Predictive validation of existing bleeding and thromboembolic scores in elderly patients with comorbid atrial fibrillation and acute coronary syndrome / 老年心脏病学杂志（英文版）

BACKGROUND@#The validation of various risk scores in elderly patients with comorbid atrial fibrillation (AF) and acute coronary syndrome (ACS) has not been reported. The present study compared the predictive performance of existing risk scores in these patients.@*METHODS@#A total of 1252 elderly patients with AF and ACS comorbidities (≥ 65 years old) were consecutively enrolled from January 2015 to December 2019. All patients were followed up for one year. The predictive performance of risk scores in predicting bleeding and thromboembolic events was calculated and compared.@*RESULTS@#During the 1-year follow-up, 183 (14.6%) patients had thromboembolic events, 198 (15.8%) patients had BARC class ≥ 2 bleeding events, and 61 (4.9%) patients had BARC class ≥ 3 bleeding events. For the BARC class ≥ 3 bleeding events, discrimination of the existing risk scores was low to moderate, PRECISE-DAPT (C-statistic: 0.638, 95% CI: 0.611-0.665), ATRIA (C-statistic: 0.615, 95% CI: 0.587-0.642), PARIS-MB (C-statistic: 0.612, 95% CI: 0.584-0.639), HAS-BLED (C-statistic: 0.597, 95% CI: 0.569-0.624) and CRUSADE (C-statistic: 0.595, 95% CI: 0.567-0.622). However, the calibration was good. PRECISE-DAPT showed a higher integrated discrimination improvement (IDI) than PARIS-MB, HAS-BLED, ATRIA, and CRUSADE (P < 0.05) and the best decision curve analysis (DCA). For thromboembolic events, the discrimination of GRACE (C-statistic: 0.636, 95% CI: 0.608-0.662) was higher than CHA2DS2-VASc (C-statistic: 0.612, 95% CI: 0.584-0.639), OPT-CAD (C-statistic: 0.602, 95% CI: 0.574-0.629) and PARIS-CTE (C-statistic: 0.595, 95% CI: 0.567-0.622). The calibration was good. Compared to OPT-CAD and PARIS-CTE, the IDI of the GRACE score slightly improved (P < 0.05). However, NRI analysis showed no significant difference. DCA showed that the clinical practicability of thromboembolic risk scores was similar.@*CONCLUSIONS@#The discrimination and calibration of existing risk scores in predicting 1-year thromboembolic and bleeding events were unsatisfactory in elderly patients with comorbid AF and ACS. PRECISE-DAPT showed higher IDI and DCA than other risk scores in predicting BARC class ≥ 3 bleeding events. The GRACE score showed a slight advantage in predicting thrombotic events.

Overexpression of Purinergic P2X4 Receptors in Hippocampus Rescues Memory Impairment in Rats with Type 2 Diabetes / 神经科学通报·英文版

Purinergic receptors have been reported to be involved in brain disorders. In this study, we explored their roles and mechanisms underlying the memory impairment in rats with type 2 diabetes mellitus (T2DM). T2DM rats exhibited a worse performance in the T-maze and Morris water maze (MWM) than controls. Microglia positive for P2X purinoceptor 4 (P2X4R) in the hippocampus were reduced and activated microglia were increased in T2DM rats. Long Amplicon PCR (LA-PCR) showed that DNA amplification of the p2x4r gene in the hippocampus was lower in T2DM rats. Minocycline significantly reduced the number of activated microglia and the mean distance traveled by T2DM rats in the MWM. Most importantly, P2X4R overexpression suppressed the activated microglia and rescued the memory impairment of T2DM rats. Overall, T2DM led to excessive activation of microglia in the hippocampus, partly through the DNA damage-mediated downregulation of P2X4Rs, thus contributing to memory impairment.

Effects of Polygonum cuspidatum on AMPK-FOXO3α Signaling Pathway in Rat Model of Uric Acid-Induced Renal Damage / 中国结合医学杂志

BACKGROUND@#To observe the effects of Chinese medicine (CM) Polygonum cuspidatum (PC) on adenosine 5'-monophosphate-activated protein kinase (AMPK), forkhead box O3α (FOXO3α), Toll-like receptor-4 (TLR4), NACHT, LRR and PYD domains-containing protein 3 (NLRP3), and monocyte chemoattractant protein-1 (MCP-1) expression in a rat model of uric acid-induced renal damage and to determine the molecular mechanism.@*METHODS@#A rat model of uric acid-induced renal damage was established, and rats were randomly divided into a model group, a positive drug group, and high-, medium-, and low-dose PC groups (n=12 per group). A normal group (n=6) was used as the control. Rats in the normal and model groups were administered distilled water (10 mL•kg) by intragastric infusion. Rats in the positive drug group and the high-, medium-, and low-dose PC groups were administered allopurinol (23.33 mg•kg), and 7.46, 3.73, or 1.87 g•kg•d PC by intragastric infusion, respectively for 6 to 8 weeks. After the intervention, reverse transcription polymerase chain reaction, Western blot, enzyme linked immunosorbent assay, and immunohistochemistry were used to detect AMPK, FOXO3α, TLR4, NLRP3, and MCP-1 mRNA and protein levels in renal tissue or serum.@*RESULTS@#Compared with the normal group, the mRNA transcription levels of AMPK and FOXO3α in the model group were significantly down-regulated, and protein levels of AMPKα1, pAMPKα1 and FOXO3α were significantly down-regulated at the 6th and 8th weeks (P<0.01 or P<0.05). The mRNA transcription and protein levels of TLR4, NLRP3 and MCP-1 were significantly up-regulated (P<0.01 or P<0.05). Compared with the model group, at the 6th week, the mRNA transcription levels of AMPK in the high- and medium-dose groups, and protein expression levels of AMPKα1, pAMPKα1 and FOXO3α in the high-dose PC group, AMPKα1 and pAMPKα1 in the mediumdose PC group, and pAMPKα1 in the low-dose PC group were significantly up-regulated (P<0.01 or P<0.05); the mRNA transcription and protein levels of TLR4 and NLRP3 in the 3 CM groups, and protein expression levels of MCP-1 in the medium- and low-dose PC groups were down-regulated (P<0.01 or P<0.05). At the 8th week, the mRNA transcription levels of AMPK in the high-dose PC group and FOXO3α in the medium-dose PC group, and protein levels of AMPKα1, pAMPKα1 and FOXO3α in the 3 CM groups were significantly up-regulated (P<0.01 or P<0.05); the mRNA transcription levels of TLR4 in the medium- and low-dose PC groups, NLRP3 in the high- and low-dose PC groups and MCP-1 in the medium- and low-dose PC groups, and protein expression levels of TLR4, NLRP3 and MCP-1 in the 3 CM groups were down-regulated (P<0.01 or P<0.05).@*CONCLUSION@#PC up-regulated the expression of AMPK and its downstream molecule FOXO3α and inhibited the biological activity of TLR4, NLRP3, and MCP-1, key signal molecules in the immunoinflammatory network pathway, which may be the molecular mechanism of PC to improve hyperuricemia-mediated immunoinflflammatory metabolic renal damage.

An investigation of ketoacidosis in children with newly diagnosed type 1 diabetes / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the incidence of diabetic ketoacidosis (DKA) in children with newly diagnosed type 1 diabetes.</p><p><b>METHODS</b>A retrospective analysis was performed for the clinical data of 224 children with newly diagnosed type 1 diabetes, and according to the presence or absence of DKA, these children were divided into DKA group and non-DKA group, with 112 children in each group. The DKA group was further divided into ≥5-year group (65 children) and <5-year group (47 children), and according to the blood gas parameters, this group was divided into mild group (26 children), moderate group (29 children), and severe group (57 children). The factors influencing the development of DKA were analyzed, as well as the clinical and laboratory features of DKA children with different ages.</p><p><b>RESULTS</b>The most common symptoms in these 224 children with type 1 diabetes were polydipsia (86.2%), polyuria (78.6%), and weight loss (57.1%). Compared with the non-DKA group, the DKA group had a significantly higher percentage of children who were aged <5 years, who had low family income, or whose parents had an educational level of senior high school or below. The DKA group had significantly higher levels of random blood glucose and HbA1C and significantly lower levels of pH, HCO3, and C-peptide than the non-DKA group (P<0.05). There was no significant difference in the percentage of children with severe DKA between the ≥5-year group and the <5-year group (P>0.05). Compared with the <5-year group, the ≥5-year group sufferred from symptoms for a significantly prolonged period, and had a significantly lower level of random blood glucose and significantly higher levels of HbA1C and C-peptide (P<0.05).</p><p><b>CONCLUSIONS</b>DKA has a high incidence rate in children with type 1 diabetes, and the development of DKA is associated with age, parents' educational level, and family income.</p>

Colonic Hypersensitivity and Sensitization of Voltage-gated Sodium Channels in Primary Sensory Neurons in Rats with Diabetes

BACKGROUND/AIMS: Patients with long-standing diabetes often demonstrate intestinal dysfunction and abdominal pain. However, the pathophysiology of abdominal pain in diabetic patients remains elusive. The purpose of study was to determine roles of voltage-gated sodium channels in dorsal root ganglion (DRG) in colonic hypersensitivity of rats with diabetes. METHODS: Diabetic models were induced by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg) in adult female rats, while the control rats received citrate buffer only. Behavioral responses to colorectal distention were used to determine colonic sensitivity in rats. Colon projection DRG neurons labeled with DiI were acutely dissociated for measuring excitability and sodium channel currents by whole-cell patch clamp recordings. Western blot analysis was employed to measure the expression of NaV1.7 and NaV1.8 of colon DRGs. RESULTS: STZ injection produced a significantly lower distention threshold than control rats in responding to colorectal distention. STZ injection also depolarized the resting membrane potentials, hyperpolarized action potential threshold, decreased rheobase and increased frequency of action potentials evoked by 2 and 3 times rheobase and ramp current stimulation. Furthermore, STZ injection enhanced neuronal sodium current densities of DRG neurons innervating the colon. STZ injection also led to a significant upregulation of NaV1.7 and NaV1.8 expression in colon DRGs compared with age and sex-matched control rats. CONCLUSIONS: Our results suggest that enhanced neuronal excitability following STZ injection, which may be mediated by upregulation of NaV1.7 and NaV1.8 expression in DRGs, may play an important role in colonic hypersensitivity in rats with diabetes.

Protective effect of ATP on skeletal muscle satellite cells damaged by H2O 2 / 华中科技大学学报（医学）（英德文版）

This study investigated the protective effect of ATP on skeletal muscle satellite cells damaged by H2O2 in neonatal rats and the possible mechanism. The skeletal muscle satellite cells were randomly divided into four groups: normal group, model group (cells treated with 0.1 mmol/L H2O2 for 50 s), protection group (cells treated with 16, 8, 4, 2, 1, 0.5, or 0.25 mmol/L ATP for 24 h, and then with 0.1 mmol/L H2O2 for 50 s), proliferation group (cells treated with 16, 8, 4, 2, 1, 0.5, or 0.25 mmol/L ATP for 24 h). MTT assay, FITC+PI+DAPI fluorescent staining, Giemsa staining and immunofluorescence were performed to examine cell viability and apoptosis, and apoptosis-related proteins. The results showed that the survival rate of skeletal muscle satellite cells was decreased and the apoptosis rate was increased after H2O2 treatment (P<0.01). Different doses of ATP had different effects on skeletal muscle satellite cells damaged by H2O2: the survival rate of muscle satellite cells treated with ATP at 4, 2, or 1 mmol/L was increased. The protective effect was most profound on cells treated with 2 mmol/L ATP. Immunofluorescence showed that ATP could increase the number of Bcl-2-positive cells (P<0.01) and decrease the number of the Bax-positive cells (P<0.01). It was concluded that ATP could protect skeletal muscle satellite cells against H2O2 damage in neonatal rats, which may be attributed to the up-regulation of the expression of Bcl-2 and down-regulation of Bax, resulting in the suppression of apoptosis.

Protective effect of ATP on skeletal muscle satellite cells damaged by H₂O₂ / 华中科技大学学报（医学）（英德文版）

This study investigated the protective effect of ATP on skeletal muscle satellite cells damaged by H₂O₂in neonatal rats and the possible mechanism. The skeletal muscle satellite cells were randomly divided into four groups: normal group, model group (cells treated with 0.1 mmol/L H₂O₂for 50 s), protection group (cells treated with 16, 8, 4, 2, 1, 0.5, or 0.25 mmol/L ATP for 24 h, and then with 0.1 mmol/L H₂O₂for 50 s), proliferation group (cells treated with 16, 8, 4, 2, 1, 0.5, or 0.25 mmol/L ATP for 24 h). MTT assay, FITC+PI+DAPI fluorescent staining, Giemsa staining and immunofluorescence were performed to examine cell viability and apoptosis, and apoptosis-related proteins. The results showed that the survival rate of skeletal muscle satellite cells was decreased and the apoptosis rate was increased after H₂O₂treatment (P<0.01). Different doses of ATP had different effects on skeletal muscle satellite cells damaged by H₂O₂: the survival rate of muscle satellite cells treated with ATP at 4, 2, or 1 mmol/L was increased. The protective effect was most profound on cells treated with 2 mmol/L ATP. Immunofluorescence showed that ATP could increase the number of Bcl-2-positive cells (P<0.01) and decrease the number of the Bax-positive cells (P<0.01). It was concluded that ATP could protect skeletal muscle satellite cells against H₂O₂damage in neonatal rats, which may be attributed to the up-regulation of the expression of Bcl-2 and down-regulation of Bax, resulting in the suppression of apoptosis.

Analysis of characteristics of using traditional Chinese and western medicine on type 1 diabetes adult patients based on electronic medical records / 中国中药杂志

To understand the kinds and the characteristics of combination of traditional Chinese medicines and western medicines using on adults with type 1 diabetes in general hospitals,This research brings into 4 602 hospitalized adult patients with type 1 diabetes from hospital information system (HIS) of 13 third class A hospitals. These research objects were hospitalized in December 2003-July 2011. The research analyzes the operating frequency and associated usage of western medicines and traditional Chinese medicines by the method of frequency statistics and association rules. Through the analysis, the research says that in the clinical treatment of adult patients with type 1 diabetes, the western medicine used most frequently is insulin, a total of 1 539 cases, accounted for 8.47%; the traditional Chinese medicine used most frequently is oral agents of pseudo-ginseng, a total of 183 cases, accounting for 6.25%; the combinations of Chinese and western medicines commonly used include Huoxue Huayu Tongmai Shuluo decoction + vasodilator, support degree is 45.93%, followed by Huoxue Huayu Tongmai Shuluo decoction + vasodilator + hypoglycemic drugs, support degree is 45.50%; Huoxue Huayu Tongmai Shuluo decoction + vasodilator + nutritional agent, support degree is 36.29%.

Association of single nucleotide polymorphism of methylenetetrahydrofolate reductase gene with susceptibility to acute leukemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene is associated with susceptibility to acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) in Chinese Han children.</p><p><b>METHODS</b>The study has included 87 patients with ALL, 22 patients with AML and 120 healthy controls. All subjects were analyzed with reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis and sequencing.</p><p><b>RESULTS</b>A 677CT genotype of the MTHFR gene was associated with decreased risk of ALL (OR=0.23, 95%CI: 0.07-0.79). However, MTHFR A1298C genotypes were not associated with the risk of either disease. 677TT/1298AA and 677CC/1298AC genotypes were associated with increased risk of ALL(OR=3.78, 95% CI: 1.38-10.40; OR=3.17, 95% CI: 1.18-8.53, respectively), whereas the genotype 677CT/1298AA was associated with susceptibility to AML (OR=0.23, 95% CI: 0.06-0.97).</p><p><b>CONCLUSION</b>Our data suggested that C677T polymorphism of MTHFR gene may increase the risk of childhood AML.</p>

A novel missense mutation of folypolyglutamate synthetase gene / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To examine allelic frequencies of coding single nucleotide polymorphisms (cSNPs) of folypolyglutamate synthetase (FPGS) gene in Chinese Han children with acute leukemia (AL), in order to provide a basis for detecting the relationship between FPGS genetic polymorphisms and tumor individualized chemotherapy.</p><p><b>METHODS</b>cSNPs of exon 5 were detected with polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) in 91 children with AL and 124 children with upper respiratory infection as controls. Genotypes and allelic frequencies were examined.</p><p><b>RESULTS</b>A novel missense mutation, 502/490 T>C (L151/101P), was found in exon 5 of FPGS from control children. The novel mutation was found in mitochondrial variants in two cases and cytosolic variants in three cases. The cytosolic and mitochondrial variants displayed allelic frequencies of 0.70 % and 0.47 % respectively. The novel mutation was not associated with susceptibility to AL.</p><p><b>CONCLUSIONS</b>A novel missense mutation 502/490 T>C (L151/101P) in exon 5 of FPGS gene is firstly found in Chinese Han children, and the cytosolic and mitochondrial variants display allelic frequencies of 0.70 % and 0.47 % respectively.</p>

Purinergic P2X receptors and diabetic neuropathic pain / 生理学报

Diabetic peripheral neuropathy (DPN), one of the most common chronic complications of diabetes, is characterized by allodynia, hyperalgesia and spontaneous pain. Chinese epidemiological studies have shown that at least 25% diabetic patients suffered from painful DPN, which compromises patients' daily functioning and becomes a major health care problem. Although the pathogenesis of painful DPN is not fully understood and current treatment options are very limited, research in the field has advanced our understanding on the mechanism of painful DPN in the past Decade of Pain Research and Control. This review will mainly focus on evaluation of current diabetic animal models, possible molecular pathways and available therapies, with an emphasis on roles of purinergic receptor and its signaling transduction pathways. Common therapies address one or two DPN symptoms, while others offer wider symptom control, presumably by targeting pathophysiological mechanisms of DPN. Purinergic receptor signaling transduction pathways might become potential targets for treatment for painful DPN.

Analysis of a 452C/T single nucleotide polymorphism in γ-glutamyl hydrolase gene in children with acute leukemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the distribution of γ-glutamyl hydrolase gene (GGH) 452C/T genotype and allele frequency in children with acute leukemia (AL) and healthy children.</p><p><b>METHODS</b>Bone marrow samples from 92 children with AL and peripheral blood samples from 124 healthy children were obtained to prepare complementary DNAs (cDNAs). The cDNAs were analyzed for a GGH 452C/T polymorphism by reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis (RT-PCR-DGGE) and direct sequencing.</p><p><b>RESULTS</b>The frequencies of the AL patients with TT, CT and CC genotypes were 2.2%, 13.0% and 84.8%, and the frequencies of the control children were 1.6%, 16.9% and 81.5%, respectively. There was no significant difference in GGH genotype or T allele frequency between the two groups (P> 0.05). However, the T allele frequency in Han Chinese children was significantly different from those reported in Japanese, Mexican and African-American populations.</p><p><b>CONCLUSION</b>The frequency of 452C/T polymorphism of GGH gene in Han Chinese children has been determined. The results suggested that an ethnic difference may exist.</p>

Expression of tau-related protein in spinal cord of patients with Alzheimer's disease / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of tau-related protein in spinal cord of Chinese patients with Alzheimer's disease.</p><p><b>METHODS</b>Gallays-Braak stain and immunohistochemical study for tau protein (AT8) were carried out in the spinal cord tissue (T2, T8, T10, L2 and S2 segments) of 3 Chinese patients with Alzheimer's disease. Seven age-matched cases without evidence of dementia or neurologic disease were used as controls.</p><p><b>RESULTS</b>Neurofibrillary tangles were identified in the neurons of anterior horn in 2 Alzheimer's disease cases but none was observed in the controls. Tau-positive axons and astroglia were detected in all Alzheimer's disease cases. Tau immunoreactivity in spinal cord of the patients correlated with that in brain tissue.</p><p><b>CONCLUSION</b>The expression of tau-related protein is demonstrated in the spinal cord of Alzheimer's disease patients suggesting that axonal transport defect may play a role in the pathogenesis of Alzheimer's disease.</p>

An experimental research of neuroglobin expression changes and neural apoptosis after traumatic brain injury / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the expression changes of neuroglobin in rats with the model of diffuse traumatic brain injury and explore the relationship between the neuroglobin and neuron apoptosis in traumatic brain injury.</p><p><b>METHODS</b>The diffuse traumatic brain injury of rats was induced by the Marmarou's 'weight-drop' device. And the immunohistochemical technique was used to detect the expression changes of neuroglobin and neuron apoptosis in rat brain at different time points post-injury.</p><p><b>RESULTS</b>The expression of neuroglobin increased twice and reached peaks at 2 hours and 72 hours post-injury respectively. And the increased expression of neuroglobin from 30 minutes to 1 hour post-injury and from 48 hours to 72 hours post-injury accompanied with the decreased expression ratio of Bax to Bcl-2.</p><p><b>CONCLUSION</b>The increased expression of neuroglobin in traumatic brain injury informed us that neuroglobin had anti-apoptosis action in post-injury neuron. It could protect the neuron from traumatic stress and secondary ischemia and hypoxia insults during ultra-early and acute stages.</p>

Morphological and quantatitive capillary changes in aging human brain / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate morphological changes of capillary in aging brain and explore the role of vascular factor in brain aging.</p><p><b>METHODS</b>Twenty-eight brains of individuals (mean age 65 years) who died without clinical or pathological involvement of nervous system and 6 brains of Alzheimer's disease (AD) patients (mean age 83 years) were obtained at autopsy. Sections from frontal lobe, occipital lobe, striatum and hippocampus of normal subjects and sections from hippocampus of AD patients were used for hematoxylin eosin (HE), lox fast blue (LFB), toluidine blue stains and ulex europaeus agglutinin (UEA) immunostaining. After observations of morphological changes of neuron and capillary, computer-aid image analysis was performed to quantify numerical density and area density of neuron and capillary in frontal lobe, occipital lobe, putamen, CA3 sector of normal subjects and CA3 sector of AD patients. Numerical ratio and area ratio of neuron and capillary were then calculated. Correlations between neuron/capillary ratio and age were estimated using Pearson's correlation test. Difference of neuron/capillary ratio in CA3 sectors between AD patients and advanced aged normal subjects (> 75 years) was analyzed with Student's t-test.</p><p><b>RESULTS</b>Several pathological microvascular changes, including increased tortuosity, looping, bundling, stringing, and effacement of endothelia were seen in aged subjects and more prevalent in AD patients. Numerical ratio and area ratio of neuron and capillary of frontal lobe, occipital lobe and putamen significantly increased with age in normal aging subjects.</p><p><b>CONCLUSIONS</b>Morphological changes and relative decrease in number and capacity of capillary in aging brain may reduce cerebral blood flow and metabolism, and consequently result in functional impairment of aging brain. Vascular factors may play an important role in the development of brain aging.</p>