscopically to determine the syndrome type of the high-choline-induced AMI mouse model and observe changes in the"deficiency-stagnation-toxicity"syndrome indicators.After 12 weeks,echocardiography,hematoxylin-eosin(HE)staining,and Masson′s trichrome staining were used to assess cardiac function,myocardial tissue cellular morphology changes,and myocardial fibrosis levels,respectively.The stability and reliability of the model were evaluated by observing the fluorescence intensity of inflammatory cytokines in the myocardial tissues of each group using immunofluorescence.Results Mice in all groups post-AMI surgery exhibited significant weight loss,dull fur,lethargy,and reduced activity.Mice in the high-choline and TMAO groups showed more sluggish responses to stimuli.The high-choline and TMAO groups displayed increased food intake but slow weight gain from weeks 1 to 4,developing into a trend of"increased food and water intake with weight loss"from 5 to 8 weeks,accompanied by yellowish urine and dry stools(P<0.01).Postoperatively(9-12 weeks),body weight significantly decreased,with the most prominent weight loss observed in the high-choline group.The high-choline and TMAO groups exhibited abnormal RGB values in auricles and paws(P<0.01),and behavioral tests showed a significant decline in open-field activity(P<0.01).Cardiac function and pathological examinations revealed that,compared with the sham-operated and normal diet groups,mice in the high-choline and TMAO groups had increased left ventricular end-diastolic and end-systolic volumes(P<0.01),decreased left ventricular ejection fraction and fractional shortening(P<0.01),and elevated heart indices(P<0.05).HE staining of myocardial tissues indicated more pyknotic nuclei and inflammatory cell infiltration in the high-choline and TMAO groups.Masson′s trichrome staining showed extensive blue-stained collagen fiber distribution in the infarct border zones of the high-choline and TMAO groups,with aggravated fibrosis(P<0.05).Immunofluorescence revealed elevated interleukin-1 beta and tumor necrosis factor-alpha levels in the high-choline and TMAO groups compared with the sham-operated and normal diet groups(P<0.01).Conclusion A high-choline diet combined with LAD ligation successfully established an animal model of AMI with CHD that integrates syndrome differentiation with disease diagnosis,based on the"deficiency-stagnation-toxicity"pathogenesis.This model not only embodies the traditional Chinese medicine theory′s understanding of the pathogenic features of"deficiency-stagnation-toxicity",but also serves as a reference for assessing the interventional effects of Chinese herbal compound prescriptions and facilitating research on syndrome patterns in traditional Chinese medicine.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.