[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

Objective:To establish a Fourier transform infrared spectroscopy (FT-IR) method for rapid identification of Cremastrae Pseudobulbus Pleiones Pseudobulbus and its adulterants.Methods:The Fourier transform infrared spectra of Cremastrae Pseudobulbus Pleiones Pseudobulbus and its adulterants were established, and the second derivative spectral analysis, clustering analysis, principal component analysis, opls-da and cluster independent soft mode classification model were analyzed to explore the difference characteristic peaks of Cremastrae Pseudobulbus Pleiones Pseudobulbus and its adulterants.Results:The first order infrared spectrum showed that the peak shape and peak intensity of Cremastrae Pseudobulbus Pleiones Pseudobulbus and its adulterants were different. Clustering analysis, principal component analysis and OPLS-DA results showed that Cremastrae Pseudobulbus Pleiones Pseudobulbus and its adulterants showed good clustering characteristics. SIMCA method was used to construct the model, and the accuracy of the training set and the verification set were 100%, which further verified the feasibility of this method in identifying the authenticity of Cremastrae Pseudobulbus Pleiones Pseudobulbus.Conclusions:The second-order infrared spectroscopy can accurately distinguish the differences between Cremastrae Pseudobulbus Pleiones Pseudobulbus and its adulterants. The method is fast and accurate, and can be used for the authenticity identification of Cremastrae Pseudobulbus Pleiones Pseudobulbus.

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

Premenstrual dysphoric disorder (PMDD) is considered a severe form of premenstrual syndrome (PMS). As a key brain region involved in emotional regulation and stress responses, the amygdala has been implicated in the pathogenesis of PMS/PMDD. The amygdala is composed of multiple subregions, each playing distinct roles in emotion, memory, and stress responses, and forms complex brain areas. Summarizing the interconnections among amygdala, subregions and their connectivity with external areas, and exploringt the neuroimaging characteristics of the amygdala, as well as changes in its neural circuits and brain networks in these patients, will help provide a theoretical foundation for targeted modulation of amygdala function in the treatment of PMS/PMDD.
Humans ; Amygdala/diagnostic imaging* ; Female ; Premenstrual Dysphoric Disorder/pathology* ; Premenstrual Syndrome/pathology* ; Emotions/physiology* ; Magnetic Resonance Imaging

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

OBJECTIVES: To investigate the characteristics and clinical significance of anorectal manometry measurements in children with tethered cord syndrome (TCS) before and after surgery. METHODS: A retrospective study was conducted on 44 children with TCS treated at the Children's Hospital of Zhejiang University School of Medicine from January 2022 to September 2023. These patients were divided into effective subgroup (n=34) and non-effective subgroup (n=10) based on postoperative symptom improvement. Additionally, 34 children with functional constipation were selected as a control group. Baseline data and manometry measurements were compared between the preoperative TCS group and the control group, as well as between the non-effective and effective subgroups. RESULTS: The TCS group had lower short contraction time and defecation relaxation rate compared to the control group (P<0.05), while defecation residual pressure and maximum rectal tolerable threshold were higher than the control group (P<0.05). The length of the anal canal in the high-pressure zone in the effective subgroup was greater postoperatively than preoperatively (P<0.05), and the initial rectal sensation threshold decreased postoperatively (P<0.05). The non-effective subgroup had lower preoperative maximum rectal expulsion pressure compared to the effective subgroup (P<0.05). Postoperative rectal anal inhibition reflex values in the effective subgroup were higher than those in the non-effective subgroup (P<0.05). CONCLUSIONS There are some differences in anorectal dynamics between children with TCS and those with functional constipation. Maximum rectal expulsion pressure may be a key predictor of surgical outcomes. Surgery can alter certain defecation functions in some children.
Humans ; Male ; Anal Canal/physiopathology* ; Female ; Rectum/physiopathology* ; Child ; Child, Preschool ; Retrospective Studies ; Manometry ; Neural Tube Defects/physiopathology* ; Infant ; Defecation ; Adolescent ; Constipation/physiopathology* ; Clinical Relevance

Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Glioblastoma/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Homeostasis/physiology* ; Ferritins/metabolism* ; Brain Neoplasms/genetics* ; Mutation ; Astrocytes/drug effects* ; Cell Line, Tumor ; Piperazines/pharmacology* ; Quaternary Ammonium Compounds/pharmacology* ; Ferric Compounds

BACKGROUND:A large number of studies have investigated the effects of whole body vibration training at different frequencies on muscle strength,but less is reported on the differences in the efficacy of vibration training at different frequencies on patellar tendinopathy. OBJECTIVE:To explore the effect of eccentric training of quadriceps combined with different frequency of whole body vibration training on patellar tendinopathy. METHODS:From April to June 2022,48 patients with patellar tendinopathy were recruited from Wuhan Sports University and randomly divided into eccentric training group(n=12),30 Hz group(n=12),40 Hz group(n=12),and 50 Hz group(n=12).The eccentric training group only completed eccentric training of the quadriceps.The 30 Hz,40 Hz and 50 Hz groups performed the whole body vibration training with the amplitude of 2 mm and frequencies of 30 Hz,40 Hz and 50 Hz respectively on the basis of the eccentric training of the quadriceps.The intervention lasted for 8 weeks,three times a week.Before and after the intervention,the patients'surface electromyography signals of the quadriceps,kinematics and dynamics data of knee joint at the time of landing in deep jump and the time of peak vertical ground reaction,Visual Analogue Scale score,Victorian Institute of Sports Assessment-Patellar score were evaluated. RESULTS AND CONCLUSION:After 8 weeks of intervention,compared with the eccentric training group,the median frequency of the lateral and medial femoris muscles were significantly higher in the 40 Hz and 50 Hz groups(P＜0.05).At the time of landing,the knee joint flexion angle and external rotation moment in the 40 Hz and 50 Hz groups were significantly lower than those in the eccentric training group(P＜0.05),while the knee joint flexion angle in the 50 Hz group was significantly lower than that in the 30 Hz group(P＜0.05).At the peak moment of vertical ground reaction,the knee extension torque in the 40 Hz group was significantly lower than that in the eccectric training group(P＜0.05);the knee flexion angle and knee extension torque in the 50 Hz group were significantly lower than those in the eccentric training group(P＜0.05).The Visual Analogue Scale scores in the 50 Hz and 40 Hz groups were significantly lower than those in the eccentric training group(P＜0.05).The Victorian Institute of Sports Assessment-Patellar score in the 50 Hz group was significantly higher than that in the eccentric training group and 30 Hz group(P＜0.05).To conclude,eccentric training of the quadriceps combined with 50 Hz whole body vibration training can significantly improve quadriceps'strength,endurance and activation rate of the vastus lateralis muscle,reduce the pain of knee joint,and improve the function of the knee joint in patients with patellar tendinopathy.