Glaucoma is a common irreversible blinding eye disease, pathological elevated intraocular pressure is the main clinical feature. The formation of intraocular pressure, related to aqueous circulation, will be pathologically elevated when the aqueous cycle is abnormal. Trabecular network, which plays a key role in maintaining normal intraocular pressure, is the main component of aqueous outflow channel. Imbalance of oxidative stress manifested as oxidation and antioxidant effects is a direct risk factor for elevated intraocular pressure in glaucoma. When it comes to the trabecular meshwork cells, a series of changes such as deposition and degeneration of extracellular matrix, autophagy and aging will eventually occur, and finally the dysfunction of trabecular meshwork cells and increased aqueous outflow resistance, causing intraocular pressure pathological elevated. In this paper, we reviewed the research progress on the relationship between oxidative stress in trabecular meshwork cells and the pathogenesis of glaucoma, in order to provide evidence for further research and reference for exploring the pathogenesis, prevention and treatment of glaucoma.

Objective: To investigate the function network and potential mechanisms of effects of Chaihu Plus Mangxiao Decoction in the treatment of functional constipation by using network pharmacology methods. Methods: TCMSP, TCMID, and Swiss Target Prediction online prediction databases were used to screen the components and their potential targets of Chaihu Plus Mangxiao Decoction using oral availability (OB) and drug-like (DL) as the qualification conditions. PubMed, CTD, TTD, and DrugBank were used to search functional constipation-related targets. STRING and Cytoscape were used to make targets network visualization, screen the key components and core targets with high a degree of the node; Finally, relevant software was applied to analyze core targets and predict the mechanism. Results: A number of 206 total components of Chaihu Plus Mangxiao Decoction were screened, and there were 998 corresponding targets, which were contained 295 targets associated with functional constipation. According to the analysis, there were 64 key components and 30 core targets involving the Chaihu Plus Mangxiao Decoction-induced treatment of functional constipation. After enrichment analysis and KEGG pathway analysis of 30 core targets, it was found that SCN9A, CFTR, HTR2A, OPRD1, PTGS1, and FGFR1 were involved in regulating biological processes including opioid receptor activity, water balance of the organism, terpenoids and biological receptors and subsequent mediating the function of serotonin receptors, arachidonic acid metabolism, transcriptional regulation of MECP2, cytochrome P450, biogenic amine-binding receptors, PI3K the aberrant expression, tyrosine-protein kinase signaling pathway, and exogenous foreign body stimulation. These biological targets and molecular signaling pathways may play a therapeutic role in the treatment of functional constipation. Conclusion: The mechanism of effect of Chaihu Plus Mangxiao Decoction in the treatment of functional constipation is characterized by multiple targets and pathways. Saponins, flavonoids, and sterols may be the material basis for core functions, and serotonin receptors, opioid receptors and chloride channel-regulated receptors may be key targets of Chaihu Plus Mangxiao Decoction.

Artificial intelligence (AI) is among the forefront science in recent years. The rapid development of intelligent medicine based on AI, a new concept in the medical field, has resulted in a large impact on traditional medicine. AI poses a great opportunity and also many challenges for clinical physicians. Recently, researches in the development and application of AI are increasingly published in the field of endocrinology, such as the diagnosis and prediction of diabetes and its complications, the optimizing treatment and blood glucose management, the development of artificial pancreas, the diagnosis and treatment of obesity, the prognosis of bariatric surgery, osteoporosis and fracture prediction, bone age analysis, non-invasive assessment of liver steatosis and fibrosis, diagnosis of acromegaly, pathological diagnosis of thyroid and pituitary tumors. Nevertheless, the clinical applications of AI for medicine are still at an initial stage. With the rapid development of AI, we are expecting that it will play a pivotal role in the field of endocrinology and metabolism in the future. This is a new era for medical community to embrace new technology. Only with the properly dealing with the innovation of AI, a win-win result could be achieved.

Artificial intelligence （AI） and population pharmacokinetics （PPK） technologies have demonstrated significant potential in the personalized medication of immunosuppressants after organ transplantation, enabling precise prediction of drug dosages. This article provides a comprehensive review of the application status of AI and PPK in the individualized administration of immunosuppressants after organ transplantation， focuses on monitoring blood drug concentration， predicting efficacy/adverse reactions， and establishing individualized dosing models for organ transplant recipients after immunosuppressant administration， and analyzes and compares the application characteristics of different methods in different organ transplant patients as well as the integration and future development of AI and PPK technologies. AI and PPK technologies can not only significantly reduce the dependence on human resources， but also greatly improve the level of individualized treatment of immunosuppressants after organ transplantation， and reduce the discomfort and burden caused by frequent blood concentration monitoring to patients.

Toxoplasma gondii is an obligatory intracellular parasite which infects a variety of warm-blooded animals and causes toxoplasmosis. Toxoplasmosis seriously endangers human health and animal husbandry production. As one of the effective gene editing tools, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system has been widely used for knockout of genes in T. gondii. This review summarizes the applications of the CRISPR/Cas9 technology in vaccines against single- and double-gene deletion strains of T. gondii, so as to provide insights into development of toxoplasmosis vaccines.

Objective To establish a scientific, comprehensive, and operable community resilience evaluation index system for emergent major infectious diseases. Methods Based on the social ecosystem theory, a preliminary evaluation index system was formed by using content analysis and boundary analysis. The index system was then supplemented and revised through panel discussions. The final index system and index weights were clarified by two rounds of Delphi method. Results The expert positive coefficient, expert authority coefficient, and expert coordination coefficient of the two rounds of expert consultations were examined. According to the screening principle of the ^“threshold method^”, the indicators were screened, and the weights of each indicator were determined in the second round of Delphi expert consultation. The analysis of the reliability of the indicator system showed Cronbach's α= 0.399 , indicating that the indicator system had a relatively high reliability. Factor analysis was carried out on 7 primary indicators, and the measure of sampling adequacy (MSA) values were all greater than 0.5, which passed the validity test. Conclusion A set of evaluation index system that can accurately reflect the resilience level of communities with emergent major infectious diseases has been constructed, including 7 primary indicators, 21 secondary indicators, 54 tertiary indicators, and 108 tertiary indicators, which has realized the quantitative evaluation of the hidden resilience level of communities.

BACKGROUNDCornea epithelial cells play early and crucial roles in the initiation of ocular surface responses to pathogens. Participation of toll-like receptor (TLR) 2 and TLR4, which are major forms of fungi receptors, may be involved in Aspergillus fumigatus induced immune responses. The objective of the present study was to examine whether inactive Aspergillus fumigatus conidia induce NF-kappaB activation and production of proinflammatory cytokines, and whether the expression of TLR2 and TLR4 were amplified by conidia in cultured immortalized human corneal epithelial cells (THCEs). This may contribute to our knowledge of the mechanism by which the host cornea can successfully defend against invasive fungi.

METHODSAspergillus fumigatus conidia were used to challenge THCE cells. THCE cells were harvested after 0.5, 1, 2 or 4 hours incubation. Real-time quantitative PCR was performed to determine the expression of TLR2, TLR4, TNF-alpha and IL-8. Western blotting was performed to determine the expression of NF-kappaB. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the expression of TNF-alpha and IL-8. And the release of TNF-alpha and IL-8 in the cell supernatant were also assessed by ELISA with or without pretreatment with TLR2 and TLR4 neutralizing antibodies.

RESULTSAspergillus fumigatus conidia elicited the expression of TLR2, TLR4, TNF-alpha and IL-8 mRNA in THCEs. Exposure of THCE cells to Aspergillus fumigatus conidia resulted in NF-kappaB activation, which increased at 30 minutes (increased from 11.35+/-2.74 in the controls to 19.12+/-3.48, P<0.05) and thereafter increased steadily up to 4 hours after challenge (P<0.01). Concomitant with NF-kappaB activation, secretion of TNF-alpha and IL-8 in conidia-challenged cells was increased in a time-dependent manner. Incubation of THCE cells with TLR2 antibody or TLR4 antibody before conidia challenge resulted in inhibition of conidia-induced TNF-alpha and IL-8 secretion (P<0.05), TLR2 antibody and TLR4 antibody together significantly increased inhibition of the conidia-induced secretion of TNF-alpha and IL-8 from THCE cells (P<0.01).

CONCLUSIONAspergillus fumigatus conidia stimulates THCEs inflammatory response through a pathway dependent on TLR2 and TLR4 signaling.

Aspergillus fumigatus ; immunology ; Cells, Cultured ; Epithelium, Corneal ; cytology ; immunology ; Humans ; Interleukin-8 ; biosynthesis ; NF-kappa B ; metabolism ; Toll-Like Receptor 2 ; physiology ; Toll-Like Receptor 4 ; physiology ; Tumor Necrosis Factor-alpha ; biosynthesis

BACKGROUNDThis research aims at identifying relative interventions on trachoma and testing the effectiveness of control measures adopted by assessing its prevalence and related risk factors in Shandong province of China.

METHODSTrachoma rapid assessment (TRA) was conducted in 6 sub-districts selected from Shandong province based on primary high risk assessment. Active trachoma in children aged 1-9 years and environmental risk factors of trachoma (unclean faces, absence of running water, and absence of flush toilets) were assessed (TRA 1). Control measures were taken in endemic areas. A second TRA (TRA 2) was conducted after 12 months in the same 6 districts and findings of the two TRAs were compared.

RESULTSIn TRA 1, we found trachoma in 3 sub-districts and the detection rate was 4% (95% CI: 0.39%-11.12%), 6% (95% CI: 1.18%-14.17%), and 6% (95% CI: 1.18%-14.17%) respectively. We could not find trachoma cases in TRA 2. Research data supports that children living with environmental risk factors face an increased risk to active trachoma. However, we could not find statistical evidence for this association, which may be caused by the limited data on prevalence.

CONCLUSIONSThis research indicates that the TRA methodology is easy to assess trachoma and its related risk factors. Based on the results of this study, we have already achieved the goal of "elimination of trachoma" in Shandong province, as the detection rate of trachomatous inflamation follicular/trachomatous inflammation intense in 1-9-year-old children was less than 5%.

Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Male ; Prevalence ; Risk Factors ; Trachoma ; epidemiology

AIM: To investigate the effect of electroacupuncture on the expression of matrix metalloproteinase-3(MMP-3), tissue inhibitor of metalloproteinase-3(TIMP-3)and collagen type III alpha 1(Col3α1)in the retina of guinea pigs with lens-induced myopia.METHODS:A total of 80 guinea pigs were randomly divided into the normal control(NC)group, negative lens-induced myopia(LIM)group, electro-acupuncture(EA)group, and sham group, with 20 guinea pigs in each group. The NC group did not receive any intervention, the LIM, EA and the sham groups were all wearing -6.0 D lens in the right eye and no lens in the left eye. The EA group was given electroacupuncture stimulation at Hegu Point and temple, and guinea pigs in the sham group were given intervention at false points. The refraction was measured by optometry, the axial length was measured by A-ultrasound, and the changes in retinal tissue structure were observed by HE staining. Quantitative polymerase chain reaction(Q-PCR)and western blot(WB)were used to detect the expression of MMP-3, TIMP-3, and Col3α1 at mRNA and protein levels before modeling and at 2 and 4 wk after modeling. RESULTS:The axial length of the negative LIM group was significantly increased compared with the NC group at 2 and 4 wk after modeling(all P<0.05), and the diopter was significantly decreased(all P<0.05); the axial length of the eye in the EA group was decreased compared with the negative LIM group(all P<0.05), and the diopter was increased(all P<0.05). HE staining showed that the boundaries of retinal tissue in the NC group were obvious and arranged regularly. The retinal thickness, the thickness of the inner and outer nuclear layers, and the number of cells were reduced and irregularly arranged in the negative LIM group. The overall structure of the retina in the group EA was relatively perfect, the arrangement was more regular, and the morphological structure of each layer of the tissue did not appear obvious abnormalities. Q-PCR and WB detection results showed that the mRNA and protein relative expression levels of MMP-3, TIMP-3, and Col3α1 in the negative LIM group were significantly higher than those in the NC group(all P<0.05); the expression levels of the EA group was significantly decreased after intervention compared with the negative LIM group(all P<0.05).CONCLUSION: Electroacupuncture can delay axial growth in negative LIM guinea pigs, and downregulate negative LIM induced expression of MMP-3, TIMP-3, and Col3α1 in the retina.

Exosomes are extracellular vesicles with a diameter of 40-100 nm, which contain a variety of functionally active substances such as proteins, microRNAs, and they are transported into the cell via different pathways. Studies have confirmed that exosomes slow down the progression of diabetic retinopathy by modifying changes in the levels of cell proliferation/apoptosis factors, antioxidant regulatory factors, inflammatory factors, and vascular endothelial growth factor in different ways, including direct regulation and delivery of different miRNAs, long-chained noncoding RNAs, which in turn inhibit high-glucose-induced retinal inflammation, neovascularization, microvascular damage, and vascular leakage and other retinal injuries caused by high glucose. This review summarizes the basic characteristics of exosomes and their research progress in diabetic retinopathy.