Address at the 60th Anniversary of Comrade MAO Ze-dong''s Instruction on Western Medicine Doctors Learning Traditional Chinese Medicine

<正>(October 11~(th), 2018)Distinguished leaders,guests,ladies and gentlemen,good morning.Today,with great reverence,we gather here to commemorate the 60th anniversary of Comrade MAO Ze-dong's instruction that Western medicine doctors should learn traditional Chinese medicine(TCM).On behalf of the National Administration of Traditional Chinese Medicine(NATCM),I would like to extend my warm congratulations on the convening of today's meeting and pay tribute to people who have been     

All roads lead to Rome-a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer’s disease

Age-related neurodegenerative disorders such as Alzheimer’s disease(AD)have become a critical public health issue due to the significantly extended human lifespan,leading to considerable economic and social burdens.Traditional therapies for AD such as medicine and surgery remain ineffective,impractical,and expensive.Many studies have shown that a variety of bioactive substances released by physical exercise(called“exerkines”)help to maintain and improve the normal functions of the brain in terms of cognition,emotion,and psychomotor coordination.Increasing evidence suggests that exerkines may exert beneficial effects in AD as well.This review summarizes the neuroprotective effects of exerkines in AD,focusing on the underlying molecular mechanism and the dynamic expression of exerkines after physical exercise.The findings described in this review will help direct research into novel targets for the treatment of AD and develop customized exercise therapy for individuals of different ages,genders,and health conditions.     

Angiotensin-(1–7)reducesα-synuclein aggregation by enhancing autophagic activity in Parkinson's disease

Abnormal accumulation ofα-synuclein contributes to the formation of Lewy bodies in the substantia nigra,which is considered the typical pathological hallmark of Parkinson's disease.Recent research indicates that angiotensin-(1-7)plays a crucial role in several neurodegenerative disorders,including Parkinson's disease,but the underlying mechanisms remain elusive.In this study,we used intraperitoneal administration of rotenone to male Sprague-Dawley rats for 4 weeks to establish a Parkinson's disease model.We investigated whether angiotensin-(1-7)is neuroprotective in this model by continuous administration of angiotensin-(1-7)into the right substantia nigra for 4 weeks.We found that angiotensin-(1-7)infusion relieved characteristic parkinsonian behaviors and reducedα-synuclein aggregation in the substantia nigra.Primary dopaminergic neurons were extracted from newborn Sprague-Dawley rat substantia nigras and treated with rotenone,angiotensin-(1-7),and/or the Mas receptor blocker A-779 for 24 hours.After binding to the Mas receptor,angiotensin-(1-7)attenuated apoptosis andα-synuclein aggregation in rotenone-treated cells.Primary dopaminergic neurons were also treated with angiotensin-(1-7)and/or the autophagy inhibitor 3-methyladenine for 24 hours.Angiotensin-(1-7)increasedα-synuclein removal and increased the autophagy of rotenone-treated cells.We conclude that angiotensin-(1-7)reducesα-synuclein aggregation by alleviating autophagy dysfunction in Parkinson's disease.Therefore,the angiotensin-(1-7)/Mas receptor axis plays an important role in the pathogenesis of Parkinson's disease and angiotensin-(1-7)has potential therapeutic value for Parkinson's disease.All experiments were approved by the Biological Research Ethics Committee of Nanjing First Hospital(approval No.DWSY-2000932)in January 2020.     

Transplantation of an eight-organ multivisceraI graft in a patient with frozen abdomen after complicated Crohn's disease

To report an extended multivisceral transplantation (MVTx) including right kidney and ascending colon in a patient with complicated Crohn's disease (CD). A 36-year old female suffering from short bowel syndrome and frozen abdomen due to fistulizing CD after multiple abdominal operations underwent MVTx of eight organs including stomach, pancreatoduodenal complex, liver, intestine, ascending colon, right kidney, right adrenal gland, and greater omentum in November 2003. Immunosuppression consisted of alemtuzumab, tacrolimus and steroids. The patient was off parenteral nutrition by postoperative wk 3. She experienced one episode of pneumonia. The patient recovered completely and discharged 2.5 mo and was doing well 30 mo after MVTx. This is one of the very rare cases in which a complete mulitivisceral graft of eight abdominal organs was transplanted orthotopically.     

Ligustrazine inhibits high voltage-gated Ca~(2+) and TTX-resistant Na~+ channels of primary sensory neuron and thermal nociception in the rat:a study on peripheral mechanism

Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinoci-ceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency ( PWL) to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion (DRG) neurons. Results Intraplantar injection of ligustrazine (0.5 mg in 25μl) significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion (DRG) neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin (TTX) -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron in the rat.     

Poly-lactic acid and agarose gelatin play an active role in the recovery of spinal cord injury

Objective To investigate the role of poly-lactic acid and agarose gelatin in promoting the functional recovery of the injured spinal cord. Methods Poly-lactic acid ( PLA) or agarose was embedded in the space between two stumps of the hemisectioned spinal cord. Immunohistochemistry was used to show astroglia proliferation and the infiltration of RhoA-positive cells. Locomotor activity recovery was evaluated by testing the function of hindlimbs. Results Astrogli-as and RhoA labeled non-neuronal cells accumulated in the area adjacent to the implant, while the number of RhoA-positive cells was decreased dramatically in the absence of implant. Animals implanted with agarose gelatin recovered more quickly than those with PLA, concomitant with a higher survival rate of the neurons. Conclusion Both PLA and agarose gelatin benefited the recovery of spinal cord after injury by providing a scaffold for astroglia processes. Modulation of the rigidity, pore size and inner structure of PLA and agarose gelatin might make these biodegradable materials more effective in the regeneration of the central nervous system (CNS).     

巯基化合物对内毒素诱导大鼠枯否细胞NF—kB活性和肿瘤坏死因子释放的影响

目的 观察巯基化合物对内毒素诱导大鼠枯否细胞（KC）NF-kB活性和肿瘤坏死因子-a（TNF-a）释放的影响。方法采用胶原酶灌注和percoll密度梯度离心法分离得到高纯度大鼠KC，在过夜培养后冲洗两遍（不含血清），加入内毒素（LPS）10ng／ml刺激原代培养的KC，观察不同浓度谷胱甘肽乙基酯（GSHEE）及N-乙酰半胱氨酸（NAC）对大鼠KCTNF-a释放和KC内谷胱甘肽（GSH）及NF-kB活性的影响。并观察使用谷胱甘肽合成抑制剂BSO后，对NAC抑制炎症因子的影响，采用凝胶滞留电泳法测NF-kB活性，采用高效液相色谱分析法测GSH水平。结果 LPS诱导KC中GSH水平无变化；GSHEE和NAC可提高KC中GSH水平（P〈0．05），降低NF-kB活性和TNF-a释放（P〈0．05）。NAC与BSO合用时KC中GSH水平无变化，TNF-a释放降低（P〈0．05）。结论 NAC通过抑制KC中NF-kB的激活和TNF-a的释放调节KC功能，但这种抑制作用并非通过增加GSH介导。     

N-Phenylethyl Amitriptyline in Rat Sciatic Nerve Blockade

Background: The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na+ channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus-discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties.

Methods: The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH3 cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model.

Results: In vitro, N-phenylethyl amitriptyline at 10 [mu]m elicits a greater block of Na+ channels than amitriptyline (resting block of approximately 90%vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses. In vivo, duration to full recovery of nociception in the sciatic nerve model was 1,932 +/- 72 min for N-phenylethyl amitriptyline at 2.5 mm (n = 7) versus 72 +/- 3 min for lidocaine at 37 mm (n = 4; mean +/- SEM). However, there was evidence of neurotoxicity at 5 mm.     

General Anesthetics Do Not Affect Release of the Neuropeptide Cholecystokinin from Isolated Rat Cortical Nerve Terminals

Background: General anesthetics inhibit evoked release of classic neurotransmitters. However, their actions on neuropeptide release in the central nervous system have not been well characterized.

Methods: The effects of representative intravenous and volatile anesthetics were studied on the release of sulfated cholecystokinin 8 (CCK8s), a representative excitatory neuropeptide, from isolated rat cerebrocortical nerve terminals (synaptosomes). Basal, elevated KCl depolarization-evoked and veratridine-evoked release of CCK8s from synaptosomes purified from rat cerebral cortex was evaluated at 35[degrees]C in the absence or presence of extracellular Ca2+. CCK8s released into the incubation medium was determined by enzyme-linked immunoassay after filtration.

Results: Elevation of extracellular KCl concentration (to 15-30 mm) or veratridine (10-20 [mu]m) stimulated Ca2+-dependent CCK8s release. Basal, elevated KCl- or veratridine-evoked CCK8s release was not affected significantly by propofol (12.5-50 [mu]m), pentobarbital (50 and 100 [mu]m), thiopental (20 [mu]m), etomidate (20 [mu]m), ketamine (20 [mu]m), isoflurane (0.6-0.8 mm), or halothane (0.6-0.8 mm).