Vasovagal reactions after COVID-19 vaccination in Japan

Coronavirus disease 2019 (COVID-19) vaccine administration started in February 2021 in Japan. As of December 2021, approximately 75% of the population aged ≥12 years had received two doses of vaccine. We conducted a study to investigate vasovagal reactions (VVR) after COVID-19 vaccination using data on adverse events following immunization. The crude reporting rate of VVR (cases/1,000,000 doses) after vaccination was 9.6 in all age groups combined, and was more frequent in the younger age groups: 28.6 and 37.2 in individuals aged 10–19 years and 20–29 years, respectively. In individuals aged 10–29 years, the rate was similar in males and females (33.0 and 34.2, respectively, p = 0.53); but was higher after dose 1 than after dose 2 (57.4 and 8.8, respectively, p < 0.001). Based on these results, caution needs to be exercised when vaccinating adolescents and young adults, especially with dose 1 of COVID-19 vaccines.     

芒针对脊髓损伤大鼠运动功能和炎症水平的影响

目的探究芒针深刺秩边穴对大鼠脊髓损伤后运动功能的影响及可能作用机制。方法选择健康雄性Wister大鼠81只,随机分为正常组、模型组和芒针组(正常组9只,其余两组各36只),采用改良Allen's造模法制备大鼠脊髓中度损伤模型,模型组不做特殊处理,芒针组采用芒针深刺秩边穴,每日1次,每次30 min。分别于术后1 d、3 d、5 d、7 d行BBB(Basso-Beattie-Bresnahan)运动功能评分;术后1 d、3 d、5 d、7 d取受损段脊髓组织行酶联免疫吸附测定(ELISA)、实时荧光定量PCR(RT-qPCR)和苏木素-伊红染色(HE染色)。结果术后5 d和7 d,芒针组大鼠BBB评分高于模型组,差异有统计学意义(P<0.01);脊髓损伤后,模型组和芒针组大鼠脊髓组织中高迁移率族蛋白B1(HMGB1)、核转录因子kB(NF-kB)、白介素-6(IL-6)含量及HMGB1mRNA、NF-kBmRNA、IL-6mRNA水平显著升高(P<0.05);受损的脊髓组织松散,灰质中有许多空洞形成,伴有炎性细胞浸润。芒针治疗后,芒针组大鼠脊髓组织中HMGB1、NF-kB、IL-6含量及HMGB1mRNA、NF-kBmRNA、IL-6mRNA水平较模型组降低,且在3 d、5 d、7 d差异有统计学意义(P<0.05);受损部位的空洞及炎性细胞逐渐减少。结论脊髓损伤后,炎症因子的大量聚集引起级联性炎症反应,影响大鼠运动功能的恢复。芒针的抗炎机制可能包括抑制HMGB1的表达,降低NF-kB信号通路的传导,下调促炎因子IL-6的分泌。     

肾炎方联合缬沙坦分散片对慢性肾小球肾炎患者的疗效与肾功能的影响

目的:探究肾炎方联合缬沙坦分散片治疗慢性肾小球肾炎患者的疗效及对肾功能的影响。方法:选取2016年2月至2019年2月重庆医科大学附属一医院合川医院肾脏内科收治的慢性肾小球肾炎患者122例作为研究对象,随机分为对照组和观察组,每组61例。对照组患者采用下缬沙坦分散片治疗,观察组在对照组基础上采用自拟肾炎方与缬沙坦分散片联合治疗,分析比较2组患者的肾功能指标的动态变化、炎性因子的表达水平、临床疗效及治疗后不良反应。结果:治疗后观察组TC、TG、BUN、Scr及24 hUPE5项指标的动态变化均低于对照组,差异有统计学意义(P<0.05),且观察组ALB动态变化高于对照组,差异有统计学意义(P<0.05);治疗后观察组IL-6、IL-10、CRP及TNF-α水平明显低于对照组,差异有统计学意义(P<0.05),观察组治疗有效率(98.4%)优于对照组(86.9%),差异有统计学意义(P<0.05);观察组不良反应发生率(6.6%)低于对照组(31.1%),差异有统计学意义(P<0.05)。结论:采用自拟肾炎方与缬沙坦分散片联合的治疗方案可增强疗效,提升肾功能,降低促炎性因子的表达水平及不良反应,值得在临床中推广普及。     

吕文良教授从“引阳入阴”论瞑眩

瞑眩反应是疾病趋愈的一种祛邪反应,古今医家对其发生机制的观点不一。文章收集、整理瞑眩反应相关文献,总结古、今对瞑眩反应成因的看法,介绍吕文良教授从引阳入阴论瞑眩的经验,以期为临床对其进一步探索提供参考。吕文良教授认为久病之体,宿邪内伏,湿热痰瘀交阻而脏腑经络不通,致卫阳独行于外,不得入阴,机体阴阳失交,而瞑眩反应是机体借助药物作用,引阳入阴,使阴阳复交、正气渐盛,疾病自去而成的一种佳兆。     

Assessment of oral ciprofloxacin impaired gut barrier integrity on gut bacteria in mice

Gut bacteria and gut barrier plays important roles in body homeostasis. Ciprofloxacin (CPFX) is widely used to treat bacterial infections. However, whether high dosage of CPFX has side effects on gut barrier integrity is still unclear. Our results indicated that the High CPFX treatment (1 mg/ml) caused weight loss, nervousness, anorexia, and increased apoptosis cells in gut, but less influence was observed in the Low CPFX group (0.2 mg/ml). Meanwhile, the High CPFX treatment impaired tight junction molecules Ocln/ZO-1 level and down-regulated antibacterial genes expression (reg3γ, pla2g2α and defb1). Further, the High CPFX treatment increased pro-inflammatory cytokine IL-1β in intestinal tract, decreased IL-17A of duodenum but increased IL-17A of colon at day 37. In addition, the gut bacterial diversity and richness behaved significantly loss regarding CPFX treatment, especially in the High CPFX group during the experiment. Indole exhibited sharply decline in both Low and High CPFX groups at day 7, and the High CPFX mice needed longer time on restoring indole level. Meanwhile, CPFX treatment strongly decreased the concentrations of butyric acid and valeric acid at day 1. Correlation analysis indicated that the linked patterns between the key bacteria (families Bacteroidales_S247, Ruminococcaceae and Desulfovibrionaceae) and metabolites (indole and butyric acid) were disturbed via the CPFX treatment. In conclusion, the High CPFX treatment impaired the gut barrier with the evidence of reduced expression of tight junction proteins, increased apoptosis cells and inflammatory cells, decreased the bacterial diversity and composition, which suggesting a proper antibiotic-dosage use should be carefully considered in disease treatment.     

Long-term Outcomes of Adolescent Anorexia Nervosa on Bone

Purpose

Anorexia nervosa (AN) is a chronic and life-threatening eating disorder that can have a considerable negative impact on the growing skeleton. We hypothesized that the long-term impact on bone health may persist even after normalization of body weight.

程序性死亡受体1和程序性死亡受体配体1在非小细胞肺癌组织中的表达情况及临床意义

目的探讨程序性死亡受体1(PD-1)和程序性死亡受体配体1(PD-L1)在非小细胞肺癌(NSCLC)组织中的表达情况及临床意义。方法选择150例NSCLC患者的NSCLC组织及其癌旁组织,采用实时荧光定量聚合酶链反应(PCR)检测两种组织中PD-1 mRNA和PD-L1 mRNA的相对表达量。采用免疫组织化学染色法检测NSCLC组织中PD-1和PD-L1的表达情况,分析PD-1和PD-L1表达情况与患者临床特征的关系。采用流式细胞术检测NSCLC组织和癌旁组织中CD4^+-PD-1、CD8^+-PD-1、CD14^+-PD-L1、CD68^+-PD-L1的表达水平。结果NSCLC组织中PD-1 mRNA和PD-L1 mRNA的相对表达量分别为(5.03±1.92)和(4.95±1.09),分别高于癌旁组织的(1.72±0.81)和(1.25±0.24),差异均有统计学意义(P﹤0.05)。TNM分期为Ⅲ~Ⅳ期、低分化、有淋巴结转移、有远处转移的NSCLC患者NSCLC组织中PD-1和PD-L1的高表达率均明显高于TNM分期为Ⅰ~Ⅱ期、高+中分化、无淋巴结转移、无远处转移的患者,差异均有统计学意义(P﹤0.01)。NSCLC组织中CD4^+-PD-1、CD8^+-PD-1、CD14^+-PD-L1、CD68^+-PD-L1的表达水平均明显高于癌旁组织,差异均有统计学意义(P﹤0.01)。结论PD-1和PD-L1在NSCLC组织中高表达,可能成为一种新的生物标志物,PD-1/PD-L1信号通路可能参与了NSCLC的免疫逃逸过程,对其逃逸机制进行研究可以为NSCLC患者的临床治疗提供新靶点。     

阿帕替尼单药在标准方案治疗失败晚期结直肠癌患者中的疗效及安全性

目的：探讨阿帕替尼单药在标准治疗方案失败晚期结直肠癌（colorectal cancer，CRC）患者中的疗效和安全性。方法：本研究为前瞻性研究设计，用PASS15 软件计算研究所需的样本量，从2017 年7 月到2018 年8 月入组标准方案治疗失败的晚期CRC患者52 例，给予阿帕替尼起始剂量750 mg或500 mg单药治疗；评估患者的客观缓解率（ORR）和疾病控制率（DCR），随访评价患者的无进展生存期（PFS）和总生存期（OS），并记录治疗过程中出现的不良反应。主要研究终点为PFS，次要研究终点为ORR、DCR、OS和安全性。结果：纳入研究的52 例CRC患者中45 例可以评价疗效及安全性，其均为既往接受过至少2 次系统性化疗的晚期CRC患者。疗效：完全缓解0 例、部分缓解5 例、疾病稳定30 例、疾病进展10 例，ORR为11.11%、DCR为77.78%；预后：45 例患者的中位PFS 为3.95 个月（95% CI=3.16~4.74），中位OS为10.3 个月（95% CI=5.70~14.90）；3 级以上不良反应：手足综合征6 例（13.33%），高血压5 例（11.11%），蛋白尿5 例（6.67%），转氨酶升高4 例（8.89%），腹泻3 例（6.67%），疲劳2 例（4.44%），出血1例（2.22%）。结论：阿帕替尼单药治疗标准方案失败的晚期CRC患者具有潜在的临床获益，安全性事件总体可控。     

Derivation of internal dose-based thresholds of toxicological concern for occupational inhalation exposure to systemically acting organic chemicals

This study aimed at deriving occupational thresholds of toxicological concern for inhalation exposure to systemically-acting organic chemicals using predicted internal doses. The latter were also used to evaluate the quantitative relationship between occupational exposure limit and internal dose. Three internal dose measures were identified for investigation: (i) the daily area under the venous blood concentration vs. time curve, (ii) the daily rate of the amount of parent chemical metabolized, and (iii) the maximum venous blood concentration at the end of an 8-hr work shift. A dataset of 276 organic chemicals with 8-hr threshold limit values-time-weighted average was compiled along with their molecular structure and Cramer classes (Class I: low toxicity, Class II: intermediate toxicity, Class III: suggestive of significant toxicity). Using a human physiologically-based pharmacokinetic model, the three identified dose metrics were predicted for an 8-hr occupational inhalation exposure to the threshold limit value for each chemical. Distributional analyses of the predicted dose metrics were performed to identify the percentile values corresponding to the occupational thresholds of toxicological concern. Also, simple linear regression analyses were performed to evaluate the relationship between the 8-hr threshold limit value and each of the predicted dose metrics, respectively. No threshold of toxicological concern could be derived for class II due to few chemicals. Based on the daily rate of the amount of parent chemical metabolized, the proposed internal dose-based occupational thresholds of toxicological concern were 5.61?×?10^?2 and 9?×?10^?4 mmol/d at the 10th percentile level for classes I and III, respectively, while they were 4.55?×?10^?1 and 8.5?×?10^?3 mmol/d at the 25th percentile level. Even though high and significant correlations were observed between the 8-hr threshold limit values and the predicted dose metrics, the one with the rate of the amount of chemical metabolized was remarkable regardless of the Cramer class (r² = 0.81; n = 276). The proposed internal dose-based occupational thresholds of toxicological concern are potentially useful for screening-level assessments as well as prioritization within an integrated occupational risk assessment framework.