The latest evidence indicates that the red nucleus (RN) contributes not only to motor control, but also to sensory processing and emotion regulation. Here, we demonstrate that the RN participates in the maintenance of neuropathic pain via CCL3-CCR5 axis. Following spared nerve injury (SNI) in male rats, a prominent upregulation of CCL3 and its receptor CCR5, instead of CCR1, was observed in RN neurons, astrocytes, and microglia during the late maintenance phase of neuropathic pain. Knockdown of red nucleus CCL3 alleviated SNI-induced allodynia, while intrarubral administration of exogenous CCL3 in naive rats induced allodynia. Pharmacological inhibition of CCR5, rather than CCR1, effectively alleviated SNI- or CCL3-induced allodynia. Further studies revealed that red nucleus CCL3-CCR5 axis contributed to the maintenance of neuropathic pain by stimulating the secretion of chemokines CCL4 and CXCL10, and complement C3. Blockade of these inflammatory mediators alleviated CCL3-mediated neuropathic pain. Moreover, our data indicated that red nucleus NF-κB, JAK2/STAT3, and ERK pathways were involved in CCL3-induced release of these inflammatory mediators. Specifically, CCL3 could induce CCL4 expression by activating NF-κB in neurons and/or microglia, and JAK2/STAT3 and ERK in neurons, astrocytes, and/or microglia. CCL3 could induce CXCL10 expression by activating JAK2/STAT3 and ERK in neurons, astrocytes, and/or microglia. CCL3 could induce C3 expression by activating NF-κB in microglia, and ERK in astrocytes and/or microglia. Inhibition of red nucleus NF-κB, JAK2/STAT3, or ERK suppressed the upregulations of CCL4, CXCL10, and/or C3, and alleviated CCL3-mediated neuropathic pain. Collectively, these findings provide potential mechanisms by which the RN contributes to the maintenance of neuropathic pain in male rats via CCL3-CCR5 axis, and provide promising therapeutic targets for intractable neuropathic pain.

Our recent studies have identified that the red nucleus (RN), a prominent motor regulatory nucleus situated in the midbrain tegmentum, is involved in the development of neuropathic pain. However, the molecular mechanisms by which the RN mediates pain regulation are still far from clear. Here, we report that the RN modulates neuropathic pain through secreting IL-15, a member of the immunomodulatory cytokine family. Following spared nerve injury (SNI) of male rats, IL-15 and its receptor IL-15Rα were boosted in the RN, especially within neurons and microglia, during the development stage of neuropathic pain. Knockdown of red nucleus IL-15 alleviated SNI-induced neuropathic pain, whereas intrarubral administration of exogenous IL-15 evoked abnormal pain in naive rats. Further studies indicated that red nucleus IL-15 exerted algesic effect by inducing the production of inflammatory factors, including cytokines TNF-α and IL-1β, chemokine CXCL11, and complement component C4a. Blockade of these inflammatory factors alleviated IL-15-mediated neuropathic pain. Additionally, our data demonstrated that NF-κB and p38 MAPK signaling pathways were involved in red nucleus IL-15-mediated neuropathic pain, in which p38 MAPK pathway contributed to IL-15-induced release of TNF-α and IL-1β, while both NF-κB and p38 MAPK pathways contributed to IL-15-induced secretion of CXCL11 and C4a. Inhibition of red nucleus NF-κB or p38 MAPK suppressed the upregulation of TNF-α, IL-1β, CXCL11 and/or C4a, and alleviated red nucleus IL-15-mediated neuropathic pain. These findings provide mechanistic insights by which red nucleus IL-15 facilitates the development of neuropathic pain and highlight its potential as a therapeutic target for refractory neuropathic pain.

Metabotropic glutamate receptors (mGluR) participate in pain modulation and mediate different effects in nociceptive stimuli, relying on the receptor subtype activated and its anatomical location. Here, we addressed the functions of mGluR Ⅲ group (mGluR4, mGluR6, mGluR7, and mGluR8) in the red nucleus (RN) in nociception and the development of neuropathic pain induced by spared nerve injury (SNI) using male rats. Our results showed that mGluR4, mGluR7, and mGluR8, except for mGluR6, were constitutively expressed in the RN of normal rats. At 2 weeks post-SNI, the expressions of mGluR4 and mGluR8 rather than mGluR7 were reduced in the RN contralateral to the nerve lesion. Unilateral administration of mGluR Ⅲ antagonist MSOP to the RN of normal rats decreased the PWT of contralateral hindpaw and evoked pronounced mechanical allodynia, which was blocked by mGluR4 agonist VU0155041 or mGluR8 agonist AZ12216052 instead of mGluR7 agonist AMN082. Moreover, administration of VU0155041 or AZ12216052 to the RN contralateral to the nerve injury at 2 weeks post-SNI alleviated SNI-induced neuropathic pain. Further studies indicated that administration of MSOP to the RN of normal rats increased the expressions of nociceptive factors TNF-α and IL-1β, which were blocked by VU0155041 or AZ12216052 instead of AMN082. Additionally, administration of VU0155041 or AZ12216052 to the RN at 2 weeks post-SNI inhibited the overexpressions of TNF-α and IL-1β induced by SNI. These findings suggest that red nucleus mGluR4 and mGluR8 instead of mGluR7 inhibit nociception and the development of neuropathic pain by restraining the expressions of TNF-α and IL-1β.

Postoperative hyperglycemia is common in gastric cancer (GC) patients, especially during enteral and parenteral nutrition. While the importance of postoperative glycemic control in diabetic patients is well-recognized, the management of blood glucose (BG) in non-diabetic patients after surgery has received less attention. This study aimed to investigate the impact of postoperative BG levels on overall survival (OS) in non-diabetic GC patients. Additionally, we explored whether postoperative BG mediates the relationship between body composition parameters and postoperative survival, and to what extent this mediation occurs. A total of 349 patients who underwent curative surgery for GC in the Department of Oncology at The First Hospital of Lanzhou University from March 2017 to June 2021 were included in the study. Patients were stratified into groups based on postoperative BG levels, and differences in OS were analyzed. Univariate and multivariate Cox regression analyses were performed to identify independent factors influencing OS. Multivariate linear regression and correlation analyses were conducted to explore factors affecting postoperative blood glucose and its association with preoperative body composition parameters. A mediation analysis was conducted to assess the role of postoperative BG in mediating the effect of body composition on long-term survival, with the significance of the mediation effect tested using the bootstrap method. Age over 65, neoadjuvant chemotherapy, visceral adipose tissue index (VATI), surgical approach, pTNM stage, and postoperative hyperglycemia (HG) were identified as independent predictors of OS. Preoperative VATI, subcutaneous adipose tissue index, skeletal muscle density, random venous plasma glucose, hemoglobin, and total protein were significant factors influencing postoperative BG, and were significantly correlated with postoperative BG levels. Postoperative BG exhibited a significant negative mediating effect (-12.9

ObjectiveTo explore whether uric acid (UR), neutrophil/lymphocyte ratio (NLR) and uric acid/albumin ratio (UAR) can predict bone metastasis in colorectal cancer (CRC).MethodsA single-center retrospective study was conducted studying patients diagnosed with colorectal cancer attending The First Affiliated Hospital of Xian JiaoTong University between January 2016 and December 2021. Patients were categorized into groups with and without bone metastasis. Receiver operating characteristic (ROC) curve analysis assessed the diagnostic accuracy of CRC bone metastases, with subsequent combined ROC curve analysis. Differences among the AUCs were calculated and compared by Delong test. Logistic regression analysis was utilized to assess the impact of these parameters on CRC bone metastasis.ResultsA total of 156 patients (32%) exhibited bone metastases from CRC. In these patients, levels of uric acid (UA), uric acid ratio (UAR), neutrophil-to-lymphocyte ratio (NLR), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) were significantly elevated. The diagnostic performance of UA, UAR and NLR is surpassed that of traditional colorectal cancer markers. The area under the curve (AUC) for the combination UA, UAR and NLR with colorectal cancer tumor markers was significantly more effective in predicting bone metastasis (P < 0.001) compared to the AUC without this combination. Multiple logistic regression analysis identified UA, NLR and CEA as independent risk factors for bone metastasis in colorectal cancer.ConclusionsUA, UAR and NLR serve as valuable makers for predicting bone metastases in patients with colorectal cancer. The integration of UA, UAR, NLR, CEA, CA199 and CA724 may enhance the prediction of bone metastases in colorectal cancer.

To observe the current situation of fertility preservation among female breast cancer patients ≤ 40 years old and analyze the related factors which influence the utilization of fertility preservation. A single-center retrospective questionnaire was conducted investigating patients diagnosed with breast cancer attending The First Affiliated Hospital of Xian JiaoTong University between January 2016 and December 2019. The questionnaire was redesigned based on previous similar research and the questions needed in this study. Rates of utilization of preservation services were compared based on patients’ demographic and economic-social information, disease characteristic information and fertility related information. Univariate and multivariate logistic regression analysis was used to assess the relationship between utilization of fertility preservation and sociodemographic factors, previous reproductive-related problems. 313 patients were successfully interviewed. 60/313patients (19.2%) had utilized fertility preservation. Younger patients (< 30 years of age), patients with 1 or no child, and patients had higher education level were more likely to pursue fertility preservation than their matched counterparts. Age, parity, and education level of breast cancer patients may impact rates of fertility preservation among reproductive age women diagnosed with breast cancer. Thus, further attention to age difference and patient’s desire for future fertility could help to improve gaps in fertility preservation. These findings have guidance for counseling young breast cancer patients.

Our previous study has verified that activation of group Ⅰ metabotropic glutamate receptors (mGluRⅠ) in the red nucleus (RN) facilitate the development of neuropathological pain. Here, we further discussed the functions and possible molecular mechanisms of red nucleus mGluR Ⅱ (mGluR2 and mGluR3) in the development of neuropathological pain induced by spared nerve injury (SNI). Our results showed that mGluR2 and mGluR3 both were constitutively expressed in the RN of normal rats. At 2 weeks post-SNI, the protein expression of mGluR2 rather than mGluR3 was significantly reduced in the RN contralateral to the nerve lesion. Injection of mGluR2/3 agonist LY379268 into the RN contralateral to the nerve injury at 2 weeks post-SNI significantly attenuated SNI-induced neuropathological pain, this effect was reversed by mGluR2/3 antagonist EGLU instead of selective mGluR3 antagonist β-NAAG. Intrarubral injection of LY379268 did not alter the PWT of contralateral hindpaw in normal rats, while intrarubral injection of EGLU rather than β-NAAG provoked a significant mechanical allodynia. Further studies indicated that the expressions of nociceptive factors TNF-α and IL-1β in the RN were enhanced at 2 weeks post-SNI. Intrarubral injection of LY379268 at 2 weeks post-SNI significantly suppressed the overexpressions of TNF-α and IL-1β, these effects were reversed by EGLU instead of β-NAAG. Intrarubral injection of LY379268 did not influence the protein expressions of TNF-α and IL-1β in normal rats, while intrarubral injection of EGLU rather than β-NAAG significantly boosted the expressions of TNF-α and IL-1β. These findings suggest that red nucleus mGluR2 but not mGluR3 mediates inhibitory effect in the development of SNI-induced neuropathological pain by suppressing the expressions of TNF-α and IL-1β. mGluR Ⅱ may be potential targets for drug development and clinical treatment of neuropathological pain.

Purpose Research on bone metastasis in esophageal cancer (EC) is relatively limited. Once bone metastasis occurs in patients, their prognosis is poor, and it severely affects their quality of life. Currently, there is a lack of convenient tumor markers for early identification of bone metastasis in EC. Our research aims to explore whether neutrophil-lymphocyte ratio (NLR) can predict bone metastasis in patients with EC. Methods Retrospective analysis of clinical indicators was performed on 604 patients with EC. They were divided into groups based on whether or not there was bone metastasis, and the patients’ coagulation-related tests, blood routine, tumor markers and other indicators were collected. The receiver operating characteristic curve (ROC) were used to determine the predictive ability of parameters such as NLR for bone metastasis in EC, and univariate and multivariate logistic regression analyses were conducted to determine the impact of each indicator on bone metastasis. Using binary logistic regression to obtain the predictive probability of NLR combined with tumor markers. Results ROC curves analysis suggested that the area under the curve (AUC) of the NLR was 0.681, with a sensitivity of 79.2% and a specificity of 52.6%, which can be used as a predictive factor for bone metastasis in EC. Multivariate logistic regression analysis showed that high NLR (odds ratio [OR]: 2.608, 95% confidence interval [CI]: 1.395-4.874, P = 0.003) can function as an independent risk factor for bone metastasis in patients with EC. Additionally, high PT, high APTT, high FDP, high CEA, high CA724, low hemoglobin, and low platelet levels can also predict bone metastasis in EC. When NLR was combined with tumor markers, the area under the curve was 0.760 (95% CI: 0.713-0.807, P < 0.001), significantly enhancing the predictability of bone metastasis in EC. Conclusion NLR, as a convenient, non-invasive, and cost-effective inflammatory indicator, could predict bone metastasis in EC. Combining NLR with tumor markers can significantly improve the diagnostic accuracy of bone metastasis in EC.

Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors (mGluR). Here, we further explored the actions and possible molecular mechanisms of red nucleus mGluR Ⅰ (mGluR1 and mGluR5) in the development of neuropathic pain induced by spared nerve injury (SNI). Our data indicated that both mGluR1 and mGluR5 were constitutively expressed in the RN of normal rats. Two weeks after SNI, the expressions of mGluR1 and mGluR5 were significantly boosted in the RN contralateral to the nerve injury. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN contralateral to the nerve injury at 2 weeks post-SNI significantly ameliorated SNI-induced neuropathic pain. However, unilateral administration of mGluRⅠ agonist DHPG to the RN of normal rats provoked a significant mechanical allodynia, this effect could be blocked by LY367385 or MTEP. Further studies indicated that the expressions of TNF-α and IL-1β in the RN were also elevated at 2 weeks post-SNI. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN at 2 weeks post-SNI significantly inhibited the elevations of TNF-α and IL-1β. However, administration of mGluR Ⅰ agonist DHPG to the RN of normal rats significantly enhanced the expressions of TNF-α and IL-1β, these effects were blocked by LY367385 or MTEP. These results suggest that activation of red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain by stimulating the expressions of TNF-α and IL-1β. mGluR Ⅰ maybe potential targets for drug development and clinical treatment of neuropathic pain.

Breast invasive carcinoma (BRCA) is the most commonly diagnosed cancer in women and exhibits the highest mortality rate among female cancers. Furthermore, the tumor microenvironment (TME) plays a crucial role in the progression of BRCA. Copper ions are essential metal elements in vivo, and cuproptosis, a recently identified mode of cell death, significantly influences tumor progression, metastasis, and angiogenesis. Utilizing 10 cuproptosis-related genes (CRGs), we developed a novel cuproptosis-tumor immunological phenotype-related gene score (CTIPRGs) comprising 14 genes through Univariate Cox (UniCOX) regression and the least absolute shrinkage and selection operator (LASSO) algorithm to predict prognosis and response to immunotherapy in BRCA. Univariate and multivariate analyses indicated that CTIPRGs serve as an independent prognostic predictor. Subsequently, we constructed nomograms to provide quantitative tools for clinical practice. Kaplan-Meier (KM) plot analysis demonstrated that CTIPRGs could significantly distinguish overall survival (OS) in BRCA patients, with low-CTIPRGs groups exhibiting better prognosis. High and low-CTIPRGs groups exhibited distinct biological behaviors, mutational characteristics, and immune cell infiltration patterns. Notably, low-CTIPRGs groups were classified as an immune-inflamed phenotype with abundant immune cells, whereas high-CTIPRGs groups were identified as immune-desert phenotypes characterized by extensive stromal cell infiltration. Additionally, notable differences in tumor immunogenicity, tumor immune dysfunction and exclusion (TIDE), and tumor mutation burden (TMB) were observed between high and low-CTIPRGs groups, indicating that low-CTIPRGs groups exhibited higher sensitivity to immunotherapy. In conclusion, the identified CTIPRGs can facilitate the prediction of prognosis and treatment efficacy in BRCA patients.

疫情防控是一场"大思政课".疫情期间,我们在《医学免疫学》课程的授课过程中,将疫情涉及的免疫学相关问题与课程中的专业知识相结合,并引导学生从免疫学的角度分析疫情中的社会热点问题,厘清我国各项防疫措施蕴含的科学逻辑,建立对防疫政策、疫苗等问题的科学认知,深刻理解我国文化和制度的优越性.我们的思政实践表明,专业课思政应充分发挥课程本身蕴涵的科学性和逻辑性的优势,紧密结合现实生活,才能达到润物细无声的思政效果.

目的 观察 RH 株弓形虫定位感染小鼠海马引起的组织病变,以构建急性弓形虫脑炎小鼠模型.方法 利用颅内定位注射技术,将定量(100、500、1 000 个)RH 株弓形虫滋养体,定位注射入小鼠海马 CA1 区,观察小鼠的生存状况;Giemsa染色方法观察小鼠腹水和脑组织匀浆中弓形虫数量的变化;尼氏染色和 HE 染色观察小鼠海马神经组织的病理改变;用免疫组化 ABC法观察弓形虫在脑组织的分布.结果 RH 株弓形虫感染各组小鼠在感染第4 天表现出明显的弓背、竖毛、腹胀、头颅细微震颤、偏瘫等症状.定量 100 感染组小鼠生存时间较长,腹水中未发现弓形虫滋养体,脑组织匀浆在 96h后发现少量的假包囊,小鼠死亡后则有较多滋养体;尼氏染色和 HE染色则在 144 h发现较多的组织坏死灶,CA1 区神经细胞缺失;随感染时间的延长而脑组织损伤加重.而定量 500 感染组和定量1 000 感染组小鼠腹水和脑匀浆中均发现弓形虫滋养体;尼氏染色发现海马区神经元丢失和大量坏死;HE染色发现组织坏死灶及炎性细胞浸润,脑组织损伤均较定量 100 感染组小鼠显著加重;免疫组化证实坏死灶中有弓形虫的分布.结论 定位感染 RH 株弓形虫 100 个滋养体小鼠存活时间较长,脑组织病理变化逐渐加重,损伤局限于脑组织内,小鼠表现典型的弓形虫脑炎症状.因此定位感染 100 个弓形虫滋养体可以构建急性弓形虫脑炎小鼠模型,可为弓形虫对脑神经的损伤机制研究奠定基础.

医学寄生虫学是一门形态学课程,所积累的大量图片和影视资料在辅助教学方面有非常重要的作用.建设医学寄生虫学数字资源库可以有效解决寄生虫病标本匮乏、种类不全、使用效率低下等问题.文章介绍西安交通大学医学部建设寄生虫标本数字资源库、视频资源库、寄生虫病例资源库、寄生虫思政资源库等情况,并将这些资源库应用于寄生虫学教学、实验、教材编写、网络平台构建等教学活动中,充分发挥其优势,提高教学水平.建设寄生虫学数字资源库共享平台是解决寄生虫学标本资源缺乏的最佳途径,也是教学改革的主要方向.

Our previous studies have clarified that red nucleus (RN) interleukin (IL)-6 is involved in the maintenance of neuropathic pain and produces a facilitatory effect by activating JAK2/STAT3 and ERK pathways. In this study, we further explored the immune molecular mechanisms of rubral IL-6-mediated descending facilitation at the spinal cord level. IL-6-evoked tactile allodynia was established by injecting recombinant IL-6 into the unilateral RN of naive male rats. Following intrarubral administration of IL-6, obvious tactile allodynia was evoked in the contralateral hindpaw of rats. Meanwhile, the expressions of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), IL-1β, and IL-6 were elevated in the contralateral spinal dorsal horn (L4–L6), blocking spinal TNF-α, IL-1β, or IL-6 with neutralizing antibodies relieved IL-6-evoked tactile allodynia. Conversely, the levels of anti-inflammatory cytokines transforming growth factor-β (TGF-β) and IL-10 were reduced in the contralateral spinal dorsal horn (L4–L6), an intrathecal supplement of exogenous TGF-β, or IL-10 attenuated IL-6-evoked tactile allodynia. Further studies demonstrated that intrarubral pretreatment with JAK2/STAT3 inhibitor AG490 suppressed the elevations of spinal TNF-α, IL-1β, and IL-6 and promoted the expressions of TGF-β and IL-10 in IL-6-evoked tactile allodynia rats. However, intrarubral pretreatment with ERK inhibitor PD98059 only restrained the increase in spinal TNF-α and enhanced the expression of spinal IL-10. These findings imply that rubral IL-6 plays descending facilitation and produces algesic effect through upregulating the expressions of spinal pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 and downregulating the expressions of spinal anti-inflammatory cytokines TGF-β and IL-10 by activating JAK2/STAT3 and/or ERK pathways, which provides potential therapeutic targets for the treatment of pathological pain.

Objective: Shaanxi is the most highly populated province with high burdens of tuberculosis in northwestern China. The aim of this study was to investigate the molecular characteristics and drug resistance of Mycobacterium tuberculosis isolates from Shaanxi province of China in 2018. Methods: Phenotypic drug susceptibility testing and spoligotyping methods were performed on 518 M. tuberculosis isolates; drug-resistant isolates were sequenced in 11 drug loci, including katG, inhA, oxyR-ahpC, rpoB, embB, rpsL, rrs(1) (nucleotides 388-1084), gyrA, gyrB, rrs(2) (nucleotides 1158-1674), and eis. Results: The prevalences of isoniazid, rifampicin, ethambutol, streptomycin, ofloxacin, and kanamycin resistance were 22.0%, 19.3%, 7.9%, 23.8%, 10.4%, and 3.3%, respectively. The Beijing family (82.8%) was the predominant genotype, followed by the T (9.3%), H (0.6%), CAS (0.4%), LAM (0.4%), and U (0.4%) families. The percentage of Beijing genotype in a central area (88.1%) was higher than in the south (77.3%) and the north area (80.1%) (p < 0.05), while the sex, age, and treatment history between Beijing and non-Beijing family were not statistically different. Mutation analysis found that the most prevalent mutations were katG315, rpoB531, embB306, rpsL43, gyrA94, and rrs1401; the Beijing family exhibited a high rate of isoniazid-resistant isolates carrying katG315 mutations (p < 0.05). Furthermore, compared with the phenotypic data, the sensitivities of isoniazid, rifampicin, ethambutol, streptomycin, ofloxacin, and kanamycin resistance by sequencing base on 11 loci were 85.1%, 94.0%, 53.7%, 74.8%, 77.8%, and 64.7%, respectively. Conclusions: Shaanxi has a serious epidemic of drug-resistant tuberculosis, Beijing family is the predominant genotype, and the distribution showed geographic diversity. The prevalence of Beijing genotypes has a tendency to promote the transmission of high-level isoniazid-resistant M. tuberculosis. Besides, the hot spot regions localized in the embB, rrs(2), and eis gene appear not to serve as excellent biomarkers for predicting ethambutol and kanamycin resistance in Shaanxi.

目的 探讨A群轮状病毒(RVA)感染情况,为明确A群轮状病毒感染所致腹泻与患者性别、年龄及季节的相关性.方法 选自2013-2018年西安交通大学附属医院门急诊和住院腹泻患者13 091例作为研究对象,进行A群轮状病毒抗原检测并进行统计学分析.结果 13 091例腹泻患者中,RVA感染4 354例,阳性率为33.3％.男性患者RVA阳性率为33.0％,女性患者RVA阳性率为33.5％,差异无统计学意义(P＞0.05).各年龄组均可检出轮状病毒,5岁以下婴幼儿是RVA腹泻的高发人群,占95.5％,且0.5～＜2岁年龄组阳性率最高(37.2％),差异有统计学意义(P＜0.05).1月、11-12月是RVA感染的高发期.结论 A群轮状病毒感染与儿童腹泻存在密切关系,婴幼儿是RVA的易感人群,RVA感染无性别差异且高发于秋冬季节.

We previously reported that interleukin (IL)‐6 in the red nucleus (RN) is involved in the maintenance of neuropathic pain induced by spared nerve injury (SNI), and exerts a facilitatory effect via Janus‐activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) and extracellular signal‐regulated kinase (ERK) signal transduction pathways. The present study aimed at investigating the roles of tumor necrosis factor‐α (TNF‐α) and IL‐1β in RN IL‐6‐mediated maintenance of neuropathic pain and related signal transduction pathways. Being similar to the elevation of RN IL‐6 three weeks after SNI, increased protein levels of both TNF‐α and IL‐1β were also observed in the contralateral RN three weeks after the nerve injury. The upregulations of TNF‐α and IL‐1β were closely correlative with IL‐6 and suppressed by intrarubral injection of a neutralizing antibody against IL‐6. Administration of either the JAK2 antagonist AG490 or the ERK antagonist PD98059 to the RN of rats with SNI remarkably increased the paw withdrawal threshold (PWT) and inhibited the up‐regulations of local TNF‐α and IL‐1β. Further experiments indicated that intrarubral injection of exogenous IL‐6 in naive rats apparently lowered the PWT of the contralateral hindpaw and boosted the local expressions of TNF‐α and IL‐1β. Pretreatment with AG490 could block IL‐6‐induced tactile hypersensitivity and suppress the up‐regulations of both TNF‐α and IL‐1β. However, injection of PD98059 in advance only inhibited the upregulation of IL‐1β, but not TNF‐α. These findings indicate that RN IL‐6 mediates the maintenance of neuropathic pain by inducing the productions of TNF‐α and IL‐1β. IL‐6 induces the expression of TNF‐α through the JAK2/STAT3 pathway, and the production of IL‐1β through the JAK2/STAT3 and ERK pathways.

为了解新冠肺炎疫情期间"医学免疫学"在线教学的效果和存在的问题,通过问卷调查,分析评估学生在线学习医学免疫学的学习效果及影响因素,以不断提升在线教学质量,并为今后的教学工作积累经验.

Objective: The aim of this study was to investigate the molecular characteristics and in vitro susceptibility to bedaquiline of Mycobacterium tuberculosis (MTB) isolates from Shaanxi, China. Methods: The minimum inhibitory concentration (MIC) of bedaquiline was determined using the microplate alamarBlue assay for 518 MTB isolates from Shaanxi. Isolates with MIC values of bedaquiline >= 0.12 mu g/mL were sequenced for the atpE, Rv0678, and pepQ genes. Drug susceptibility testing and spoligotyping were also conducted for all strains. Results: Ten (1.93%) bedaquiline-resistant strains were isolated from 518 tuberculosis patients. The resistance rate of bedaquiline was not correlated to sex, age, treatment history, region, or genotype. Five bedaquiline-resistant isolates and one bedaquiline-susceptible isolate were found to carry Rv0678 mutations; six mutation types were identified, including G5T, A263G, C185T, G19deletion, C265T, and T323C. No mutations within the atpE and pepQ genes were observed. Conclusions: Bedaquiline showed strong in vitro antibacterial activity against MTB isolates, and the Rv0678 gene serves as the major mechanism contributing to bedaquiline resistance among MTB isolates from Shaanxi, China. Two novel mutation types (C265 T and T323 C) of the Rv0678 gene were associated with resistance to bedaquiline. Furthermore, in addition to the current three resistance-associated genes (atpE, Rv0678, and pepQ), other mechanisms of resistance to bedaquiline may exist that need further study. (c) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

目的 探讨西安交通大学第一附属医院中心ICU病房患者感染病原菌类型、分布及耐药情况,为指导医院感染病原菌耐药性监测和临床合理应用抗菌药物提供依据.方法 对该院2013年1月～2016年12月中心ICU住院患者送检标本中的病原菌进行培养、分离及鉴定,采用纸片扩散法、E-test法或全自动细菌分析仪测定细菌对不同抗菌药物的敏感性.结果 共分离出3 526株病原菌,包括革兰阴性杆菌2 446株(69.4％)、革兰阳性球菌659株(18.7％)和真菌421株(11.9％).革兰阴性杆菌主要为鲍曼不动杆菌、铜绿假单胞菌、肺炎克雷伯菌、大肠埃希菌和嗜麦芽窄食单胞菌.革兰阳性球菌主要为屎肠球菌、金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌和溶血葡萄球菌.耐碳青霉烯类(亚胺培南)鲍曼不动杆菌和铜绿假单胞菌的检出率分别为92.9％和56.8％.产超广谱β-内酰胺酶的大肠埃希菌和肺炎克雷伯菌分别占76.1％和63.6％.多重耐药葡萄球菌主要为耐甲氧西林金黄色葡萄球菌(65.9％)和耐甲氧西林凝固酶阴性葡萄球菌(＞90％),其对万古霉素、替加环素和利奈唑胺的敏感率为100％.肠球菌属的整体耐药性十分严重,屎肠球菌比粪肠球菌的耐药率高.真菌主要为白色假丝酵母菌,对抗真菌药物的敏感率为90％.结论 中心ICU患者医院感染的致病菌主要为革兰阴性杆菌,且主要为多重耐药的非发酵革兰阴性杆菌.ICU应加强对病原菌的耐药性监测,并根据药敏结果指导临床合理应用抗生素.