Glutamoptosis: A new cell death mechanism inhibited by autophagy during nutritional imbalance

Glutaminolysis plays a critical role in nutrient sufficiency and cell signaling activation in mammalian cells. Unexpectedly, our recent investigations revealed that the unbalanced activation of glutaminolysis during nutritional restriction causes a particular form of apoptotic cell death, that we termed “glutamoptosis.“ We found that the inhibition of autophagy is a key step to allow glutamoptosis-mediated cell death. Thus, autophagy controls glutamoptosis during nutritional imbalance.     

Genetic changes in skin tumor progression: correlation between presence of a mutant ras gene and loss of heterozygosity on mouse chromosome 7

Initiation of tumorigenesis in mouse skin can be accomplished by mutagenesis of the H-ras gene by treatment with chemical carcinogens. A mouse model system has been developed to study the additional genetic events that take place during tumor progression. Skin carcinomas were induced in F1 hybrid mice exhibiting restriction fragment length polymorphisms at multiple chromosomal loci. Analysis of loss of heterozygosity in such tumors showed that imbalance of alleles on mouse chromosome 7, on which the H-ras gene is located, occurs very frequently in skin carcinomas. The chromosomal alterations detected, which included both nondisjunction and mitotic recombination events, were only seen in tumors that have activated ras genes. We conclude that gross chromosomal alterations that elevate the copy number of mutant H-ras and/or lead to loss of normal H-ras are a consistent feature of mouse skin tumor development.     

妊娠期女性HPV感染及阴道微生态失衡对妊娠结局及新生儿的影响

探讨妊娠期女性人乳头瘤病毒（HPV）感染及阴道微生态失衡对妊娠结局及新生儿结局的影响,为该类患者的治疗提供参考。

选取2020年6月至2023年6月于我院产检的102例HPV阳性妊娠妇女（HPV阳性组）以及同期产检的78例HPV阴性妊娠妇女（HPV阴性组）为研究对象,于怀孕28～34周时,收集阴道分泌物评价阴道微生态状况;另根据微生态评价结果将HPV阳性组对象分为微生态正常组（n=26）和微生态失调组（n=76）;比较HPV阳性组与HPV阴性组对象阴道微生态情况、妊娠结局及新生儿结局,比较微生态正常组与微生态失调组对象妊娠结局及新生儿结局。

HPV阳性组和HPV阴性组对象滴虫性阴道炎（TV）和外阴阴道假丝酵母菌病（VVC）发生率、阴道清洁度比较差异均无统计学意义（χ²=1.520、0.678、0.111,均P＞0.05）,而阴道pH、细菌性阴道病（BV）发生率、阴道菌群密集度、阴道菌群多样性以及微生态失调发生率比较差异均有统计学意义（χ²=10.106、8.247、4.337、5.236、13.865,均P＜0.05）。HPV阳性组对象早产、宫内感染、产褥感染及产后出血发生率显著高于HPV阴性组（χ²=5.710、10.721、6.799、4.294,均P＜0.05）,而两组对象剖宫产率及胎膜早破发生率比较差异无统计学意义（χ²=1.067、0.666,均P＞0.05）。HPV阳性组新生儿感染发生率显著高于HPV阴性组（χ²=9.001,P＜0.05）,两组胎儿窘迫、新生儿窒息和胎儿宫内生长受限（FGR）发生率比较差异均无统计学意义（χ²=2.503、1.547、0.560,均P＞0.05）。微生态失调组对象早产发生率显著高于微生态正常组（χ²=4.130,P＜0.05）,而两组胎膜早破、宫内感染、产褥感染及产后出血发生率比较差异均无统计学意义（χ²=1.401、0.578、0.141、1.368,均P＞0.05）。微生态失调组与微生态正常组胎儿窘迫、新生儿窒息、FGR和新生儿感染发生率比较差异均无统计学意义（χ²=0.261、0.698、1.057、0.242,均P＞0.05）。

妊娠期HPV感染能引发阴道微生态失调,增加不良母婴结局发生风险。

     

Chronic food shortage and seasonal modulations of daily torpor and locomotor activity in the grey mouse lemur (Microcebus murinus)

The extent to which seasonal plasticity in torpor displayed by one of the smallest Malagasy primates (Microcebus murinus) will help survival in the context of ongoing global change-induced chronic food shortage, is unknown. Body temperature (Tb) and locomotor activity were measured by telemetry in short- (SD, winter-acclimated) and long-days (LD, summer-acclimated) males (n = 24) during an experimental 35-day calorie restriction of 40 or 80%. Under SD exposure, regardless of calorie restriction intensity, mouse lemurs immediately increased torpor depth and duration by 4.6-fold, and showed greater phase-advanced entry into torpor (2.4-fold). Tb adjustments were efficient under 40% calorie restriction to maintain body mass, whereas they did not prevent a 0.71 +/- 0.11 g/day mass loss during 80% calorie restriction. The 40% food-deprived LD animals combined an early shallow deepening of torpor (1 degrees C) and a late 18% decrease in locomotor activity, resulting in a moderate 6% mass loss. After 15 days of 80% calorie restriction, LD animals exhibited a SD phenotype by increasing their torpor duration and phase-advancing the entry of torpor (16 min/day). Those adjustments had no impact on mass loss (0.93 +/- 0.07 g/day) as locomotor activity increased four-fold. Daily torpor allows M. murinus to face moderate food shortage whatever the photoperiod but poorly mitigates energy imbalance during severe food deprivation, especially under LD exposure. Although the behavioral thermoregulation role warrants further investigation in energy savings, M. murinus survival would be impaired during long-term food shortage in summer.     

妊娠中晚期阴道微生态失调及乳酸菌胶囊干预对不良妊娠结局的作用

目的 观察妊娠中晚期妇女阴道微生态状况,探讨应用乳杆菌活菌胶囊纠正阴道微生态失调对不良妊娠结局的预防价值。方法 选择孕13~36周单胎妊娠期妇女560例,取其阴道分泌物,经革兰染色后油镜下观察,进行阴道微生态（阴道菌群的密集度、多样性、优势菌、炎症反应等）状况评价,检测阴道分泌物成分、阴道病原菌类型。对阴道微生态失调孕妇,根据是否接受乳杆菌活菌胶囊治疗分为治疗组和对照组,治疗组给予乳杆菌活菌胶囊,对照组不采用药物干预。追踪随访所有孕妇的妊娠情况,比较阴道微生态正常组、微生态失调治疗组及微生态失调对照组的不良妊娠结局。结果 560例研究对象中,阴道微生态正常 335 例（59.82%）,微生态失调225例（40.18%）。225例微生态失调孕妇中,细菌性阴道病（bacterial vaginosis,BV）32例（14.22%）,阴道假丝酵母菌病（vulvovaginal candidiasis,VVC）56例（24.89%）,滴虫性阴道炎（triehomonal vaginitis,TV）11例（4.89%）,BV和VVC混合感染4例（1.78%）,BV和TV混合感染3例（1.33%）,菌群增殖过度75例（33.33%）,菌群抑制44例（19.56%）。微生态失调组pH值>4.5、过氧化氢、白细胞酯酶、唾液酸苷酶、脯氨酸氨基肽酶、乙酰氨基葡萄糖苷酶阳性比例均明显高于微生态正常组（χ2=55.59~340.06,Ps0.05）。结论 妊娠中晚期容易导致阴道微生态失调,造成不良妊娠结局,乳杆菌活菌胶囊纠正阴道微生态失调对于改善不良妊娠结局有较好的预防作用。     

口服益生菌对慢性阻塞性肺病患者肠道菌群和肺功能及预后的影响

目的 探讨口服益生菌对慢性阻塞性肺病(COPD)患者肠道菌群、肺功能及预后等的影响。 方法 选取我科收治的90例COPD稳定期患者,分为研究组及对照组,各45例。其中研究组在常规治疗基础上联合口服双歧杆菌乳杆菌三联活菌片治疗,对照组采用常规治疗,检测两组治疗前、后肠道菌群失调率、肺功能指标水平、血清炎性指标水平和生活质量情况,比较两组患者临床疗效。 结果 治疗后,研究组患者的肠道菌群失调率为22.2%,较对照组的53.3%明显下降(P结论 口服双歧杆菌乳杆菌三联活菌片可显著提高COPD患者的治疗效果,改善其肠道菌群失调情况和肺功能,降低机体的炎性反应程度,改善预后,值得临床推广应用。     

血清G-CSF、ADPN在奥沙利铂联合卡培他滨治疗Ⅲ期结直肠癌患者术后辅助中的表达及其与肠道菌群失调的相关性

摘要 目的：探究III期结直肠癌手术患者接受奥沙利铂联合卡培他滨治疗后血清粒细胞集落刺激因子（G-CSF）、人脂联素（ADPN）水平的变化,分析血清G-CSF、ADPN水平与肠道菌群失调的相关性。方法：选择2021年1月至2021年12月于我院接受手术治疗的220例III期结直肠癌患者为研究对象,均对其联合应用奥沙利铂与卡培他滨进行治疗,分析治疗前后患者血清G-CSF、ADPN水平变化,将入组患者按照肠道菌群情况分为肠道正常组（n=80）、菌群失调I度组（n=90）、菌群失调II度组（n=50）,分析肠道菌群失调对入组患者治疗前后血清G-CSF、ADPN水平的影响,最后评估血清G-CSF、ADPN水平与肠道菌群失调的相关性。结果：（1）治疗后入组患者血清G-CSF、ADPN水平均较治疗前出现了明显的降低,前后比较有差异（P<0.05）;（2）治疗后菌群正常组患者血清G-CSF、ADPN水平明显低于菌群失调I度组,菌群失调I度组明显低于菌群失调II度组,各组间血清G-CSF、ADPN水平有差异（P<0.05）;（3）不同肠道菌群失调组患者肠道菌群数量存在差异,患者肠道菌群失调情况越严重,其肠球菌数量越高,乳杆菌数量越低（P<0.05）;（4）血清G-CSF、ADPN水平与乳杆菌数量呈现负相关（r=-0.872、-0.781,P<0.05）,与肠球菌数量呈现正相关（r=0.772、0.819,P<0.05）。结论：Ⅲ期结直肠癌行手术治疗患者术后联用奥沙利铂与卡培他滨可以显著降低其血清G-CSF、ADPN水平,且其降低程度与患者肠道菌群失调情况相关,提示可以考虑将调节结直肠癌患者肠道菌群作为降低患者化疗后炎性反应措施之一推广于临床。     

Osmoregulatory defect in adult mice associated with deficient prenatal expression of six2

Suboptimal kidney development resulting from a genetic deficit in nephron number can have lifelong consequences that may lead to cardiorenal complications upon exposure to secondary insults in later life. To determine whether the inherited reduced renal reserve compromises the ability to handle osmotic stress in the adult animal, we challenged the heterozygous 3H1 Brachyrrhine (Br/+) mouse, which displays heritable renal hypoplasia associated with reduced embryonic six2 expression, to a solution of 2% NaCl for 5 days or to fluid restriction for 48 h. Blood chemistry, fluid intake, and physiological parameters, including renal measurements, were determined. Systemic hypertonicity by prolonged salt loading led to significant increases in plasma osmolality and plasma Na(+), along with polydipsia and polyuria, with a significant urine-concentrating defect that was resistant to DDAVP treatment in the adult Br/+ mouse compared with wild-type littermates. The Br/+ mouse also developed a significant increase in blood urea nitrogen at baseline that was further elevated when 2% NaCl was given. Fluid restriction for 48 h further enhanced plasma osmolality and plasma Na(+) responses, although the Br/+ mouse was evidently able to produce a small amount of concentrated urine at this time. Hypothalamic c-Fos expression was appropriately activated in the Br/+ mouse in response to both osmotic challenges, indicating an intact central neuroendocrine pathway that was not affected by the lack of congenital six2 expression. Collectively, our results demonstrate impaired osmoregulatory mechanisms consistent with chronic renal failure in the Br/+ mouse and indicate that six2 haploinsufficiency has a direct effect on postnatal fluid and electrolyte handling associated with fluid imbalance.     

肠道菌群与肠易激综合征相关研究进展

肠易激综合征(irritable bowel syndrome,IBS)是一种功能性肠病,目前已有研究表明IBS的致病机制、症状的产生和持续时间可能与肠道菌群失调有关,且不同IBS亚型患者体内的肠道菌群种类有差异。IBS的发病机制尚不完全清楚,临床表现存在较大的个体差异。IBS的诊断和治疗尚未形成统一的标准。但已经有较多研究提示IBS可能与胃肠道动力、内脏高敏感性、肠道免疫反应和模式识别受体等密切相关,并且可以通过益生菌、益生元、抗生素、粪菌移植和饮食习惯等调节肠道菌群的失调,从而改善IBS的症状。这也为未来治疗IBS提供了新的思路。本文就肠道菌群的概况、IBS患者肠道菌群的特点、肠道菌群失衡导致IBS发病的可能机制以及IBS肠道菌群的相关治疗方法的研究进展作一综述。     

Ouderen uit balans

Balance disorders in the elderly often have several contributing causes. The search for these causes focuses on vision, proprioception, coordination and medication. The peripheral vestibular system is often overlooked. This is probably due to the fact that most clinicians overlook the vestibular system, when complaints of vertigo are missing. However, dysfunction of the vestibular system may cause imbalance without vertigo. Three cases are presented. One case illustrates several contributing causes leading to imbalance. Two other cases illustrate causes of vestibular dysfunction resulting in imbalance without vertigo: a bilateral vestibulopathy and benign paroxysmal positional vertigo. Symptoms, examination and treatment are discussed. All patients with imbalance should undergo a Head Impulse Test and Dix-Hallpike maneuver.     

LenkeⅡ型青少年特发性脊柱侧凸患者内固定冠状面失衡的相关因素分析

目的:探讨Lenke II型青少年特发性脊柱侧凸患者内固定冠状面失衡相关因素分析。方法:选取我院骨科已确诊为Lenke II青少年特发性脊柱侧凸患者60例,根据术前脊柱柔韧度、risser分级水平、支具支持治疗、椎体融合数、内固定系统选择等多方面影响因素对内固定后冠状面失平衡情况发生率进行分析评估,其数据结果应用统计学软件SPSS 17.0处理。结果:对术后患者评估比较,多种因素均可影响内固定后冠状面失平衡情况发生,表现为:脊柱柔韧度低、risser分级高、长时间支具佩戴、延长融合椎体范围、先进钉棒系统方案选择均可明显提高术后疗效,降低内固定后冠状面失平衡情况发生率(P0.05),其结果均有统计学意义。结论:临床上通过对患者脊柱柔韧度、risser分级情况评估来判断脊柱成熟度,并在术后积极支具辅助治疗,选用钉棒固定系统并延长融合椎体节段,可明显降低内固定后冠状面失平衡情况发生,提高远期随访疗效。     

补充肠道益生菌治愈灰指甲8例分析

目的总结补充肠道益生菌治愈甲真菌病的经验。方法对2007年2月至2008年2月期间采用口服肠道益生菌治愈甲真菌病8例的临床资料进行分析。结果补充肠道益生菌可以治愈甲真菌病。结论补充肠道益生菌可以调节体内正常菌群的失衡,对肠道外的微生态失衡同样有效。     

肠道菌群对帕金森病并发抑郁症影响机制探析

抑郁作为帕金森病最为常见的非运动症状, 具有患病率高, 起病隐匿等特点, 不仅造成患者生活质量的降低, 也给病情的控制造成很大困难, 因此加强对此病的研究尤为必要。对于帕金森病并发抑郁症的治疗, 目前多采用对症治疗的方案, 将抗帕金森病与抗抑郁症相联合, 忽视了抑郁症作为帕金森病的并发症, 双方必然存在内在联系。研究发现肠道菌群失调会导致抑郁症的发生, 而帕金森病患者体内肠道微生态明显失衡, 因此本文提出肠道菌群失调可能是帕金森病并发抑郁症发生的关键影响因素。肠道菌群失调会导致血清素能系统异常、炎症反应和脑源性神经营养因子缺乏, 从而造成抑郁症的发生, 因此认为调节肠道菌群可能成为治疗帕金森病并发抑郁症的新方向。

     

间充质干细胞对Th17/Treg平衡的影响及与IBD的关系

辅助性T细胞17（Th17）/调节性T细胞（Treg）失衡是炎症性肠病（IBD）发病的重要因素,纠正Th17/Treg细胞失衡可以减缓或抑制IBD的发生发展,成为治疗IBD的靶点。间充质干细胞具有抗炎及免疫调节功能,通过可溶性因子、细胞接触及外泌体的方式调节适应性和先天性免疫,纠正Th17/Treg失衡缓解IBD,这给IBD的治疗提供新的方向。目前,MSCs和IBD的关系研究较少,本文综述了MSCs调节Th17/Treg平衡及与IBD的关系。     

Run-Reversal Equilibrium for Clinical Trial Randomization

In this paper, we describe a new restricted randomization method called run-reversal equilibrium (RRE), which is a Nash equilibrium of a game where (1) the clinical trial statistician chooses a sequence of medical treatments, and (2) clinical investigators make treatment predictions. RRE randomization counteracts how each investigator could observe treatment histories in order to forecast upcoming treatments. Computation of a run-reversal equilibrium reflects how the treatment history at a particular site is imperfectly correlated with the treatment imbalance for the overall trial. An attractive feature of RRE randomization is that treatment imbalance follows a random walk at each site, while treatment balance is tightly constrained and regularly restored for the overall trial. Less predictable and therefore more scientifically valid experiments can be facilitated by run-reversal equilibrium for multi-site clinical trials.     

Is modification sufficient to protect a bacterial chromosome from a resident restriction endonuclease?

It has been generally accepted that DNA modification protects the chromosome of a bacterium encoding a restriction and modification system. But, when target sequences within the chromosome of one such bacterium (Escherichia coli K-12) are unmodified, the cell does not destroy its own DNA; instead, ClpXP inactivates the nuclease, and restriction is said to be alleviated. Thus, the resident chromosome is recognized as 'self' rather than 'foreign' even in the absence of modification. We now provide evidence that restriction alleviation may be a characteristic of Type I restriction-modification systems, and that it can be achieved by different mechanisms. Our experiments support disassembly of active endonuclease complexes as a potential mechanism. We identify amino acid substitutions in a restriction endonuclease, which impair restriction alleviation in response to treatment with a mutagen, and demonstrate that restriction alleviation serves to protect the chromosome even in the absence of mutagenic treatment. In the absence of efficient restriction alleviation, a Type I restriction enzyme cleaves host DNA and, under these conditions, homologous recombination maintains the integrity of the bacterial chromosome.     

Polyploidizing mitoses and the biological meaning of polyploidy in liver cells]

The ontogenetic polyploidization of hepatocytes is regarded, within which normal mitoses are changed to polyploidizing mitoses, and diploid hepatocytes transform into polyploid mono- and binuclear cells. A new hypothesis is put forward of the biological significance of the liver cell polyploidy. The hypothesis takes into account a high level of spontaneous chromosomal aberrations in mitotic hepatocytes. The chromosome structural changes interfere with mitosis resulting in the chromosomal imbalance. Polyploidy bestows for hepatocytes a tolerance towards a chromosomal imbalance. Some implications of the hypothesis are discussed: unbalanced genome of hepatocytes after the treatment with mutagens and mitotic stimulators; the reasons of liver cell polyploidy differences in mammalian species; mechanisms of radioresistance of hepatocytes. Chromosomal imbalance of polyploid hepatocytes is assumed to be the basis for wome chronic liver diseases in man.