[摘 要] 目的：探讨IL-22通过STAT3信号轴损害NK细胞功能并促进膀胱癌细胞耐药的机制。方法：常规培养T24细胞，用梯度递增法构建耐药T24/顺铂（DDP）细胞。将细胞分为对照组（不处理）、DDP组、IL-22组、IL-22 + DDP组、IL-22 + anti-IL-22组、IL-22 + DDP + Stattic（STAT3抑制剂）组。qPCR法检测各组T24细胞中IL-22、cyclin D1、Bcl-2 mRNA的表达，WB法检测各组细胞中BAX、BCL2和p-STAT3的表达，CCK-8法检测各组细胞的增殖活性，流式细胞术检测各组细胞的凋亡，ELISA检测各组细胞上清液中乳酸脱氢酶（LDH）、TNF-α、IFN-γ、颗粒酶B（GzmB）和穿孔素（PRF）蛋白的水平。结果：T24/DDP细胞对DDP敏感性降低（P < 0.05）；其耐药相关基因P-糖蛋白（P-gp）、肺耐药蛋白（LRP)、多药耐药相关蛋白1（MRP1）和IL-22及其受体表达水平均明显升高（均P < 0.05），说明T24/DDP细胞构建成功。与对照组比较，DDP组T24细胞的增殖活力明显降低、凋亡率升高、BAX蛋白表达升高、BCL2表达下降（均P < 0.05）；与DDP组比较，IL-22 + DDP组T24细胞的增殖活明显升高、凋亡率明显下降、BAX蛋白表达降低、BCL2表达升高（均P < 0.05），表明IL-22通过调节BAX/Bcl-2的表达促进T24细胞对DDP耐药性。与对照组比较，IL-22组T24细胞总细胞和核中p-STAT3表达水平均明显升高（均P < 0.05）；与IL-22组比较，IL-22 + anti IL-22组T24细胞中 p-STAT3水平明显降低（P < 0.05），说明IL-22激活T24细胞中STAT3的磷酸化过程，并促进其转核。与对照组比较，DDP组T24与NK92细胞共培养上清液中LDH、TNF-α、IFN-γ、GzmB及PRF蛋白水平均明显升高（均P < 0.05），与DDP组比较，IL-22 + DDP组共培养上清液中上述蛋白水平均明显降低（均P < 0.05）；与对照组比较，IL-22组共培养上清液中LDH、TNF-α、IFN-γ、GzmB及PRF蛋白水平明显降低（均P < 0.05）；与IL-22组比较，IL-22 + Stattic组共培养上清液中上述蛋白水平均明显升高（均P < 0.05），说明IL-22可降低NK92细胞对T24细胞的毒性，STAT3抑制剂可逆转此作用。与DDP组比较，IL-22 + DDP组T24细胞增殖活力明显升高（P < 0.05）；与IL-22 + DDP组比较，IL-22 + DDP + Stattic组T24细胞增殖活力明显降低（P < 0.05）；与DDP组比较，IL-22 + DDP组T24细胞的凋亡率明显升高（P < 0.05）；与IL-22 + DDP组比较，IL-22 + DDP + Stattic组T24细胞的凋亡率明显升高（P < 0.05），说明IL-22调控STAT3影响T24细胞DDP耐药性及NK细胞免疫功能。结论： IL-22通过激活STAT3信号轴促进T24细胞的DDP耐药性，抑制NK细胞功能。

ObjectiveTo explore the effect of cluster scalp acupuncture combined with Taijiquan training on depressive symptom, motor function, activities of daily living, serum markers, as well as brain functional connectivity (FC) and network topological properties in patients with post-stroke depression (PSD). MethodsA total of 40 PSD patients in the Second Affiliated Hospital of Heilongjiang University of Chinese Medicine from September, 2022 to September, 2023 were enrolled and randomly divided into control group (n = 20) and experimental group (n = 20). The control group received cluster scalp acupuncture alone, while the experimental group underwent Taijiquan training in addition, for four weeks. They were assessed with Hamilton Depression Scale-17 (HAMD-17), Fugl-Meyer Assessment (FMA) and Barthel Index (BI) before and after treatment, while the serum levels of dopamine (DA), 5-hydroxytryptamine (5-HT), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected with enzyme-linked immunosorbent assay. Resting-state functional magnetic resonance imaging (rs-fMRI) was applied to assess brain FC, as well as the global efficiency (Eg) and small-world property (σ) of brain networks. ResultsThe scores of HAMD-17, FMA and BI improved in both groups (t > 2.922, P < 0.01) after treatment, and improved more in the experimental group than in the control group (t > 2.517, P < 0.05). The serum levels of DA and 5-HT increased in both groups (t > 2.637, P < 0.05), and increased more in the experimental group (t > 2.192, P < 0.05). The serum levels of IL-6 and TNF-α decreased in the experimental group after treatment (t > 4.059, P < 0.001), and they were less than those in the control group (t > 2.154, P < 0.05). FC between left middle frontal gyrus and right anterior cingulate gyrus, as well as between left hippocampus and right precuneus were higher in the experimental group than in the control group after treatment (t > 3.867, P < 0.001), while Eg and σ increased in both groups (t > 2.828, P < 0.05), and they were higher in the experimental group (t > 2.675, P < 0.05). ConclusionCombination of Taijiquan training is more effective on depressive symptoms, motor function and activities of daily living in PSD patients, which may be related to up-regulation of serum DA and 5-HT, reduction of inflammatory factors, enhancement of prefrontal-limbic system functional connectivity and optimization of brain network topological properties.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective:To explore the deubiquitination modification of the deubiquitinase BRCC3 in rats with neuropathic pain (NPP) treated with meridian tuina of Zhuang medicine and its analgesic molecular mechanism.Methods:Rats were divided into normal group, sham-operation group, model group, sham-tuina group, and meridian tuina of Zhuang medicine group using a random number table method, with 9 rats in each group. Except for the normal and sham operation groups, spinal nerve ligation models were prepared in all other groups. On the first day after surgery, intervention was carried out on the meridian tuina of Zhuang medicine and sham-tuina groups for 14 days, while the other three groups were not intervened; the paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) of each group of rats were measured at 0 days before operation, 1, 7, and 14 days after operation. Western blot was used to detect the expressions of BRCC3 and NLRP3 proteins in spinal cord tissue, and ELISA was used to detect the level of IL-1β in serum.Results:On postoperative 7 and 14 d, compared with the model group, the meridian tuina of Zhuang medicine group showed an increase in PWMT and PWTL, a decrease in NLPR3 and BRCC3 expression in spinal cord tissue, and a decrease in serum IL-1β levels ( P<0.05). Compared with the sham-tuina group, the meridian tuina of Zhuang medicine group showed an increase in PWMT and PWTL, a decrease in NLRP3 protein expression in spinal cord tissue, and a decrease in IL-1β levels in serum ( P<0.05). Conclusion:Meridian tuina of Zhuang medicine can alleviate pain sensitivity in SNL model rats, and its mechanism is related to the inhibition of the expression of deubiquitinase BRCC3 by meridian massage of Zhuang medicine, which increases the ubiquitination level of NLRP3 and hinders its activation, thereby blocking the immune inflammatory response mediated by inflammatory factors.

Objective To initially explore the possibility of applying the fluorescence micro-optical sectioning tomography(fMOST)high-resolution 3D reconstruction system to the morphological study of the intestinal nervous system and to preliminarily establish a method for studying the morphology of the intestinal nervous system using this system.Methods fMOST high-resolution 3D reconstruction system was used to study the intestinal nervous system of C57BL/6 mice in detail.Based on this method,a new morphological method of the visceral nervous system of small animal models was explored at the single-cell level.Results Compared with the large intestine,the small intestine lacked the typical myenteric plexus(Auerbach),deep mucosal plexus(Henley),and submucosal superficial plexus(Meissner).Conclusion The result of this paper provide a clearer and systematic display of the anatomical structure of the enteric nervous system in C57BL/6 mice,and further clarify the similarities and differences between the enteric nervous system of mice and human,and provide a theoretical basis for its rational application in the study of digestive system diseases.The morphological study of fMOST high-resolution 3D reconstruction system is not limited to the central nervous system,but can be extended to the morphological study of multiple visceral nervous systems.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

BACKGROUND: Several randomized controlled studies have suggested that the prophylactic use of proton pump inhibitors (PPIs) in intensive care unit (ICU) patients could not reduce the incidence of gastrointestinal bleeding (GIB) and may increase adverse events such as intestinal infection and pneumonia. Gut microbiota may play a critical role in the process. PPIs have been widely prescribed for GIB prophylaxis in patients with acute coronary syndrome (ACS). This study aimed to determine the short-term effects of PPI and histamine-2 receptor antagonist (H2RA) treatment on gut microbiota of ACS patients. METHODS: The study was designed as a single-blind, multicenter, three-parallel-arm, randomized controlled trial conducted at three centers in Beijing, China. We enrolled ACS patients at low-to-medium risk of GIB and randomized (2:2:1) them to either PPI ( n = 40), H2RA ( n = 31), or control group ( n = 21). The primary outcomes were the alterations in gut microbiota after 7 days of acid suppressant therapy. Stool samples were collected at baseline and 7 days and analyzed by 16S ribosomal RNA (rRNA) gene sequencing. RESULTS: There were no significant changes in the diversity of gut microbiota after the short-term use of acid suppressants, but the abundance of Fusobacterium significantly increased and that of Bifidobacterium significantly decreased, especially in PPI users. In addition, the abundance of some pathogenic bacteria, including Enterococcus and Desulfovibrio, was significantly elevated in the PPI users. The fecal microbiota of the PPI users included more arachidonic acid metabolism than that of control group. CONCLUSIONS: PPIs may increase the risk of infection by adversely altering gut microbiota and elevating arachidonic acid metabolism, which may produce multiple proinflammatory mediators. For ACS patients at low-to-medium risk of GIB, sufficient caution should be paid when acid-suppressant drugs are prescribed, especially PPIs. REGISTRATION www.chictr.org.cn (ChiCTR2000029552).
Humans ; Proton Pump Inhibitors/therapeutic use* ; Acute Coronary Syndrome/microbiology* ; Female ; Gastrointestinal Microbiome/drug effects* ; Male ; Middle Aged ; Histamine H2 Antagonists/therapeutic use* ; Aged ; Single-Blind Method

This article systematically reviews the characteristics and trends of the writing, editing, publication and promotion of physiology textbooks in China from the late 19th century to the present, focusing on the introduction, development and innovation of Chinese physiology textbooks. The development of physiology textbooks in China is divided into four main stages: the introduction and initial development of physiology textbooks from the late 19th century to 1925; the localization and diversification of textbooks from 1926 to 1949, after the establishment of the Chinese Physiological Society; the exploratory phase of textbook construction after the founding of the People's Republic of China from 1949 to 1976; the formation and innovation of the textbook development process from 1977 to the present, following the restoration of the college entrance examination. For each phase, the article not only records the historical development of physiology textbooks, but also analyzes the evolution of their content, writing styles and the interaction with the social and political contexts. The article summarizes the characteristics and experiences of all these four phases. Special attention is given to the comprehensive statistical analysis of physiology textbooks published since the restoration of the college entrance examination and Economic Reform and Opening-up in 1977, revealing the changes in the number, publication trends and academic features of textbooks during this period. Finally, the article presets the future development of physiology textbooks in China, proposing that textbook writing should integrate aspects such as ideological and political education, medical humanities, basic and clinical medicine, health education, scientific research and international exchange and collaboration. The article also advocates for the application of new technologies and methods, such as artificial intelligence, virtual teaching models and knowledge graphs, to support "personalized learning". This research provides a systematic reference for the study of the history of medical education and offers theoretical support for the future innovation of physiology textbook in China.
Humans ; China ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Physiology/education* ; Textbooks as Topic/history*

OBJECTIVE: To evaluate the short-term effectiveness of Ilizarov technique combined with steel needle internal fixation in treating Charcot neuroarthropathy (CN) of the foot and ankle. METHODS: Between June 2020 and December 2023, 12 patients with Eichenholtz stage Ⅲ CN of the foot and ankle were treated with Ilizarov technique and steel needle internal fixation. There were 9 males and 3 females with an average age of 48.6 years (range, 19-66 years). The disease duration ranged from 1 to 16 months (mean, 6.8 months). Ankle joint involvement predominated in 7 cases, while midfoot involvement occurred in 5 cases; 3 cases presented with skin ulceration and soft tissue infection. Preoperative American Orthopedic Foot and Ankle Society (AOFAS) score was 31.2±9.0, 36-Item Short-Form Health Survey (SF-36)-Physical Component Summary (PCS) score was 32.6±6.8, and Mental Component Summary (MCS) score was 47.8±8.4. Postoperative assessments included wound healing, regular X-ray film/CT evaluations of fusion status, and effectiveness via AOFAS and SF-36-PCS, MCS scores. RESULTS: All operations were successfully completed without neurovascular complication. Two patients experienced delayed wound healing requiring intervention, and the others achieved primary healing. All patients were followed up 15-43 months (mean, 23.3 months). Imaging confirmed successful joint fusion within 13-21 weeks (mean, 16.8 weeks). At last follow-up, the AOFAS score was 72.5±6.4, and the SF-36-PCS and MCS scores were 63.2±8.4 and 76.7±5.3, respectively, all of which improved compared to preoperative levels, with significant differences ( P<0.05). CONCLUSION Ilizarov technique combined with steel needle internal fixation effectively restores walking function and achieves satisfactory short-term effectiveness in CN of the foot and ankle.
Humans ; Middle Aged ; Male ; Female ; Adult ; Ilizarov Technique ; Arthropathy, Neurogenic/surgery* ; Aged ; Ankle Joint/surgery* ; Treatment Outcome ; Needles ; Fracture Fixation, Internal/instrumentation* ; Steel ; Young Adult ; Foot Joints/surgery*