OBJECTIVE: To investigate the clinical efficacy of bilateral targeted puncture in percutaneous vertebroplasty(PVP) based on the vertebral osteodense zone. METHODS: A retrospective analysis was conducted on 76 patients with fresh symptomatic osteoporotic vertebral compression fractures, characterized by the presence of a dense zone, who underwent percutaneous vertebroplasty (PVP) between January 2021 and December 2021. All patients involved single-level vertebral fractures. There were 19 males and 57 females, aged from 62 to 88 years old, with an average of (68.5±12.5) years old. All patients underwent bilateral transpedicular puncture procedures. Preoperative CT or MRI was utilized to ascertain the relative position of the bone osteodense zone within the vertebral body (specifically, whether this zone is situated in the upper one-third or one-quarter of the left or right sagittal plane). Considering the head and tail regions of the dense zone as puncture targets, the puncture points and paths were meticulously planned, and the working channel was subsequently established. Under continuous monitoring by a C-arm X-ray machine, bone cement was carefully and gradually injected. The operation time, bone cement injection volume, and bone cement leakage were recorded. The visual analogue scale (VAS) and Oswestry disablity index (ODI) were used to evaluate the effectiveness of the operation. ODI and anterior height (AH) of the vertebral body were used to evaluate the efficacy. RESULTS: All patients successfully completed the surgery and were followed up for (8.0±1.0) months. The operation time was (36.57±11.25) min, the volume of bone cement injection was(6.07±1.19) ml, and 21 patients of bone cement leakage. There were 3 patients with the VAS exceeded 4 points two days postoperatively, indicating suboptimal pain management. At the three time points of pre-operation, 2 days post-operation and 6 months post-operation, the VAS scores were(7.82±1.29), (2.11±0.44), and (2.04±0.67) respectively;the ODI percentages were(75.65±7.23)%, (29.45±4.16)%, and(28.68±5.62)%;and the AH values were (11.02±1.30), (12.87±3.91), and (12.91±3.86) cm. The differences were all statistically significant(P<0.05). The aforementioned three indices demonstrated significant improvement at both 2 days and 6 months post-operation (all P<0.05). There were no statistically significant differences in these indices between the 2-day and 6-month post-operative periods(P>0.05). The postoperative outcome was satisfactory and durable, with no evidence of vertebral height reduction. CONCLUSION Bilateral targeted puncture based on the osteodense dense zone within the vertebral body can achieve bilateral symmetrical and upright full vertebral bone cement reinforcement without increasing bone cement leakage, achieving good early efficacy and preventing late vertebral collapse. This has positive significance for further improving the efficacy of percutaneous vertebroplasty.
Humans ; Male ; Female ; Vertebroplasty/methods* ; Aged ; Middle Aged ; Aged, 80 and over ; Retrospective Studies ; Spinal Fractures/surgery* ; Fractures, Compression/surgery* ; Punctures ; Bone Cements ; Osteoporotic Fractures/surgery*

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Objective:To investigate the differences in hippocampal subfield volumes and structural covariance network between participants with subjective cognitive decline (SCD) and healthy individuals, and to analyze the correlations of the volumes of the different subfields and altered covariance brain regions with memory function.Methods:A total of 57 SCD individuals(SCD group) and 44 normal controls(NC group) participants were assessed for memory function using composite scores from the auditory verbal learning test (AVLT) and the Wechsler memory scale visual reproduction (VR) test from June 2022 to October 2023.T1-weighted structural magnetic resonance imaging (MRI) data were collected from all participants, and hippocampal subfields, cortical regions, and subcortical nuclei were segmented using FreeSurfer to measure the gray matter volume of each structure. A structural covariance network was constructed based on the correlation of gray matter volumes across regions. Statistical analysis was performed using R 4.3.1 software. Inter-group differences in hippocampal subfield volumes were compared using multivariate analysis of covariance. Differences in structural covariance connectivity between groups were assessed using Z-test, while network topology differences were compared through permutation testing. Finally, partial correlation analysis was used to examine correlation of the volumes of the differential hippocampal subfields and covariance brain regions with memory function. Results:The SCD group exhibited significantly lower years of education, AVLT-immediate score, AVLT-delayed score, VR-immediate score, VR-delayed score, and memory function Z-score compared to the NC group ( t=2.064, 3.888, 2.622, 3.222, 4.761, 5.184, all P<0.05). The volumes of the right subiculum((387.75±55.20)mm 3, (352.70±70.25)mm 3), left presubiculum((263.12±38.52)mm 3, (239.79±46.02)mm 3), left subiculum((388.12±49.34)mm 3, (351.74±67.30)mm 3) and left CA1((571.01±80.01)mm 3, (526.51±98.80)mm 3) in the SCD group were smaller than the corresponding volumes in NC group ( F=9.139, 8.039, 11.207, 7.266, all P<0.05, FDR correction). Differences in structural covariance connectivity were found between the SCD and NC groups in the following pairs: right CA1-right subiculum, right CA1-left subiculum, right CA3-left parasubiculum and right hippocampus-amygdala transition area-left subiculum ( Z=-3.848, -3.896, -3.597, -3.895, all P<0.05, FDR correction).Partial correlation analysis revealed that in the SCD group, the volume of the left subiculum ( r=0.359, P=0.007), left CA1 ( r=0.430, P=0.001), right entorhinal cortex ( r=0.296, P=0.029), right middle temporal gyrus ( r=0.361, P=0.007), right parahippocampal gyrus ( r=0.313, P=0.021)were positively correlated with the total memory function score. Conclusion:Hippocampal subfields atrophy, as well as alterations in structural covariance network, have been found in SCD individuals. Furthermore, the decline in memory function may be closely associated with atrophy in hippocampal subfields and structurally covariant regions.

Objective:To explore the prognosis of patients with gastric cancer peritoneal metastasis (PM) receiving programmed cell death-1 (PD-1) antibody therapy, and investigate the biomarkers that affect the prognosis of anti-PD-1 therapy.Methods:This restrospecific study collected the clinic-pathological data of 56 patients with peritoneal metastasis of gastric cancer who received first-line treatment in the Nanjing Drum Town Hospital from March 2020 to September 2023, among which 41 had received anti-PD-1 immunotherapy and 15 hadn't. The relationship between overall survival (OS) and anti-PD-1 immunotherapy was evaluated by Kaplan-Meier analysis. The relationship between baseline peripheral blood indicators and treatment response of patients with anti-PD-1 treatment was analyzed using unpaired t-test. Subsequently, the Cox proportional risk regression model was used to explore the clinical prognostic factors that may affect anti-PD-1 immunotherapy by univariate and multivariate analysis. The clinical prognostic factors included baseline data and baseline peripheral blood indexes such as anti-PD-1 treatment lines, Eastern Cooperative Oncology Group performance status (ECOG PS), combined positive score (CPS), expression of human epidermal growth factor receptor 2 (Her-2), EBER status, pathological types, other metastatic lesions, ascites content before immunotherapy, with or without abdominal drainage during anti-PD-1 treatment, blood lipid indicators, inflammatory indicators, and tumor indicators. Results:Kaplan-Meier survival statistics showed similar OS (15.9 vs. 15.2 months, P=0.600) in patients with anti-PD-1 therapy compared to those without anti-PD-1 therapy. Patients with baseline high-density lipoprotein (HDL) ≥0.97 mmol/L ( n=22) demonstrated a significantly longer median OS compared to those with HDL＜0.97 mmol/L (15.2 vs. 13.5 months; P=0.018). Similarly, the cohort with apolipoprotein A1 (ApoA1) levels ≥0.86 g/L ( n=21) showed superior survival outcomes, with a median OS of 17.7 months versus 12.3 months in the ApoA1＜0.86 g/L group ( n=20; P=0.006). In contrast, elevated baseline alpha-fetoprotein (AFP) levels ( n=2) were associated with markedly reduced survival (median OS: 5.7 vs. 15.2 months in normal AFP group, n=37; P=0.005). Notably, elevated pretreatment ApoA1 levels correlated with enhanced immunotherapy response ( P=0.017). Multivariate Cox regression analysis revealed that ApoA1 deficiency (≥0.86 g/L) independently predicted better OS following PD-1 antibody therapy ( HR=0.35, 95% CI: 0.12-0.98, P=0.046) in gastric cancer patients with PM. Conclusions:In our study, it is first proposed that ApoA1 could be a significant predictor of the survival advantages of immunotherapy in gastric cancer patients with PM.

Objective:To investigate the differences in hippocampal subfield volumes and structural covariance network between participants with subjective cognitive decline (SCD) and healthy individuals, and to analyze the correlations of the volumes of the different subfields and altered covariance brain regions with memory function.Methods:A total of 57 SCD individuals(SCD group) and 44 normal controls(NC group) participants were assessed for memory function using composite scores from the auditory verbal learning test (AVLT) and the Wechsler memory scale visual reproduction (VR) test from June 2022 to October 2023.T1-weighted structural magnetic resonance imaging (MRI) data were collected from all participants, and hippocampal subfields, cortical regions, and subcortical nuclei were segmented using FreeSurfer to measure the gray matter volume of each structure. A structural covariance network was constructed based on the correlation of gray matter volumes across regions. Statistical analysis was performed using R 4.3.1 software. Inter-group differences in hippocampal subfield volumes were compared using multivariate analysis of covariance. Differences in structural covariance connectivity between groups were assessed using Z-test, while network topology differences were compared through permutation testing. Finally, partial correlation analysis was used to examine correlation of the volumes of the differential hippocampal subfields and covariance brain regions with memory function. Results:The SCD group exhibited significantly lower years of education, AVLT-immediate score, AVLT-delayed score, VR-immediate score, VR-delayed score, and memory function Z-score compared to the NC group ( t=2.064, 3.888, 2.622, 3.222, 4.761, 5.184, all P<0.05). The volumes of the right subiculum((387.75±55.20)mm 3, (352.70±70.25)mm 3), left presubiculum((263.12±38.52)mm 3, (239.79±46.02)mm 3), left subiculum((388.12±49.34)mm 3, (351.74±67.30)mm 3) and left CA1((571.01±80.01)mm 3, (526.51±98.80)mm 3) in the SCD group were smaller than the corresponding volumes in NC group ( F=9.139, 8.039, 11.207, 7.266, all P<0.05, FDR correction). Differences in structural covariance connectivity were found between the SCD and NC groups in the following pairs: right CA1-right subiculum, right CA1-left subiculum, right CA3-left parasubiculum and right hippocampus-amygdala transition area-left subiculum ( Z=-3.848, -3.896, -3.597, -3.895, all P<0.05, FDR correction).Partial correlation analysis revealed that in the SCD group, the volume of the left subiculum ( r=0.359, P=0.007), left CA1 ( r=0.430, P=0.001), right entorhinal cortex ( r=0.296, P=0.029), right middle temporal gyrus ( r=0.361, P=0.007), right parahippocampal gyrus ( r=0.313, P=0.021)were positively correlated with the total memory function score. Conclusion:Hippocampal subfields atrophy, as well as alterations in structural covariance network, have been found in SCD individuals. Furthermore, the decline in memory function may be closely associated with atrophy in hippocampal subfields and structurally covariant regions.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

CRM 197(cross-reacting material 197),a naturally occurring mutant of diphtheria toxin,is a safe and effective vaccine vector and extensively used on developing conjugate or combined vaccines.The mutant loses its enzymatic activity,but fully retains its receptor-binding ability and immunogenicity.In current work,the diphtheria toxin mutant CRM 197 and its fusion proteins with the receptor-binding do-main of botulinum neurotoxin serotype E(EHc)were developed using genetic engineering technology.These recombinant proteins were confirmed by Western blotting and SDS-PAGE.BALB/c mice were im-munized with the CRM197-EHc and EHc-CRM197 fusion proteins,and their immunogenicity was evalua-ted.These two fusion protein molecules,CRM197-EHc and EHc-CRM197,as subunit vaccines,elicited a robust humoral immune response targeting both CRM197 and EHc antigens in the immunized mice.Compared to the mixture of CRM197 and EHc,the mice vaccinated with the fusion proteins(CRM197-EHc and EHc-CRM197)induced higher levels of anti-CRM197 antibodies,and the mice vaccinated with EHc-CRM197 also generated strongest anti-EHc antibodies.Consequently,as a carrier molecule in the fusion protein vaccine,EHc enhances the immunogenicity of CRM197 molecules.Likewise,CRM197 boosts the immunogenicity of EHc in the EHc-CRM197 fusion protein.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

CRM 197(cross-reacting material 197),a naturally occurring mutant of diphtheria toxin,is a safe and effective vaccine vector and extensively used on developing conjugate or combined vaccines.The mutant loses its enzymatic activity,but fully retains its receptor-binding ability and immunogenicity.In current work,the diphtheria toxin mutant CRM 197 and its fusion proteins with the receptor-binding do-main of botulinum neurotoxin serotype E(EHc)were developed using genetic engineering technology.These recombinant proteins were confirmed by Western blotting and SDS-PAGE.BALB/c mice were im-munized with the CRM197-EHc and EHc-CRM197 fusion proteins,and their immunogenicity was evalua-ted.These two fusion protein molecules,CRM197-EHc and EHc-CRM197,as subunit vaccines,elicited a robust humoral immune response targeting both CRM197 and EHc antigens in the immunized mice.Compared to the mixture of CRM197 and EHc,the mice vaccinated with the fusion proteins(CRM197-EHc and EHc-CRM197)induced higher levels of anti-CRM197 antibodies,and the mice vaccinated with EHc-CRM197 also generated strongest anti-EHc antibodies.Consequently,as a carrier molecule in the fusion protein vaccine,EHc enhances the immunogenicity of CRM197 molecules.Likewise,CRM197 boosts the immunogenicity of EHc in the EHc-CRM197 fusion protein.

Objective This study aims to develop a guideline for assessing and maintaining intrinsic capacity in older adults,offer recommendations to professionals regarding these assessments,and encourage the implementation of evidence-based clinical practices across various settings,including communities,hospitals,nursing homes,and other geriatric care environments.Methods An evidence-based approach guided the collection of questions through a lit-erature review.Preliminary recommendations were developed through a systematic search of domestic and interna-tional guideline networks,professional association websites,and comprehensive databases.Subsequently,the recom-mendations were revised,and the consensus was achieved through a round of expert consensus meetings and 3 rounds of expert correspondence,culminating in the formation of the guidelines.Results The developed guideline encompasses 2 aspects and 5 dimensions of assessment and maintenance,comprising a total of 28 questions and 39 recommendations.Specifically,6 questions and 9 recommendations were formulated for the cognitive dimension,5 questions and 7 recommendations for the locomotion dimension,6 questions and 7 recommendations for the vitality dimension,6 questions and 9 recommendations for the psychological dimension,and 5 questions and 7 recommenda-tions for the sensory dimension.Among these,34 are classified as strong recommendations,while 5 are categorized as weak recommendations.Conclusion The guideline offers scientifically robust,acceptable,and comprehensible rec-ommendations that equip the professionals with a foundation for decision-making aiming at preserving the intrinsic capacity of older adults.