Moderate physical exercise and ATP modulate the P2X7 receptor and improve cisplatin-induced gastric emptying delay in rats

Patients undergoing chemotherapy with cisplatin commonly present gastrointestinal effects such as constipation and gastric emptying (GE) delay. Both the purinergic system and physical exercise modulate the gastrointestinal (GI) tract. In the current study, we investigated the role of ATP, physical exercise, and P2X7 receptor blocking on GE delay induced by cisplatin in rats. Male rats were divided into the following groups: control (C), cisplatin (Cis), exercise (Ex), Brilliant Blue G (BBG), ATP, Cis+Ex, Cis+ATP, Cis+BBG, Cis+Ex+BBG, Cis+Ex+BBG+ATP, and Cis+ATP+BBG. GE delay was induced by treatment with 1 mg/kg cisplatin (1 time/week for 5 weeks, ip). The moderate physical exercise was swimming (1 h/day, 5 days/week for 5 weeks). At the end of the treatment or exercise and 30 min before the GE assessment, some groups received BBG (50 mg/kg, sc) or ATP (2 mg/kg, sc). Then, GE was assessed after a 10-min postprandial period. Chronic use of Cis decreased GE delay (P<0.05) compared to the control group. Both exercise and ATP prevented (P<0.05) GE delay compared to Cis. The pretreatment with BBG significantly inhibited (P<0.05) the effect of exercise and ATP. On the other hand, the association between exercise and ATP reversed (P<0.05) the effect of the BBG and prevented GE delay. Therefore, we suggest that both exercise and treatment with ATP activate P2X7 receptors and prevent GE delay induced by cisplatin in rats.

ATP5J regulates mitochondrial function through TOMM20 and promotes metastasis of human hepatocellular carcinoma cells / 中国病理生理杂志

AIM:To explore the mechanism of ATP synthase mitochondrial F0 complex H+ transporting,sub-unit F6(ATP5J)in affecting the metastasis of hepatoma carcinoma cells by regulating mitochondrial function-mediated cy-toskeletal remodeling.METHODS:Hepatocellular carcinoma cells Li-7 were used to construct the ATP5J overexpression and knockdown models.JC-1 staining was used to detect the mitochondrial membrane potential in each group,reactive oxygen species(ROS)levels were examined by DCHF-DA,and mitochondrial ATP fluorescence probe was used to assess mito-chondrial function.Cytoskeletal remodeling was detected with a microfilament green fluorescent probe(Actin-Tracker Green-488).Transwell assay was used to assess cell invasion ability.The expression levels of ATP5J and translocase of outer mitochondrial membrane 20(TOMM20)were determined by Western blot.RESULTS:Overexpression of ATP5J up-regulated mitochondrial membrane potential and mitochondrial ATP fluorescence intensity,induced cytoskeletal re-modeling,promoted cell invasion and TOMM20 expression,and inhibited ROS production(P＜0.01).On the contrary,knockdown of ATP5J significantly decreased mitochondrial membrane potential and mitochondrial ATP fluorescence inten-sity,significantly decreased cell invasion ability and TOMM20 expression,promoted ROS production and blocked cyto-skeletal remodeling(P＜0.01).CONCLUSION:ATP5J regulates mitochondrial energy transformation in hepatocellular carcinoma cells,and affects metastasis of hepatoma carcinoma cells by regulating mitochondrial membrane potential and mitochondrial ATP production-mediated cytoskeletal remodeling through TOMM20.

Clinical features of Menkes disease(report of one case) / 临床神经病学杂志

Objective To investigate the clinical features of Menkes disease(MD)caused by ATP7A gene mutation.Methods Clinical data of one MD patient was retrospectively analyzed,and the literature on the MD cases was reviewed.Results The patient was a 7-month-old male.The initial symptoms were epilepsy,feeding difficulties and psychomotor retardation,followed by distinctive facial appearance,hair abnormality,pectus excavatum and hypotonia.Biochemical tests revealed reduced serum ceruloplasmin and copper.Brain MRI showed diffuse cerebral atrophy,cerebral dysplasia and subdural effusion.Genetic testing showed that there was a new hemizygous mutation c.2916+2(IVS14)T＞C in the ATP7A gene splicing site on the X chromosome,which verified that the mother was a heterozygous carrier with a normal phenotype.Conclusions MD often starts in infancy and childhood.MD may involve multi-system such as the nervous system and connective tissues,and should be diagnosed with genetic testing.

The role and mechanism of purinergic signaling in oligodendrocytes development and myelin repair:A literature review / 实用医学杂志

Oligodendrocytes(OLs)play a crucial role in myelination during the development and repair of the central nervous system.ATP serves not only as an important signaling molecule involving in the intercellular com-munications,but also as an energetic molecule,with its purinergic receptor subtypes widely present in neurons and glial cells.These subtypes are composed of two purinergic receptors:P1 and P2:The former are primarily activated by adenosine,and the latter mainly by ATP,ADP,and UTP.The two receptors paly their respective role in various regions of the CNS under physiological or pathological conditions through distinct mechanisms.In this paper,we review recent literature on the roles and mechanisms of the purinergic receptors in OL development,myelination,and myelin repair.It may be of great significance for further understanding the role of purinergic signaling in demy-elinating diseases and myelin dysplasia and exploring potential therapeutic targets.

Clinical features of CAPOS syndrome caused by maternal ATP1A3 gene variation: a case report / 临床耳鼻咽喉头颈外科杂志

CAPOS syndrome is an autosomal dominant neurological disorder caused by mutations in the ATP1A3 gene. Initial symptoms, often fever-induced, include recurrent acute ataxic encephalopathy in childhood, featuring cerebellar ataxia, optic atrophy, areflflexia, sensorineural hearing loss, and in some cases, pes cavus. This report details a case of CAPOS syndrome resulting from a maternal ATP1A3 gene mutation. Both the child and her mother exhibited symptoms post-febrile induction,including severe sensorineural hearing loss in both ears, ataxia, areflexia, and decreased vision. Additionally, the patient's mother presented with pes cavus. Genetic testing revealed a c. 2452G>A（Glu818Lys） heterozygous mutation in theATP1A3 gene in the patient . This article aims to enhance clinicians' understanding of CAPOS syndrome, emphasizing the case's clinical characteristics, diagnostic process, treatment, and its correlation with genotypeic findings.

Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

Solute carriers (SLCs) constitute the largest superfamily of membrane transporter proteins. These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions. They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake (e.g., SLC2A4/GLUT4), glucose reabsorption (e.g., SLC5A2/SGLT2), thermogenesis (e.g., SLC25A7/UCP-1), and ATP production (e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone (SLCO1B1/OATP1B1) and metformin (SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

Research progress of microRNA in oxidative stress and lipid metabolism of non-exudative age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Age-related macular degeneration(ARMD)is a neurodegenerative disease associated with oxidative stress. It is characterized by progressive death of photoreceptors and retinal pigment epithelium(RPE), and is one of the leading causes of irreversible loss of central vision in patients over the age of 65 years old. MicroRNA(miRNA)is a class of regulatory short-chain non-coding RNA that can bind and inhibit multiple gene targets in the same biological pathway. This unique property makes microRNA an ideal target for exploring the pathogenesis, diagnosis and treatment of non-exudative ARMD. Previous studies have found that the pathogenesis of non-exudative ARMD involves age, genetics, environment, oxidative stress, lipid metabolism, autophagy and immunity. However, the exact mechanisms have not been fully clarified. As biomarkers of non-exudative ARMD, miRNA play a role in oxidative stress and lipid metabolism. This article summarizes the role of various miRNA in targeting Nrf2 and HIF-1α to inhibit hypoxia-related angiogenesis signaling, thereby affecting oxidative stress. Additionally, miRNA regulate lipid uptake and the expression of ABCA1 in RPE and macrophages, thereby influencing lipid metabolism. This deepens the understanding of the role of miRNA in oxidative stress and lipid metabolism in non-exudative ARMD, and provides directions for further improving the understanding of the pathogenesis and prevention of non-exudative ARMD.

Mechanism of Total Saponin of Astragali Radix and Total Alkaloids of Nelumbinis Folium Against Hyperlipidemia Based on PPARγ/LXRα/ABCG1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of the combination of total saponin of Astragali Radix-total alkaloids of Nelumbinis Folium on reversal cholesterol transport （RCT） in hyperlipidemia rats， and to discuss its mechanism. MethodSixty SD rats were randomly divided into control group， high-fat diet group， total saponin of Astragali Radix-total alkaloids of Nelumbinis Folium low （17 mg·kg-1+40 mg·kg-1）， middle （34 mg·kg-1+80 mg·kg-1）， high dose （68 mg·kg-1+160 mg·kg-1） groups and simvastatin （2.1 mg·kg-1） group， with 10 mice in each group. The Hyperlipidemia model was duplicated by feeding rats with a high-fat diet for 6 weeks. From the 3rd week， except for the control group and the high-fat diet group given distilled water， other groups were given corresponding drugs intragastric treatment for 4 weeks. The changes in blood lipid and liver function of rats were detected by an automatic biochemical analyzer. Hematoxylin-eosin （HE） and oil red O staining were used to observe the pathological morphological changes and steatosis of rat liver tissue. The contents of total cholesterol （TC） and total bile acid （TBA） in rat liver tissue and feces were determined by a semi-automatic biochemical analyzer. The mRNA and protein expression levels of peroxisome proliferators-activated receptors γ （PPARγ）， liver X receptors α （LXRα）， ATP-binding cassette transporter G1 （ABCG1） and cholesterol 7α-hydroxylase （CYP7A1） in rat liver tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the control group， the contents or activities of TC， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， TBA， aspartate aminotransferase （AST）， alanine aminotransferase （ALT） in serum were significantly increased （P<0.01）， and the contents of high-density lipoprotein cholesterol （HDL-C） in the high-fat diet group were significantly decreased （P<0.01）. The hepatocyte was clearly swollen like ballooning degeneration， with a lot of fat vacuoles and red fat droplets. The contents of TC and TBA in liver tissue and feces were significantly increased （P<0.01）， and the mRNA and protein expression levels of PPARγ， LXRα， ABCG1， and CYP7A1 in liver tissue were significantly decreased （P<0.01）. Compared with the high-fat diet group， the contents or activities of TC， TG， LDL-C， TBA， AST， and ALT in the serum of rats in administered groups were significantly decreased （P<0.01）， while the content of HDL-C was significantly increased （P<0.01）. Hepatocyte swelling was significantly reduced， and the ballooning degeneration， fat vacuoles， and red lipid droplets in liver tissue were significantly decreased. The contents of TC and TBA in liver tissue were significantly decreased （P<0.05， P<0.01）， and the contents of TC and TBA in feces were significantly increased （P<0.05， P<0.01）. The mRNA and protein expression levels of PPARγ， LXRα， ABCG1， and CYP7A1 in liver tissue were significantly increased （P<0.05， P<0.01）. ConclusionTotal saponin of Astragali Radix-total alkaloids of Nelumbinis Folium has a positive effect on the prevention and treatment of hyperlipidemia rats， and its mechanism may be related to the activation of PPARγ/LXRα/ABCG1 signaling pathway and regulation of RCT.

Correlation between metabolic markers and blood lipid levels in kidney transplant recipients / 器官移植

Objective To analyze the co-expressed genes in blood lipid metabolism, hyperlipidemia and tacrolimus metabolism and their correlation with blood lipid levels in kidney transplant recipients. Methods Co-expressed genes were screened from Comparative Toxicogenomic Database (CTD). Baseline data of 25 kidney transplant recipients were collected. The expression levels of ATP binding cassette subfamily A member 1(ABCA1), peroxisome proliferator activated receptor γ (PPAR-γ) and glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 (GPIHBP1) were measured. All recipients were followed up. The concentrations of fasting blood glucose, glycosylated hemoglobin, triglyceride, total protein, albumin, globulin, cholesterol, high-density lipoprotein, low-density lipoprotein and tacrolimus blood concentration were collected at postoperative 1, 3, 6 and 12 months, and the incidence of hyperlipidemia in the recipients was analyzed. The correlation between ABCA1, GPIHBP1, PPAR-γ and clinical indexes was assessed. The diagnostic efficiency of related indexes for hyperlipidemia after kidney transplantation was evaluated. Results Three co-expressed genes including ABCA1, PPAR-γ and GPIHBP1 were screened. ABCA1 was positively correlated with cholesterol level at postoperative 6 months and tacrolimus blood concentration at postoperative 3 months, whereas negatively correlated with fasting blood glucose level at postoperative 3 months (all P<0.05). GPIHBP1 was negatively correlated with preoperative cholesterol and triglyceride levels, whereas positively correlated with tacrolimus blood concentration at postoperative 3 months (all P<0.05). PPAR-γ was negatively correlated with preoperative globulin and low-density lipoprotein levels (both P<0.05). ABCA1, GPIHBP1 and PPAR-γ combined with preoperative globulin and blood glucose level at postoperative 1 and 6 months after operation yielded high diagnostic efficiency for hypertriglyceridemia after kidney transplantation (AUC=0.900). ABCA1, GPIHBP1 and PPAR-γ combined with tacrolimus blood concentrations at postoperative 1 and 6 months and blood glucose level at postoperative 6 months had high diagnostic efficiency for hypercholesterolemia after kidney transplantation (AUC=0.931). Conclusions ABCA1, GPIHBP1 and PPAR-γ are correlated with blood lipid level and tacrolimus blood concentration after kidney transplantation to different degrees. No definite evidence has been supported for predicting hyperlipidemia after kidney transplantation. Immunity improvement and rational blood glucose management may be beneficial factors for hyperlipidemia control.

Control of astrocytic Ca2+ signaling by nitric oxide-dependent S-nitrosylation of Ca2+ homeostasis modulator 1 channels

Background Astrocytes Ca2+ signaling play a central role in the modulation of neuronal function. Activation of metabotropic glutamate receptors (mGluR) by glutamate released during an increase in synaptic activity triggers coordinated Ca2+ signals in astrocytes. Importantly, astrocytes express the Ca2+-dependent nitric oxide (NO)-synthe-tizing enzymes eNOS and nNOS, which might contribute to the Ca2+ signals by triggering Ca2+ influx or ATP release through the activation of connexin 43 (Cx43) hemichannels, pannexin-1 (Panx-1) channels or Ca2+ homeostasis modulator 1 (CALHM1) channels. Hence, we aim to evaluate the participation of NO in the astrocytic Ca2+ signaling initiated by stimulation of mGluR in primary cultures of astrocytes from rat brain cortex. Results Astrocytes were stimulated with glutamate or t-ACPD and NO-dependent changes in [Ca2+]i and ATP release were evaluated. In addition, the activity of Cx43 hemichannels, Panx-1 channels and CALHM1 channels was also analyzed. The expression of Cx43, Panx-1 and CALHM1 in astrocytes was confirmed by immunofluorescence analysis and both glutamate and t-ACPD induced NO-mediated activation of CALHM1 channels via direct S-nitrosylation, which was further confirmed by assessing CALHM1-mediated current using the two-electrode voltage clamp technique in Xenopus oocytes. Pharmacological blockade or siRNA-mediated inhibition of CALHM1 expression revealed that the opening of these channels provides a pathway for ATP release and the subsequent purinergic receptordependent activation of Cx43 hemichannels and Panx-1 channels, which further contributes to the astrocytic Ca2+ signaling. Conclusions Our findings demonstrate that activation of CALHM1 channels through NO-mediated S-nitrosylation in astrocytes in vitro is critical for the generation of glutamate-initiated astrocytic Ca2+ signaling.

Effect of Endometriosis on Cumulus ATP, Number of Mitochondria and Oocyte Maturity in Cumulus Oocyte Complex in Mice / Efeito da endometriose no cumulus ATP, número de mitocôndrias e maturidade oocitária no complexo oocitário cumulus em camundongos

Abstract Objective Endometriosis causes a decrease in oocyte quality. However, this mechanism is not fully understood. The present study aimed to analyze the effect of endometriosis on cumulus cell adenosine triphosphate ATP level, the number of mitochondria, and the oocyte maturity level. Methods A true experimental study with a post-test only control group design on experimental animals. Thirty-two mice were divided into control and endometriosis groups. Cumulus oocyte complex (COC) was obtained from all groups. Adenosine triphosphate level on cumulus cells was examined using the Elisa technique, the number of mitochondria was evaluated with a confocal laser scanning microscope and the oocyte maturity level was evaluated with an inverted microscope. Results The ATP level of cumulus cells and the number of mitochondria in the endometriosis group increased significantly (p < 0.05; p < 0.05) while the oocyte maturity level was significantly lower (p < 0.05). There was a significant relationship between ATP level of cumulus cells and the number of mitochondrial oocyte (p < 0.01). There was no significant relationship between cumulus cell ATP level and the number of mitochondrial oocytes with oocyte maturity level (p > 0.01; p > 0.01). The ROC curve showed that the number of mitochondrial oocytes (AUC = 0.672) tended to be more accurate than cumulus cell ATP level (AUC = 0.656) in determining the oocyte maturity level. Conclusion In endometriosis model mice, the ATP level of cumulus cells and the number of mitochondrial oocytes increased while the oocyte maturity level decreased. There was a correlation between the increase in ATP level of cumulus cells and an increase in the number of mitochondrial oocytes.

MT-ATP6 gene 9176T>C mutation leading to late-onset leigh syndrome:a family report and literature review / 中风与神经疾病杂志

@#Objective To investigate the clinical,brain MRI and MT-ATP6 gene variation characteristics of late-onset Leigh syndrome (LS). Methods The clinical data,brain imaging and genetic test results of two patients with late-onset Leigh syndrome in a family were collected in detail,and discussed in combination with the literature. Results The proband,male,9 years old,complained of "bilateral ptosis,unstable walking for half a year,abnormal mental behavior for 4 months".He was admitted to our hospital on April 10,2020.Patient was born normally,his physique and intelligence was worse that of his peers since childhood.Six months ago,the patient had bilateral ptosis and double vision,and he gradually developed unstable walking and difficulty in running.Brain MRI examination showed abnormal signals in bilateral basal ganglia and brain stem.4 months ago,he had intermittent nausea and vomiting,abnormal mental behavior without any inducement.Two months ago,he suddenly fell into a coma and twitched after catching a cold and fever.He was rescued and treated in a local hospital.His vital signs were stable and transferred to our hospital.Physical examination:short stature,thin physique,coma with eyes open.Bilateral ptosis covers more than half of the pupil,bilateral eyeball center fixation,dysphagia,nasal feeding diet.Muscle tension in the limbs was high,tendon reflex was active,and the limbs were flexing,Bilateral pathological signs were positive.Family history:the child's parents are not consanguineous marriage,the father is in good health,the mother is short and has a history of mental and behavioral abnormalities.The proband's brother,14 years old,was less developed than his peers.At the age of 7,he developed ptosis,unstable walking and no history of coma and convulsions.No ragged red fibers were found in skeletal muscle pathological biopsies of the proband and his brother.The mutation of MT-ATP6 gene 9176T>C was found by mitochondrial genome detection. Conclusions The clinical phenotype of late-onset Leigh syndrome is heterogeneous,which may be accompanied by mental and behavioral abnormalities and cognitive impairment.Brain MRI is characterized by abnormal signals in bilateral basal ganglia and midbrain periaqueductal region.Gene detection is an important basis for the diagnosis of Leigh syndrome.

Development of the novel ACLY inhibitor 326E as a promising treatment for hypercholesterolemia

Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC50 = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.

Lipid-lowering effect of atorvastatin on patients with acute cerebral infarction with different genotypes of ATP-binding cassette subfamily B member 1 G2677T / 中华行为医学与脑科学杂志

Objective:To observe the lipid-lowering effect of atorvastatin on patients with acute cerebral infarction with different ATP-binding cassette subfamily B member 1(ABCB1) genotypes, and thus to provide clinical research evidence for individual application of atorvastatin in patients with acute cerebral infarction.Methods:From March 2021 to December 2021, 131 patients with acute cerebral infarction admitted to the Department of Neurology of Xuchang Central Hospital were included. The ABCB1 G2677T gene polymorphism rs2032582 of patients was detected by fluorescence staining in situ hybridization.Based on the detection results, patients were divided into GG group, GT group and TT group.All patients were given atorvastatin (20 mg/d) for lipid-lowering treatment.The levels of low density lipoprotein cholesterol(HDL-C), high density lipoprotein cholesterol(HDL-C), total cholesterol(TC)and triglyceride(TG) in serum of patients in the three groups before and 2 months after treatment were recorded and analyzed.The adverse drug reactions in the three groups were recorded. When the serum LDL-C level was less than 1.8 mmol/L, it was considered that the lipid-lowering treatment was effective.The binary Logistic regression analysis was used to explore the influencing factors of atorvastatin lipid lowering therapy.The software of SPSS 25.0 was used for statistical analysis.Results:There were 50 (38.17%), 49 (37.40%) and 32 (24.43%) patients in GG group, GT group and TT group, respectively. The serum TC levels of patients in GG group, GT group and TT group after treatment were (3.47±0.70) mmol/L, (3.59±1.09) mmol/L and (3.48±1.02) mmol/L, respectively, which were lower than those before treatment ((4.27± 0.99) mmol/L, (4.02±0.98) mmol/L and (4.03±1.31) mmol/L), all of which were statistically significant ( t=7.652, 3.092, 5.593, all P<0.01). The serum LDL-C levels in GG group, GT group and TT group after treatment were (1.89±0.53) mmol/L, (2.07±0.92) mmol/L and (1.96±0.79) mmol/L, respectively, which were lower than those before treatment ((2.87±0.92) mmol/L, (2.56±0.89) mmol/L and (2.55±1.11) mmol/L) ( t=9.896, 4.055, 5.980, all P<0.001). The differences of serum LDL-C level before and after treatment in GG group, GT group and TT group were (-0.97±0.69) mmol/L, (-0.50±0.86) mmol/L and (-0.59±0.56) mmol/L, respectively. The difference of serum LDL-C level before and after treatment in the three groups was statistically significant ( F=5.614, P=0.005). The difference of TC, TG and HDL-C before and after treatment was not statistically significant( F=2.783, 0.490, 1.677, all P>0.05). The binary Logistic regression analysis showed that ABCB1 G2677T gene type and staying up late were independent influencing factors for atorvastatin lipid-lowering therapy. The probability of effective lipid-lowering in GT patients with ABCB1 G2677T gene was 27.9% of that in GG patients ( OR=0.279, 95% CI: 0.110-0.709, P=0.007), and the probability of TT type patients was 33.8% of GG type patients ( OR=0.338, 95% CI: 0.121-0.943, P=0.038). The probability of effective lipid-lowering in patients who had the habit of staying up late was 26.4% of the patients who did not stay up late ( OR=0.264, 95% CI: 0.118-0.591, P=0.001). There was no significant difference in the total incidence of adverse drug reactions among the three groups( χ2=0.868, P=0.648). Conclusion:The lipid-lowering effect in patients with GG type of ABCB1 G2677T is better than that of GT type and TT type when atorvastatin is used to treat patients with acute cerebral infarction.

Study on the effect of polysaccharide from stigma maydison on ATP synthesis in renal mitochondria and its mechanism in D-galactose-induced aging mice / 中华老年医学杂志

Objective:To investigate the effect of Stigma Maydis Palysaccharide(SMPS)on ATP synthesis in kidney mitochondria of D-galactose-induced aging mice, and to clarify its possible mechanism.Methods:The aging mouse model was established by subcutaneous injection of D-galactose solution in the back of the neck.The 48 SPF male mice were randomly divided into normal control group(control group), D-galactose model group(D-Gal group), SMPS low-dose group and SMPS high-dose group(n=12 for each). The control group was subcutaneously injected with 150 mg/kg normal saline on the back of the neck every day, while the other three groups were subcutaneously injected with 150 mg/kg of D-gal solution on the back of the neck every day.SMPS-L and-H dose groups were given 30 mg/kg and 60 mg/kg of SMPS solution by gavage at the same day of D-Gal injection.The control group and D-GAL group were given the same volume of normal saline daily by gavage for 42 days.Blood samples were collected from the eyeball under general anesthesia after 42 days of intervention for the detection of serum levels of superoxide dismutase(SOD), glutathione peroxidase(GSH-Px)and MDA.After harvesting the kidney tissue, various tests were used to detect ATP content, the mRNA expression levels and protein expression levels in kidney.Luciferase assay was used to detect ATP content in renal tissue.Real-time fluorescent quantitative PCR was used to detect the mRNA expression levels of succinate dehydrogenase(SDH)of complex Ⅱ, cytochrome C reductase(Cycs)of complex Ⅲ, complex Ⅳ(COXⅣ)and ATP5b in ATP synthase in mitochondrial oxidative respiratory chain.Western blot was used to detect the expression levels of mitochondrial fusion protein 2(MFN2), dynamin-related protein1(DRP1)and mitochondrial autophagy related protein P62 in renal tissues of each group.Results:Compared with control group, the activities of serum of SOD(116.53±10.01)U/mg and GSH-Px(127.58±8.74)μmol/L were significantly decreased in D-GAL group(both P< 0.01), and serum MDA content(15.42±0.91)μmol/L increased significantly in D-GAL group( P<0.01). Compared with D-GAL group, the activities of SOD(152.80±9.29)U/mg and GSH-Px(274.07±10.73)μmol/L were significantly increased in SMPS intervention group( P< 0.01), while the MDA content(8.10±0.66)μmol/L decreased significantly in SMPS intervention group( P< 0.01). Compared with control group, the content of ATP(178±4)10 -4 μmol in D-gal group was significantly decreased( P<0.01), the mRNA expression levels of SDH, Cycs and COXⅣ were not significantly changed in D-gal group, and the mRNA expression level of ATP5b(0.67±0.01)was down-regulated in D-gal group( P<0.01), the expression of MFN2 protein(0.29±0.02)was significantly decreased in D-gal group( P<0.01), and the expression of DRP1 and P62 protein(0.31±0.02 and 0.21±0.01)was significantly increased in D-gal group(both P<0.01). Compared with the D-gal group, the ATP content(193±1)10 -4 μmol in the kidney tissue of the mice was significantly increased in SMPS intervention group( P< 0.01), and the ATP5b mRNA expression and MFN2 protein expression(0.87±0.05 and 0.71±0.08)were significantly increased in SMPS intervention group(both P< 0.01), DRP1 and P62 protein expressions(0.20±0.01 and 0.10±0.01)were significantly down-regulated in in SMPS intervention group(both P< 0.01). Conclusions:SMPS can improve the mitochondrial dynamic homeostasis disorder in aging mice by increasing the activity of antioxidant enzymes, up-regulating the expression of ATP5b mRNA and MFN2 protein, down-regulating the expression of DRP1 and P62 protein, and promoting the generation of mitochondrial ATP in D-gal-induced aging mice kidney tissue.

Detection of ATP2C1 gene mutations in a family with generalized familial benign chronic pemphigus / 中华皮肤科杂志

A 60-year-old female proband presented with recurrent erythema, blisters and erosions all over the body for 30 years, which had been aggravated 10 days prior to the presentation. Skin examination showed erythematous swelling of the bilateral eyelids with scattered dark red crusts, scattered erythema and erosions on the nasolabial folds and chin, large areas of erythema and erosions on the neck, bilateral axillae, left cubital fossa, perineum and perianal area, accompanied by bright red granulation tissues and positive Nikolsky′s sign. The proband had two sons, both of whom occasionally presented with erythema and erosions on the axillae and groin, and had not been diagnosed or treated. Blood samples were collected from the proband and her two sons, and genomic DNA was extracted and subjected to whole-exome sequencing. A heterozygous deletion mutation c.955_957del (p.A319del) was identified in the ATP2C1 gene in the proband and her two sons, which had not been previously reported. The patient was finally diagnosed with generalized familial benign chronic pemphigus.

Rapid determination of microbial contamination of Bupleurum chinense DC. decoction slices by ATP bioluminescence technology combined with statistical analysis methods / 药学学报

This study focuses on the microbial quality control of the Chinese herbal decoction pieces. In view of the shortcomings of traditional culture methods such as slow detection speed and inability to detect unculturable microorganisms, a new method based on ATP bioluminescence technology combined with statistical analysis methods was established to rapidly predict and quantitatively detect the total aerobic microbial count (TAMC) and total yeast and mold count (TYMC) contaminated Bupleurum chinense DC. decoction pieces. Based on the optimized ATP bioluminesence detection system, accurate detection of pure bacterial solution of Escherichia coli, Bacillus subtilis and Staphylococcus aureus can be achieved, with detection limits of 47.86, 89.13 and 1 862.09 CFU·mL-1, respectively. The detection time was 6.5 h, and the detection cost was as low as 2 yuan/time. The upper and lower warning limits of TAMC were determined by the misjudgment rates of 10% and 20%, respectively. And the warning limit of TYMC was determined by the misjudgment rate of 20%. The proposed crossing method could quickly predict the amount of microbial contamination in Bupleurum chinense DC. decoction pieces. The constructed partial least squares regression (PLSR) model could accurately quantify the quantity of microbial contamination in Bupleurum chinense DC. decoction pieces. The optimal PLSR prediction model for TAMC had a correction coefficient (R2) of 0.826, a root mean square error of correction set (RMSEE) of 0.468 and a root mean square error of cross-validation set (RMSECV) of 0.465. The R2, RMSEE and RMSECV in the prediction model of TYMC were 0.778, 0.543 and 0.541, respectively. The aim of this study is to establish a kind of rapid detection method and prediction models for the microbial limit of traditional Chinese medicine and Chinese herbal decoction pieces, and to provide a more convenient and sensitive detection technology for the microbial quality process control of traditional Chinese medicine products.

Study of glycine solution in preparation of frozen thawed deglycerolized erythrocytes / 中国输血杂志

【Objective】 To study the protective effect of glycine solution on frozen red blood cell thawing process. 【Methods】 A total of 20 bags of 1 U of leukocytes reduced suspended red blood cells within 6 days were selected for the study. After mixing, each 2 bags of suspended red blood cells were divided into 2 bags and into two groups with 10 bags of 1 U in each group, and were frozen for storage. One group was deglycerolized with sodium chloride solution (control group), and one group was deglycerolized with glycine solution (experimental group). The hemoglobin, free hemoglobin, residual glycerol, total glycerol in red blood cells, adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) were detected in the two groups. 【Results】 Compared with the free hemoglobin content (0.90±0.05)g/L and residual glycerol content (1.17± 0.08)g/L in the control group, the final product red blood cell supernatant free hemoglobin content (0.77±0.15)g/L and residual glycerol content (0.79±0.33)g/L in the experimental group were decreased, and the difference was statistically significant (P<0.05). Compared with the ATP content (4.03±0.38)µmol/gHb and 2,3-DPG content (485.65±78.08)µg/L in the control group, the ATP content (4.41±0.35)µmol/gHb and 2,3-DPG content (656.28±116.68)µ g/L in the experimental group were significantly increased, with statistical significance (P<0.05). 【Conclusion】 Using glycine solution instead of sodium chloride solution to prepare frozen thawed deglycerolized erythrocytes achieved the effect of protecting erythrocytes, reduced the hemolysis rate of erythrocytes and glycerin residue, and increased the recovery rate of erythrocytes.

Peptide P3 ameliorates foam cell formation in RAW264.7 cells and its molecular mechanisms / 中国药理学通报

Aim To examine the effect of peptide P3 on lipid accumulation in RAW264.7 cells and the underlying molecular mechanism. Methods MTT method was used to screen the concentration of peptide P3 and oxidized low density lipoprotein(ox-LDL),and RAW.264.7 cells were induced to form foam cells by ox-LDL with 80 mg·L

Hyperuricemia in adolescents: four case series and literature review / 中华内分泌代谢杂志

Objective:To summarize and analyze the clinical characteristics of hyperuricemia in adolescents, and improve the awareness of diagnosis and treatment among clinicians.Methods:Four adolescent cases of hyperuricemia with a clear family history were admitted to the Department of Endocrinology, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from November 2015 to August 2021. Their clinical manifestations, laboratory tests, gene sequencing, and therapeutic effects were analyzed.Results:Among the 4 patients, there were 2 cases with mutation in uromodulin(UMOD)gene(c.453C>T, 1 homozygous mutation in p. C151C; c. 453C>Y, 1 heterozygous mutation in p. C151C); 1 case with compound heterozygous mutation in adenosine triphosphate binding cassette transporter G2(ABCG2)gene(c.421C>A p. Q141K; c. 34G>A p. V12M); and 1 case with homozygous mutation in the ABCG2 gene(c.421C>A, p. Q141K). The blood uric acid levels of 4 patients decreased significantly after medical treatment and lifestyle interventions.Conclusions:In addition to primary etiology, the cause of hyperuricemia in the adolescent can be associated with certain acute and chronic diseases as well as genetic conditions. Genetic testing is recommended for patients with a family history. Medication safety should be stressed in the treatment of adolescents.