HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

During the hyperacute phase of intracerebral hemorrhage (ICH), the mass effect and blood components mechanically lead to brain damage and neurotoxicity. Our findings revealed that the mass effect and transferrin precipitate neuronal oxidative stress and iron uptake, culminating in ferroptosis in neurons. M6A (N6-methyladenosine) modification, the most prevalent mRNA modification, plays a critical role in various cell death pathways. The Fto (fat mass and obesity-associated protein) demethylase has been implicated in numerous signaling pathways of neurological diseases by modulating m6A mRNA levels. Regulation of Fto protein levels in neurons effectively mitigated mass effect-induced neuronal ferroptosis. Applying nanopore direct RNA sequencing, we identified voltage-dependent anion channel 3 (Vdac3) as a potential target associated with ferroptosis. Fto influenced neuronal ferroptosis by regulating the m6A methylation of Vdac3 mRNA. These findings elucidate the intricate interplay between Fto, Vdac3, m6A methylation, and ferroptosis in neurons during the hyperacute phase post-ICH and suggest novel therapeutic strategies for ICH.
Ferroptosis/physiology* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Animals ; Neurons/metabolism* ; Transferrin/pharmacology* ; Mice ; Methylation ; Mice, Inbred C57BL ; Adenosine/metabolism* ; RNA, Messenger/metabolism* ; Male ; Oxidative Stress/physiology*

Objective To summarize the diagnosis and treatment experience of surgical site infection(SSI)after percutaneous endoscopic lumbar discectomy(PELD).Methods A retrospective analysis was made on 11 cases of postoperative SSI after PELD from January 2016 to December 2022.After PELD surgery,severe lower back or lower limb pain occurred in all the patients,with a Visual Analog Scale(VAS)score of 7-9(average,8.1).The erythrocyte sedimentation rate(ESR)was 17-114 mm/h(average,54.4 mm/h),and the level of C-reactive protein(CRP)was 8-151 mg/L(average,56.5 mg/L).The MRI showed changes of inflammatory signals in the intervertebral space of the surgical area.The SSI was diagnosed at 2-17 d(average,9.5 d)after PELD surgery.All the cases were treated with antibiotics(4 cases with empiric antibiotic therapy and 7 cases with sensitive antibiotic treatment),8 of which underwent combined surgery,including percutaneous endoscopic lesion removal,catheter irrigation and drainage in 4 cases,posterior lesion removal in 2 cases,and posterior lesion removal combined with internal fixation in 2 cases.Results The patients were followed up for 14-75 months(average,36.8 months).According to the modified MacNab criteria,5 cases were excellent,4 cases were good,and 2 cases were fair.Conclusions SSI after PELD is characterized by acute onset,recurrent severe lower back or lower limb pain,elevated inflammatory markers,and characteristic imaging features.Standardized antibiotic treatment combined with surgery can achieve good therapeutic effects.

Objective:To analyze the superficial retinal blood flow around the optic disc of optical coherence tomography angiography (OCTA) in non-arteritic anterior ischemic optic neuropathy (NA-AION) patients with affected eyes and contralateral healthy eyes, compared with healthy people.Methods:From May 2018 to may 2019, 30 patients with NA-AION in Xi′an No. 1 Hospital were selected. The changes of superficial retinal blood flow density and perfusion around the optic disc on OCTA of 30 patients with NA-AION, whose contralateral healthy eyes were compared. The pattern visual evoked potential (PVEP) of both eyes was also compared. 30 healthy people with no history of eye disease and history of eye surgery were selected as healthy control group, and differences between healthy control group and contralateral healthy eye group in NA-AION patients of the superficial retinal blood flow density and perfusion around the optic disc were compared.Results:The average values of serum homocysteine, apolipoprotein E and low density lipoprotein in 30 patients with NA-AION were higher than the normal reference range. Compared with the contralateral healthy eyes, the effected eyes of NA-AION patients had lower retinal blood flow density and perfusion in the center, inner layer and complete area of the optic disc, with significantly difference ( P<0.05); there was no significant difference in the latency and amplitude of PVEP-P100 between the two groups ( P>0.05). There was no significant difference in the density and perfusion of superficial retinal blood flow in the center, inner layer and complete area of the optic disc between the contralateral healthy eyes of NA-AION patients and healthy control ( P>0.05). Conclusions:OCTA is a safe, rapid and non-invasive test, and it can detect blood perfusion defects promptly, which can be used as the most commonly test method for patients with NA-AION in order to make auxiliary diagnosis and gain time for clinical treatment.

Objective To observe the effects of electroacupuncture on the expressions of autophagy related protein Beclin-1 and apoptosis related protein p53 of hippocampus in rats;To explore the mechanism of electroacupuncture on Alzheimer's disease (AD).Methods The rats were randomly divided into the normal group, the sham-operation group, the model group, and the electroacupuncture treatment group. “Baihui” and “Yongquan” points were taken for electroacupuncture treatment and the treatment course was 7 days. The rats were treated once a day for 4 courses. Changes in morphology and number of Nissl positive cells were examined by Nissl staining in hippocampal CA1 regions. Expressions of Beclin-1 and p53 protein were determined by Western blot analysis.Results Number of Nissl positive cells in CA1 region of the model group was significantly less than that of normal group (P<0.01). After electroacupuncture treatment, number of pyramidal cells and expression of Nissl body significantly increased (P<0.05). Expression of Beclin-1 decreased, while expression of p53 increased in the hippocampus of the model group, compared with that in the normal group (P<0.05). However, electroacupuncture treatment could significantly upregulate the expression of Beclin-1 protein (P<0.01), but downregulate the level of p53 (P<0.05).Conclusion Electro-acupuncture treatment could fight against Aβ-induced neuronal apoptosis, and improve the morphological changes of AD’s hippocampus.

Objective To explore the protective effects of electro-acupuncture (EA) serum onβ-amyloid protein (Aβ) induced primary rat hippcampal neurons. Methods The rat models of Alzheimer's disease were established by intracerebral injection of Aβ1-40. After treated them with EA, the serum was harvested. Primary cultured hippocampal neurons were treated with Aβ25-35 to establish neuronal damage model in vitro, and divided into normal group, model group and EA serum group. The proliferation of neurons was detected by MTT test. Neuronal apoptosis was examined by TUNEL staining, and expression of cysteine aspartic acid proteases-3 (Caspase-3) was detected by immunocytochemical staining. Results MTT test showed that the cell viability was significantly decreased after treated with Aβ. While compared with the model group, cell proliferation of EA serum group was significantly enhanced (P<0.01). TUNEL staining showed that the number of apoptotic cells in EA serum group decreased significantly compared with the model group (P<0.01). After 48 h of Aβ treatment, Caspase-3 expression levels were significantly elevated. However, compared with the model group, the number of Caspase-3 positive cells in EA serum group was significantly reduced (P<0.01). Conclusion The EA serum could promote the proliferation of hippocampal neurons, reduce the expression of Caspase-3, counteract the neurotoxicity of β-amyloid protein, and reduce neuronal apoptosis.

This paper describes the digital earth technology and its core technology-"3S" integration technology. The advance and promotion of the "3S" technology provide more favorable means and technical support for Chinese medicine resources survey, evaluation and appropriate zoning. Grid is a mature and popular technology that can connect all kinds of information resources. The author sums up the application of digital earth technology in the research of traditional Chinese medicine resources in recent years, and proposes the new method and technical route of investigation in traditional Chinese medicine resources, traditional Chinese medicine zoning and suitability assessment by combining the digital earth technology and grid.
Conservation of Natural Resources ; Medicine, Chinese Traditional ; methods ; Research ; Satellite Communications ; Technology

Objective To investigate the predictive value of early prognosis of the 40 Hz auditory steady-state response (40 Hz ASSR) in patients with coma following cardiopulmonary resuscitation (CPR). Methods Thirty patients with coma following CPR admitted in the Neurological Intensive Care Unit (NICU) were examined with the 40 Hz ASSR and shortlatency somatosensory evoked potential (SLSEP), and both were graded. Using transferred out of NICU as the short-term outcome end point, the patients with coma following CPR were divided into a survival group (n =21) and a death group (n =9; including brain death). The correlation between the 40 Hz ASSR and SLSEP grading and prognosis was analyzed. Results The grades of the 40 Hz ASSR (r = 0. 722, P = 0.000) or SLSEP (r = 0. 430, P = 0.018) was significantly correlated with the short-term prognosis. The sensitivity, specificity and accuracy of the 40 Hz ASSR for predicting the short-term prognosis were 77. 8%, 100% and 93.3%, respectively; and those of SLSEP were 88. 9%, 61. 9% and 70. 0%, respectively. Conclusions The 40 Hz ASSR has a certain prognostic value in patients with coma following CPR. The higher the grade of the 40 Hz ASSR is, the greater the likelihood of the recent death.

Objective To investigate the predictive value of prognosis of the 95% spectral edge frequency (SEF95) and total power (TP) in quantitative electroencephalography (qEEG) in patients with disturbance of consciousness. Methods The patients with disturbance of consciousness admitted in the neurointensive care unit (NICU) in Nanfang Hospital from January 2008 to June 2010 were included. Glasgow Coma Scale (GCS) scores were performed on admission and EEG monitoring was performed simultaneously. The patients were divided into either a survival group or a death group according to the survival status of the patients at the time of leaving NICU. The age, sex, hypertension, diabetes, GCS scores, SEF95, and TP were compared between the two groups. A multivariate logistic regression analysis was performed for the above factors. The prognostic indicators were analyzed with the receiver operating characteristic (ROC) curves and the of qEEG predictive ability of death in patients with disturbance of consciousness were determined. Results A total of 109 patients with supratentorial lesions were enrolled in the study, 79 of them were in the survival group and 30 of them were in the death group. The GCS scores (5 ±3vs. 9 ±3, P =0. 000) and SEF95 (7. 0 ±4.0 vs. 10. 0 ±4. 0, P = 0. 002) in the death group were significantly lower than those in the survival group. Multivariate logistic regression analysis showed that GCS scores (odds ratio 0. 100, 95% confidence interval 0. 029-0. 353) and SEF95 (odds ratio 0. 853, 95% confidence interval 0. 740-0. 983) were the independent predictors of recent prognosis. ROC curve analysis showed that the lower the GCS scores and SEF95 were, the greater the likelihood of death in patients. When SEF95 was ＜7. 75, the sensitivity to determine the death was 60. 0%, the specificity was 72. 2%, the positive predictive value was 82. 6%, and the negative predictive value was 45. 0%; when the GCS score was ＜8, the sensitivity to determine the death was 83. 3%, the specificity was 73. 4%,the positive predictive value was 82. 6%, and the negative predictive value was 45. 0%. Conclusions SEF95 helps determine the prognosis of patients with disturbance of consciousness, and it is expected to become an important means of bedside assessment of prognosis in patients with disturbance of consciousness in NICU.