双环醇治疗EB病毒肝炎儿童疗效分析

目的 探讨应用双环醇治疗EB病毒肝炎儿童的疗效。方法 2018年1月～2019年12月我院诊治的EB病毒肝炎儿童366例,采用随机数字表法分为两组,每组183例,分别给予丁二磺酸腺苷蛋氨酸或丁二磺酸腺苷蛋氨酸联合双环醇治疗4周。采用Real-time荧光定量PCR法检测血清EBV DNA。结果 在治疗结束时,联合组儿童血清ALT和AST水平分别为(26.65±3.92)U/L和(29.17±3.76)U/L,显著低于丁二磺酸腺苷蛋氨酸治疗组【分别为(32.87±3.23)U/L和(34.97±3.55)U/L,P<0.05】;血清透明质酸和层连蛋白水平分别为(59.51±2.04)μg/L和(60.84±3.96)μg/L,显著低于丁二磺酸腺苷蛋氨酸治疗组【分别为(78.84±3.51)μg/L和(111.44±13.11)μg/L,P<0.05】;治疗前,两组血清EBV DNA阳性,在1.45±0.14×10⁴ copies/ml水平,治疗后均转阴,在5.16±0.04×10³ copies/ml水平以下。结论 应用双环醇联合丁二磺酸腺苷蛋氨酸治疗儿童EB病毒感染所致肝损害可能加速病情康复,缩短病期。     

新疆地区少数民族静脉吸毒HCV感染者基因型与病毒载量的研究

目的了解新疆地区通过静脉吸毒途径HCV感染者体内HCV基因型特点、病毒载量以及二者相关性。方法收集317例有明确静脉吸毒史的丙肝患者血清,提取病毒RNA,荧光定量PCR检测血清HCV载量,并用逆转录—巢式PCR扩增HCV RNA阳性血清病毒cDNA片段进行酶切分析,测定基因型。结果本组114例血清HCVRNA阳性,其中基因1型90例,HCV RNA含量1×10（6.90±1.26）IU/ml;基因2型22例,HCV RNA含量1×10（5.12±0.77）IU/ml;2例未能分型。1型患者比例及病毒载量均高于2型（P均〈0.05）。结论新疆地区通过静脉吸毒途径HCV感染者体内病毒载量与其基因型有关,HCV1型病毒载量明显高于2型。     

索磷布韦和维帕他韦联合利巴韦林治疗基因2、3型慢性丙型肝炎患者近期疗效和耐受性观察*

目的 研究应用索磷布韦/维帕他韦联合利巴韦林治疗基因2、3型慢性丙型肝炎(CHC)患者的近期疗效及耐受性。方法 2018年6月～2019年4月收治的58例基因2、3型CHC患者,采用抽签随机法分为两组,每组29例。给予对照组利巴韦林联合干扰素α-2b治疗,观察组接受索磷布韦/维帕他韦联合利巴韦林治疗,两组均持续治疗3个月。采用实时荧光定量聚合酶链反应法检测血清HCV RNA载量,采用基因芯片法检测HCV基因分型。结果 观察组快速病毒学应答(RVR)和早期病毒学应答(EVR)率分别为72.4%和89.7%,显著高于对照组的44.8%和65.5%(P＜0.05);在治疗4周末,观察组外周血白细胞计数为(5.8±2.1)×10⁹/L,显著高于对照组【(3.7±1.9)×10⁹/L,P＜0.05】;在治疗12周结束时,观察组外周血白细胞和血小板计数分别为(3.4±0.4)×10⁹/L和(99.60±24.2)×10⁹/L,均显著高于对照组【分别为(2.9±0.9)×10⁹/L和(82.01±14.8)×10⁹/L,P＜0.05】;两组不良反应发生率比较差异无统计学意义(P＞0.05),均未出现终止治疗情况。结论 应用索磷布韦/维帕他韦联合利巴韦林治疗基因2、3型CHC患者近期临床疗效确切,安全性较好,值得进一步观察。     

原发性高血压患者CYP2D6＊10不同基因型的心率震荡及美托洛尔的干预作用

目的：观察美托洛尔对CYP2D6＊ 10不同基因型原发性高血压患者心率震荡的影响,及原发性高血压患者CYP2D6＊ 10不同基因型对美托洛尔代谢的影响.方法：比较入选患者美托洛尔干预前后心率震荡值,又根据患者基因型被分为C/C组（39例,野生型）,T/C组（30例,突变型杂合子）和T/T组（21例,突变型纯合子）,并对美托洛尔干预后各组心率震荡值及美托洛尔血药浓度进行对比.结果：（1）与美托洛尔用药前比较,用药后患者震荡初始[TO,（-0.0742±1.46）％比（-0.864±1.62）％]显著降低,震荡斜率[TS,（3.49±3.02） ms/RR比（4.75±3.31） ms/RR]显著升高（P＜0.05～＜0.01）;与T/C组比较,C/C组,T/T组的TO值降低,TS值升高得更显著（P＜0.05）; （2） T/T组美托洛尔血药浓度明显高于C/C组和T/C组[（87.6±21.4） ng/ml比（25.6±13.3） ng/ml比（19.2±11.4） ng/ml,P＜0.01].结论：（1）美托洛尔对原发性高血压患者心率震荡有改善作用;（2） CYP2D6＊10突变纯合子型的美托洛尔血药浓度最高,突变纯合子患者心率震荡改善情况最明显.     

荧光RT-PCR法检测丙型肝炎病毒基因型

目的应用荧光RT-PCR方法对慢性丙型肝炎（CHC）患者血清进行HCV基因型分析。方法采用荧光RT-PCR方法与测序方法比较,对118例CHC阳性患者血清进行HCV RNA分型,比较两种方法分型结果的一致性;为了考察该方法的特异性,对98例慢性乙型肝炎（CHB）患者血清进行HCV RNA分型检测。结果在118例HCV RNA阳性血清标本中,用荧光RT-PCR方法检测有HCV基因1型79例（66.9%）,2型29例（24.6%）,1/2混合型8例（6.8%）;另有2例（1.7%）HCV RNA定量为1×103IU/ml弱阳性标本未分出型。测序法分出1型81例（68.4%）,2型29例（24.6%）,1/2混合型6例（5.1%）,与荧光RT-PCR方法一致2例（1.7%）HCV RNA定量结果为1×103IU/ml的阳性标本测序法未分出型。未发现其他基因型的病例。98例CHB患者血清检测结果均为阴性。结论荧光HCV基因分型的方法具有良好的敏感性、特异性、可重复性且省时省力,可选择该方法为临床诊断服务。     

器官移植受者人巨细胞病毒糖蛋白H基因型分析

目的分析器官移植受者人巨细胞病毒（HCMV）临床分离株糖蛋白H基因型，为进一步研究其致病性、免疫性以及研制HCMV亚单位疫苗提供依据。方法以巢式聚合酶链反应（nested—PCR）检测97例器官移植受者外周血细胞中的巨细胞病毒gH基因并测序分型。结果有23例移植受者的标本经nPCR检出gH基因阳性，阳性率为23．71％，其中骨髓移植受者阳性率10．31％，肝移植受者阳性率5．15％，肾移植受者阳性率8．25％。在23例HCMV分离株中，20例得到gH基因型结果，其中gH1型10例，占50％，gH2型6例，占30％，gH1、2混合型4例，占20％，呈散在分布（χ2=4．00，P〉0．05）；gH基因型在各移植类型间也呈散在分布（χ2=5．652，P〉0．05）。结论HCMV临床分离株糖蛋白基因分别属于gH基因型1～2型，呈散在分布。     

不同手术方法治疗伴有脾功能亢进症的原发性肝癌患者临床疗效研究

目的 探讨脾脏处理对行肝癌切除术的原发性肝癌（PLC）患者临床疗效的影响。方法 2006年1月～2016年1月在我院接受治疗的140例PLC患者, A组46例行肝癌切除术联合脾切除术,B组34例行肝癌切除术/脾切除术/贲门周围血管离断术,C组30例行肝癌切除术联合脾动脉结扎术, D组30例行肝癌切除术。结果 治疗后C、D组患者血小板计数（PLT）为【（215.4±118.9）×10⁹/L和（176.4±105.5）×10⁹/L】,白细胞（WBC）计数为【（3.36±1.23）×10⁹/L和（2.36±1.21）×10⁹/L】,均显著低于A、B组（P均<0.05）;术后D组患者总胆红素（TBIL）水平为（37.7±5.1） μmol/L,明显高于A组或B组或C组（P均<0.05）;治疗后D组患者CD4+细胞为（28.3±5.9）%,CD4+/CD8+比值为（1.3±0.3）%,均明显低于A、B、C组（P均<0.05）;D组患者术后并发症发生率为33.3%,明显高于A组的17.4%、B组的23.5%和C组的20.0%（P<0.05）。结论 行脾处理可以有效改善行肝癌切除术治疗的PLC患者术后肝功能和免疫功能,减少并发症。     

不同剂量重组腺病毒HIF-1α对兔缺血后肢血管新生和通透性的影响

目的探讨不同剂量重组腺病毒低氧诱导因子-1α（Adenovirus mediated hypoxia-inducible factor-1α,Ad-HIF-1α）对兔缺血后肢的促血管新生作用和对新生血管通透性的影响。方法 （1）Ad-HIF-1α在HEK293A细胞内大量扩增,透析纯化,PCR及基因测序鉴定,终点稀释法测定病毒滴度。（2）20只新西兰大白兔高位结扎、离断左侧股动脉及其分支建立急性后肢缺血模型,随机分为4组,每组5只,分别以Ad-HIF-1α1.0×10¹⁰ Pfu（低剂量组）、1.0×10¹¹ Pfu（中剂量组）、1.0×10¹² Pfu（高剂量组）和生理盐水0.5 ml（NS对照组）)肌注术肢骨骼肌。术后28天伊文思兰法检测左侧后肢局部新生血管通透性并处死动物取左侧后肢内收肌行病理切片CD31免疫组化微血管密度（microvasculardensity,MVD）计数检查。结果转染后28天CD31免疫组化结果显示低、中、高剂量组及NS组MVD分另别为（114.40±4.83）num/mm²、（139.60±4.16）num/mm²、（175.40±6.69）num/mm²及（80.40±6.66）num/mm²,提示随剂量增加MVD计数增加,各组间对比有统计学意义（F=248.308,P=0.000）;伊文思兰法检测4组新生血管通透性相似,低、中、高剂量组及NS组伊文思兰浓度分别为（7.25±0.83）μg/mL、（7.23±0.69）μg/mL、（7.22±0.63）μg/mL及（7.12±0.48）μg/mL,各组间差异无统计学意义（P>0.05）。结论 Ad-HIF-1α转基因治疗能促进兔缺血后肢血管新生且呈正相关量-效关系;新生血管通透性接近生理状态。     

替诺福韦治疗不同HBV基因型慢性乙型肝炎患者疗效研究*

目的 探讨替诺福韦治疗不同HBV基因型感染的慢性乙型肝炎(CHB)患者的疗效和血清金属硫蛋白(MT)、白细胞介素29(IL-29)和外周血淋巴细胞程序性死亡受体-1(PD-1)表达的变化。方法 2017年1月～2020年11月我院诊治的CHB患者119例,均接受替诺福韦治疗。采用ELISA法检测血清MT和IL-29水平,使用流式细胞仪检测外周血T 淋巴细胞PD-1表达水平。结果 在本组119例CHB患者中,检出HBV B基因型31例(26.1%),C基因型77例(64.7%),B/C 混合基因型11例(9.2%);基线资料比较,B基因型CHB患者血清ALT和AST水平分别为(154.1±46.7)U/L和(83.3±26.8)U/L,显著高于C基因型患者【分别为(135.8±40.3)U/L和(68.5±20.6)U/L,P＜0.05】或B/C混合基因型患者【分别为(138.9±50.2)U/L和(71.6±23.9)U/L,P＜0.05】,而血清HBV DNA水平为(6.7±1.1)lg copies/ml,显著低于C基因型感染患者【(7.8±1.4)lg copies/ml,P＜0.05】或B/C混合型感染者【(7.4±1.0)lg copies/ml,P＜0.05】;在治疗24 w和48 w末,三组血清ALT复常率无显著性差异(P>0.05),而B基因型和C基因型感染患者血清HBV DNA阴转率分别为96.8%和96.8%,和88.3%和93.5%,均显著高于B/C混合型感染患者(分别为63.6%和81.8%,P<0.05);在治疗48 w,B基因型CHB患者血清MT水平显著高于C基因型或B/C基因型(P＜0.05),血清IL-29水平显著高于C基因型(P＜0.05),而外周血CD4⁺和CD8⁺T淋巴细胞表面PD-1表达水平显著低于C基因型或B/C混合基因型患者(P＜0.05)。结论 不同HBV基因型感染的CHB患者可能对替诺福韦治疗的疗效存在差异,深入了解这些差异可能对研究不同基因型病毒感染患者临床转归有帮助。     

格卡瑞韦/哌仑他韦治疗基因1b型慢性丙型肝炎患者疗效及安全性分析*

目的 探讨应用格卡瑞韦/哌仑他韦治疗基因1b型慢性丙型肝炎(CHC)患者疗效及安全性。方法 2019年7月～2020年8月周口市中心医院收治的基因1b型CHC患者138例,采用随机数字表法将患者分为DAA组69例,给予格卡瑞韦/哌仑他韦治疗,和PR组69例,给予聚乙二醇干扰素-α2b注射剂联合利巴韦林治疗,两组均治疗12 w,随访12 w。常规检测血清天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、HCV RNA及白细胞(WBC)和血小板(PLT)计数。结果 在治疗结束时,DAA治疗组血清AST和ALT水平分别为(35.2±6.2)U/L和(30.7±5.4)U/L,均显著低于PR治疗组【分别为(48.4±6.9)U/L和(45.4±6.1)U/L,均P＜0.05】;DAA治疗组快速病毒学应答率、治疗结束病毒学应答率和持续病毒学应答率分别为78.3%、95.7%和95.7%,均显著高于PR治疗组的65.2%、76.8%和76.8%(均P＜0.05);在治疗过程中,PR治疗组外周血白细胞计数和血小板计数分别为(3.4±1.4)×10⁹/L和(110.7±30.8)×10⁹/L,均显著低于DAA治疗组【分别为(6.3±1.3)×10⁹/L和(208.3±30.2)×10⁹/L,P<0.05】;在治疗期间,DAA组不良反应发生率为5.8%,显著低于PR组的84.1%(P<0.001)。结论 应用格卡瑞韦/哌仑他韦治疗基因1b型CHC患者病毒学应答率高,疗效好,而不良反应小,值得进一步临床观察。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Language of CTO interventions – Focus on hardware

The knowledge of variety of chronic total occlusion (CTO) hardware and the ability to use them represents the key to success of any CTO interventions. However, the multiplicity of CTO hardware and their physical character and the terminology used by experts create confusion in the mind of an average interventional cardiologist, particularly a beginner in this field. This knowledge is available but is scattered. We aim to classify and compare the currently used devices based on their properties focusing on how physical character of each device can be utilized in a specific situation, thus clarifying and simplifying the technical discourse.