The eye serves critical visual functions. However, the occurrence of diseases such as diabetic retinopathy and age-related macular degeneration leads to visual impairment. O-glycosylation, as an important mode of protein modification, affects the structure, stability, and function of various ocular proteins. Recent studies have found that O-glycosylation has a dual role in the eye. On one hand, its normal presence maintains ocular surface barrier function and retinal photoreceptor survival. On the other hand, aberrant O-glycosylation mediates the pathological processes of ocular diseases through activating signaling pathways and regulating gene expression. Moreover, the crosstalk between O-glycosylation and phosphorylation contributes to the complex molecular mechanisms underlying these pathologies. This review summarizes the physiological protection and pathological mechanisms of three types of O-glycosylation in the eye, and explores the therapeutic prospects for ocular diseases. It further envisions future integration with emerging technologies such as nanodelivery to provide targeted therapeutic strategies, facilitating the transition from theory to practice.

Both cathartic colon （CC） and cathartic-dependent constipation （CDC） are caused by the abuse of stimulant laxatives， while their concepts are not completely the same.Starting from the disease name of CC， this article traced the origin and evolution of the concept of CC， summarizes and compared the similarities and differences between CC， CDC， and slow transit constipation （STC）， and called for strict differentiation among the three.Furthermore， this article explored the specific contents of Western medicine clinical subtypes and traditional Chinese medicine （TCM） syndrome differentiation of CDC and delved into the TCM pathogenesis of CDC according to both literature and clinical practice.The relationship between clinical subtypes and TCM syndromes was established， and the syndrome characteristics of CDC of different clinical subtypes and TCM syndromes were summarized.The recommended prescriptions for corresponding syndromes were listed.A systematic CDC diagnosis and treatment approach of "clinical subtypes-syndrome differentiation-syndrome characteristics-recommended prescriptions" was thus formed.Additionally， the paper provides an overview of current research on CDC in both Western medicine and TCM contexts， identifies future research directions， and suggests research pathways for refining and advancing CDC studies.

ObjectiveTo observe the clinical efficacy of the Yiqi Yangyin Huoxue prescription （YYHP） in the treatment of cathartic colon （CC） and its effects on fecal short-chain fatty acids （SCFAs）， and to explore the correlations among CC severity indicators and between these indicators and patient history. MethodsAccording to the inclusion and exclusion criteria， 98 patients meeting the diagnostic criteria of both traditional Chinese and Western medicine for CC with the syndrome of Qi-Yin deficiency complicated by blood stasis were randomly assigned to an observation group and a control group. The observation group received YYHP granules， while the control group received lactulose. Both medications were administered twice daily， one sachet each time， half an hour after breakfast and dinner， with a treatment course of 8 weeks. The primary constipation symptom score， Patient Assessment of Constipation Quality of Life （PAC-QOL） score， and TCM syndrome score were assessed before and after treatment and at the 8^th week after the end of treatment. The overall clinical effective rate， as well as the efficacy attenuation index and degree， were evaluated. Fecal SCFA levels were measured using gas chromatography-mass spectrometry （GC-MS）. Spearman correlation analysis was performed to explore the correlations among CC severity indicators and between these indicators and patient history. ResultsThe overall clinical effective rate in the observation group （95.83%） was higher than that in the control group （78.72%） （P<0.05）. After treatment， the total scores for primary constipation symptoms， PAC-QOL， and TCM syndromes decreased in both groups （P<0.05）， with more significant reductions in the observation group （P<0.05）. The severity of all primary constipation symptoms was alleviated in both groups （P<0.05）. In terms of "excessive straining and difficult defecation"， "anal heaviness， incomplete evacuation， and bloating sensation"， "abdominal distension"， and "defecation frequency"， the observation group showed better efficacy than the control group （P<0.05）. Scores of the four PAC-QOL dimensions and the scores and severity of primary and secondary TCM symptoms were reduced in both groups （P<0.05）， with more significant reductions in the observation group （P<0.05）. After treatment， acetic acid， propionic acid， butyric acid， and total SCFAs in the observation group increased significantly （P<0.05）. The efficacy attenuation index and degree in the observation group were lower than those in the control group （P<0.05）. No severe adverse reactions occurred in either group， and there was no statistically significant difference in the incidence of adverse reactions between the two groups. Positive correlations of varying degrees were observed among the total scores of primary constipation symptoms， PAC-QOL， and TCM syndromes， as well as between these scores and the history of stimulant laxative use， disease duration， and age. ConclusionYYHP can effectively alleviate the primary constipation symptoms in CC patients， improve quality of life， and ameliorate TCM syndromes， with good safety. It also has the advantage of a lower rebound degree after drug withdrawal， and its mechanism may be related to increasing fecal SCFA levels. Long-term abuse of stimulant laxatives may aggravate the severity of CC and prolong the disease course.

ObjectiveTo evaluate and analyze the syndrome characteristics of Qi and Yin deficiency accompanied by Qi stagnation and blood stasis in a rhein-induced cathartic colon （CC） rat model. MethodsTwenty-four rats were divided into a normal group and a model group （CC group）. The rats were administered equal volumes of physiological saline or 2% rhein suspension by gavage to establish the model over three cycles （approximately 118 days）. The first cycle lasted 46 days， with a dosage of 12 mL·kg^-1·d^-1， administered every other day. The second cycle lasted 37 days， with a dosage of 12 mL·kg^-1·d^-1， administered for 5 consecutive days followed by 2 days of cessation. The third cycle lasted 35 days， with a dosage of 16 mL·kg^-1·d^-1， also administered for 5 consecutive days followed by 2 days of cessation. Each cycle ended when 80% of the rats no longer exhibited loose stools. Body mass， 24 h food intake， coat condition， and coat red （R）， green （G）， and blue （B） values were recorded. The open field test （OFT） was used to measure the total distance traveled to evaluate Qi deficiency. The body mass coefficient and 24 h water intake were recorded to assess Yin deficiency. The sucrose preference test （SPT） was used to determine the sucrose preference rate （SPR）， and the average speed in OFT was measured to evaluate depressive status （liver depression and Qi stagnation）. Tongue images and their R， G， and B values were recorded. Whole blood viscosity （WBV） and plasma viscosity （PV） were measured using an automatic hemorheological analyzer to evaluate blood stasis. A carbon ink propulsion test was performed to determine the intestinal transit rate （ITR） for disease model evaluation. Hematoxylin-eosin （HE） staining was used to observe histopathological changes in the colon. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of transient receptor potential ankyrin 1 （TRPA1） and tryptophan hydroxylase 1 （TPH1） in colon tissue. Western blot was used to detect the protein expression of TRPA1 and TPH1. ResultsIn terms of syndrome indicators， compared with the normal group， the body mass of the CC group decreased （P<0.05）， while 24 h food intake increased （P<0.01）. The coats of the CC group appeared withered， disheveled， and dull， and the R， G， and B values of the coat decreased （P<0.01）. The total distance traveled in OFT decreased （P<0.01）. The body mass coefficient decreased （P<0.01）， while 24 h water intake increased （P<0.05， P<0.01）. The SPR decreased （P<0.01）， and the average speed in OFT slowed （P<0.01）. The tongue appeared dark red， and the R， G， and B values of tongue images decreased （P<0.01）. WBV and PV increased （P<0.01）. Regarding disease indicators， compared with the normal group， the ITR decreased in the CC group （P<0.01）. Pathologically， HE staining showed necrosis and shedding of colonic mucosal epithelial cells， disruption of mucosal continuity， and infiltration of inflammatory cells in the lamina propria in the CC group. Semi-quantitative analysis showed increased HAI scores （P<0.05） and increased inflammatory cell counts and area proportion （P<0.05）. In terms of molecular biological indicators， compared with the normal group， the mRNA and protein expression levels of TRPA1 and TPH1 in colon tissue decreased in the CC group （P<0.05， P<0.01）. ConclusionThe rhein-induced CC rat model conforms to the traditional Chinese medicine syndrome characteristics of Qi and Yin deficiency accompanied by Qi stagnation and blood stasis.

A quantitative method for the analysis of the multi-component contents in Marsdenia tenacissimae was established, and the quality differences were evaluated by principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), factor analysis (FA) and weighted technique for order preference by similarity to ideal solution (TOPSIS) method. The contents of chlorogenic acid, cryptochlorogenic acid, sinapic acid, tenacigenoside A, tenacissoside G, tenacissoside I, tenacissoside H, drevogenin A, betulinic acid and lupeol were determined by HPLC wavelength switching method. At the same time, the contents of alcohol-soluble extract and total ash were detected. PCA, OPLS-DA and FA methods were used to identify the origin of M. tenacissimae from different producing areas. According to the OPLS-DA model, the index weight was determined to construct the weighted TOPSIS evaluation model. The qualities of M. tenacissimae from different producing areas were analyzed by model scoring results. The contents of 12 indexes in 18 batches of M. tenacissimae varied to different degrees, and the repeatability and accuracy of the test method were satisfactory. PCA analysis divided 18 batches of M. tenacissimae into three categories. OPLS-DA identified five main potential quality markers, including tenacissoside A, tenacissoside I, lupeol, tenacissoside H and chlorogenic acid. The evaluation results of FA and weighted TOPSIS method were consistent, which showed that the quality of M. tenacissimae from Yunnan and Guizhou was better. The established multi-component quantitative analysis method is accurate and reliable, the chemometrics model has strong predictive ability, and the evaluation results of FA and weighted TOPSIS method are scientific and objective. The combination of the four methods can clearly determine the qualities of M. tenacissimae from different producing areas.

AIM: To investigate and clarify the intervention mechanism of trigonelline(TRG)in preventing ferroptosis in ARPE-19 cells based on the Nrf2/HO-1/GPX4 pathway.METHODS: The ARPE-19 cells were cultured and subsequently treated with varying concentrations of trigonelline to ascertain the most effective concentration for modulating the cells. Then the cells were categorized into distinct groups, including normal control(NC)group, high glucose(HG)group, Fer-1 group, TRG group based on the determined concentration. Samples from each group were then gathered to assess relevant indicators. The intracellular levels of glutathione(GSH), malondialdehyde(MDA), and Ferrion were quantified in accordance with the protocols provided by the GSH, MDA, and Ferrion detection kits. Flow cytometry was employed to measure the ROS levels within each group. Additionally, Western blot analysis was conducted to examine the expression of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase-1(HO-1), glutathione peroxidase(GPX4), and acyl-CoA synthetase long-chain family member 4(ACSL4)across the different groups.RESULTS: The preconditioning intervention with 40 μg/mL TRG effectively mitigated the decline in cell activity induced by high glucose levels. The levels of reactive oxygen species(ROS)and MDA in the HG group were markedly elevated compared to the NC group; and the TRG group exhibited significantly reduced levels of ROS and MDA compared to those of the HG group, with the antioxidant stress index GSH showing opposite trends to those of ROS and MDA across all the groups. Whereas the Fer-1 and TRG groups showed decreased expression levels of ACSL4 protein and iron ions, and the expression levels of Nrf2, HO-1 and GPX4 in the Fer-1 and TRG groups were increased.CONCLUSION: TRG protects ARPE-19 cells from the detrimental effects of high glucose by targeting the Nrf2/HO-1/GPX4 signaling pathway to counter ferroptosis.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Background: A simple superoposterior approach to thoracic transforaminal epidural injections (TFEIs) under ultrasonographic guidance was proposed to reduce zoster-associated pain (ZAP) involving multiple thoracic nerves and the likelihood of transitioning to postherpetic neuralgia (PHN). Methods: Patients were prospectively enrolled. Primary endpoints were the burden of illness (BOI) scores and epidural contrast spread. Secondary endpoints included number of needle insertion attempts, sensory blockade, hemodynamic changes, procedure time, radiation dose, adverse events, rescue analgesics, PHN incidence and EuroQoL 5-Dimension scores. Results: Thirty-five injections were performed in 27 patients. Median levels of cephalad-caudad epidural contrast spread were 3, 4, and 5 ml following injections of 2, 3, and 4 ml. Dorsal epidural spread was observed at levels 3, 4, and 5, whereas concurrent ventral spread was observed at levels 2, 3, and 4. BOI scores at 30–180 days significantly decreased (mean difference: −25.3, 95% CI [−57.4 to 6.6], P = 0.005), accounting for reduced rescue analgesic requirements and PHN occurrence and improved EuroQoL 5-Dimension scores. Median sensory blockade at 5 min post-procedure was at level 2, 3, and 4 after 2, 3, and 4 ml of therapeutic injectate. No significant hemodynamic changes were noted at 15 min post-injection. No serious adverse events were observed. Conclusions Spread of thoracic epidural contrast to all involved nerves was confirmed using this novel technique. Simplified needle placement reduced the technical difficulty and risk of complications. It might be a promising alternative approach for ZAP.

AIM: To explore the efficacy of 0.05% cyclosporine A combined with olopatadine eye drops in treating allergic conjunctivitis-related dry eye disease.METHODS: A total of 63 patients(63 eyes)with allergic conjunctivitis-related dry eye disease in the People's Hospital of Guangxi Zhuang Autonomous Region from August 2022 to April 2023 were enrolled and randomly divided into control group(n=33)and observation group(n=30). The patients of the control group were administrated with 0.1% olopatadine eye drops and 0.3% sodium hyaluronate eye drops, while the observation group was administrated with 0.1% olopatadine eye drops and 0.05% cyclosporine A eye drops. The ocular surface disease index(OSDI), total ocular symptom score(TOSS), conjunctival congestion score, conjunctival papillae and follicle score, Schirmer I test(SⅠt), tear meniscus height(TMH), meibomian gland secretion ability and property score, meibomian gland loss area score, corneal fluorescein staining(CFS), tear film break-up time(BUT), noninvasive first tear film break-up time(NIBUTf), noninvasive average tear film break-up time(NIBUTav)before and after treatment and the drug safety during the treatment period of both groups of patients were evaluated.RESULTS: After treatment, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, SⅠt, TMH, meibomian gland secretion ability score and property score, CFS, BUT, NIBUTf, and NIBUTav of the observation group showed improvements compared with those before treatment(all P<0.017). Among these, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, BUT, NIBUTf, and NIBUTav demonstrated significant improvement compared with the control group(all P<0.05). There was no statistically significant difference in meibomian gland loss area score between the two groups before and after treatment(P>0.05). During the treatment period, there were no local or systemic adverse reactions.CONCLUSION: The combined use of 0.05% cyclosporine A and olopatadine eye drops can significantly improve ocular discomfort symptoms of patients with dry eye disease associated with allergic conjunctivitis, such as red eyes, itchy eyes and foreign body sensation, promote tear film stability and have high safety.