Epigenetics is a researching hot topic of worldwide now.Increasing evidence shows that the pathogenesis of human diseases is not only influenced by the abnormalities of genetic factors but also by epigenetic mechanisms.Recent technological advances in epigenomic profiling has led to further understanding of the role epigenetic factors played in development,inflammation,aging,immunity,angiogenesis,tumorigenesis,and stem cell biology.The researchers in ophthalmology should pay close attention to the current research of major epigenetic mechanisms and their involvement in human diseases,especially ocular diseases.Moreover,the potential application of epigenetic drugs in the treatment of common human diseases also should be understood.Finally,the challenges and future perspectives underlying epigenetic research are discussed in this editorial paper.

Objective:To evaluate the effect of decalcified freeze-dried bone allograft(DFDBA) and DFDBA with platelet-rich plasma(PRP) in the treatment of periodontal infrabony defects.Methods: Fifteen periodontal infrabony defects(30 sites) in 12 patients with periodontitis(9 patients with chronic periodontitis and 3 patients with aggressive periodontitis) were selected.Three months after initial therapy,they were assigned to either the DFDBA group(10 defects with 20 sites) or the DFDBA with PRP group(5 defects with 10 sites).The patients were evaluated for plaque index(PI),bleeding index(BI),probing depths(PD) and clinical attachment loss(CAL) before the treatment and at 6 months after periodontal bone graft surgery.Results: The PI,BI,PD and CAL in the DFDBA group were 1.7,2.7,6.0 mm and 7.0 mm at baseline;1.5,1.8,3.9 mm and 4.4 mm at the 6 months after periodontal surgery.The PD,CAL and BI in DFDBA with PRP group at baseline were 6.2 mm,7.1 mm and 2.9;3.2 mm,3.6 mm and 1.7 at the 6 months after periodontal surgery.The PI did not change significantly after surgery in both groups.While both groups showed significant improvement(P

0.99.The quantitive restriction was 0.1 ?g/mL,the recovery rate was over 70%.The RSD of intra-and inter-day was less than 15%.The pharmacokinetic parameters of flavonoids were different from each other after ig and iv administration.The absolute bioavailability of flavonoids were 12.9%,10.8%,2.2%,10.2% and 5.9%,respectively.Conclusion The method is sensitive,specific,accurate,and is not only useful for guiding the bioavailability study on the corolla of A. manihot,but also for establishing a reasonable clinical dosage program.The four flavonols in the corolla of A.manihot can be rapidly distributed and eliminated in rats,the pharmacokinetics of two routes of administration are different.A novel integrated pharmacokinetic approach to describing the holistic pharmacokinetic properties of Chinese materia medica has been successfully developed and validated using four flavonols of A.manihot as a model herbal medicine.This study would be a new try for guiding the holistic pharmacokinetic study in consistence with the intrinsic theory and characteristics of traditional Chinese medicine.

Abstract: Objective　China was certified by World Health Organization as a malaria-free country in 2021. Malaria has become a rare infectious disease, and preventing the re-transmission of imported malaria and reducing deaths are the main challenges facing China after elimination of malaria. To analyze and clarify the characteristics of imported malaria deaths, and to provide prevention and treatment recommendations for overseas workers and health care workers. Methods　The data of 17 imported malaria deaths in the analysis of malaria deaths from 2016 to 2020 by the National Severe Malaria Treatment Expert Group were collected, and the relevant clinical epidemiological data and disease course records were analyzed. Results　The 17 malaria deaths were all imported from Africa with Plasmodium falciparum infection (malarial cerebral type), with no obvious regularity in the month of onset. Among them, 16 were male patients, 5 cases with underlying diseases such as diabetes mellitus, and 10 patients were first diagnosed in a second-level or lower hospital. Excluding patients who died of respiratory cardiac arrest in ambulances, the mean time difference between first onset and malaria diagnosis in 16 patients was 6.8 days (median 5.5 days), and the mean time between first onset and antimalarial treatment was 7.4 days (median 6 days), the mean time difference from initial onset to death was 10.3 days (median 8.5 days). Excluding cases with onset abroad and unknown time of return, all 14 patients developed the disease within 30 days after returning to China. Conclusion　All the fatal cases were infected with Plasmodium falciparum imported from Africa. The patients' awareness of actively seeking medical treatment is weak, and the delay in seeking medical treatment caused by the insufficient diagnosis and treatment capacity of health institutions at the township level and below is the main reason for the deaths. It is recommended to strengthen the self-protection awareness of staff in malaria-endemic areas overseas and raise their awareness of malaria. For returnees from areas with high malaria risk, primary medical institutions should pay attention to the patient's travel history in Africa, improve the awareness of malaria diagnosis, malaria diagnosis and treatment capabilities.

Objective To investigate the effects of timosaponins, one group of the two major components of A nemarrhean asphodeloides Bge, on the learning and memory capacities of rats with dementia induced by amyloid β-peptide (25-35) [Aβ(25-35)]. Methods Sixty SD rats were randomized into 6 groups (n=10) and except for those in the control group, all other rats were subjected to lateral cerebral ventriclar injection of aggregated Aβ (25-35) to prepare rat models of dementia. Twenty four hours after the injection, the rats received intragastric administration of timosaponins at 3 different doses (treatment group) or Ginkgo biloba extract EGB761 on a daily basis for 14 consecutive days. From postoperative days 8 to 14 after Aβ (25-35) injection, Morris water maze test was performed to evaluate the effects of Aβ (25-35) and the therapeutic agents timosaponins on the learning and memory capacity of the rats. On day 14, the level of malonaldehyde (MDA), superoxide dismutase (SOD) activity and total antioxidation capacity in the brain tissue of the rats were measured. Results Aβ (25-35) induced significant learning and memory impairment in the rats, which had lowered SOD activity and total antioxidation capacity (P＜0.01) with elevated MDA level (P＜0.05). Compared with the rats in dementia model group, those receiving timosaponin treatment at different doses all manifested alleviation of learning and memory impairment (P＜0.05), with enhanced SOD activity (P＜0.05) and total antioxidation capacity (P＜0.01) and reduced MDA level (P＜0.05) in the brain tissue. Conclusion Timosaponins can remarkably enhance the learning and memory capacities in rats with Aβ (25-35) -induced dementia, presumably in relation to their actions to promote the scavenging of the free radicals.

Objective To investigate the effects of timosaponins, one group of the two major components of A nemarrhean asphodeloides Bge, on the learning and memory capacities of rats with dementia induced by amyloid β-peptide (25-35) [Aβ(25-35)]. Methods Sixty SD rats were randomized into 6 groups (n=10) and except for those in the control group, all other rats were subjected to lateral cerebral ventriclar injection of aggregated Aβ (25-35) to prepare rat models of dementia. Twenty four hours after the injection, the rats received intragastric administration of timosaponins at 3 different doses (treatment group) or Ginkgo biloba extract EGB761 on a daily basis for 14 consecutive days. From postoperative days 8 to 14 after Aβ (25-35) injection, Morris water maze test was performed to evaluate the effects of Aβ (25-35) and the therapeutic agents timosaponins on the learning and memory capacity of the rats. On day 14, the level of malonaldehyde (MDA), superoxide dismutase (SOD) activity and total antioxidation capacity in the brain tissue of the rats were measured. Results Aβ (25-35) induced significant learning and memory impairment in the rats, which had lowered SOD activity and total antioxidation capacity (P＜0.01) with elevated MDA level (P＜0.05). Compared with the rats in dementia model group, those receiving timosaponin treatment at different doses all manifested alleviation of learning and memory impairment (P＜0.05), with enhanced SOD activity (P＜0.05) and total antioxidation capacity (P＜0.01) and reduced MDA level (P＜0.05) in the brain tissue. Conclusion Timosaponins can remarkably enhance the learning and memory capacities in rats with Aβ (25-35) -induced dementia, presumably in relation to their actions to promote the scavenging of the free radicals.

Objective To investigate regional spontaneous brain activity in mild cognition impairment (MCI) patients with amnesic (aMCI) and non-amnesic (naMCI).Methods Twenty-five aMCI patients,21 naMCI patients and 15 normal controls (NC) underwent resting-state functional magnetic resonance imaging.The regional homogeneity (ReHo) map of the whole brain was obtained by calculating the similarity of each voxel with its nearest 26 voxel time series.The differences of ReHo map across the whole brain among three groups were compared.Results In aMCI group,ReHo values were lower in right frontal lobe and higher in left middle temporal gyrus and left cerebellum compared with NC (P＜0.05,Alphasim correction).In naMCI group,ReHo values were higher in anterior cingulate cortex and right middle frontal gyrus and lower in right parahippocampa gyrus,right middle temporal gyrus as well as right precuneus compared with NC (P＜0.05,Alphasim correction).Compared with naMCI,the ReHo values were significantly higher in left prefrontal gyrus,left middle temporal gyrus and lower in right cerebellum (P＜0.05,Alphasim correction).Conclusion There are differences in spontaneous brain activity of left prefrontal gyrus,left middle temporal gyrus and right cerebellum between aMCI and naMCI,which may be used to differentiate brain function between aMCI and naMCI patients.

OBJECTIVETo detect the expression of Toll-like receptor 9 (TLR9) in ovarian cancer, and to explore their clinical significance.

METHODSWestern blot method and immunohistochemical staining were used to examine the expression of TLR9 in the ovarian cancer, paracancerous tissues and normal ovarian tissues, obtained during operation from 30 ovarian carcinoma patients and 30 normal non-tumor patients. The relationships of TLR9 with pathological grade, clinical stage, and metastasis of ovarian cancer were statistically analyzed.

RESULTSThe percentage of positive cells expressing TLR9 protein in human ovarian cancer tissues, paracancerous tissues and normal ovarian tissues were 80.0%, 36.7% and 20.0%, respectively. The protein expression level of TLR9 was gradually descending (P < 0.01). The highly expressed TLR9 significantly correlated with the degree of tumor differentiation, an advanced FIGO stage and lymph node metastasis. The Western blot results showed that TLR9 protein expression in ovarian cancer, paracancerous tissues and normal ovarian tissues were 0.803 ± 0.072, 0.411 ± 0.087 and 0.113 ± 0.065, respectively. The expression of TLR9 in ovarian cancer was significantly higher than that in normal tissue and paracancerous tissues (P < 0.01).

CONCLUSIONSTLR9 has a higher expression in ovarian cancer tissues. TLR9 expression has a close relationship with pathological grades of ovarian cancer, suggesting that TLR9 plays an important role in the development and progression of ovarian cancer through immunologic mechanisms.

Adult ; Blotting, Western ; Carcinoma, Endometrioid ; metabolism ; pathology ; Case-Control Studies ; Cystadenocarcinoma, Mucinous ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Staging ; Ovarian Neoplasms ; metabolism ; pathology ; Ovary ; metabolism ; Toll-Like Receptor 9 ; metabolism

Objective To study the epidemiological characteristics of Keshan disease(KD) and its fiend so as to provide evidences for further research,prevention and treatment of the disease in Sichuan province.Methods Based on KD related data from 1990 to 2008,descriptive method was used to analyze the epidemiological characteristics of KD.Results 87 KD cases were identified during the 19 years.All cases were children from the countryside,with majority of them were Yi nationality.Age of the patients ranged from 5 months to 18 years,with majority at 2-6 year-olds.The annual incidence rates Were from 0/100 000 to 1.73/100 000 with 1999 the highest(1.73/100 000).A total number of 310 preclinical or chronic KD cases were identified and the total detection rates were between 0.28% and 2.8%.with 1992 the highest.As for levels of blood selenium during the 19 years:1995 appeared the lowest(0.1345 μg/g),followed by 1990-2000(0.1558 μg/g) but all of them fell in to the level in the KD epidemic areas.Conclusion There were 5 stages in the development trend of KD disease in Sichuan province,with 2 ascending and 3 descending.The differences between any of the two stages were statistically significant.The 3 descending stages all appeared right after the selenium supplement intervention was taken.Our data showed that the program of selenium supplement was closely related to the incidence of KD,suggesting that a long term mechanism of Selenium supplement in the epidemic areas should be taking into account.

OBJECTIVETo investigate the possibility of applying multiplex ligation-dependent probe amplification (MLPA) to the detection of azoospermia factor (AZF) microdeletion on the Y chromosome in infertile men with azoospermia or severe oligozoospermia.

METHODSDNA samples were obtained from 147 azoospermia or severe oligozoospermia patients and 154 normal controls. After denatured at 95 degrees C, the samples were hybridized to the specific probes designed for the AZF region. With the ligase, the hybrid products were amplified by a pair of universal primers labeled with FAM fluorescence, and then separated by capillary electrophoresis for data analysis. Meanwhile all the samples were subjected to multiplex-PCR (mPCR) analysis for sequence-tagged sites (STS) in the AZF region.

RESULTSSTS deletion was detected in 22 (15.0%) of the 147 patients but not in the normal controls. By MLPA, 40 (27.2%) of the patients were found with specific probe omission in the AZF region, as compared with 20 cases in the control group.

CONCLUSIONCompared with mPCR, MLPA has a better sensitivity in detecting AZF microdeletions, and it provides more precise genetic information on the AZF regions, which may contribute to in-depth exploration into the etiological mechanism of impaired spermatogenesis.

Adult ; Azoospermia ; genetics ; Case-Control Studies ; Chromosome Deletion ; Chromosomes, Human, Y ; genetics ; DNA Probes ; Genetic Loci ; Humans ; Infertility, Male ; Male ; Nucleic Acid Amplification Techniques ; methods ; Oligospermia ; genetics ; Polymerase Chain Reaction ; methods ; Seminal Plasma Proteins ; genetics ; Sequence Tagged Sites ; Sex Chromosome Aberrations ; Sex Chromosome Disorders of Sex Development ; genetics ; Young Adult