Stroke is a cerebrovascular disease with high fatality and disability rates， which brings heavy psychological burden along with physical disorder to patients. In recent years， transcranial magnetic stimulation （TMS） has attracted great attention in the research on functional prognosis of stroke patients. TMS can reveal the degree of corticospinal tract injury from a neurophysiological point of view and provide key information for functional recovery， and it is widely used in the rehabilitation treatment of post-stroke dysfunction. This article reviews the basic principle， classification， mechanism of TMS in promoting functional recovery of stroke， as well as its application in rehabilitation treatment， so as to lay a foundation for individualized neurological rehabilitation and improve the long-term prognosis of patients to the largest extent.
Stroke ; Prognosis

ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E₂) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E₂ levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.

ObjectiveThe full name of vertebroplasty is percutaneous vertebroplasty (PVP). It is a clinical technique that injects bone cement into the diseased vertebral body to achieve strengthening of the vertebra. The research on the safety and efficacy of bone cement is the basis for clinical application. In this study, vertebroplasty is used to evaluate and compare the safety and efficacy of Tecres and radiopaque bone cement in experimental pigs, and to determine the puncture method suitable for pigs and the pre-clinical evaluation method for the safety and efficacy of bone cement. MethodsTwenty-four experimental pigs (with a body weight of 60-80 kg) were randomly divided into an experimental group (Group A) and a control group (Group B). Group A was the Tecres bone cement group, and Group B was the radiopaque bone cement group, with 12 pigs in each group. Under the monitoring of a C-arm X-ray machine, the materials were implanted into the 1st lumbar vertebra (L1) and 4th lumbar vertebra (L4) of the pigs via percutaneous puncture using the unilateral pedicle approach. The animals were euthanized at 4 weeks and 26 weeks after the operation, respectively. The L4 vertebrae were taken for compressive strength testing, and the L1 vertebrae were taken for hard tissue pathological examination to observe the inflammatory response, bone necrosis, and degree of osseointegration at the implantation site. ResultsThe test results of compressive strength between groups A and B showed no significant difference at 4 weeks and 26 weeks after bone cement implantation (P > 0.05). Observation under an optical microscope (×100) revealed that at 4 weeks postoperatively, both groups A and B showed that the bone cement was surrounded by proliferative fibrous tissue, with lymphocyte infiltration around it. The bone cement was combined with bone tissue, the trabecular arrangement was disordered, and osteoblasts and a small amount of osteoid were formed. At 26 weeks postoperatively, bone cement was visible in both groups A and B. The new bone tissue was mineralized, the trabeculae were fused, the trabecular structure was regular and dense with good continuity, and no obvious inflammatory reaction was observed. ConclusionIn experimental pig vertebrae, there were no significant differences observed in the compressive strength, inflammation response, bone destruction, and integration with the bone between Tecres and non-radiopaque bone cement. Both exhibited good biocompatibility and osteogenic properties. It indicates that using vertebroplasty to evaluate the safety and efficacy of bone cement in pigs is scientifically sound.

Objective:To compare the differences in postoperative healing rates, hearing improvement, and complication rates between endoscopic butterfly inlay cartilage tympanoplasty and underlay cartilage tympanoplasty in Small-to-Medium-Sized Tympanic Membrane Perforations, and to provide clinical basis for indication of the butterfly inlay cartilage tympanoplasty. Methods:This study enrolled patients with chronic suppurative otitis media or traumatic tympanic membrane perforations who were treated at the Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Chongqing Medical University, between January 2022 and May 2023. Inclusion criteria comprised a dry ear period exceeding 3 months, absence of middle ear or mastoid pathology confirmed by temporal bone CT, and an air-bone gap of less than 40 dB. All surgeries were performed by the same surgeon using tympanoplasty techniques. Based on the surgical approach and perforation size, patients were categorized into four groups: Group A（butterfly cartilage tympanoplasty, perforation ≤3 mm）: 23 cases. Group B（butterfly cartilage tympanoplasty, perforation 3-5 mm）: 17 cases. Group C（full-thickness cartilage underlay tympanoplasty, perforation ≤3 mm）: 12 cases. Group D（full-thickness cartilage underlay tympanoplasty, perforation 3-5 mm）: 22 cases. Data collected included perforation duration, preoperative Eustachian Tube Score（ETS）, pure-tone audiometry, otoscopic findings, and postoperative follow-up data on pure-tone thresholds, otoscopic outcomes, and complications such as graft infection and otorrhea. Results: The mean postoperative follow-up period was 4 months （range: 3-12 months）. A total of 74 patients were enrolled, including 40 undergoing butterfly cartilage tympanoplasty and 34 receiving full-thickness cartilage inlay tympanoplasty. In the <3 mm perforation subgroup, the patients receiving butterfly technique （23 cases） exhibited a postoperative air-bone gap （ABG） improvement of （2.33±8.21） dB, and those receiving the inlay technique （12 cases） showed an ABG improvement of （2.49±7.9） dB, with no statistically significant difference between the two groups （P>0.05）. In the 3-5 mm perforation subgroup, the patients receiving butterfly technique （17 cases） demonstrated an ABG improvement of （8.16±5.69） dB, and those receiving the inlay technique （22 cases） achieved an ABG improvement of （8.08±10.42） dB, which were not significantly different （P>0.05）. Tympanic membrane healing rates across the four subgroups were 95.65%, 94.12%, 100%, and 95.45%, respectively, with no statistically significant differences （P>0.05）. Conclusion:In patients with tympanic membrane perforations ≤3 mm and 3-5 mm, butterfly cartilage tympanoplasty achieves comparable audiological outcomes to full-thickness cartilage underlay tympanoplasty. Compared with the underlay technique, the butterfly method is less invasive, preserves the normal anatomical structure of the tympanic membrane, requires a shorter dry ear period, and yields higher patient satisfaction. Therefore, it can be safely recommended for perforations ≤5 mm that do not require tympanotomy exploration.
Humans ; Tympanic Membrane Perforation/surgery* ; Tympanoplasty/methods* ; Treatment Outcome ; Endoscopy ; Cartilage/transplantation* ; Male ; Female ; Adult ; Middle Aged ; Myringoplasty/methods* ; Otitis Media, Suppurative/surgery* ; Aged

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

Multimorbidity is significantly associated with life quality decline, disability, and increased mortality risk. Additionally, it leads to greater consumption of healthcare resources, presenting substantial challenges to healthcare systems globally. To better assess the burden of multimorbidity, its impact on patient health outcomes and healthcare services, and to explore the underlying mechanisms in its development, this paper summarizes the existing methods used for measuring and analyzing multimorbidity in research and practice, including disease count, disease-weighted indices, multimorbidity pattern recognition (such as disease association analysis, clustering analysis, and network analysis) and longitudinal methods to provide references for the accurate assessment of the prevalence of multimorbidity and its changes and improve the validity and universality of research findings.

OBJECTIVE To systematically summarize the working model of pharmacy consultation in medical institutions in China， and to provide reference for the normalization of process， standardization of content and homogenization of services of pharmacy consultation. METHODS A systematic search of Chinese and English literature databases was conducted to incorporate the literature on the working model of pharmacy consultation published by medical institutions in China. Two researchers screened and extracted the key information， and ultimately conducted qualitative summary and descriptive analysis. RESULTS Based on the included 11 articles， the pharmacy consultation working models were explored by clinical pharmacists in China. The contents of consultation mainly involved anti-infection， parenteral nutrition， cancer pain， etc. The general concept of pharmacy consultation should refer to the constructed flowchart， specific consultation problems could refer to the pathway， mind map， or decision tree and other framework guidance to carry out the work. Finally， consultation opinions could be written according to the consultation system or specialty consultation templates， and the adoption of a new working model （such as pharmacist active consultation） could also promote the number and acceptance rate of pharmacy consultation. CONCLUSIONS A series of working models of pharmacy consultation have been initially explored in medical institutions in China. However， it is not yet perfect and lacks a unified quality control and evaluation system for pharmacy consultation， which should be the focus of future research and practice.

Objective To compare the early outcomes of domestic third-generation magnetically levitated left ventricular assist device (LVAD) with or without concomitant mitral valvuloplasty (MVP). Methods The clinical data of 17 end-stage heart failure patients who underwent LVAD implantation combined with preoperative moderate to severe mitral regurgitation in Fuwai Central China Cardiovascular Hospital from May 2018 to March 2023 were retrospectively analyzed. The patients were divided into a LVAD group and a LVAD+MVP group based on whether MVP was performed simultaneously, and early outcomes were compared between the two groups. Results There were 4 patients in the LVAD group, all males, aged (43.5±5.9) years, and 13 patients in the LVAD+MVP group, including 10 males and 3 females, aged (46.8±16.7) years. All the patients were successful in concomitant MVP without mitral reguragitation occurrence. Compared with the LVAD group, the LVAD+MVP group had a lower pulmonary artery systolic pressure and pulmonary artery mean pressure 72 h after operation, but the difference was not statistically different (P>0.05). Pulmonary artery systolic pressure was significantly lower 1 week after operation, as well as pulmonary artery systolic blood pressure and pulmonary artery mean pressure at 1 month after operation (P<0.01). There was no statistically significant difference in blood loss, operation time, cardiopulmonary bypass time, aortic cross-clamping time, mechanical ventilation time, or ICU stay time between the two groups (P>0.05). The differences in 1-month postoperative mortality, acute kidney injury, reoperation, gastrointestinal bleeding, and thrombosis and other complications between the two groups were not statistically significant (P>0.05). Conclusion Concomitant MVP with implantation of domestic third-generation magnetically levitated LVAD is safe and feasible, and concomitant MVP may improve postoperative hemodynamics without significantly increasing perioperative mortality and complication rates.

BACKGROUND:In the past,it was necessary to cut off the pronator quadratus muscle in the treatment of distal radius fractures.Failure to repair the pronator quadratus muscle can lead to a series of complications. OBJECTIVE:To explore the clinical efficacy of different methods of preserving the pronator quadratus muscle combined with a palmar steel plate in the treatment of distal radius fractures. METHODS:Clinical data of 66 patients with distal radius fractures were retrospectively included,divided into the traditional Henry approach group(group A),the split brachioradialis tendon approach group(group B),and the posterior pronator quadratus muscle approach group(group C),with 22 patients in each group.Postoperative internal fixation,fracture healing,and postoperative complications were observed in the three groups.The visual analog scale score of postoperative wrist pain and forearm rotation angle were compared among the three groups.The Dienst Joint Scale was used to evaluate the wrist function of patients. RESULTS AND CONCLUSION:(1)The surgical time,intraoperative blood loss,and fracture healing time of groups B and C were significantly lower than those of group A(P<0.01).There was no significant difference in intraoperative blood loss and fracture healing time between groups B and C,but the surgical time was shorter in group B.(2)The anteroposterior and lateral wrist X-ray examination 3 days and 1 and 3 months after surgery exhibited that there were no significant differences in radial height,palm angle,and ulnar deviation angle among the three groups(P>0.05).No significant difference was detected in various indicators during the same phase among the three groups(P>0.05).(3)At a follow-up of 12 months after surgery,there were no significant differences in visual analog scale scores and forearm rotation angle among the three groups.However,the evaluation results at 1 and 3 months after surgery demonstrated significant differences in visual analog scale scores and forearm rotation angle among the three groups(P<0.05).Among them,group C had a lower visual analog scale score and a larger forearm rotation angle.(4)According to the Dienst joint scoring standard,the excellent and good rate of wrist joint function evaluation was 86%(19/22),91%(20/22),and 95%(21/22)in groups A,B,and C,respectively 12 months after surgery.(5)All patients did not experience any postoperative vascular or neurological damage or surgical site infection.Group A had three cases of tendon irritation,two cases of traumatic arthritis,and two cases of carpal tunnel syndrome.In group B,tendon irritation occurred in 1 case and joint stiffness in 1 case.There was 1 case of traumatic arthritis and 1 case of carpal tunnel syndrome in group C.(6)It is suggested that different surgical methods for treating distal radius fractures have achieved good clinical results.Placing a steel plate under the pronator muscle can alleviate early postoperative pain,promote early activity,and restore normal life.The brachioradialis tendon approach has more advantages in exposing intraoperative fractures and can shorten the surgical time.