[摘 要] 目的：用组织代谢组学方法，探讨甲状腺乳头状癌（papillary thyroid carcinoma, PTC）组织及癌旁组织的代谢差异，寻找PTC的潜在生物标志物，探索PTC的发病机制与治疗策略。方法：收集2018年10月至2020年2月期间湖南省人民医院乳甲外科手术切除的40例PTC患者的癌组织及癌旁组织标本。利用HPLC-MS技术平台对PTC组织及癌旁组织样本的差异性代谢物进行多维统计分析，寻找与PTC相关的异常代谢通路。结果：经PCA、PLS-DA、OPLS-DA分析得知癌组织和癌旁组织的代谢轮廓具有显著性差异。经OPLS-Loading plot分析，结合VIP>1、FC>2，且P<0.05，筛选出76个潜在差异性代谢物。其中亮氨酸、2-褪黑素、香草酸等33种代谢物在PTC组织中表达上调；3-葡萄糖苷、甘油磷脂、磷脂酰胆碱、乳糖等43代谢物在PTC癌组织中表达下调。寻找到与差异性代谢物相关的13条异常代谢通路，如半胱氨酸与蛋氨酸代谢、与甘油磷脂代谢、嘧啶代谢、半乳糖代谢以及丙氨酸、天冬氨酸和谷氨酸代谢、柠檬酸循环等，这些代谢通路可能参与PTC代谢的病理生理过程。ROC曲线下面积大于0.9的差异性代谢物有5种，分别是庚二酸、糖醇、辛二酸、乳糖和L-丝氨酸。结论：PTC组织中半乳糖代谢和氨基酸代谢发生改变，PTC组织细胞中存在沃伯格效应(Warburg effect)。庚二酸、糖醇、辛二酸、乳糖、L-丝氨酸五种差异性代谢物可以用来区分PTC患者与正常人。

Objective:To investigate the difference of vitamin A and E levels in children with different respiratory diseases at different ages.Methods:A total of 671 children in Hunan Children's Hospital from July 2017 to October 2019 were selected as the disease group, including 197 cases of pneumonia, 152 cases of recurrent respiratory tract infection, 91 cases of asthma, 88 cases of cough variant asthma and 143 cases of Mycoplasma pneumoniae pneumonia; At the same time, 245 healthy children were selected as the normal group. The serum vitamin A and vitamin E levels of the two groups were detected by high performance liquid chromatography (HPLC).Results:⑴ The vitamin A level [(0.31±0.09)mg/L] of the disease group was lower than the normal group [(0.35±0.25)mg/L], and the vitamin E level [(8.92±2.57)mg/L] was lower than the normal group [(9.62±2.79)mg/L], with statistically significant difference ( P<0.05); ⑵ The level of vitamin A in the disease group at the age of >1-3 years [(0.32±0.09)mg/L] was lower than that in the normal group of the same age group [(0.35±0.08)mg/L]; the level of vitamin A in the disease group at the age of >3-6 years old [(0.30±0.08)mg/L] was lower than that of the same age group [(0.32±0.07)mg/L], with statistically significant difference ( P<0.05); ⑶ The vitamin E level of the disease group at >1-3 years old [(9.23±2.56)mg/L], >3-6 [(8.02±1.86)mg/L] and >6-14 years old [(8.02±1.82)mg/L] were lower than that of the same age normal group [(9.76±2.81)mg/L, (9.67±2.87)mg/L, (9.19±2.58)mg/L], with statistically significant difference ( P<0.05); ⑷ There were significant differences in vitamin A levels among different age in disease group ( P<0.05). Among them, the children with high risk of subclinical deficiency accounted for the largest proportion (45.78%) in the 6-month-1-year-old group, and the proportion of children with normal vitamin A levels in other age groups was the largest; ⑸ There are significant differences in vitamin E levels in different age groups in the disease group ( P<0.05), the levels in the normal range accounts for the largest proportion of all ages; ⑹ The levels of vitamin A and vitamin E in mycoplasma pneumoniae infection group were increased compared with in recurrent respiratory infection group , asthma group, and cough variant asthma group, and the difference was statistically significant ( P<0.05). Compared with the pneumonia group, the level of vitamin E increased in the recurrent respiratory infection group, and the difference was statistically significant ( P<0.05); The vitamin E levels in the cough variant asthma group were reduced compared with the repeated respiratory infection group, asthma group and pneumonia group ( P<0.05). Conclusions:The Vitamin A and E levels of children suffering from respiratory diseases are lower than those of normal children. The Vitamin A and E levels of different respiratory diseases and different age groups are different. Vitamin A and E supplementation may be significantly targeted according to different ages and different respiratory diseases in clinical practice.

[Objective]To investigate the effect of Donepezil on dysgnosia in patients with mild-moderate general paralysis of the insane(GPI).[Methods]Forty-seven patients with GPI were assigned into study group(n=24)or control group(n=23). All these patients were treated with a large dose of penicillin for 2 weeks and then with Benzathine for 3 weeks. And the Donepezil admin-istered to patients in study group.The mini-mental state examination(MMSE)and the clinical dementia rating(CDR)were scored as the measurement of efficiency.[Result]The scores of the MMSE and CDR were not statistically different between the two groups at baseline and 4 weeks after treatment,and both were increased 12 weeks after treatment(P<0.05),especially in study group as com-pared with those in control group(P < 0.05).[Conclusion]Donepezil as an adjunctive therapy may be effective for dysgnosia in patients with mild-moderate GPI. Donepezil is also safe and well tolerated.

Objective: The aim of the study is to validate whether the Recognition Of Stroke In the Emergency Room (ROSIER) scale can be used by general practitioners (GPs) in an emergency medical service (EMS) protocol to transfer stroke patients from primary care center to advanced hospital with acute stroke center. Methods: GPs prospectively performed the ROSIER scale and the Cincinnati Prehospital Stroke Scale (CPSS) on suspected stroke patients as a transfer protocol. All patients were immediately transferred to the Level-II hospital for further treatment. Results: 468 of the 512 suspected stroke patients met the inclusion criteria in this study. The ROSIER scale showed a diagnostic sensitivity of 83.13% (95% confidence intervals [CI] 79.74-86.52%) and specificity of 80.88% (95% CI 77.32- 84.44%). The CPSS showed a diagnostic sensitivity of 78.01% (95% CI 74.26-81.76%) and specificity of 70.59% (95% CI 66.46-74.72%). The Kappa statistic value of the ROSIER scale and the CPSS were 0.601 and 0.454, respectively. The area under the curve (AUC) of ROSIER scale was large than the CPSS (AUC 0.855 vs. 0.791). However, the difference was not significantly different. Conclusions: This study suggest that ROSIER and CPSS could be used in an EMS protocol to transfer stroke patients from a primary care center to an advanced hospital offering thrombolysis service
Stroke

OBJECTIVETo observe the impacts of electroacupuncture (EA) on microgliacytes and astrocytes of cervical spinal cord in rats with thyroid incisional pain and explore the mechanism of acupuncture anesthesia in thyroid surgery.

METHODSSixty Wistar male rats were randomized into a normal group, a model group, a Futu (LI 18) group, a Hegu (LI 4)-Neiguan (PC 6) group and a Zusanli (ST 36)-Yanglingquan (GB 34) group, 12 rats in each one. Except the normal group, a longitudinal incision, about 1.5 cm in length was done along the neck midline in the rats of the rest groups to prepare the model of thyroid incisional pain. In the Futu (LI 18) group, the Hegu (LI 4)-Neiguan (PC 6) group and the Zusanli (ST 36)-Yanglingquan (GB 34) group, after modeling for 4 h, 24 h and 48 h, EA was applied to bilateral "Futu" (LI 18), "Hegu" (LI 4) "Neiguan" (PC 6) and"Zusanli" (ST 36) "Yanglingquan" (GB 34) separately, once a day, continuously for 3 days. In the normal group and the model group, no any intervention was applied. The thermal radiant apparatus was used to detect the thermal pain threshold (PT). The fluorescence quantitative RT-PCR and the Western blotting (WB) were used to determine the expressions of protein and gene of microglia activation markers Iba1 and CD11b and the astrocyte specific protein marker, glial fibrillary acid protein (GFAP) in cervical spinal cord (Cto C) after intervention in the rats of each group.

RESULTSAfter intervention, as compared with the normal group, in the model group, the neck PT was reduced apparently (<0.05), the expressions of Iba1 and CD11b and GFAP mRNA as well as the protein expressions in the spinal cord of Cto Cwere up-regulated apparently (<0.05,<0.01). As compared with the model group, in the Futu (LI 18) and the Hegu (LI 4)-Neiguan (PC 6) group, PT was increased significantly (both<0.05) and that did not change apparently in the Zusanli (ST 36)-Yanglingquan (GB 34) group (>0.05). In the Futu (LI 18) group, the protein and gene expressions of Iba1, CD11b and GFAP were lower than those in the model group (all<0.05). In the Hegu (LI 4)-Neiguan (PC 6) group, the expressions of Iba1 mRNA, CD11b protein, GFAP mRNA and protein were all lower apparently than those in the model group (all<0.05). In the Zusanli (ST 36)-Yanglingquan (GB 34) group, the expressions of Iba1, CD11b and GFAP proteins were not different significantly as compared with the model group (all>0.05). In the Zusanli (ST 36)-Yanglingquan (GB 34) group, the expressions of Iba1 mRNA and CD11b mRNA and protein expressions in the spinal cord of Cto Cwere higher apparently than those in the Futu (LI 18) group (<0.01,<0.05); the expressions of Iba1 mRNA and CD11b protein expressions were higher than those in the Hegu (LI 4)-Neiguan (PC 6) group (all<0.05); GFAP mRNA and protein expressions were higher apparently than those in the Futu (LI 18) group and the Hegu (LI 4)-Neiguan (PC 6) group (all<0.05).

CONCLUSIONSEA at "Futu" (LI 18) or "Hegu" (LI 4), "Neiguan" (PC 6) relieves the acute neck incisional pain in the rats and its effect may be closely relevant with the down-regulation of the activities of microgliacytes and astrocytes in the spinal cords.

Objective To evaluate the efficacy of pregabalin on painful radiation-induced brachial plexus injury.Methods A total of forty-five patients with painful radiation-induced brachial plexus injury were assigned to treatment group with pregabalin 150-600 mg/d combined with conventional therapy, and to control group with conventional treatment for 12 weeks.The visual analogue scale (VAS) and neuropathic pain symptom inventory (NPSI) were evaluated.The response rate (proportion of subjects with at least a 30％ to 50％ reduction in visual analogue scale) was evaluated as the primary endpoint.Results The response rate of the pregabalin group(36.4％) was significantly higher than that of the control group (9.1％) (x2 =4.98, P ＜ 0.05).Although hospital anxiety and depression level, clinical global impression of change, and clinical global impression of change (CGIC) did not differ significantly between pregabalin group and control group (P ＞ 0.05), improvements in neuropathic pain symptom inventory (NPSI), patient global impression of change (PGIC) and the sleep interference score(t =-6.62,-5.65,-6.16, P ＜ 0.05)suggested some utility in the management of radiation-induced brachial plexus.Conclusions Pregabalin treatment combined with conventional treatment exerts efficacy on patients with painful radiation-induced brachial plexus and patients are well tolerated.

Objective To investigate the association between the phosphodiesterase 4D(PDE4D) gene rs153031 polymorphism and the susceptibility of unstable angina pectoris(UAP) in Chinese Han population of Changwu region .Methods The PDE4D gene rs153031 polymorphism was genotyped by Taqman probe in 172 UAP patients(UAP group) ,as well as in gender-and-age-matched 220 subjects without coronary heart disease(CHD)(control group) .Results In this crowd ,there was PDE4D gene rs153031 poly-morphism in patients with UAP and in subjects without CHD .Compared with control group ,frequencies of GG ,GA ,AA genotypes and G allele of rs153031 in UAP group showed no statistical differences (P> 0 .05) .Conclusion In Chinese Han population of Changwu region ,PDE4D gene rs153031 polymorphism shows no association with the susceptibility of UAP .

OBJECTIVETo investigate the effect of smoking on the microRNAs (miRNAs) expression in pneumoconiosis patients.

METHODSReal-time qPCR was used to measure the expression levels of miR-21, miR-200c, miR-16, miR-204, miR-206, miR-155, let-7g, miR-30b, and miR-192 in 36 non-smoking patients with pneumoconiosis and 38 smoking patients with pneumoconiosis, and the differences in expression levels between the two groups were evaluated by two-independent samples t-test.

RESULTSThe expression of miR-192 in serum showed a significant difference between non-smoking and smoking pneumoconiosis patients (P < 0.05), and it decreased gradually in smoking patients with stage I and II pneumoconiosis. In the serum of all pneumoconiosis patients, the expression level of miR-16 was the highest, while the expression level of miR-204 was the lowest.

CONCLUSIONPneumoconiosis patients have differential expression of miRNAs in serum, and smoking has an effect on the miRNAs expression in pneumoconiosis patients.

AIM: To explore the role of P2X7 receptor in inhibition of lipopolysaccharide (LPS)-stimulated BV-2 cell activation by minocycline .METHODS:BV-2 cells were divided into 5 groups:control group, LPS group, LPS+0.1 μmol/L Mino group, LPS+1 μmol/L Mino group and LPS+10 μmol/L Mino group.The expression of P2X7 re-ceptor was determined by real-time PCR and Western blotting .The levels of TNF-αand IL-1βin the microglia culture su-pernatants were measured by ELISA .The morphological changes of the cells were also observed .RESULTS: After ex-posed to LPS, the expression of P2X7 receptor increased in BV-2 cells at mRNA and protein levels .The concentrations of TNF-αand IL-1βin the microglia culture supernatants also increased .Meanwhile, 0.1~10μmol/L minocycline inhibited those changes in a dose-dependent manner .CONCLUSION:Minocycline inhibits the activation of microglia .The mecha-nism may be related to the P2X7 receptor.

Objective To investigate the relationship between serum C-reactive protein(CRP) level ,CRP gene C+1444T poly-morphism and the risk with Acute myocardial infarction (AMI) in Chinese Han population in Sunan region .Methods The CRP gene C+1444T polymorphism was genotyped by Polymerase reaction restriction-fragment length polymorphism (PCR-RFLP) and the serum CRP level was measured by enzyme linked immunosorbent assay (ELISA) between 227 patients with AMI(AMI group) and 161 control subjects .Results No differences were found in genotype distribution between AMI group and controls (CC 82 .38% ,CT 17 .62% ,TT 0% vs 86 .96% ,13 .04% ,0% )(P>0 .05) .The serum CRP level in AMI group was significantly higher than controls(P< 0 .01) .There was no differences in the serum level between any genotypes of the CRP gene C + 1444T (P<0 .05) .Conclusion The CRP gene C+1444T polymorphism is not associate with increased risk of AMI ,and it have no effect with the serum level in Chinese Han population in Sunan region .