JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias.
Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Leukemia, Myeloid, Acute/pathology* ; Jumonji Domain-Containing Histone Demethylases/chemistry* ; Gene Expression Regulation, Leukemic ; Oxidoreductases, N-Demethylating/genetics* ; Cell Line, Tumor

Objective To evaluate the application of problem-based learning(PBL)and case-based learning(CBL)combined with ideological-political elements in surgical clinical ethics.Methods Eighty graduate students of grade 2022 majoring in surgery from Peking Union Medical College were selected as the subjects for the clinical ethics course offered in the first semester of the 2022-2023 academic year.They underwent the innovative pedago-gies of PBL and CBL combined with ideological-political elements.The satisfaction investigation and questionnaire surveys were performed to evaluate the effects.Results A total of 78 valid questionnaires were received.The results showed that 96.2%of students believed that this course supported them to understand the fundamental prin-ciples and knowledge of surgical clinical ethics and 94.9%of students expressed their willingness to expand their knowledge,indicating high satisfaction with the course.There were 91%of students acknowledged this model in terms of improving active learning and 93.6%stated that the course helped in developing good professional ethics.Most students responded positively to this model because of its contribution to enhance core clinical competencies.Conclusions The PBL and CBL combined with ideological-political elements have a better effect on surgical clini-cal ethics with high satisfaction of the students.

OBJECTIVE: To evaluate the clinical effect and safety of acupuncture manipulation on treatment of intractable facial paralysis (IFP), and verify the practicality and precision of the Anzhong Facial Paralysis Precision Scale (Eyelid Closure Grading Scale, AFPPS-ECGS). METHODS: A multicentre, single-blind, randomized controlled trial was conducted from October 2022 to June 2024. Eighty-nine IFP participants were randomly assigned to an ordinary acupuncture group (OAG, 45 cases) and a characteristic acupuncture group (CAG, 44 cases) using a random number table method. The main acupoints selected included Yangbai (GB 14), Quanliao (SI 18), Yingxiang (LI 20), Shuigou (GV 26), Dicang (ST 4), Chengjiang (CV 24), Taiyang (EX-HN 5), Jiache (ST 6), Fengchi (GB 20), and Hegu (LI 4). The OAG patients received ordinary acupuncture manipulation, while the CAG received characteristic acupuncture manipulation. Both groups received acupuncture treatment 3 times a week, with 10 times per course, lasting for 10 weeks. Facial recovery was assessed at baseline and after the 1st, 2nd and 3rd treatment course by AFPPS-ECGS and the House-Brackmann (H-B) Grading Scale. Infrared thermography technology was used to observe the temperature difference between healthy and affected sides in various facial regions. Adverse events and laboratory test abnormalities were recorded. The correlation between the scores of the two scales was analyzed using Pearson correlation coefficient. RESULTS: After the 2nd treatment course, the two groups showed statistically significant differences in AFPPS-ECGS scores (P<0.05), with even greater significance after the 3rd course (P<0.01). Similarly, H-B Grading Scale scores demonstrated significant differences between groups following the 3rd treatment course (P<0.05). Regarding temperature measurements, significant differences in temperatures of frontal and ocular areas were observed after the 2nd course (P<0.05), becoming more pronounced after the 3rd course (P<0.01). Additionally, mouth corner temperature differences reached statistical significance by the 3rd course (P<0.05). No safety-related incidents were observed during the study. Correlation analysis revealed that the AFPPS-ECGS and the H-B Grading Scale were strongly correlated (r=0.86, 0.91, 0.93, and 0.91 at baseline, and after 1st, 2nd, and 3rd treatment course, respectively, all P<0.01). CONCLUSIONS Acupuncture is an effective treatment for IFP, and the characteristic acupuncture manipulation enhances the therapeutic effect. The use of the AFPPS-ECGS can more accurately reflect the recovery status of patients with IFP. (Trial registration No. ChiCTR2200065442).
Humans ; Acupuncture Therapy/methods* ; Facial Paralysis/therapy* ; Female ; Male ; Middle Aged ; Adult ; Treatment Outcome ; Acupuncture Points ; Aged

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective:To investigate and summarize the imaging and pathological features of non-acute occlusion following flow diverter (FD) implantation in animal models.Methods:Four experimental pigs (experimental group) that experienced non-acute occlusion (occlusion time exceeding 24 hours) within the FD stent implanted in the common carotid artery, and 19 pigs (control group) that did not experience stent occlusion during the same period were involved. Using an interventional approach under digital subtraction angiography (DSA), the 4 occluded FD lumens were mechanically opened. Optical coherence tomography (OCT), intravascular ultrasound (IVUS) and histopathological examinations were performed to evaluate the intraluminal composition and characteristics of the occlusive tissues. These findings were compared with non-occluded FD stents to summarize the imaging and pathological changes within the occluded FD lumen.Results:The occlusion times of the FD stents in the 4 experimental pigs were 16 weeks, 20 weeks, 20 weeks, and 24 weeks postoperatively. All occluded stents were successfully recanalized under DSA, with a technical success rate of 4/4. Among the 19 non-occluded FD stents, OCT and IVUS revealed uniform (16 stents) or non-uniform (3 stents) neointimal coverage of the stent struts, presenting as homogeneous high/slightly high signal intensity or medium echogenicity. Histopathological examination indicated that the neointima was primarily composed of smooth muscle cells and a small amount of fibrous connective tissues. In contrast, the 4 occluded FD stents demonstrated excessive neointimal proliferation and plaque formation, leading to luminal loss, as shown by OCT and IVUS. The occlusion tissues predominantly presented as homogeneous high signal intensity with weak attenuation (fibrous plaques) on OCT, with some regions showing blurred low signal intensity and strong attenuation (lipid plaques). IVUS presented homogeneous echogenicity (fibrous plaques) and hypoechogenic zones (lipid plaques). Histopathological examination showed that the occlusion tissues mainly consisted of smooth muscle cells, fibrous connective tissues, and lipids, accompanied by numerous foam cells and a minor presence of inflammatory cells.Conclusions:Histopathological examinations confirm that non-acute occlusion of FD is mainly caused by excessive hyperplasia of intima along with the formation of fibrous plaques and lipid plaques. OCT and IVUS have typical finding in imaging that can assist in determining the cause of stent occlusion as well as the lesion's nature, thereby providing crucial guidance for subsequent clinical treatment and drug selection.

Objective:To compare the efficacy of the transverse process-lateral pedicle approach and curved vertebroplasty in the treatment of osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 66 patients with OVCF admitted to the Second People′s Hospital of Hefei from December 2021 to June 2023, including 9 males and 57 females aged 60-89 years [(75.6±7.5)years]. The injured segments included T 11 in 17 patients, T 12 in 17, L 1 in 17, and L 2 in 15. Among them, 33 patients underwent vertebroplasty via the transverse process-lateral pedicle approach (lateral approach group), while other 33 patients underwent curved vertebroplasty (curved group). The surgical duration, number of X-ray fluoroscopy, bone cement injection volume, and length of hospital stay were compared between the two groups. Additionally, the restoration efficiency of vertebral height and the correction degree of spinal scoliosis Cobb angle at 2 days postoperatively were compared between the two groups. The changes in serum levels of stress factors including noradrenaline, adrenaline, and cortisol preoperatively and at 2 days postoperatively, the visual analogue scale (VAS) and Oswestry disability index (ODI) preoperatively, at 2 days, 6 months postoperatively, and at the last follow-up were compared between the two groups. The incidence of complications was assessed in the two groups. Results:All the patients were followed up for 12-14 months [(13.2±0.5)months]. The surgical duration and number of X-ray fluoroscopy in the lateral approach group were (30.9±4.1)minutes and (5.9±3.3)times, which were significantly lower than (35.8±3.9)minutes and (9.9±4.4)times in the curved group ( P<0.01). There were no statistically significant differences between the two groups in terms of bone cement injection volume, length of hospital stay, restoration efficiency of vertebral height at 2 days postoperatively, or the correction degree of spinal scoliosis Cobb angle ( P>0.05). The levels of noradrenaline, adrenaline, and cortisol at 2 days postoperatively were (57.3±4.8)ng/ml, (49.9±4.2)ng/ml, (159.3±20.5)nmol/L in the lateral approach group, and (64.3±4.5)ng/ml, (58.3±4.4)ng/ml, (183.5±21.2)nmol/L in the curved group, which were all significantly increased compared with those preoperatively [(42.3±3.5)ng/ml, (38.5±2.8)ng/ml, (128.4±12.3)nmol/L in the lateral approach group and (42.0±3.5)ng/ml, (39.0±3.0)ng/ml, (128.5±12.3)nmol/L in the curved group] ( P<0.01). There were no significant differences between the two groups in terms of the levels of noradrenaline, adrenaline, and cortisol preoperatively ( P>0.05). The levels of noradrenaline, adrenaline, and cortisol at 2 days postoperatively in the lateral approach group were significantly lower than those in the curved group ( P<0.01). The VAS scores for low back pain in the lateral approach group and the curved group were 3(2, 5)points and 5(3, 6)points at 2 days postoperatively, 3(2, 4)points and 3(2, 4)points at 6 months postoperatively, and 2(2, 3)points and 2(2, 4)points at the last follow-up, which were all significantly lower than those preoperatively [7(7, 9)points and 8(6, 9)points] ( P<0.05). Moreover, the VAS scores for low back pain were further decreased over time postoperatively ( P<0.05). The ODI values in the lateral approach group and curved group were (33.4±4.4)% and (33.7±4.3)% at 2 days postoperatively, (23.8±1.6)% and (23.8±1.7)% at 6 months postoperatively, and (15.6±0.9)% and (15.6±0.9)% at the last follow-up, which were all significantly lower than (67.4±4.3)% and (67.5±4.3)% preoperatively ( P<0.05). Moreover, the ODI values were further decreased over time postoperatively ( P<0.05). There were no significant differences between the two groups in terms of the VAS scores for low back pain or ODI values preoperatively, at 2 days, 6 months postoperatively or at the last follow-up ( P>0.05). The complication rate was 12.1% (4/33) in the lateral approach group, which was significantly lower than 51.5% (17/33) in the curved group ( P<0.05). Conclusion:Although both the transverse process-lateral pedicle approach vertebroplasty and the curved vertebroplasty can achieve good therapeutic effects in the treatment of OVCF, the former has shorter surgical duration, fewer times of X-ray fluoroscopy, lower trauma stress levels at 2 days postoperatively, and fewer complications.

Objective:To investigate the effects of 3 D laparoscopic radical resection prostatectomy(LRP)on urinary control and sexual function of patients with prostatic cancer.Methods:A total of 268 patients who were treated with LRP in the Fifth People's Hospital of Huai an City from January 2019 to May 2022 were selected and divided into 2 groups according to surgical methods,with 134 cases in each group.The patients in the control group were treated with traditional LRP,and the 3D LRP was used in the observa-tion group.The clinical effects of the two groups were compared.Results:The patients in observation group had less blood loss([135.62±13.58]mL vs[143.18±14.89]mL)and shorter indwelling catheter time([8.26±1.47]d vs[9.78±1.73]d)compared with control group,but the operation time([160.52±10.78]min vs[154.47±10.41]min)was longer than that in the control group(P＜0.05).The recovery of sexual function and urinary control in the observation group was better than that in the con-trol group after 3,6 and 12 months of the surgery(P＜0.05).After one month of surgery,the scores of ICIQ-SF and 1 h urine pad test were lower than those of the control group.The EPIC-UIN score([72.63±6.85]points vs[67.15±5.09]points)of the observation group was higher than that of the control group(P＜0.05).The patients in the observation group had lower level of residual urine volume([60.26±6.63]mL vs[76.89±7.89]mL),higher maximum urine flow rate([7.52±0.46]mL/s vs[6.17±0.43]mL/s)and detrusor pressure([85.19±7.18]mL vs[76.29±6.85]mL)at maximum urine flow rate compared with the control group(P＜0.05).There was no difference in the incidence of complications between the observation group and the control group(5.97％vs 8.27％,P＞0.05).The recurrence rate of tumor 3 years after operation in the observation group was lower than that in the control group(11.94％vs 29.10％,x2=12.102,P＜0.05).Conclusion:3D LRP has obvious advantages in surgical clarity and preci-sion,which reduces the risk of postoperative complications and improves urinary control ability and sexual function of patients.

Objective:To compare the efficacy of the transverse process-lateral pedicle approach and curved vertebroplasty in the treatment of osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 66 patients with OVCF admitted to the Second People′s Hospital of Hefei from December 2021 to June 2023, including 9 males and 57 females aged 60-89 years [(75.6±7.5)years]. The injured segments included T 11 in 17 patients, T 12 in 17, L 1 in 17, and L 2 in 15. Among them, 33 patients underwent vertebroplasty via the transverse process-lateral pedicle approach (lateral approach group), while other 33 patients underwent curved vertebroplasty (curved group). The surgical duration, number of X-ray fluoroscopy, bone cement injection volume, and length of hospital stay were compared between the two groups. Additionally, the restoration efficiency of vertebral height and the correction degree of spinal scoliosis Cobb angle at 2 days postoperatively were compared between the two groups. The changes in serum levels of stress factors including noradrenaline, adrenaline, and cortisol preoperatively and at 2 days postoperatively, the visual analogue scale (VAS) and Oswestry disability index (ODI) preoperatively, at 2 days, 6 months postoperatively, and at the last follow-up were compared between the two groups. The incidence of complications was assessed in the two groups. Results:All the patients were followed up for 12-14 months [(13.2±0.5)months]. The surgical duration and number of X-ray fluoroscopy in the lateral approach group were (30.9±4.1)minutes and (5.9±3.3)times, which were significantly lower than (35.8±3.9)minutes and (9.9±4.4)times in the curved group ( P<0.01). There were no statistically significant differences between the two groups in terms of bone cement injection volume, length of hospital stay, restoration efficiency of vertebral height at 2 days postoperatively, or the correction degree of spinal scoliosis Cobb angle ( P>0.05). The levels of noradrenaline, adrenaline, and cortisol at 2 days postoperatively were (57.3±4.8)ng/ml, (49.9±4.2)ng/ml, (159.3±20.5)nmol/L in the lateral approach group, and (64.3±4.5)ng/ml, (58.3±4.4)ng/ml, (183.5±21.2)nmol/L in the curved group, which were all significantly increased compared with those preoperatively [(42.3±3.5)ng/ml, (38.5±2.8)ng/ml, (128.4±12.3)nmol/L in the lateral approach group and (42.0±3.5)ng/ml, (39.0±3.0)ng/ml, (128.5±12.3)nmol/L in the curved group] ( P<0.01). There were no significant differences between the two groups in terms of the levels of noradrenaline, adrenaline, and cortisol preoperatively ( P>0.05). The levels of noradrenaline, adrenaline, and cortisol at 2 days postoperatively in the lateral approach group were significantly lower than those in the curved group ( P<0.01). The VAS scores for low back pain in the lateral approach group and the curved group were 3(2, 5)points and 5(3, 6)points at 2 days postoperatively, 3(2, 4)points and 3(2, 4)points at 6 months postoperatively, and 2(2, 3)points and 2(2, 4)points at the last follow-up, which were all significantly lower than those preoperatively [7(7, 9)points and 8(6, 9)points] ( P<0.05). Moreover, the VAS scores for low back pain were further decreased over time postoperatively ( P<0.05). The ODI values in the lateral approach group and curved group were (33.4±4.4)% and (33.7±4.3)% at 2 days postoperatively, (23.8±1.6)% and (23.8±1.7)% at 6 months postoperatively, and (15.6±0.9)% and (15.6±0.9)% at the last follow-up, which were all significantly lower than (67.4±4.3)% and (67.5±4.3)% preoperatively ( P<0.05). Moreover, the ODI values were further decreased over time postoperatively ( P<0.05). There were no significant differences between the two groups in terms of the VAS scores for low back pain or ODI values preoperatively, at 2 days, 6 months postoperatively or at the last follow-up ( P>0.05). The complication rate was 12.1% (4/33) in the lateral approach group, which was significantly lower than 51.5% (17/33) in the curved group ( P<0.05). Conclusion:Although both the transverse process-lateral pedicle approach vertebroplasty and the curved vertebroplasty can achieve good therapeutic effects in the treatment of OVCF, the former has shorter surgical duration, fewer times of X-ray fluoroscopy, lower trauma stress levels at 2 days postoperatively, and fewer complications.

Objective:To investigate and summarize the imaging and pathological features of non-acute occlusion following flow diverter (FD) implantation in animal models.Methods:Four experimental pigs (experimental group) that experienced non-acute occlusion (occlusion time exceeding 24 hours) within the FD stent implanted in the common carotid artery, and 19 pigs (control group) that did not experience stent occlusion during the same period were involved. Using an interventional approach under digital subtraction angiography (DSA), the 4 occluded FD lumens were mechanically opened. Optical coherence tomography (OCT), intravascular ultrasound (IVUS) and histopathological examinations were performed to evaluate the intraluminal composition and characteristics of the occlusive tissues. These findings were compared with non-occluded FD stents to summarize the imaging and pathological changes within the occluded FD lumen.Results:The occlusion times of the FD stents in the 4 experimental pigs were 16 weeks, 20 weeks, 20 weeks, and 24 weeks postoperatively. All occluded stents were successfully recanalized under DSA, with a technical success rate of 4/4. Among the 19 non-occluded FD stents, OCT and IVUS revealed uniform (16 stents) or non-uniform (3 stents) neointimal coverage of the stent struts, presenting as homogeneous high/slightly high signal intensity or medium echogenicity. Histopathological examination indicated that the neointima was primarily composed of smooth muscle cells and a small amount of fibrous connective tissues. In contrast, the 4 occluded FD stents demonstrated excessive neointimal proliferation and plaque formation, leading to luminal loss, as shown by OCT and IVUS. The occlusion tissues predominantly presented as homogeneous high signal intensity with weak attenuation (fibrous plaques) on OCT, with some regions showing blurred low signal intensity and strong attenuation (lipid plaques). IVUS presented homogeneous echogenicity (fibrous plaques) and hypoechogenic zones (lipid plaques). Histopathological examination showed that the occlusion tissues mainly consisted of smooth muscle cells, fibrous connective tissues, and lipids, accompanied by numerous foam cells and a minor presence of inflammatory cells.Conclusions:Histopathological examinations confirm that non-acute occlusion of FD is mainly caused by excessive hyperplasia of intima along with the formation of fibrous plaques and lipid plaques. OCT and IVUS have typical finding in imaging that can assist in determining the cause of stent occlusion as well as the lesion's nature, thereby providing crucial guidance for subsequent clinical treatment and drug selection.

Fluorescence anisotropy(FA)analysis has many advantages such as no requirement of separation,high throughput and real-time detection,and thus has been widely used in many fields,including biochemical analysis,food safety detection,environmental monitoring,etc.However,due to the small volume or mass of the target,its combination with the fluorescence probe cannot produce significant signal change.To solve this issue,researchers often use nanomaterials to enhance the mass or volume of fluorophore to improve the sensitivity.Nevertheless,this FA amplification strategy also has some disadvantages.Firstly,nanomaterials are easy to quench fluorescence.As a result,the FA value is easily influenced by light scattering,which reduces the detection accuracy.Secondly,fluorescent probes in most methods require complex modification steps.Therefore,it is necessary to develop new FA probes that do not require the amplification of volume and mass or modification.As a new kind of nanomaterials,luminescent metal-organic framework(MOF)has a large volume(or mass)and strong fluorescence emission.It does not require additional signal amplification materials.As a consequence,it can be used as a potential FA probe.This study successfully synthesized a lanthanide metal organic framework(Ce-TCPP MOF)using cerium ion(Ce3+)as the central ion and 5,10,15,20-tetra(4-carboxylphenyl)porphyrin(H2TCPP)as the ligand through microwave assisted method,and used it as a novel unmodified FA probe to detect phosphate ions(Pi).In the absence of Pi,Ce-TCPP MOF had a significant FA value(r).After addition of Pi,Pi reacted with Ce3+in MOF and destroyed the structure of MOF into the small pieces,resulting in a decrease in r.The experimental results indicated that with the increase of Pi concentration,the change of the r of Ce-TCPP MOF(Δr)gradually increased.The Δr and Pi concentration showed a good linear relationship within the range of 0.5-3.5 μmol/L(0.016-0.108 mg/L).The limit of detection(LOD,3σ/k)was 0.41 μmol/L.The concentration of Pi in the Jialing River water detected by this method was about 0.078 mg/L,and the Pi value detected by ammonium molybdate spectrophotometry was about 0.080 mg/L.The two detection results were consistent with each other,and the detection results also meet the ClassⅡwater quality standard,proving that this method could be used for the detection of Pi in complex water bodies.