Research progress on the involvement of poly (ADP-ribose) polymerase-1-dependent cell death in ischemia-reperfusion injury / 中国医师杂志

Ischemia reperfusion injury (IRI) of organs is a major challenge for clinicians, but the mechanism is still not elucidated, and the clinical treatment effect is still unsatisfactory. PARP-1-dependent cell death (parthanatos) is a non-apototic programmed cell death pathway involved in the development of the occurrence of IRI of organs. At the same time, parthanatos is also a multi-step pathway. There are many molecules in the parthanatos cascade that can be exploited to create therapeutic interventions for IRI, including PARP1, apoptosis inducing factor (AIF), and macrophage migration inhibitory factor (MIF). These critical molecules are involved in DNA damage, energy depletion and homeostasis imbalance. Therefore, these molecular signals in the parthanatos cascade represent promising therapeutic targets for the treatment of IRI. In the following, we will elaborate on the mechanisms and molecular characteristics of the parthanatos pathway and the relation between parthanatos pathway and IRI of vital organs. It aims to explore the posibility of IRI mechanism research and clinical treatment and to provide new ideas for clinicians and researchers.

Changes of high mobility group protein B1 in condyloma acuminatum and its clinical significance / 中国医师进修杂志

Objective:To investigate the changes and clinical significance of high mobility group protein B1 (HMGB1) in condyloma acuminatum (CA).Methods:Sixty four patients with initial CA(initial group) and 48 patients with recurrent CA(recurrent goup) treated in the Second Affiliated Hospital of PLA Air Force Military Medical University Hospital from January 2019 to November 2020 were included. In the same period, 31 patients who underwent circumcision and 19 female underwent sexual organ cosmetic plastic surgery were taken as the control group, and the normal foreskin and healthy vulva were collected. The expression of HMGB1 in wart was detected by real-time quantitative polymerase chain reaction(RT-PCR), and the expression of soluble apoptosis related factor ligand (sFasL), cell lymphoma-2 gene (Bcl-2), soluble apoptosis related factor (SFAS) and Survivin, caspase-3 were detected. At the same time, serum interleukin (IL) - 6, IL-17, IL-23 and tumor necrosis factor - α (TNF- α) were detected by enzyme-linked immunosorbent assay(ELISA).Results:The expression of HMGB1 mRNA in the warts of patients in the initial group, recurrence group and control group were 1.96 ± 0.20, 1.53 ± 0.14, 1.05 ± 0.11, there was statistical difference ( F = 15.20, P<0.05) ; the expression of HMGB1 mRNA in the warts of patients in the initial group was significantly higher than that in the recurrence group and the control group ( P<0.05), and the recurrence group was also significantly higher than that in the control group ( P<0.05). The mRNA expressions of sFas, Bcl-2, sFasL and caspase-3 in the warts of patients in the initial group were significantly lower than those in the recurrence group and the control group: 0.52 ± 0.08 vs. 0.82 ± 0.16, 1.10 ± 0.19; 0.50 ± 0.05 vs. 0.79 ± 0.13, 1.08 ± 0.21; 0.47 ± 0.06 vs. 0.81 ± 0.15, 1.01 ± 0.19; 0.35 ± 0.04 vs. 0.68 ± 0.09, 0.91 ± 0.16, P<0.05; and the recurrence group were also significantly lower than those in the control group ( P<0.05). The expression of Survivin mRNA in the warts of patients in the initial group was significantly higher than those in the recurrence group and the control group: 2.14 ± 0.40 vs. 1.60 ± 0.27, 0.99 ± 0.18, P<0.05, and the recurrence group was also significantly higher than that in the control group ( P<0.05). The serum levels of TNF-α and IL-6 in the initial group were significantly lower than that in the recurrence group and the control group: (20.08 ± 1.95) μg/L vs. (26.93 ± 2.74), (37.65 ± 3.83) μg/L; (31.05 ± 3.24) μg/L vs. (38.13 ± 3.76), (45.98 ± 4.69) μg/L, P<0.05; and the recurrence group were also significantly lower than those in the control group ( P<0.05). The serum levels of IL-17 and IL-23 in the primary group were significantly higher than those in the recurrence group and the control group: (423.71 ± 28.68) ng/L vs. (384.26 ± 21.70) and (335.43 ± 19.65) ng/L; (289.50 ± 18.53) ng/L vs. (251.07 ± 15.96) and (214.67 ± 13.20) ng/L, P<0.05; and the recurrence group were also significantly higher than those in the control group ( P<0.05). The results of correlation analysis showed that the mRNA expression of HMGB1 in the warts of CA patients were negatively correlated with the mRNA expression of caspase-3, sFas, Bcl-2 and sFasL in the warts ( r = - 0.602, - 0.734, - 0.692, - 0.717, P<0.05), and was positive correlation with Survivin mRNA expression ( r = 0.645, P<0.05); and were positive correlation with the contents of IL-17 and IL-23 in serum ( r = 0.673, 0.685, P<0.05), and negatively correlated with the contents of TNF-α and IL-6 ( r = - 0.698, - 0.764, P<0.05). Conclusions:HMGB1 is obviously abnormal in the warts of patients with condyloma acuminatum, and is closely related to apoptosis, immune and inflammation-related factors, and may be jointly involved in the occurrence and recurrence of CA.

Progress on AIFM1 gene mutation related diseases / 国际儿科学杂志

The apoptosis-inducing factor, mitochondrion-associated 1(AIFM1)gene encodes an apoptosis-inducing factor(AIF)protein with apoptosis and redox function.AIF is widely expressed within cells in human tissues, and playing an important role in the mitochondria.Mutations in the AIFM1 gene are associated with severe X-linked mitochondrial encephalomyopathy, Cowchock syndrome, X-linked spondyloepimeta-physeal dysplasia with hypomyelinating leukodystrophy, auditory neuropathy and other diseases.AIFM1 gene mutations exhibit a wide range of clinical phenotypes, but the pathogenesis between mutations and phenotypes and phenotypic severity remains unclear.This paper summarizes the reported AIFM1 mutation-related loci, phenotypes, and possible pathogenesis mechanisms, and provide a brief review of AIFM1 mutation-related diseases and their progression.

AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

Research progress on treatment strategies for related diseases based on Parthanatos / 中国生物制品学杂志

@#Parthanatos is a form of programmed cell death,which is also known as poly(ADP-ribose)polymerase 1(PARP1)-mediated apoptosis-inducing factor(AIF)and macrophage migration inhibitory factor(MIF)-dependent cell death according to its molecular mechanism. Parthanatos is the main cause of a variety of neurodegenerative diseases,such as Parkinson's disease(PD),Alzheimer's disease(AD),motor neuron disease,and is also involved in the pathogenesis of some tumors,such as lung cancer and breast cancer. Therefore,a thorough understanding of the molecular mechanism of Parthanatos is crucial for the therapeutic strategies of related diseases. In recent years,studies have found that effective regulation of the occurrence of Parthanatos by regulating the key proteins PARP1,AIF and MIF is expected to become a therapeutic target for many diseases. Based on the specific molecular mechanism of Parthanatos,this paper reviewed the research progress of therapeutic strategies for related diseases from the aspects of inhibiting and promoting Parthanatos.

Research progress on whitening of brown adipose tissues / 中国药理学通报

Brown adipose tissues can consume energy by generating heat. The whitening of BAT will damage its thermogenic function and cause diseases related to obesity and metabolic disorders. It is of great significance to slow down or inhibit the process of BAT whitening. This article reviews the inducing factorsand the key regulators of brown adipose tissue whitening, hoping to provide some ideas for the prevention and treatment of obesity and metabolic disorders.

Recommendations for the use of the acetaminophen hepatotoxicity model for mechanistic studies and how to avoid common pitfalls

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, which is safe at therapeutic doses but can cause severe liver injury and even liver failure after overdoses. The mouse model of APAP hepatotoxicity recapitulates closely the human pathophysiology. As a result, this clinically relevant model is frequently used to study mechanisms of drug-induced liver injury and even more so to test potential therapeutic interventions. However, the complexity of the model requires a thorough understanding of the pathophysiology to obtain valid results and mechanistic information that is translatable to the clinic. However, many studies using this model are flawed, which jeopardizes the scientific and clinical relevance. The purpose of this review is to provide a framework of the model where mechanistically sound and clinically relevant data can be obtained. The discussion provides insight into the injury mechanisms and how to study it including the critical roles of drug metabolism, mitochondrial dysfunction, necrotic cell death, autophagy and the sterile inflammatory response. In addition, the most frequently made mistakes when using this model are discussed. Thus, considering these recommendations when studying APAP hepatotoxicity will facilitate the discovery of more clinically relevant interventions.

Solute carrier transporters: the metabolic gatekeepers of immune cells

Solute carrier (SLC) transporters meditate many essential physiological functions, including nutrient uptake, ion influx/efflux, and waste disposal. In its protective role against tumors and infections, the mammalian immune system coordinates complex signals to support the proliferation, differentiation, and effector function of individual cell subsets. Recent research in this area has yielded surprising findings on the roles of solute carrier transporters, which were discovered to regulate lymphocyte signaling and control their differentiation, function, and fate by modulating diverse metabolic pathways and balanced levels of different metabolites. In this review, we present current information mainly on glucose transporters, amino-acid transporters, and metal ion transporters, which are critically important for mediating immune cell homeostasis in many different pathological conditions.

Effect of acupuncture on neurological function, cerebral infarction volume, thrombolysis time window and cerebral cell apoptosis signaling pathway in cerebral infarction rats / 针刺研究

OBJECTIVE: To observe the effect of acupuncture (Acupunct) on cerebral infarction volume and expression of poly ADP ribose polymerase 1 (PARP1), apoptosis-inducing factor (AIF) and endonuclease G (Endo-G) in the cerebral cortex tissue at different time-points after cerebral ischemia (CI) in acute cerebral infarction rats, so as to explore its underlying mechanisms in prolonging time window of thrombolysis. METHODS: Forty-eight SD rats were randomly divided into sham operation, model, intravenous thrombolysis (IVT)-4.5 h, IVT-6 h, IVT-9 h, Acupunct＋IVT-4.5 h, Acupunct ＋IVT-6 h, Acupunct＋IVT-9 h groups (n＝6 in each group). The CI model was established by using modified autologous thromboembolism via the right common carotid artery. Two hours after modeling, rats of the Acupunct groups received Acupunct stimulation of "Shuigou" (GV26) and bilateral "Neiguan" (PC6) for 30 min. Thrombolysis was conducted by injection of recombinant human tissue-type plasminogen activator (rt-PA, 10 mg/kg) via caudal vein. The neurological deficit was assessed with reference to Bederson's methods. 2，3，5-triphenyltetrazolium chloride (TTC) staining was used to assess the cerebral infarction volume, and the expression of cerebral PARP1, AIF and Endo-G proteins detected by Western blot. RESULTS: Compared with the sham operation group, the neurological score and percentage of cerebral infarction volume, expression levels of PARP1, AIF and Endo-G proteins were significantly increased in the model group (P0.05). The levels of neurological score, percentage of cerebral infarction volume, and AIF expression were significantly lower in both the Acupunct＋IVT 4.5 h and Acupunct＋IVT-6 h groups than in the simple IVT-4.5 h and simple IVT-6 h groups, respectively (P<0.05), and the expression levels of PARP1 and Endo-G proteins were obviously lower in the Acupunct＋IVT-4.5 h group than in the IVT-4.5 h group (P<0.05). Endo-G proteins were obviously lower in the Acupunct＋IVT-9 h group than in the IVT-9 h group (P<0.05). CONCLUSION: Acupuncture may improve neurological function, reduce cerebral infarction volume and prolong the time window of thrombolysis in CI rats, which may be associated with its effect in suppressing AIF/PARP1/ Endo-G signaling.

Effect of hot water extract of Korean ginseng on neuroblastoma cell parthanatos / 南方医科大学学报

OBJECTIVE@#To explore the effect of pretreatment of neuroblastoma cells with hot water extract of Korean ginseng on MNNG-induced parthanatos and its mechanism.@*METHODS@#Neuroblastoma SH-SY5Y cells were pretreated with 1 mg/L hot water extract of Korean ginseng before induction with 250 μmol/L MNNG for 1 h or 4 h. CCK-8 and cell flow cytometry were used to detect cell survival rate. Western blotting was used to detect the changes in poly(ADP-ribose) (PAR) expression in the treated cells. Immunofluorescence assay was used to detect nuclear distribution of apoptosis-inducing factor (AIF), and flow cytometry was used to detect the level of reactive oxygen species (ROS) in the cells.@*RESULTS@#Compared with the blank control cells, MNNG-treated SH-SY5Y cells showed significantly decreased survival rate as the concentration of MNNG and the stimulation time increased ( < 0.05). Stimulation with MNNG also resulted in significantly increased expression of PAR protein in the cells ( < 0.05). Pretreatment of the cells with hot water extract of Korean ginseng obviously inhibited MNNG-induced cell death and significantly reduced AIF expression and nucleation in the cells ( < 0.05). MNNG stimulation significantly increased ROS level in the cells, which was decreased significantly by pretreatment of the cells with the extract ( < 0.05).@*CONCLUSIONS@#Pretreatment with hot water extract of Korean ginseng reduces MNNG-induced parthanatos and ROS production in SH-SY5Y cells.

The effect of butylphthalide on cell necroptosis in cerebral ischemia reperfusion injury model mice / 中华行为医学与脑科学杂志

Objective To explore the protective effect and mechanism of butylphthalide on cerebral ischemia reperfusion injury in mice.Methods The cerebral ischemia reperfusion injury model was established by middle cerebral ischemia occlusion (MCAO).Thirty mice were divided into sham group,ischemia reperfusion group(I/R group) and butylphthalide group (NBP group) with 10 in each group.Neurological defect score and brain infarction volume were detected by TTC to evaluate the treatment effects of butylphthalide.Western blot was used to detect expression of RIP,RIP3 and AIF.Immunocoprecipitation (IP) was used to detect the interaction of AIF and RIP3.Immunofluorescence(IF) was used to detect the nuclear translocation and co-localization of AIF and RIP3.Results Compared with the I/R group,NBP treatment reduced the neurological defect score (I/R:(2.60 ± 0.22),NBP:(1.90 ± 0.23),t =2.18,P＜ 0.05) and brain infarction volume(I/R:(38.32±2.22) ％,NBP:(25.23±2.70) ％,t=3.74,P＜0.01).I/R elevated the expression of RIP1 and RIP3 whereas NBP significantly inhibited the expression of these two proteins (RIP1 (I/R:0.99±0.24,NBP:0.47±0.10,t=2.71,P＜0.05);RIP3 (I/R:0.52±0.17,NBP:0.15±0.04,t=2.87,P＜0.05)).I/R and NBP had no significant effects on the expression of AIF,but the IP results showed that I/R increased the interaction between AIF and RIP3 compared with the sham group.NBP alleviated the interaction between AIF and RIP3.IF results showed that the colocalization and nuclear expression of AIF and RIP3 increased after I/R whereas NBP treatment decreased the effect induced by I/R.Conclusion Butylphthalide alleviated cerebral ischemia reperfusion injury in mice through inhibiting the cell necroptosis.The mechanisms may correlate with decreasing the expression of RIP1 and RIP3 and alleviating the interaction and nuclear translocation of AIF and RIP3.

Effects of ginsenoside Rg1 on survivin protein expression and apoptosis in rats with spinal cord ischemia-reperfusion injury / 西安交通大学学报(医学版)

Objective: To observe the effects of ginsenoside Rg1 pretreatment on the expression of survivin protein and apoptosis after spinal cord ischemia-reperfusion injury (SCII) in rats so as to explore the possible mechanism of ginsenoside Rg1 on motor function recovery after SCII in rats. Methods: We selected 120 adult healthy SD rats to construct the model of SCII and randomly divided them into four groups: sham operation group, ischemia group, ischemia-reperfusion group, and drug group. Basso Beattie and Bresnahan score (BBB score) was used to evaluate the motor function of the hind limbs of the rats. The expressions of survivin protein and apoptosis-inducing factor (AIF) was observed by immunohistochemistry. The expression and activity of survivin protein and Caspase-9 in each group were observed and analyzed by Western blot and RT-PCR. Results: The intervention of ginsenoside Rg1 could increase the score of the motor function of the rat hind limbs. It could decrease the number of AIF positive cells, but increase the number of survivin protein positive cells. Ginsenoside Rg1 could decrease the expressions of survivin and Caspase-9, and decrease the apoptosis of nerve cells in SCII. Conclusion: Ginsenoside Rg1 could inhibit the expression of Caspase-9 by promoting the expression of survivin protein and decrease the apoptosis of rat SCII induced by the level of cytoplasmic AIF.

Berberine Induces Cell Apoptosis through Cytochrome C/Apoptotic Protease-Activating Factor 1/Caspase-3 and Apoptosis Inducing Factor Pathway in Mouse Insulinoma Cells / 中国结合医学杂志

OBJECTIVE@#To investigate apoptotic effects of berberine, a significant alkaloids component existing in Rhizoma coptidis, and its possible acting mechanism in insulinoma cells.@*METHODS@#Different concentrations of berberine were used to treat mouse insulinoma (MIN6) cells for various period of time. The viability and apoptosis of the cells were analyzed using methylthiazolyldiphenvl-tetrazolium bromide assay, flow cytometry and enzyme-linked immuno sorbent assay. Changes in the relating pro- and anti-apoptosis proteins were detected by western-blotting.@*RESULTS@#The half-maximal inhibitory concentration (IC) of berberine was 5.7 μmol/L on MIN6 cells viability for 16 h. Berberine caused a 20% reduction (P<0.05) in cell number after only 4-h incubation; which reached 50% after 24 h (P<0.01). Berberine treatment for 16 h significantly increased the level of DNA fragmentation. The flow cytometry showed the apoptotic rate increased 2.9- and 4.6-fold after treating with berberine (5 μmol/L) for 8 and 16 h, while 3- and 8.7-fold after 10 μmol/L treatment for 8 and 16 h (P<0.01). Berberine treatment dramatically elevated the expression ratio of Bax to Bcl-2. Meanwhile, berberine notably increased the apoptosis-inducing factors and cytochrome C transforming from the mitochondria to the cytoplasm. Apoptotic protease-activating factor 1 (Apaf-1) was subsequently activated after cytochrome C release. Furthermore, caspase-3 and poly adenosine diphosphate-ribose polymerase were also activated to trigger apoptosis cascade.@*CONCLUSION@#High concentration (5 and 10 μmol/L) of berberine could induce the apoptosis of MIN6 cells through cytochrome C/Apaf-1/caspase-3 and apoptosis inducing factor (AIF) pathway.

Expression of CD147, MMP-9 and HER-2 in patients with gastric cancer and their correlation with clinicopathology and prognosis / 中国基层医药

Objective@#To investigate the correlation between the expression of extracellular matrix metalloproteinase-inducible factor (CD147), matrix metalloproteinase-9 (MMP-9) and human epidermal growth factor receptor-2 (HER-2) in gastric cancer tissues and clinical pathology and prognosis.@*Methods@#From June 2016 to June 2018, 80 gastric cancer specimens from the First People's Hospital of Taizhou were collected as observation group, and another 60 normal specimens of gastric mucosa adjacent to cancer were selected as control group.The expressions of CD147, MMP-9 and HER-2 were detected by SP immunohistochemical method.The positive rates of CD147, MMP-9 and HER-2 protein expression, the positive rates of CD147, MMP-9 and HER-2 protein expression in different pathological characteristics, and the positive rates of CD147, MMP-9 and HER-2 protein expression in different prognosis were compared between the two groups.@*Results@#The positive rates of CD147 (73.75%), MMP-9 (76.25%) and HER-2 (42.50%) in the observation group were higher than those in the control group (21.67%, 25.00%, 5.00%), the differences were statistically significant (χ2=37.233, 36.288, 24.797, all P<0.05). There were no statisticallysignificant differences in the positive expression rates of CD147, MMP-9 and HER-2 protein among different gender, age, tumor diameter and differentiation (all P>0.05). The positive rates of CD147 (93.88%), MMP-9 (95.92%) and HER-2 (61.22%) with lymph node metastasis were higher than those without lymph node metastasis (41.94%, 45.16%, 12.90%), the differences were statistically significant (χ2=26.462, 27.012, 18.142, all P<0.05). The positive rates of CD147 (96.15%), MMP-9 (92.31%) and HER-2 (69.23%) in the death group were higher than those in the survival group (62.96%, 68.52%, 29.63%), the differences were statistically significant(χ2=9.987, 5.484, 11.263, all P<0.05).@*Conclusion@#High expression of CD147, MMP-9 and HER-2 proteins in gastric cancer tissues is closely related to invasion and metastasis, which can become a new prognostic marker and therapeutic target of gastric cancer.

Type I and Ⅱ Cardiorenal Syndrome-related Biomarkers / 中国实验方剂学杂志

The physiology and pathology of the heart and kidney are interdependent and interact with each other, and dysfunction of any one of them causes dysfunction of the other, namely cardiorenal syndrome, in which type I and type Ⅱ have the highest incidence rate and are the commonest in clinic. Traditional Chinese medicine has a long history of treating the cardiorenal syndrome. It believes that the disease is located in the heart and kidney, and Wenyang Yiqi, Huoxue Lishui and other methods shall be adopted to effectively improve the heart and kidney function of patients. However,the pathogenesis of cardiorenal syndrome is complicated, and the clinical manifestations are diverse, which makes it difficult to diagnose and treat in the early stage, and causes missing of the best intervention timing and a poor prognosis. Biomarkers play a vital role in predicting the occurrence and development of cardiorenal syndrome. Therefore, efforts shall be made to look for biomarkers with better specificity and sensitivity, accurately evaluate physiological and pathological changes in heart and kidney, so as to achieve early diagnosis and early intervention of cardiorenal syndrome, and improve the effect of disease diagnosis and treatment. At present, domestic and foreign scholars have studied and applied more markers mainly in renal tubular injury, including neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 and urinary interleukin-18. In addition, other studies have found cell cycle arrest inducing factors, such as insulin-like growth factor binding protein 7, tissue inhibitor metallo proteinase-2, and fibroblast growth factor 23 associated with mineral metabolism. The increase of the content of these biomarkers in the body is earlier than the rise of serum creatinine, which can better predict the occurrence of early cardiorenal syndrome, and has a high application value and research value. After summarization of the biomarkers relating to type I and Ⅱ cardiorenal syndrome in domestic and foreign literatures, the research progress of several representative markers were reviewed to provide reference for related research.

The role of caspase-3, apoptosis-inducing factor, and B-cell lymphoma-2 expressions in term premature rupture of membrane

Abstract Objective To determine the role of caspase-3, apoptosis-inducing factor (AIF), and Bcell lymphoma-2 (Bcl-2) expressions in term premature rupture of membrane (PROM). Methods An analytic observational study with case-control design was conducted, involving 52 subjects (37-42 weeks of gestation) who were divided into 2 groups: 26 cases of term delivery with PROM, and 26 controls of term delivery without PROM. The expressions of caspase-3, AIF, and Bcl-2 in the amniotic membrane were determined by immunohistochemistry. Data were analyzed using the chi-squared test. The risk of PROM was expressed by odds ratio (OR). Results There were no significant differences in age, parity and body mass index between the two groups (p > 0.05). High caspase-3 and AIF expressions increased the risk of PROM 17.64 times (OR = 17.64; 95% CI = 4.44-70.07; p = 0.001) and 9.45 times (OR = 9.45; 95% CI= 2.62-34.07; p = 0.001), respectively, while low Bcl-2 expression increased 10.39 times (OR = 10.39; 95% CI = 2.73-39.56; p = 0.001)the risk of PROM . Conclusion High caspase-3 and AIF expressions and low Bcl-2 expression were risk factors for term PROM. Caspase-dependent and independent pathways of apoptosis were involved in the mechanism of PROM in term pregnancy.

Effect of Iduna protein overexpression on PARP-1∕AIF pathway during oxygen-glucose deprivation-in-duced damage to hippocampal neurons in neonatal rats / 中华麻醉学杂志

Objective To evaluate the effect of Iduna protein overexpression on poly(ADP-ribose) polymerase 1 ( PARP-1)∕apoptosis-inducing factor ( AIF) pathway during oxygen-glucose deprivation (OGD)-induced damage to hippocampal neurons in neonatal rats. Methods Primarily cultured hippocam-pal neurons of healthy Sprague-Dawley rats born within 24 h were isolated and cultured. Hippocampal neu-rons were divided into 4 groups (n = 40 each) using a random number table: control group (group C), OGD group ( group O), negative control lentivirus group ( group NL) and Iduna protein overexpression group (group IO). OGD was induced by incubating the neurons in glucose-free medium and hypoxic envi-ronment. Negative control lentivirus and recombinant lentivirus overexpressing Iduna were added at 48 h be-fore establishing the model in NL and IO groups, respectively. Neurons were cultured in the normal culture medium for 24 h in group C. The cell survival rate was detected using methyl thiazolyl tetrazolium assay, the lactic dehydrogenase (LDH) leakage rate was measured using colorimetric method, the comet assay was used to detect DNA content in the tail of neurons, and the expression of PARP-1, cytochrome C (Cyt c) and AIF in the nucleus was detecteded by Western blot. Results Compared with group C, the survival rate of neurons was significantly decreased, the LDH leakage rate and DNA content in the tail of neurons were increased, and the expression of PARP-1, Cyt c and AIF was up-regulated in the other three groups (P<0. 05). Compared with group O, the survival rate of neurons was significantly increased, the LDH leakage rate and the DNA content in the tail of neurons was decreased, and the expression of PARP-1, Cyt c and AIF was down-regulated in group IO (P<0. 05), and no significant change was found in group NL (P>0. 05). Compared with the group NL, the survival rate of neurons was significantly increased, and the LDH leakage rate and DNA content in the tail of neurons were decreased, and the expression of PARP-1, AIF and Cyt c was down-regulated in the group IO (P<0. 05). Conclusion Iduna protein overexpression reduces OGD-induced damage to hippocampal neurons through inhibiting PARP-1∕AIF pathway in neonatal rats.

A retrospective study of the inducing factors and clinical characteristics of patients hospitalized for asthma exacerbation in China in 2013-2014 / 中华内科杂志

Objective To study the inducing factors and clinical characteristics of patients hospitalized for asthma exacerbation in China. Methods Patients hospitalized for asthma exacerbation at 29 hospitals in China were retrospectively recruited during 2013-2014. Results Clinical data of 3 240 asthmatic patients were collected and analyzed including 1 369(42.3%) males and 1 871(57.7%)females. The patients hospitalized for asthma exacerbation counted for 2.95% (6 375/215 955) of all patients hospitalized during the same period. The leading six inducing factors, in sequence, were acute upper respiratory tract infection[42.3%(1 370/3 240)],changes of weather[22.8%(738/3 240)],noxious gas[(4.3% (140/3 240), allergy challenges [3.5%(115/3 240)], strenuous exercise [1.8%(57/3 240)], and air pollution [1.5%(49/3 240)].In older patients,more exacerbations were induced by weather changes,yet less sensitive to allergy challenges. As to middle-aged patients, they were less sensitive to upper respiratory tract infections,however the difference was not statistically significant(P>0.05).In winter more asthma patients were induced by upper respiratory tract infections,while in autumn more patients were induced by weather changes,strenuous exercise and air pollution.In spring and summer more patients were induced by allergy challenges, but the differences failed to achieve statistical significance (P>0.05). In northern cities more patients were induced by upper respiratory infections, whereas in southern cities more by noxious gases. Allergy challenges and air pollution tended to affect more patients in northern cities,but the difference was of no significance (P>0.05). The differences of inducing factors among patients of different gender, with or without a smoking history, and with different exacerbation severity didn't show any statistical significance. The patients with severe and life-threatening exacerbations counted for 20.1%(652/3 240).The percentage of patients older than 60 years was higher in patients with severe or life-threatening exacerbations than in whose with mild or moderate exacerbations,so did the percentage of male patients,of patients with disease duration longer than 10 years, with smoking history, and with a history of hospitalization or emergency department visits due to asthma exacerbation during the last year.Conclusion The acute upper respiratory tract infection ranks top among all the inducing factors. Senility, male gender, long duration of disease, smoking history, and a history of frequent hospital visits might be the risk factors for severe or life-threatening asthma exacerbations.

Expression of GRIM-19 in adenomyosis and its mechanism for promoting disease progress / 重庆医学

Objective To study the expression level of GRIM-19 in endometrial tissue of the patients with adenomyosis and to investigate its molecular mechanism during disease occurrence and progress process.Methods The ectopic and eutopic endometrial tissues were obtained from 30 patients with adenomyosis.Immunohistochemistry and Western blot were performed to detect the expression of GRIM-19,pSTAT3 and VEGF.The endometrial tissueapoptosis was assayed by TUNEL.Immunohistoehemistry with anti-CD34 antibody was performed to detect angiogenesis in endometrial tissue.GRIM-19 small interfering RNA(siRNA) and recombinant GRIM-19 plasmid were constructed and transfected into Ishikawa cells for detecting the change of downstream signal molecules pSTAT3,STAT3 and VEGF.Results The expression level of GRIM-19 was decreased in the ectopic and eutopic endometrial tissues of patients with adenomyosis compared with control group.Apoptosis in ectopic and eutopic endometrial tissues was reduced;the microvessel density and expression levels of pSTAT3 and VEGF were increased.Transfecting Ishikawa cells and downregulating GRIM-19 expression could significantly activate pSTAT3 and VEGF.Conclusion GRIM-19 promotes the occurrence and development of adenomyosis by inhibiting apoptosis and angiogenesis.

Expression of GRIM-19 in adenomyosis and its mechanism for promoting disease progress / 重庆医学

Objective To study the expression level of GRIM-19 in endometrial tissue of the patients with adenomyosis and to investigate its molecular mechanism during disease occurrence and progress process.Methods The ectopic and eutopic endometrial tissues were obtained from 30 patients with adenomyosis.Immunohistochemistry and Western blot were performed to detect the expression of GRIM-19,pSTAT3 and VEGF.The endometrial tissueapoptosis was assayed by TUNEL.Immunohistoehemistry with anti-CD34 antibody was performed to detect angiogenesis in endometrial tissue.GRIM-19 small interfering RNA(siRNA) and recombinant GRIM-19 plasmid were constructed and transfected into Ishikawa cells for detecting the change of downstream signal molecules pSTAT3,STAT3 and VEGF.Results The expression level of GRIM-19 was decreased in the ectopic and eutopic endometrial tissues of patients with adenomyosis compared with control group.Apoptosis in ectopic and eutopic endometrial tissues was reduced;the microvessel density and expression levels of pSTAT3 and VEGF were increased.Transfecting Ishikawa cells and downregulating GRIM-19 expression could significantly activate pSTAT3 and VEGF.Conclusion GRIM-19 promotes the occurrence and development of adenomyosis by inhibiting apoptosis and angiogenesis.