Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1

Trigeminal neuralgia is a debilitating condition, and the pain easily spreads to other parts of the face. Here, we established a mouse model of partial transection of the infraorbital nerve (pT-ION) and found that the Connexin 36 (Cx36) inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia. Mefloquine reversed the pT-ION-induced upregulation of Cx36, glutamate receptor ionotropic kainate 2 (GluK2), transient receptor potential ankyrin 1 (TRPA1), and phosphorylated extracellular signal regulated kinase (p-ERK) in the trigeminal ganglion. Cold allodynia but not mechanical allodynia induced by pT-ION or by virus-mediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS102, and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanical allodynia. In conclusion, we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2, TRPA1, and p-ERK signaling.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00594-4) contains supplementary material, which is available to authorized users.     

低氧限光方案与早产儿视网膜病的相关研究

目的:探讨低氧限光方案对预防极低出生体重儿(VLBW I)视网膜病(Rop)的有效性、安全性。方法:将2002年10月~2005年4月广州市重症孕产妇抢救中心出生后入住该科需氧疗的VLBW I 40例,随机分为低氧限光方组(II组)及常规给氧无限光组(III组)各20例,另取近5年我科住院资料完整的VLBW I15例作为对照组(I组),对照组在出生后无需氧疗或低氧治疗时间少于5 d。全部研究对象于纠正胎龄33、34、35、36周接受4次眼底检查,根据Rop结果复查直至视网膜血管发育成熟为止,连续随访视力、眼底、眼位及客观检影、脑瘫及支气管肺发育不良的发生情况。结果:①III组发生Rop达40%,显著高于I、II组(P均<0.05),各组Rop发生时间均在34~36周,平均发病年龄为纠正胎龄35.3周。②各组Rop的发生与高危单因素的分析显示出生体重、胎龄、住院时间、败血症的发生与Rop有关,对照组(I组)Rop的发生还与1 m in Apgar评分及其血压有关(P<0.05),低氧限光组(II组)Rop的发生还与BE>-10有关。用logistic综合分析发现与Rop的发生有显著相关的因素为胎龄(P<0.05)、出生体重(P<0.05)。③其中40例随访10~16个月的资料示III组视力异常及支气管肺发育不良的发生率分别为50%、25%,显著高于I、II组(P<0.05),而脑瘫的发生率在3组间无显著差异。结论:在临床上应用低氧限光方案对预防VLBW I的Rop发生是有效和安全的,且可降低支气管肺发育不良的发生率,并不增加脑瘫的发生率。     

情绪障碍患儿气质类型的临床研究

目的：　了解儿童情绪障碍的气质类型,探讨其规律性。方法：　采用儿童气质量表家长问卷法(PTQ)对48例儿童情绪障碍(观察组)及60例健康儿童(对照组)进行气质调查研究。结果：　观察组儿童气质类型D型占多数(64.6%),与对照组(30.0%)比较差异有显著性(P<0.01);对照组儿童E型气质占多数(53.3%),观察组(18.7%)与之比较差异有显著性(P<0.01);S型气质类型在两组之间构成比差异不显著(P>0.05)。结论：　儿童情绪障碍气质类型D型占多数,持有此气质儿童容易出现情绪障碍。     

Synergistic anti-hyperalgesia of electroacupuncture and low dose of celecoxib in monoarthritic rats: involvement of the cyclooxygenase activity in the spinal cord

Electroacupuncture (EA) can effectively control the exaggerated pain in humans with inflammatory disease and animals with experimental inflammatory pain. However, there have been few investigations on the effect of co-administration of EA and analgesics and the underlying synergistic mechanism. Using behavioral test, RT-PCR analysis, enzyme immunoassay (EIA) and enzyme-linked immunosorbent assay (ELISA), the present study demonstrated that (1) Unilateral intra-articular injection of complete Freund's adjuvant (CFA) produced a constant hyperalgesia and an up-regulation of the prostaglandin E(2) (PGE(2)) level as well as the tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 levels in the spinal cord; (2) Celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2), at a dose of 2, 10, and 20 mg/kg (twice daily, p.o.), presented a dose-dependent anti-hyperalgesic effect; (3) Repeated EA stimulation of ipsilateral 'Huan-Tiao' (GB30) and 'Yang-Ling-Quan' (GB34) acupoints significantly suppressed CFA-induced hyperalgesia, and markedly inhibited the CFA-induced increase of the level of PGE(2) as well as IL-1beta, IL-6, and TNF-alpha in the spinal cord; (4) EA combined with low dose of celecoxib (2 mg/kg, twice daily, p.o.) greatly enhanced the anti-hyperalgesic effects of EA, with a synergistic reversing effect on CFA-induced up-regulation of spinal PGE(2), but not on the IL-1beta, IL-6, or TNF-alpha. These data indicated that repeated EA combined with low dose of celecoxib produced synergistic anti-hyperalgesic effect in the CFA-induced monoarthritic rats, which could be made possible by regulating the activity of spinal COX, hence the spinal PGE(2) level. Thus, this combination may provide an effective strategy for pain management.     

北京地区儿童同型半胱氨酸正常参考范围的探讨

目的:确立北京地区儿童同型半胱氨酸正常参考范围。方法 :250名正常儿童按年龄段分为5组,每组50例,男女各25例;使用美国雅培公司Axsym全自动免疫分析仪测定血清同型半胱氨酸含量。结果:北京地区男女儿童血清同型半胱氨酸含量差异无统计学意义,但新生儿、婴儿与幼儿、学龄儿童之间差异有统计学意义。结论:北京地区儿童同型半胱氨酸正常参考范围为:<1个月为1.7～17.5μmol/L,1月～1岁为1.6～16.0μmol/L,1～6岁为1.98～12.8μmol/L,>6岁为3.2～14.4μmol/L。     

重型颅脑损伤并发急性肾功能衰竭的危险因素和病因分析

目的探讨重型颅脑损伤合并急性肾功能衰竭（ARF）的危险因素。方法回顾性分析了27例重型颅脑损伤合并ARF患者的临床资料，对其危险因素及发病原因进行探讨。结果GCS评分低、脑挫裂伤程度重、甘露醇治疗、氨基糖甙类药物治疗、年龄大以及开颅手术后与ARF显著相关，属于风险因素。结论重型颅脑损伤合并ARF为多种因素的共同作用。     

出生早期体重增长速率对早产儿矫正12月龄时神经发育的影响

目的 研究早产儿出生早期的体重增长速率对矫正12月龄时神经发育的影响。方法 收集2015年7月1日至2019年12月31日期间在广州医科大学附属第三医院新生儿科出院,且在该院高危儿门诊随访的早产儿的相关资料,根据其出生至矫正胎龄40周时的体重增长速率分为低速率组[< 10 g/（kg·d）;21例]和高速率组[≥10 g/（kg·d）;87例],在矫正3月、6月、12月龄时采用Gesell发育量表进行神经发育评估,并比较两组间的差异。结果 在矫正12月龄时,低速率组的精细运动能评分明显低于高速率组（P < 0.05）,语言能评分异常率明显高于高速率组（P < 0.05）。其中在出生体重 < 1 500 g与出生体重≥1 500 g的早产儿中,低速率组精细运动能评分均较高速率组评分低（P < 0.05）;出生体重≥1 500 g早产儿中,低速率组语言能评分异常率较高速率组高（P < 0.05）。结论 早产儿出生至矫正胎龄40周时的体重增长速率可能影响其12月龄时的精细运动及语言发育,但有待更大样本量的研究进一步论证。     

Involvement of Spinal Neurotrophin-3 in Electroacupuncture Analgesia and Inhibition of Spinal Glial Activation in Rat Model of Monoarthritis

Although electroacupuncture (EA) has been proven to effectively relieve pain associated with arthritis, the underlying mechanism of EA analgesia requires further investigation. Here, the involvement of spinal neurotrophin-3 (NT-3) in EA’s analgesic effects on complete Freund’s adjuvant (CFA)-induced inflammatory pain was examined. The present study demonstrated that: 1) repeated EA stimulation of ipsilateral GB30 and GB34 acupoints remarkably suppressed CFA-induced hyperalgesia; 2) EA treatment markedly enhanced the upregulation of spinal NT-3 mRNA and protein levels following CFA injection; 3) antisense oligodeoxynucleotides (ODN) specifically against NT-3 intrathecally administered during EA treatment for 7 days significantly attenuated the EA analgesia; and 4) the suppressed expression of spinal GFAP (astrocytic marker), OX-42 (microglial marker) as well as proinflammatory cytokines, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α by EA treatment was significantly attenuated following NT-3 antisense ODN delivery. These results suggested that endogenous NT-3 may be involved in the analgesic effect of EA on inflammatory pain in rats, mediated through the inhibition of spinal glial activity as well as proinflammatory cytokine production.

Perspective

The present study may initiate a discussion on the possible roles of NT-3/glia/cytokines in the therapeutic effects of acupuncture and provide insight on the mechanism underlie the analgesic effects of acupuncture on pain associated with arthritis.     

Effects of Waterborne Chronic Copper Exposure on Hepatic Lipid Metabolism and Metal-Element Composition in Synechogobius hasta

The present study was conducted to determine hepatic lipid metabolism and metal-element composition in Synechogobius hasta exposed to waterborne chronic copper (Cu) concentrations of control, 57, and 118 μg Cu/l, respectively, for 30 days. Growth decreased, but hepatosomatic index, viscerosomatic index, and hepatic lipid content increased with increasing waterborne Cu levels. Staining with oil red O showed extensive steatosis in liver of Cu-exposed fish. Cu exposure increased hepatic 6-phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase, and malic enzyme activities, whereas fatty acid synthetase, isocitrate dehydrogenase, and carnitine palmitoyltransferases I activities remained unaffected. Cu, zinc, iron, and manganese contents were also changed in several tissues (gill, liver, spleen, gastrointestinal tract, and muscle) in a tissue-, dose-, and time-dependent manner. This was the first study to examine the effects of waterborne Cu exposure on several enzymatic activities mediating hepatic lipogenesis and lipolysis in fish as well as to show that waterborne Cu exposure could enhance the metabolism of lipid synthesis and consequently induce the increase of hepatic lipid deposition in S. hasta.