Diabetic retinopathy(DR)is a late-stage peripheral micro-neurovascular complication of chronic hyperglycemia, leading to blood-retinal barrier impairment and retinal dysfunction. Recent studies have found that diabetic neuroretinopathy(DN)may be one of the earliest events in diabetic retinal alterations. The main features include defective electroretinographic responses in newly diagnosed patients, early self-activation of microglia and Müller cells, reduced activity of neurotransmitters(e.g., DOPA/GABA), and early mitochondrial dysfunction, such as persistent Drp1-Fis1 fission and mtDNA methylation mismatches. Understanding the molecular basis of DN is essential for elucidating its pathogenesis and developing early treatments. This review summarizes pathological changes and mechanisms of retinal function, glial cells, neurotransmitters, mitochondria, and other factors in early diabetes mellitus, in order to provide a theoretical foundation for investigating early DN mechanisms and developing targeted therapies.

OBJECTIVE To investigate the impact of dapagliflozin on contrast-induced acute kidney injury （CIAKI） and prognosis in patients with diabetes mellitus type 2 （T2DM） and acute coronary syndrome （ACS） who underwent percutaneous coronary intervention （PCI）. METHODS Retrospective selection of data on T2DM patients with ACS who underwent PCI treatment in the Cardiology Department of Tianjin Chest Hospital from January 1st 2021 to December 31st 2022. The patients were divided into dapagliflozin group （96 cases） and control group （148 cases） based on whether they received dapagliflozin or not. Renal function indicators were measured for all enrolled patients before PCI and at 48 h and 1 week after PCI， including blood urea nitrogen （BUN）， serum creatinine （Scr）， estimated glomerular filtration rate （eGFR）， cystatin-C （Cys-C）， kidney injury molecule-1 （KIM-1） and β2-microglobulin （β2-MG）. All patients were followed up for at least 1 year. The incidence of CIAKI and major adverse cardiac event （MACE） during follow-up were recorded for both groups. Logistic regression was used to analyze the impact of dapagliflozin on the occurrence of CIAKI， while the Log-rank test was applied to compare the incidence of MACE between the two groups. Cox regression was employed to analyze the impact of dapagliflozin on prognosis. RESULTS At 48 h and 1 week after PCI， serum levels of Cys-C， KIM-1 and β2-MG were significantly lower in the dapagliflozin group compared to the control group （P＜0.05）. The incidence of CIAKI was lower in the dapagliflozin group compared to the control group （6.25% vs. 14.86%， P＝0.042）. Logistic regression analysis revealed that dapagliflozin was an independent protective factor against CIAKI （OR＝0.280， 95%CI 0.101-0.780，P＝0.015）. During the follow-up period， the incidence of MACE was lower in the dapagliflozin group compared to the control group （7.29% vs. 17.57%， P＝0.049）. Cox regression analysis indicated that dapagliflozin reduced the occurrence of MACE after PCI （HR＝0.374， 95%CI 0.161-0.866， P＝0.022）. CONCLUSIONS With adequate hydration， the use of dapagliflozin does not increase the risk of CIAKI following PCI in T2DM patients with ACS.

Acute lung injury （ALI） is a clinically critical disease with limited treatment options and poor prognosis， with high morbidity and mortality. Pulmonary inflammation caused by trauma， infection， and other factors in vivo and in vitro can damage alveolar epithelial and vascular endothelial barriers， resulting in lung tissue congestion and edema and eventually leading to significant dyspnea and hypoxemia， It can further develop into acute respiratory distress syndrome. Oxidative stress is one of the pathogenesis of ALI. A large number of reactive oxygen species （ROS） can promote the aggregation of inflammatory cells， increase pulmonary capillary permeability， and even directly damage lung tissue. Therefore， regulating oxidative stress becomes one of the effective means to reduce the degree of lung injury. According to the theory of traditional Chinese medicine （TCM）， ALI is divided into the categories of "sudden wheezing" and "dyspnea due to wheezing". TCM treats the causes of dampness， heat， poison， and stasis by syndrome differentiation and treatment， regulates Qi and blood， and balances Yin and Yang to restore the physiological function of the lung. In recent years， a large number of studies have shown that TCM can regulate ROS through multiple targets and mechanisms and play a role in reducing lung inflammation and protecting alveolar epithelial cells and endothelial vessels， in which the nuclear factor E₂ associated factor 2 （Nrf2） antioxidant pathway plays an important role. Based on the generation and clearance of ROS， this article summarized the related mechanisms of TCM monomers， TCM pairs， and TCM compounds in regulating oxidative stress to prevent ALI， so as to provide theoretical reference for the research and development of new TCM for ALI and clinical treatment.

AIM:To study the relationship between ocular parameters and lens thickness(LT)in myopic patients with different anterior chamber depth(ACD).METHODS:Cross-sectional study. A total of 118 myopic subjects(236 eyes)underwent posterior chamber phakic implantable collamer lens(Phakic-ICL)implantation in the refractive department of our hospital from May 2022 to May 2024 were selected. Ocular parameters examined before surgery included uncorrected visual acuity(UCVA), subjective refraction, best corrected visual acuity(BCVA), contactless intraocular pressure(IOP), ACD, white-to-white(WTW), horizontal sulcus-to-sulcus(STSH), vertical sulcus-to-sulcus(STSV), and LT. ACD without corneal thickness was measured by Pentacam, and subjects were divided into three groups: shallow anterior chamber group(2.8 mm≤ACD≤3.2 mm), middle anterior chamber group(3.2 mm3.4 mm). The differences in WTW, STSH, STSV, and LT among groups were compared, and the correlation between the above parameters under different ACD groups was analyzed, as well as the multiple linear regression analysis was used to research LT with the above ocular parameters.RESULTS:There was no statistically significant difference in LT between the middle ACD group and the deep ACD group(P=1.00), while there were statistically significant differences in LT between shallow and middle ACD groups(P<0.0167); there were statistical significant differences in WTW, STSH and STSV among different ACD groups(F=226.36, 15.58, 11.92, all P<0.01), but the differences were varied after pairwise comparison. There was a weak negative correlation between LT and ACD only in the shallow ACD group and overall data of patients(r=-0.231, P<0.05; r=-0.222, P<0.01). There was no correlation in LT and ocular parameters between the middle ACD group and deep ACD group(all P>0.05); moderate correlations were discovered among WTW, STSH and STSV in different ACD groups and overall data(all P<0.01); in the overall data of patients, ACD had weak to low correlations with WTW, STSH, STSV and LT(all P<0.01). Through multiple linear regression analysis, it was found that only the shallow ACD group and the overall data had statistically significant independent variables that were linearly correlated with LT, and their equations were as follows: LTS=5.492-0.167×WTW+0.267×STSV-0.448×ACD; LTT=3.884-0.303×ACD, the corrected R2 of equations showed low values, revealed 0.141 and 0.056, respectively.CONCLUSION:Among different ACD groups, there was no correlation or linear relationship between LT and WTW, STSH and STSV; in the shallow ACD group and the overall data, LT had a weak negative correlation with ACD, and its corrected R2 was low. Therefore, there is no linear relationship between LT and ocular diameter parameters under different ACD.

OBJECTIVE To establish a method for determining the contents of clopidogrel （CLP）， clopidogrel carboxylate （CLP-C）， clopidogrel acyl-β-D-glucuronide （CLP-G） and contents of clopidogrel active metabolite （CAM） in rat plasma， and to investigate their in vivo pharmacokinetic characteristics. METHODS The Shisedo CAPCELL ADME column was used with a mobile phase consisting of water and acetonitrile （both containing 0.1% formic acid） in a gradient elution. The flow rate was 0.4 mL/min， and the column temperature was maintained at 20 ℃. The injection volume was 2 μL. The analysis was performed in positive ion mode using electrospray ionization with multiple reaction monitoring. The ion pairs for quantitative analysis were m/z 322.1→211.9 （for CLP）， m/z 308.1→197.9 （for CLP-C）， m/z 322.1→154.8 （for CLP-G）， m/z 504.1→154.9 [for racemic CAM derivative （CAMD）]. Six rats were administered a single intragastric dose of CLP （10 mg/kg）. Blood samples were collected before medication and at 0.08， 0.33， 0.66， 1， 2， 4， 6， 10， 23 and 35 hours after medication. The established method was used to detect the serum contents of various components in rats. Pharmacokinetic parameters were then calculated using WinNonlin 6.1 software. RESULTS The linear ranges for CLP， CLP-C and CAMD were 0.08-20.00， 205.00-8 000.00， and 0.04-25.00 ng/mL， respectively （r≥0.990）. The relative standard deviations for both intra-day and inter-day precision tests were all less than 15%， and the relative errors for accuracy ranged from －11.68% to 14.40%. The coefficients of variation for the matrix factors were all less than 15%， meeting the requirements for bioanalytical method validation. The results of the pharmacokinetic study revealed that， following a single intagastric administration of CLP in rats， the exposure to the parent CLP in plasma was extremely low. Both the area under the drug concentration-time curve （AUC0-35 h） and the peak concentration of the parent CLP were lower than those of its metabolites. The AUC0-35 h of the active metabolite CAM was approximately 43 times that of CLP， though it had a shorter half-life （2.53 h）. The inactive metabolite CLP-C exhibited the highest exposure level， but it reached its peak concentration the latest and was eliminated slowly. The AUC0-35 h of CLP-G was about four times that of CAM， and its half-life was similar to that of CLP-C. CONCLUSIONS This study successfully established an liquid chromatography-tandem mass spectrometry method for the determination of CLP and its three metabolites， and revealed their pharmacokinetic characteristics in rats. Specifically， the parent drug CLP was rapidly eliminated， while the inactive metabolites CLP-C and CLP-G exhibited long half-lives， and active metabolite CAM displayed a transient exposure pattern.

ObjectiveTo clarify the repair effect of Mume Fructus on the intestinal mucosal epithelial barrier in the mouse model of inflammatory bowel disease （IBD） and explore the repair mechanism. MethodsThirty-six male C57BL/6 mice were randomly assigned into six groups： normal， model， low-， medium-， and high-dose （200， 400， and 800 mg·kg^-1） Mume Fructus， and sulfasalazine （300 mg·kg^-1）. Except the normal group， the rest groups had free access to 2% dextran sulfate sodium （DSS） solution for seven days to establish the IBD model， followed by a seven-day drug intervention. The body weight change and disease activity index （DAI） were recorded. After the last administration， spleen and colon tissue samples were collected to analyze the differences in colon length and spleen index. Hematoxylin-eosin staining was used to observe the morphology of the colon tissue. The level of diamine oxidase （DAO） in the serum was measured by the DAO assay kit. Immunohistochemistry was employed to determine the expression of tight junction proteins such as Claudin-1， Occludin， and zonula occludens-1 （ZO-1） in the colon tissue. Real-time PCR was performed to measure the mRNA levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the colon tissue. Finally， Western blot was employed to determine the protein levels of mitogen-activated protein kinase kinase （MEK）， extracellular signal-regulated kinase （ERK）， phosphorylated （p）-MEK， and phosphorylated ERK in the colon tissue. ResultsCompared with the normal group， the model group exhibited decreases in body weight and colon length （P<0.01）， increases in DAI， spleen index， and serum DAO level （P<0.01）， damaged colonic epithelium and goblet cells， and obvious infiltration of inflammatory cells. In addition， the model group exhibited higher positive expression of Claudin-1， Occludin， and ZO-1 （P<0.01）， higher mRNA levels of TNF-α and IL-1β （P<0.01）， and higher protein levels of p-MEK and p-ERK （P<0.05， P<0.01） than the normal group. However， sulfasalazine and three doses of Mume Fructus markedly decreased the body weight and DAI （P<0.05）， recovered the colon length and spleen index， alleviated colon tissue damage， lowered the level of DAO in the serum （P<0.01）， and down-regulated the mRNA levels of TNF-α and IL-1β （P<0.01） and the protein levels of p-MEK and p-ERK （P<0.05）. Sulfasalazine and low- and medium-dose Mume Fructus increased the positive expression of Occludin， Claudin-1， and ZO-1 （P<0.05， P<0.01）. Furthermore， high-dose Mume Fructus elevated the protein expression of Occludin （P<0.05）. ConclusionMume Fructus can restore the expression of intestinal epithelial tight junction proteins by inhibiting the phosphorylation of proteins in the MEK/ERK signaling pathway and down-regulating the levels of TNF-α and IL-1β， thus repairing the intestinal mucosal barrier in the mouse model of IBD.

ObjectiveIn nature, objects cast shadows due to illumination, forming the basis for stereoscopic perception. Birds need to adapt to changes in lighting (meaning they can recognize stereoscopic shapes even when shadows look different) to accurately perceive different three-dimensional forms. However, how neurons in the key visual brain area in birds handle these lighting changes remains largely unreported. In this study, pigeons (Columba livia) were used as subjects to investigate how neurons in pigeon’s ventrolateral mesopallium (MVL) represent stereoscopic shapes consistently, regardless of changes in lighting. MethodsVisual cognitive training combined with neuronal recording was employed. Pigeons were first trained to discriminate different stereoscopic shapes (concave/convex). We then tested whether and how light luminance angle and surface appearance of the stereoscopic shapes affect their recognition accuracy, and further verify whether the results rely on specify luminance color. Simultaneously, neuronal firing activity of neurons was recorded with multiple electrode array implanted from the MVL during the presentation of difference shapes. The response was finally analyzed how selectively they responded to different stereoscopic shapes and whether their selectivity was affected by the changes of luminance condition (like lighting angle) or surface look. Support vector machine (SVM) models were trained on neuronal population responses recorded under one condition (light luminance angle of 45°) and used to decode responses under other conditions (light luminance angle of 135°, 225°, 315°) to verify the invariance of responses to different luminance conditions. ResultsBehavioral results from 6 pigeons consistently showed that the pigeons could reliably identify the core 3D shape (over 80% accuracy), and this ability wasn’t affected by changes in light angle or surface appearance. Statistical analysis of 88 recorded neurons from 6 pigeons revealed that 83% (73/88) showed strong selectivity for specific 3D shapes (selectivity index>0.3), and responses to convex shapes were consistently stronger than to concave shapes. These shape-selective responses remained stable across changes in light angle and surface appearance. Neural patterns were consistent under both blue and orange lighting. The decoding accuracy achieves above 70%, suggesting stable responses under different conditions (e.g., different lighting angles or surface appearance). ConclusionNeurons in the pigeon MVL maintain a consistent neural encoding pattern for different stereoscopic shapes, unaffected by illumination or surface appearance. This ensures stable object recognition by pigeons in changing visual environments. Our findings provide new physiological evidence for understanding how birds achieve stable perception (“invariant neural representations”) while coping with variations in the visual field.

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC₅₀) and selectivity index (SI) values of 2.36 μmol·L^-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (K_D) value of 1.36 μmol·L^-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

Objective To comprehensively excavate and analyze the research status,research hotspots and future trends of the literature related to the field of acupoint catgut embedding therapy for pain treatment in the CNKI database.Methods We searched the CNKI database from its establishment to June 2022,and scientifically analyzed the authors,keywords,and institutions of the included literature of acupoint catgut embedding therapy for pain treatment through specific algorithms of Citespace to generate a visual knowledge map.Results A total of 319 documents were included for statistical analysis,the number of publications in the field of acupoint catgut embedding therapy for the treatment of pain was generally on the rise,the number of publications by various authors was on the low side,and there was a lack of co-operation between the research teams,with the main institutions being the Guang'anmen Hospital,Chinese Academy of Chinese Medical Sciences,Affiliated Hospital of Youjiang Medical Universities of Nationalities and the Guangzhou University of Chinese Medicine,forming a 10-keyword clustering,and the hotspots of diseases under study were mainly mixed haemorrhoids,postoperative pain,low back and leg pain and dysmenorrhoea,etc..The main interventions were pure acupoint catgut embedding therapy and the combination of acupoint catgut embedding therapy and other acupuncture therapies,and the main research method was clinical research.Conclusion Acupoint catgut embedding therapy for the treatment of pain has a good development prospect,the future needs to deepen the clinical research,strengthen the mechanism research,pay attention to the joint use of acupoint catgut embedding therapy and other traditional Chinese medicine methods,and pay attention to the research of different thread materials.

Objective To analyze the clinical efficacy of the Qianyang Fengsui Dan(combined with flying needle therapy)in the treatment of kidney-yang deficiency type of insomnia.Methods A retrospective study was conducted to select 82 patients with insomnia admitted to the Department of Traditional Chinese Medicine of Dezhou Hospital of Traditional Chinese Medicine from November 2020 to November 2021,and they were divided into an observation group and a control group according to whether or not they were treated with Qianyang Fengsui Dan combined with flying needle therapy,with 41 cases in each group.The control group was treated with Estazolam,while the observation group was treated with Qianyang Fengsui Dan combined with flying needle therapy on the basis of the treatment of the control group,and the course of treatment was 1 month.The changes of Pittsburgh Sleep Quality Index(PSQI)scores and Epworth Sleepiness Scale(ESS)scores,as well as polysomnographic parameters were observed before and after treatment in the two groups.The changes of γ-aminobutyric acid(GABA),glutamate(GA),substance P(SP),and neuropeptide Y(NPY)levels were compared before and after treatment between the two groups.And followed up for 1 year to compare the incidence of relapce of the two groups of patients.Results(1)The total effective rate was 95.12%(39/41)in the observation group and 63.41%(26/41)in the control group,and the efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,PSQI scores and ESS scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving PSQI scores and ESS scores,and the differences were statistically significant(P＜0.05).(3)After treatment,sleep efficiency,awakening time,sleep latency,REM,and total sleep time were significantly improved in the two groups(P＜0.05),and the observation group was significantly superior to the control group in improving sleep efficiency,awakening time,sleep latency,REM,and total sleep time,and the differences were statistically significant(P＜0.05).(4)After treatment,the serum GABA,GA,SP,and NPY levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the serum GABA,GA,SP,and NPY levels,and the differences were all statistically significant(P＜0.05).(5)After treatment,follow-up for 1 year,the recurrence rate of the observation group was 0,and there were 7 cases of recurrence in the control group,and the recurrence rate of the control group was 17.07%(7/41),and the recurrence rate of the observation group was lower than that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The combination of flying needle therapy and Qianyang Fengsui Dan can effectively relieve insomnia and fatigue in patients with insomnia,reduce daytime drowsiness,regulate the release of blood monoamine neurotransmitters,and reduce the relapse rate,and its efficacy is superior to that of simple western medicine treatment.