[摘 要] 目的：探讨lncRNA DLEU2通过EZH2/H3K27me3途径调控IKKα介导甲状腺癌（TC）放射性碘抵抗的作用机制。方法：利用TCGA数据库分析TC中DLEU2的表达及其与EZH2的相关性。构建放射性碘抵抗的TPC-1细胞（RR-TPC-1细胞）模型及裸鼠移植瘤模型，通过敲低或过表达DLEU2（si-DLEU2/OE-DLEU2）、抑制EZH2（UNC1999）、过表达IKKα（OE-IKKα）进行干预，采用qPCR、WB、RIP、ChIP、CCK-8、流式细胞术、TUNEL染色及体内成瘤实验检测基因与蛋白表达、表观修饰、细胞增殖、凋亡及肿瘤生长。结果：TCGA分析显示，DLEU2在TC组织中显著上调（P < 0.001），与患者不良预后相关（P = 0.008 4），且与EZH2表达呈正相关（r = 0.390, P < 0.001）；RIP证实EZH2与DLEU2存在相互作用/结合（P < 0.05）。体外实验表明，敲低DLEU2可显著下调RR-TPC-1细胞中EZH2、IKKα表达及H3K27me3修饰水平，抑制NF-κB通路活化（P < 0.05或P < 0.01），抑制细胞增殖、促进凋亡（均P < 0.05）。联合敲低DLEU2与抑制EZH2进一步增强上述效应，而过表达IKKα则可部分逆转上述效应（P < 0.05或P < 0.01）。体内实验进一步证实，敲低DLEU2联合抑制EZH2可显著抑制移植瘤生长，增加肿瘤细胞凋亡（均P < 0.01）；IKKα过表达则部分逆转上述抗肿瘤效应（P < 0.05或P < 0.01）。结论：lncRNA DLEU2通过招募EZH2催化H3K27me3修饰，间接激活IKKα/NF-κB信号并形成正反馈环路，介导TPC-1细胞131I抵抗。

OBJECTIVE: To observe the effects of the "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture on key regulatory factors during mitochondrial apoptosis of testicular tissue in asthenozoospermia mice, and explore the potential mechanism of the protective effect of acupuncture on reproductive function. METHODS: Thirty C57BL/6 male mice were randomly divided into a blank group, a model group and an acupuncture group, 10 mice in each group. In the model and the acupuncture groups, the intraperitoneal injection of cyclophosphamide (30 mg•kg^-1•d^-1) was delivered for 7 days to prepare the asthenozoospermia model. After the success of modeling, the modeled mice in the acupuncture group were intervened with "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture, once daily and the needles were retained for 20 min. The duration of the intervention was 2 weeks. The general condition of each mouse was observed, and the body mass was recorded before modeling, after modeling and after intervention completion. After intervention, the testicular mass was recorded and the weight coefficient was calculated, and the mouse sperm quality was examined; the serum contents of testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were detected using ELISA, the morphology of testicular tissue was observed using HE, the mitochondrial ultra-microstructure of testicular tissue was observed under transmission electrone microscopy, the mitochondrial membrane potential level of testicular tissue was detected using JC-1 staining, the positive rate of apoptosis cell of testicular tissue was observed using TUNEL; and the mRNA and protein expression of b-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cytochrome c (Cyt C), apoptotic protease-activating factor1 (Apaf-1), Caspase-9 and Caspase-3 of testicular tissue was detected using real-time quantitative fluorescence PCR and Western blot methods separately; and the positive expression of Cleaved Caspase-3 of the testicular tissue was detected using immunohistochemistry. RESULTS: Compared with the blank group, the mice were in listless spirits, had shaggy hairs, the reduced appetite and movement, and weight loss in the model group (P<0.01); the testicular mass and the weight coefficient decreased (P<0.01); the total number of sperms, sperm motility, and sperm viability were declined (P<0.01); while the levels of serum T, FSH, and LH were dropped (P<0.01). The morphology of seminiferous tubules in testicular tissue was abnormal, the number of spermatogenic cells and the number of mitochondria decreased, the inner mitochondrial crest was fractured and lost, and vacuoles appeared. The level of mitochondrial membrane potential was reduced (P<0.01); and the positive rate of apoptosis cell in testicular tissue increased (P<0.01). The mRNA and protein expression of Bax, Cyt C, Apaf-1, Caspase-9 and Caspase-3 was elevated (P<0.01, P<0.05), the mRNA and protein expression of Bcl-2 was dropped (P<0.01), and the average absorbance value of Cleaved Caspase-3 increased (P<0.01). When compared with the model group, in the acupuncture group, the general condition of mice was improved, the testicular mass and the weight coefficient elevated (P<0.01); the total number of sperms, sperm motility, and sperm viability increased (P<0.01); while the levels of serum T, FSH, and LH rose (P<0.01). The pathological morphology of testicular tissue and the inner mitochondrial ultra-microstructure were ameliorated, the level of mitochondrial membrane potential was elevated (P<0.01); the positive rate of apoptosis cell was reduced (P<0.01). The mRNA and protein expression of Bax, Cyt C, Apaf-1, Caspase-9 and Caspase-3 was dropped (P<0.01, P<0.05), the mRNA and protein expression of Bcl-2 elevated (P<0.05), and the average absorbance value of Cleaved Caspase-3 declined (P<0.01). CONCLUSION "Zhibian" (BL54)-toward- "Shuidao" (ST28) acupuncture may ameliorate mouse reproductive function by inhibiting mitochondrial apoptosis pathway, alleviating testicular tissue damage in the asthenospermia mice induced by cyclophosphamide.
Animals ; Male ; Mice ; Apoptosis ; Acupuncture Therapy ; Mitochondria/metabolism* ; Asthenozoospermia/genetics* ; Humans ; Testis/metabolism* ; Mice, Inbred C57BL ; Spermatozoa/metabolism* ; Acupuncture Points ; Sperm Motility ; Testosterone/blood* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Caspase 3/genetics* ; Follicle Stimulating Hormone/blood* ; Reproduction ; Cytochromes c/genetics* ; bcl-2-Associated X Protein/genetics* ; Apoptotic Protease-Activating Factor 1/genetics*

Objective To propose a classification model based on a pseudo-bag strategy and feature adjustment for whole slide imaging in pathology.Methods A pseudo-bag generator was constructed to divide a parent bag into 3 pseudo-bags for increasing the number of training bags.Then,a pseudo-bag learning method based on Nystr?m-based algorithm for approximating self-attention and a selective feature fusion method were employed to process the pseudo-bags.Specifically,the pseudo-bag learning method based on Nystr?m-based algorithm for approximating self-attention reduced computational complexity through an improved multi-head self-attention mechanism while deeply extracting instance features to obtain pseudo-bag classification predictions,thereby enhancing pseudo-bag classification accuracy;and the selective feature fusion method refined pseudo-bag features by filtering and extracting relevant instances.Finally,the model adjusted bag features by extracting confounding factors to avoid interference from irrelevant information and further improve classification accuracy.Results The proposed model was evaluated on two datasets(CAMELYON-16 and TCGA-NSCLC)and compared with 10 other methods,and the results demonstrated that the proposed model achieved the best performance.The proposed method reached an accuracy of 0.943 on the CAMELYON-16 dataset and 0.906 on the TCGA-NSCLC dataset.Conclusion The proposed model can significantly improve the accuracy of whole-slide pathological image classification by effectively mitigating the overfitting and avoiding interference from irrelevant information.

Objective To analyze the epidemiology and trends of measles,tuberculosis,pertussis,scarlet fever,influenza,mumps and rubella in Beijing between 2014 and 2023 in order to provide data for prevention and control of related diseases.Methods Data on the incidences of seven respiratory infectious diseases in Beijing between 2014 and 2023 was collected.Descriptive epidemiological methods were employed to analyze their demographic,temporal and spatial distribution.Joinpoint regression analysis was used to assess temporal trends in incidence.Results A total of 1 406 777 cases of seven respiratory infectious diseases were reported in Beijing between 2014 and 2023,which corresponded to an average crude rate of 649.76/100 000 reported annually.The crude rate of incidencewas higher among females than among males,with the most vulnerable age groups being 0-4 years and 5-19 years,and was higher in the six districts than on the outskirts.Most of the respiratory infectious diseases peaked in winter and spring.The annual increase in the incidence of respiratory infectious diseases in Beijing in this period averaged 27.27％,with no statistically significant differences in trends.The incidence rates of measles,tuberculosis,scarlet fever,mumps and rubella decreased significantly while those of pertussis and influenza increased,but with no statistically significant difference.Conclusion The overall incidence of major respiratory infectious diseases in Beijing is increasing.It is recommended that more people get vaccinated,surveillance of such diseases as pertussis and influenza be enhanced,and regional health resources be allocated more effectively,all of which will be critical to subsequent prevention and control of respiratory infectious diseases in Beijing.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Arginine methylation is a critical post-translational modification that plays multifaceted biological functions. However, the manipulation of protein arginine methylation largely depends on genetic or pharmaceutic inhibition of the regulatory enzymes, protein arginine methyltransferases (PRMTs), or non-methylation substitution of corresponding arginine residue to lysine or alanine of protein of interest (POI), which inevitably affects other substrates, or disrupts the structure of POI. Thus, it urges an approach to specifically modulate the arginine methylation of a POI under physiological conditions. To this end, we report the discovery of a methylation tagging system (MeTAG), that enables targeted modification of protein arginine methylation. Through bridging the methyltransferase PRMT5 proximity to a POI, MeTAG facilitates the arginine methylation of POIs, including known arginine methylated proteins, androgen receptor (AR) and protein kinase B (AKT), as well as a neo-substrate E1A binding protein (p300), in a reversible and PRMT5-dependent manner. Moreover, MeTAG can regulate downstream signaling in a methylation dependent manner, leading to downregulation of PSMA mRNA level and activation of AKT. Therefore, MeTAG represents a feasible approach to modulate protein methylation and thereby perturbs protein function in biological and therapeutic contexts.

Objective:This study aimed to explore neurobiomarkers for schizophrenia relapse by comparing brain functional activity between first-diagnosed drug-na?ve schizophrenia (FDS) patients and relapsed schizophrenia (RS) patients.Methods:In this cross-sectional study, a total of 85 RS patients, 75 FDS patients, and 82 controls were recruited from the outpatient and inpatient departments of the Affiliated Brain Hospital of Nanjing Medical University between September 2018 and June 2020. All participants underwent magnetic resonance imaging scans. The fractional amplitude of low-frequency fluctuation (fALFF) was calculated to assess individual′s brain activity. The severity of psychiatric symptoms among patients with schizophrenia was evaluated using the Positive and Negative Syndrome Scale (PANSS). Voxel-based analysis of covariance (ANCOVA) with post-hoc two-sample t-tests was used to compare fALFF values among groups, and partial correlation analysis was employed to examine relationships between aberrant fALFF values and psychiatric symptoms. Results:The RS group demonstrated significantly higher negative symptom scores (21.5±9.1) compared to the FDS group (18.4±8.3; t=-2.28, P<0.05). Relative to the control group, the FDS group showed increased fALFF values in the cerebellum vermis 4/5 and the right putamen( t=4.45, 4.55, GRF-corrected, voxel-level P<0.001, cluster-level P<0.05), while fALFF values were decreased in the right precentral gyrus/postcentral gyrus, bilateral precuneus, and right paracentral lobule ( t=-4.77--4.20, GRF-corrected, voxel-level P<0.001, cluster-level P<0.05). The RS group exhibited increased fALFF values in the left cerebellum 9/10, bilateral cerebellum 6/8/Crus Ⅰ, right inferior temporal gyrus, right middle temporal gyrus, right inferior frontal gyrus (orbital part), and right putamen( t=4.78-5.44, GRF-corrected, voxel-level P<0.001, cluster-level P<0.05), while decreased fALFF values were observed in the bilateral calcarine/cuneus, left superior medial frontal gyrus, right precuneus/cuneus, bilateral precuneus, and right precentral gyrus/postcentral gyrus ( t=-4.97--4.38, GRF-corrected, voxel-level P<0.001, cluster-level P<0.05). Compared with the FDS group, the RS group showed increased fALFF values in the right cerebellum Crus Ⅰ (GRF-corrected, t=3.83, voxel-level P<0.001, cluster-level P<0.05). In the FDS group, correlation analysis revealed that fALFF values in the bilateral precuneus were negatively correlated with negative symptom scores, general psychopathology scores, and the PANSS total score ( r=-0.32, -0.26, -0.26,all P<0.05), while no such correlation was found in the RS group. Conclusions:RS patients exhibit more severe negative symptoms and more diffuse brain functional abnormalities compared to FDS patients, particularly affecting the default mode network and cerebellar regions. Functional alterations in the right cerebellum Crus Ⅰ and bilateral precuneus may serve as potential neuroimaging markers for identifying relapse in schizophrenia.

Objective To propose a classification model based on a pseudo-bag strategy and feature adjustment for whole slide imaging in pathology.Methods A pseudo-bag generator was constructed to divide a parent bag into 3 pseudo-bags for increasing the number of training bags.Then,a pseudo-bag learning method based on Nystr?m-based algorithm for approximating self-attention and a selective feature fusion method were employed to process the pseudo-bags.Specifically,the pseudo-bag learning method based on Nystr?m-based algorithm for approximating self-attention reduced computational complexity through an improved multi-head self-attention mechanism while deeply extracting instance features to obtain pseudo-bag classification predictions,thereby enhancing pseudo-bag classification accuracy;and the selective feature fusion method refined pseudo-bag features by filtering and extracting relevant instances.Finally,the model adjusted bag features by extracting confounding factors to avoid interference from irrelevant information and further improve classification accuracy.Results The proposed model was evaluated on two datasets(CAMELYON-16 and TCGA-NSCLC)and compared with 10 other methods,and the results demonstrated that the proposed model achieved the best performance.The proposed method reached an accuracy of 0.943 on the CAMELYON-16 dataset and 0.906 on the TCGA-NSCLC dataset.Conclusion The proposed model can significantly improve the accuracy of whole-slide pathological image classification by effectively mitigating the overfitting and avoiding interference from irrelevant information.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Objective:This study aimed to explore neurobiomarkers for schizophrenia relapse by comparing brain functional activity between first-diagnosed drug-na?ve schizophrenia (FDS) patients and relapsed schizophrenia (RS) patients.Methods:In this cross-sectional study, a total of 85 RS patients, 75 FDS patients, and 82 controls were recruited from the outpatient and inpatient departments of the Affiliated Brain Hospital of Nanjing Medical University between September 2018 and June 2020. All participants underwent magnetic resonance imaging scans. The fractional amplitude of low-frequency fluctuation (fALFF) was calculated to assess individual′s brain activity. The severity of psychiatric symptoms among patients with schizophrenia was evaluated using the Positive and Negative Syndrome Scale (PANSS). Voxel-based analysis of covariance (ANCOVA) with post-hoc two-sample t-tests was used to compare fALFF values among groups, and partial correlation analysis was employed to examine relationships between aberrant fALFF values and psychiatric symptoms. Results:The RS group demonstrated significantly higher negative symptom scores (21.5±9.1) compared to the FDS group (18.4±8.3; t=-2.28, P<0.05). Relative to the control group, the FDS group showed increased fALFF values in the cerebellum vermis 4/5 and the right putamen( t=4.45, 4.55, GRF-corrected, voxel-level P<0.001, cluster-level P<0.05), while fALFF values were decreased in the right precentral gyrus/postcentral gyrus, bilateral precuneus, and right paracentral lobule ( t=-4.77--4.20, GRF-corrected, voxel-level P<0.001, cluster-level P<0.05). The RS group exhibited increased fALFF values in the left cerebellum 9/10, bilateral cerebellum 6/8/Crus Ⅰ, right inferior temporal gyrus, right middle temporal gyrus, right inferior frontal gyrus (orbital part), and right putamen( t=4.78-5.44, GRF-corrected, voxel-level P<0.001, cluster-level P<0.05), while decreased fALFF values were observed in the bilateral calcarine/cuneus, left superior medial frontal gyrus, right precuneus/cuneus, bilateral precuneus, and right precentral gyrus/postcentral gyrus ( t=-4.97--4.38, GRF-corrected, voxel-level P<0.001, cluster-level P<0.05). Compared with the FDS group, the RS group showed increased fALFF values in the right cerebellum Crus Ⅰ (GRF-corrected, t=3.83, voxel-level P<0.001, cluster-level P<0.05). In the FDS group, correlation analysis revealed that fALFF values in the bilateral precuneus were negatively correlated with negative symptom scores, general psychopathology scores, and the PANSS total score ( r=-0.32, -0.26, -0.26,all P<0.05), while no such correlation was found in the RS group. Conclusions:RS patients exhibit more severe negative symptoms and more diffuse brain functional abnormalities compared to FDS patients, particularly affecting the default mode network and cerebellar regions. Functional alterations in the right cerebellum Crus Ⅰ and bilateral precuneus may serve as potential neuroimaging markers for identifying relapse in schizophrenia.