Synthesis of nanocapsules blended polymeric hydrogel loaded with bupivacaine drug delivery system for local anesthetics and pain management

Local anesthetics are used clinically for the control of postoperative pain management. This study aimed to develop chitosan (CS) with genipin (GP) hydrogels as the hydrophilic lipid shell loaded poly(ε-caprolactone) (PC) nanocapsules as the hydrophobic polymeric core composites (CS-GP/PC) to deliver bupivacaine (BPV) for the prolongation of anesthesia and pain relief. The swelling ratio, in vitro degradation, and rheological properties enhancement of CS-GP/PC polymeric hydrogel. The incorporation of PC nanocapsules into CS-GP hydrogels was confirmed by SEM, FTIR, and XRD analysis. Scanning electron microscopy results demonstrated that the CS-GP hydrogels and CS-GP/PC polymeric hydrogels have a porous structure, the pore dimensions being non-uniform with diameters between 25 and 300 μm. The in vitro drug release profile of CS-GP/PC polymeric hydrogel has been achieved 99.2 ± 1.12% of BPV drug release in 36 h. Cellular viability was evaluated using the CCK-8 test on 3T3 fibroblast cells revealed that the obtained CS-GP/PC polymeric hydrogel with BPV exhibited no obvious cytotoxicity. The CS-GP/PC polymeric hydrogel loaded with BPV showed significant improvement in pain response compared to the control group animals for at least 7 days. When compared with BPV solution, CS-GP hydrogel and CS-GP/PC polymeric hydrogel improved the skin permeation of BPV 3-fold and 5-fold in 24 h, respectively. In vitro and in vivo results pointed out PC nanocapsules loaded CS-GP hydrogel can act as effective drug carriers, thus prolonging and enhancing the anesthetic effect of BPV. Histopathological results demonstrated the excellent biodegradability and biocompatibility of the BPV-loaded CS-GP/PC polymeric hydrogel system on 7, 14, and 21 days without neurotoxicity.

HIGHLIGHTS

• Preparation and characterization of CS-GP/PC polymeric hydrogel system.
• BPV-loaded CS-GP/PC exhibited prolonged in vitro release in PBS solution.
• Cytotoxicity of BPV-loaded CS-GP/PC polymeric hydrogel against fibroblast (3T3) cells.
• Development of CS-GP/PC a promising skin drug-delivery system for local anesthetic BPV.

     

Pain management in patients with hepatocellular carcinoma after transcatheter arterial chemoembolisation: A retrospective study

BACKGROUND Pain after transcatheter arterial chemoembolisation(TACE) can seriously affect the prognosis of patients and the insertion of additional medical resources.AIM To develop an early warning model for predicting pain after TACE to enable the implementation of preventive analgesic measures.METHODS We retrospectively collected the clinical data of 857 patients(from January 2016 to January 2020) and prospectively enrolled 368 patients(from February 2020 to October 2022; as verification cohor...     

Imbalance Model of Heart Rate Variability and Pulse Wave Velocity in Psychotic and Nonpsychotic Disorders

ObjectivesPatients with psychiatric disorders have an increased risk of cardiovascular pathologies. A bidirectional feedback model between the brain and heart exists widely in both psychotic and nonpsychotic disorders. The aim of this study was to compare heart rate variability (HRV) and pulse wave velocity (PWV) functions between patients with psychotic and nonpsychotic disorders and to investigate whether subgroups defined by HRV and PWV features improve the transdiagnostic psychopathology of psychiatric classification.MethodsIn total, 3448 consecutive patients who visited psychiatric or psychological health services with psychotic (N = 1839) and nonpsychotic disorders (N = 1609) and were drug-free for at least 2 weeks were selected. HRV and PWV indicators were measured via finger photoplethysmography during a 5-minute period of rest. Canonical variates were generated through HRV and PWV indicators by canonical correlation analysis (CCA).ResultsAll HRV indicators but none of the PWV indicators were significantly reduced in the psychotic group relative to those in the nonpsychotic group. After adjusting for age, gender, and body mass index, many indices of HRV were significantly reduced in the psychotic group compared with those in the nonpsychotic group. CCA analysis revealed 2 subgroups defined by distinct and relatively homogeneous patterns along HRV and PWV dimensions and comprising 19.0% (subgroup 1, n = 655) and 80.9% (subgroup 2, n = 2781) of the sample, each with distinctive features of HRV and PWV functions.ConclusionsHRV functions are significantly impaired among psychiatric patients, especially in those with psychosis. Our results highlight important subgroups of psychiatric patients that have distinct features of HRV and PWV which transcend current diagnostic boundaries.     

胚胎培养液中线粒体DNA拷贝数与胚胎质量关系的研究

目的 研究第3天(day 3,D3)卵裂期胚胎质量与胚胎培养液中线粒体DNA(mitochondrial DNA,mtDNA)拷贝数的关系.方法 选择2017年7月至2018年10月于成都中医药大学医学与生命科学学院/附属生殖妇幼医院生殖医学中心行辅助生殖技术助孕的67个新鲜卵裂期胚胎移植周期的共93个胚胎,应用数字聚...     

腰痛定对大鼠髓核自体免疫反应的影响

目的:探讨中药腰痛定对大鼠髓核自体免疫异常改变的影响,为中药治疗腰椎间盘突出症提供依据.方法:通过手术将成年大鼠尾椎髓核移植于耳后部皮下组织中,造成局部免疫炎性反应.实验动物随机分为空白组、模型组、腰痛定组、腰腿痛丸组,后两组经灌胃给药,每天1次;测定术后7天、21天血液中IgG、IgM的变化,并观察移植组织病理变化.结果:术后7天,腰痛定组、腰腿痛丸组血液中IgG、IgM与造模组比较差异无显著意义(P＞0.05),术后21天比较差异有显著意义(P<0.05～P<0.01);术后7天、21天,腰痛定组血液中IgG、IgM与腰腿痛丸组比较,差异无显著意义;腰痛定组、腰腿痛丸组、模型组血液中IgG、IgM与空白组比较差异,均有极显著意义(P＜0.01).术后7天、21天病理切片显示,腰痛定组、腰腿痛丸组移植组织局部免疫炎症反应较模型组明显减轻.结论:腰痛定对大鼠髓核引起的自体免疫反应,具有良好抑制作用.     

当归四逆加吴萸生姜汤加味联合枸地氯雷他定片治疗慢性荨麻疹的临床观察

目的:观察用当归四逆加吴萸生姜汤加味联合枸地氯雷他定片治疗慢性荨麻疹患者的临床效果及对血清总IgE、白细胞介素-13(IL-13)、凝血酶敏感蛋白-1(TSP-1)、D-二聚体水平的影响。方法:选取2017年6月至2018年4月沈阳市第七人民医院皮肤科门诊收治的慢性荨麻疹患者110例作为研究对象,按照随机数字表法分为对照组和观察组,每组55例。对照组患者给予枸地氯雷他定片口服;观察组患者则在对照组基础上加用当归四逆加吴萸生姜汤加味而成的汤剂内服,2组患者均连续治疗1个月为疗程。通过观察2组患者的风团发作情况、中医证候积分变化比较2组患者的临床疗效,治疗前后采用皮肤病生命质量指数(DLQI)量表评价生命质量,测定血清总IgE、白细胞介素-13(IL-13)、凝血酶敏感蛋白-1(TSP-1)、D-二聚体水平,随访半年,统计治愈患者的复发率,统计治疗过程中的不良反应。结果:对照组的临床有效率74.55%明显低于观察组的90.91%(P0.05);观察组患者治疗后的风团发作情况明显改善,风团数目、风团最大直径、风团发作频率、持续时间等评分较对照组明显下降(P0.05);中医证候积分、生命质量DLQI评分均明显低于对照组(P0.05);血清总IgE水平呈明显下降趋势(P0.05),同一时间点组间比较,以观察组明显低于对照组(P0.05);观察组患者的血清中IL-13、D-二聚体水平均较对照组有所降低(P0.05),TSP-1水平则有所升高(P0.05)(P0.05);随访半年,观察组复发率12.5%明显低于对照组的复发率30%(P0.05);观察组患者治疗过程中不良反应率为7.27%,低于对照组的不良反应率21.82%(P0.05)。结论:当归四逆加吴萸生姜汤加味联合枸地氯雷他定片利于减轻慢性荨麻疹患者的风团发作程度,缓解临床症状,提高生命质量,其起效可能与调整血清中IL-13、TSP-1、D-二聚体水平以降低IgE的异常分泌、改善血管通透性、机体凝血状态等途径有关,值得临床进一步探究。     

气机逆乱是脓毒症MODS的根本病机

脓毒症是机体对于感染导致失调的宿主反应所引发的危及生命的器官功能障碍或衰竭。多器官功能障碍综合征(MODS)是脓毒症的严重并发症,也是脓毒症高死亡率的主要原因。本文从中医气机升降出入角度讨论MODS发生,认为脓毒症时外邪引起的脏腑气机升降出入失常,即气机逆乱是MODS发生的根本病机,且其具有始于肺、困于中焦,后期气血皆乱的特点。临床应重视调理气机,升降相宜,初期重在治肺,宜调气降气,尤重视恢复中焦气机,后期调气不忘治血。     

Expression of TLR2 and TLR5 in distal ileum of mice with obstructive jaundice and their role in intestinal mucosal injury

IntroductionThe aim was to investigate the expression of TLR2 and TLR5 in the distal ileum of mice with obstructive jaundice (OJ) and their role in intestinal mucosal injury.Material and methodsA total of 100 male C57BL/6J mice were randomly assigned to two groups: (I) sham operation (SH); (II) bile duct ligation (BDL). The mice were respectively sacrificed before operation and on the 1^st, 3^rd, 5^th and 7^th days after operation to collect specimens. Various indicators were detected by PCR, immunohistochemistry and other methods.ResultsTLR2 was increased gradually with the extension of OJ time in the BDL group (p < 0.05). However, the changes in the expression of TLR5 were not obvious at different time points. The amount of Bifidobacteria and Lactobacillus showed downward trends in intestinal tract of the BDL group. Furthermore, the amount of Escherichia coli was increased in intestinal tract of the BDL group. The pathological score of intestinal mucosa and the expression of NF-κB increased gradually in the BDL group with the extension of OJ time. There were positive correlations between the pathological score of intestinal mucosa and expressions of TLR2(r = 0.767, p < 0.05) and NF-κB (r = 0.817, p < 0.05) in BDL group. NF-κB expression was positively correlated with TLR2 expression(r = 0.706, p < 0.05).ConclusionsDisturbance of intestinal flora caused by OJ could increase the expression of NF-κB via up-regulating the expression of TLR2 to activate the downstream signaling pathway, thus aggravated the injury of intestinal mucosa.