Objective To observe the toxicity of fangyouling after one month’s transdermal administration in rabbits and evaluate its security. Methods Forty rabbits were randomly divided into 4 groups including a control group and low,middle and high dose groups of fangyouling. The rabbits in the control group were administered with sunflower oil,and the other rabbits were administrated dermally with fangyouling of 50,300 and 2 000 mg/kg respectively once a day for 4 weeks. The general con?dition,the skin irritation reaction,body weight,food consumption,hematology,blood biochemistry,organ coefficients and his?topathological changes of all the rabbits were observed. Results There was no obvious effect on the general condition in all the rabbits. However,the mild skin irritation was observed in 2 rabbits of the middle dose group and 4 rabbits of the high?dose group. The decreases of body weight and food consumption were noted in the high dose group. No changes were detected of hema?tology,blood biochemistry or viscera pathological at all dose levels. Conclusion The dose of non?toxic response of fangyouling is 50 mg/kg at this study condition.

Biomedical Research ; Clustered Regularly Interspaced Short Palindromic Repeats ; Humans

Objective To investigate the role of hippocampal α7 nicotinic acetylcholine receptor (α7nAChR) in sevoflurane-induced deficit in long-term cognitive function in neonatal rats.Methods Sixty-four male Sprague-Dawley rats,aged 7 days,weighing 10-15 g,were randomly divided into 4 groups (n =16each) using a random number table:control group (group C),sevoflurane anesthesia group (group S),sevoflurane anesthesia + α7nAChR agonist PNU-282987 group (group PS),and α7nAChR inhibitor MLA group (group M).In C and S groups,the rats inhaled 30％ oxygen and 3％ sevoflurane for 6 h,respectively.In group PS,PNU282987 (5 mg/kg) was injected intraperitoneally and 24 h later the rats were exposed to 3％ sevoflurane for 6 h.In group M,MLA 3 mg/kg was injected intrappritoneally and 24 h later the rats inhaled 30％ oxygen for 6 h.Eight rats in each group were randomly chosen and sacrificed immediately after oxygen or sevoflurane inhalation.The hippocampus was renoved for determination of the expression of α7nAChR and NR1,NR2A and NR2B subunitscontaining NMDA receptors in the total protein and membrane protein in hippocampal neurons.When the left rats in each group were raised to 2 months,Y-maze test was performed to detect the cognitive function.Results Compared with group C,the expression of α7nAChR and NR1,NR2A and NR2B subunits-containing NMDA receptors in the membrane protein was significantly down-regulated,and the percentage of spontaneous alternation was decreased in group S,the expression of NRI and NR2A subunits-containing NMDA receptors in the membrane protein was down-regulated (P ＜ 0.05),and no significant change was found in the expression of NR2B subunitscontaining NMDA receptors in the membrane protein and percentage of spontaneous alternation in group PS (P ＞ 0.05),and no significant change was found in the expression of NR1 and NR2A subunits-containing NMDA receptors in the membrane protein (P ＞ 0.05),and the expression of NR2B subunits-containing NMDA receptors in the membrane protein was down-regulated,and the percentage of spontaneous alternation was decreased in group M (P ＜ 0.05).Compared with group S,no significant change was found in the expression of NR1 and NR2A subunits-containing NMDA receptors in the membrane protein (P ＞ 0.05),and the expression of NR2B subunitscontaining NMDA receptors in the membrane protein was significantly up-regulated,and the percentage of spontaneous alternation was increased in PS group (P ＜ 0.05).There was no significant difference in the expression of α7nAChR and NR1,NR2A and NR2B subunits-containing NMDA receptors in the total protein and the number of entries into each arm in Y-maze test between the four groups (P ＞ 0.05).Conclusion The mechanism by which sevoflurane induces deficit in long-term cognitive function may be related to decreased function of hippocampal α7nAChR and inhibition of function of NMDA receptors in neonatal rats.

Objective To investigate the clinical features, prognosis and risk factors of patients of acquired immunodeficiency syndrome (AIDS) complicated with cryptococcal meningitis (CM). Methods Totally 26 patients of AIDS with CM who were hospitalized in the No. 8th People's Hospital of Guangzhou were enrolled in this study. The clinical data including diagnosis,experimental and etiological test,treatments and prognosis from all the patients were analyzed retrospectively. The results of cerebrospinal fluid routine test and CD4+ T lymphocyte were compared with those of AIDS patients complicated with tuberculous meningitis. Results Among the 26 patients enrolled in the study, the positive rate of cerebrospinal fluid india ink smear or Crypotococcus neoforrnans euhure was 84.6%. The most common symptoms were fever, headache and meningeal irritation sign. The average CD4+ lymphocyte count was 17.83 × 106/L, which was statistically different from that of tuberculous meningitis patients. All the patients showed concomitant multiple organ infections. The mortality rate was as high as 42.3%. At the end of therapy, the cell counts in the eerebrospinal fluid were remarkably higher in the patients with unfavorable prognosis compared to the patients with good prognosis, which was statistically different. Conclusions CD4+ lymphocyte count is an important marker for differentiating CM from tuberculous meningitis in AIDS patients. The results of cerebrospinal fluid routine test can predict the prognosis.

Objective To investigate the effect of sevoflurane anaesthesiaon the expression of N-methyl-D-aspartate (NMDA ) receptor in the developing hippocampal neurons in neonatal rats .Methods Sixty-four healthy male Sprague-Dawley rats ,aged 7 days ,weighing 10-15 g ,were randomly divided into 2 groups with 32 rats in each group using a random number table:control group (group C ) and sevoflurane anaesthesia group (group S ) . Animals in group C inhaled 30% oxygen for 6 h ,while animals in group S inhaled 3% sevoflurane for 6 h .Y-maze test was performed in the rats at 21 and 28 days after birth to evaluate the memory function .On 7 days after birth (immediately after the end of oxygen inhalation or sevoflurane anesthesia ) ,and 14 ,21 and 28 days after birth ,the expression of 1 ,2A and 2B subunits-containing NMDA receptors in the total protein and membrane protein in hippocampal neurons was determined by Western blot .The ratio of NMDA receptors in the membrane protein to those in the total protein (m/t ratio ) was calculated .Results Compared with group C ,the percentage of spontaneous alternation was significantly decreased on 21 and 28 days after birth ,the expression of 1 ,2A and 2B subunits-containing NMDA receptors in the membrane protein was down-regulated on 7-28 days after birth ,and m/t ratio was decreased in group S ( P<0.05) .There was no significant difference in the number of entries into each arm and expression of 1 ,2A and 2B subunits-containing NMDA receptors in the total protein between group C and group S ( P>0.05 ) .Conclusion The mechaism by which sevoflurane anaesthesia induces memory impairment in neonatal rats is related to inhibition of trafficking of NMDA receptors in the developing hippocampal neurons to the cell membrane ,and down-regulation of the number of NMDA receptors in the membrane protein .

Protein arginine methylation is an important post-translational modification (PTM) mediated by protein arginine methyltransferase (PRMTs), which is closely related to the occurrence and development of many diseases. Methylation of arginine is closely related to inflammatory diseases and fracture healing. Decreased expression of PRMTs can lead to delayed or even non-healing of fractures. Both PRMT5 and PRMT6 play an important role in fracture healing and are closely related to the PI3K-AKT and NF-κB pathways. Exploration the relationship between protein arginine methylation and fracture healing can provide a new way to prevent delayed or even non-healing fracture.

Objective:To explore the clinical phenotype and genetic basis of a child with Neutral lipid storage disease with myopathy (NLSDM).Methods:A child who was admitted to the First Affiliated Hospital of Zhengzhou University in February 2021 for a history of elevated creatine kinase (CK) for over 2 months was selected as the study subject. Clinical and laboratory examinations were carried out, and the child was subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing of her family members.Results:The patient, a 9-year-old female, had exhibited weakness in the lower limbs, elevated CK level, and refractory cardiomyotrophy. Genetic testing revealed that she has harbored c. 32C>G (p.S11W) and c. 516C>G (p.N172K) compound heterozygous variants of the PNPLA2 gene, which were respectively inherited from her mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PM1+ PM2_Supporting+ PP3+ PP4). Conclusion:The c. 32C>G (p.S11W) and c. 516C>G (p.N172K) compound heterozygous variants of the PNPLA2 gene probably underlay the myasthenia gravis and elevated creatine kinase in this child.

Objective:To investigate the clinical value of the expression levels of biological protein markers regenerating islet-derived protein 3-alpha(REG3α), soluble tumor suppressor factor 2(sST2) and tumor necrosis factor receptor 1(TNFR1) in peripheral blood in the diagnosis and efficacy evaluation of intestinal acute graft-versus-host disease (aGVHD) in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Retrospective analysis of 50 children who underwent allo-HSCT, in the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from January 2020 to February 2021 were enrolled, including 39 males and 11 females [median age: 8.5 (1-13) years]. The expression levels of above 3 biological proteins were detected before transplantation, 1 week, 2 weeks, 3 weeks, 5 weeks, 7 weeks, 9 weeks, 11 weeks and 13 weeks after transplantation, when intestinal aGVHD occured, and after treatment.Children with intestinal aGVHD were taken as the observation group, and children without intestinal aGVHD were taken as the control group.Whether differences in the expression levels of the 3 biological proteins in the peripheral blood of the 2 groups of children were statistically significant was analyzed.The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic value of the above three biological proteins for intestinal aGVHD, and independent sample t test was performed to compare the expression levels of the 3 biological proteins before and after treatment in children with intestinal aGVHD. Results:(1) The concentrations of REG3α, sST2, and TNFR1 in the peripheral blood of the observation group were (33 985.42±24 631.33) ng/L, (139 899.66±115 825.65) ng/L, (3 041.65±2 418.72) ng/L, respectively, which were higher than the control group of (7 457.39±4 547.49) ng/L, (32 059.57±23 452.85) ng/L, (1 944.51±1 170.35) ng/L, the difference was statistically significant ( t=6.04, 5.19, 2.17, all P<0.05). (2) The area under ROC curve (AUC) of REG3α combined with sST2 in the diagnosis of intestinal aGVHD was 0.952 (95% CI: 0.851-0.992, P<0.001), the maximum Youden index was 0.894, the corresponding sensitivity was 83%, and the specificity was 99%.Its diagnostic value was better than REG3α, sST2 and TNFR1 ( Z=1.763, 1.332, 3.001, all P<0.05). (3) The concentrations of REG3α, sST2, and TNFR1 before treatment in the peripheral blood of children having received effective treatment were (31 343.01±25 364.71) ng/L, (146 629.52±110 501.04) ng/L and (2 489.00±859.70) ng/L, respectively, which were (12 104.37±11 704.60) ng/L, (93 539.55±81 920.93) ng/L and (2 048.15±813.47) ng/L after treatment, lower than those before treatment.The expression levels of REG3α and sST2 were significantly reduced ( t=-3.23, -2.10, all P<0.05), while the difference of the expression level of TNFR1 before and after treatment was not statistically significant ( P>0.05). Conclusions:REG3α and sST2 can be used as important reference indicators for clinical auxiliary diagnosis of intestinal aGVHD, and have good auxiliary diagnostic value.REG3α and sST2 can be used as objective indicators to evaluate the efficacy of clinical treatment of intestinal aGVHD.

The impact of parental obesity on offspring health attracts increasing attention with the rising obese population worldwide. Much more studies have concentrated on the influences of maternal obesity, while studies regarding paternal obesity were relatively few and mainly focused on glucose and insulin regulation, adiposity, etc. Several large cohort studies and animal experiments have shown that paternal obesity can damage the neuropsychological development in offspring, which has become a risk factor for autistic spectrum disorders, cognitive disorders, and lower intelligence quotient, and epigenetic studies have explored the related mechanisms. This review summarizes the progress in this field, aiming to provide a reference for basic and clinical research in the future.

SARS-CoV-2 may have potential effects on the male reproductive system. Evidence has shown that SARS-CoV-2 is not likely to transmit through sexual intercouse. However, male infected with SARS-CoV-2 may experience sexual dysfunction, semen quality decline, testicular damage and abnormal sex hormones. The extent and duration of these damages are still unclear, and further multidimensional research is necessary.