Mitochondria-associated endoplasmic reticulum membranes(MAMs)are crucial structural links between the endoplasmic reticulum and mitochondria, formed by a complex protein network. They play a central role in cellular calcium signaling homeostasis, mitochondrial stability, endoplasmic reticulum stress, and inflammatory response. In recent years, advances in subcellular ultrastructure research techniques have gradually uncovered the relationship between MAMs dysfunction and blinding ocular diseases. Studies indicate that structural or functional impairments in MAMs can disrupt retinal pigment epithelial cells homeostasis, compromise the survival microenvironment of retinal ganglion cells, and trigger corneal endothelial cells apoptosis, thereby contributing to the pathogenesis of various blinding ocular diseases including age-related macular degeneration, diabetic retinopathy, Fuchs endothelial corneal dystrophy, and glaucoma. This article reviews the molecular mechanisms linking MAMs in common blinding ocular diseases.

N-glycosylation is a crucial posttranslational modification of proteins that can modulate their functions and plays key roles in various biological processes. Current research has revealed that alterations in protein N-glycosylation are closely associated with the pathogenesis and progression of multiple ocular diseases. N-glycosylation detection methods can identify changes in N-glycans on proteins; therefore, understanding these techniques and their application value in ocular diseases is important. This article provides a systematic review of the current state of N-glycosylation detection methods, including techniques such as capillary electrophoresis, liquid chromatography, and mass spectrometry. It also offers a detailed discussion on the specific applications of these technologies in the study of various ocular diseases, including diabetic retinopathy, age-related macular degeneration and vernal keratoconjunctivitis/atopic keratoconjunctivitis.

Objective To evaluate the predictive ability and clinical application value of artificial intelligence (AI) systems in the benign and malignant differentiation and pathological type of pulmonary nodules, and to summarize clinical application experience. Methods A retrospective analysis was conducted on the clinical data of patients with pulmonary nodules admitted to the Department of Thoracic Surgery, Second Hospital of Lanzhou University, from February 2016 to February 2025. Firstly, pulmonary nodules were divided into benign and non-benign groups, and the discriminative abilities of AI systems and clinicians were compared. Subsequently, lung nodules reported as precursor glandular lesions (PGL), microinvasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) in postoperative pathological results were analyzed, comparing the efficacy of AI systems and clinicians in predicting the pathological type of pulmonary nodules. Results In the analysis of benign/non-benign pulmonary nodules, clinical data from a total of 638 patients with pulmonary nodules were included, of which there were 257 males (10 patients and 1 patient of double and triple primary lesions, respectively) and 381 females (18 patients and 1 patient of double and triple primary lesions, respectively), with a median age of 55.0 (47.0, 61.0) years. Different lesions in the same patient were analyzed as independent samples. Univariate analysis of the two groups of variables showed that, except for nodule location, the differences in the remaining variables were statistically significant (P<0.05). Multivariate logistic regression analysis showed that age, nodule type (subsolid pulmonary nodule), average density, spicule sign, and vascular convergence sign were independent influencing factors for non-benign pulmonary nodules, among which age, nodule type (subsolid pulmonary nodule), spicule sign, and vascular convergence sign were positively correlated with non-benign pulmonary nodules, while average density was negatively correlated with the occurrence of non-benign pulmonary nodules. The area under the receiver operating characteristic curve (AUC) of the malignancy risk value given by the AI system in predicting non-benign pulmonary nodules was 0.811, slightly lower than the 0.898 predicted by clinicians. In the PGL/MIA/IAC analysis, clinical data from a total of 411 patients with pulmonary nodules were included, of which there were 149 males (8 patients of double primary lesions) and 262 females (17 patients of double primary lesions), with a median age of 56.0 (50.0, 61.0) years. Different lesions in the same patient were analyzed as independent samples. Univariate analysis results showed that, except for gender, nodule location, and vascular convergence sign, the differences in the remaining variables among the three groups of PGL, MIA, and IAC patients were statistically significant (P<0.05). Multinomial multivariate logistic regression analysis showed that the differences between the parameters in the PGL group and the MIA group were not statistically significant (P>0.05), and the maximum diameter and average density of the nodules were statistically different between the PGL and IAC groups (P<0.05), and were positively correlated with the occurrence of IAC as independent risk factors. The average AUC value, accuracy, recall rate, and F1 score of the AI system in predicting lung nodule pathological type were 0.807, 74.3%, 73.2%, and 68.5%, respectively, all better than the clinical physicians’ prediction of lung nodule pathological type indicators (0.782, 70.9%, 66.2%, and 63.7% respectively). The AUC value of the AI system in predicting IAC was 0.853, and the sensitivity, specificity, and optimal cutoff value were 0.643, 0.943, and 50.0%, respectively. Conclusion This AI system has demonstrated high clinical value in predicting the benign and malignant nature and pathological type of lung nodules, especially in predicting lung nodule pathological type, its ability has surpassed that of clinical physicians. With the optimization of algorithms and the adequate integration of multimodal data, it can better assist clinical physicians in formulating individualized diagnostic and treatment plans for patients with lung nodules.

In the study of kidney ischemia-reperfusion injury, rhabdomyolysis induced kidney injury, hyperuricemia induced kidney injury and other diseases, Diaphragma Juglandis Fructus extract has shown various pharmacological effects such as lowering uric acid, anti-inflammatory, anti-tumor, sedative and sedative effects. It can improve kidney function by reducing inflammatory response, inhibiting oxidative stress, regulating related enzyme activity and other mechanisms. At the same time, Diaphragma Juglandis Fructus extract also has hypoglycemic and lipid-lowering effects, which can regulate glucose and lipid metabolism, inhibit inflammatory reaction, and reduce oxidative stress. It has potential application prospects in the treatment of diabetes nephropathy. At present, current research is mostly focused on animal and cellular experiment levels. Although certain achievements have been made, further clinical research is still needed to clarify its effectiveness and safety in the human body, and to further explore the active components to promote its application in the treatment of kidney diseases in clinical practice.

Objective:To investigate the clinical application value of commonly used preoperative indicators of sarcopenia in predicting postoperative pneumonia in patients aged 70 years and above with esophageal cancer.Methods:A retrospective analysis was conducted on the clinical data of 398 elderly patients(≥70 years old)with esophageal squamous cell carcinoma who underwent thoracic laparoscopic radical resection of esophageal cancer in our hospital from January 2020 to December 2021.The study aimed to investigate the correlation between clinical pathological indicators and commonly used measurement indicators of sarcopenia and postoperative pneumonia.Statistical analysis was performed to analyze the data.Results:The study found that the proportion of postoperative pneumonia in esophageal squamous cell carcinoma patients aged 70 years and above was 27.9%(111 out of 398). The pneumonia group had significantly lower preoperative BMI and peak expiratory flow(PEF)measurements compared to the non-pneumonia group, with statistically significant differences( t=2.799, 2.674, both P<0.05). Logistic multivariate analysis revealed that low PEF, low psoas major muscle index(PMI), and low psoas muscle density(PMD)were the primary risk factors for postoperative pneumonia in esophageal cancer patients aged 70 years and above(Wald χ2 values were 7.577, 6.091, 6.845, all P<0.05). The risk of postoperative pneumonia in esophageal cancer patients aged 70 years and above with low PEF, low PMI, and low PMD was found to be 1.969 times higher(95% CI: 1.215-3.185, P=0.006), 1.912 times higher(95% CI: 1.143-3.205, P=0.014), and 1.832 times higher(95% CI: 1.164-2.882, P=0.009)respectively, compared to patients with high PEF, high PMI, and high PMD. Conclusions:Low PEF, low PMI, and low PMD are significant risk factors for postoperative pneumonia in esophageal cancer patients aged 70 years and older.Preoperative PEF, PMI, and PMD, which are commonly utilized measurement indicators for sarcopenia, can be utilized as early screening indicators for postoperative pneumonia.

A family carrying a homozygous variant of DNAJB2 gene C.91C>T (p.His31Tyr) with distal hereditary motor neuropathy (dHMN) associated with early-onset Parkinson′s disease was reported. The patient presented with distal limb weakness and atrophy at the early stage of the disease, and developed Parkinson′s symptoms more than 10 years later. Neuroelectrophysiological examination suggested motor and sensory axonal involvement. This mutation site had not been reported and was considered to be a neogenic mutagenicity of dHMN, excluding other mutations that can cause early-onset Parkinson′s disease.

OBJECTIVE To investigate the effect of bs-5-YHEDA iron chelating peptide combined with semaglutide on the cognitive ability and pathological characteristics of D-Gal-induced Alzheimer's disease(AD) model mice. METHODS Forty mice were randomly divided into 5 groups, namely the healthy control group, PBS group, bs-5-YHEDA iron chelating peptide group, combined treatment group and positive control group, with 8 mice in each group, half of each sex. Except for the healthy control group, D-galactose was injected to induce the AD mice model for 6 weeks. For 3 consecutive weeks starting from the 4th week, the bs-5-YHEDA iron chelating peptide group was injected with bs-5-YHEDA(1 mg·mL–1) once every other day at 200 µL in the tail vein; the bs-5-YHEDA iron chelating peptide(1 mg·mL–1) and semaglutide(25 nmol·kg–1·d–1) were given alternately once a day in the combination treatment group; the positive control group was given memantine(3.3 mg·kg–1·d–1) by gavage every other day. The healthy control group and PBS group were injected with the equal dose of PBS. At the end of treatment, the learning memory ability of mice was detected by the Morris water maze method, whole brain and whole blood were dissected, and pathological changes in hippocampal region were observed by HE staining, and Aβ expression and Tau protein phosphorylation levels were detected by immunohistochemistry, enzyme-linked immunosorbent assay and immunoblotting. RESULTS In the Morris water maze spatial exploration experiment, the differences in the number of times the mice traversed the platform, the ratio of swimming distance to the target quadrant, and the time ratio were statistically significant in each group(P<0.05); compared with the PBS group, the ratio of swimming distance to the target quadrant increased in the combined treatment group, and the differences were statistically significant(P<0.05). The results of HE staining showed that compared with the healthy control mice, the hippocampal area in the PBS group showed reduced levels of pyramidal cells, disorganized arrangement, cell edema, and deep staining of nuclei consolidation. Cellular disorganization, deep staining of nuclei and apoptosis in the hippocampus were significantly improved in each treatment group after drug treatment. Immunohistochemistry and Western blotting results showed that the Aβ expression levels and Tau protein phosphorylation levels were significantly higher in the PBS-administered mice compared with the healthy control mice, and the Aβ expression levels and Tau protein phosphorylation levels were reduced in each group after drug treatment, with statistically significant differences(P<0.01 or P<0.001 ). CONCLUSION The combination of bs-5-YHEDA iron chelating peptide and semaglutide can effectively improve the learning and memory ability and pathological characteristics of AD mice, but from the results of immunohistochemistry and immunoblotting experiments, the improvement of pathological characteristics of AD mice in the combination treatment group is not obvious compared with the single bs-5-YHEDA iron chelating peptide group, suggesting that there may be a threshold effect of our designed dual-target combination treatment on the cognitive improvement of AD mice, and the optimization and validation of the effect of multi-target combination treatment need further study.

A novel amide alkaloid,bursatamide A(1),featuring an unprecedented propyl-hexahydronaphthalene carbon frame-work,was isolated from the infrequently studied sea hare Bursatella leachi,alongside a new 3-phenoxypropanenitrile alkaloid,bursatellin B(2),and twelve known compounds.The structures of 1 and 2 were elucidated through comprehensive spectroscopic data analyses,while their relative and absolute configurations(ACs)were established through total synthesis and a series of quantum chem-ical calculations,including calculated electronic circular dichroism(ECD)spectra,optical rotatory dispersion(ORD)methods,and DP4+probability analyses.Bursatamide A(1)demonstrated inhibitory effects against the human pathogenic bacteria Listeria monocyt-ogenes and Vibrio cholerae.Erythro-bursatellin B(21),a diastereoisomer of 2,exhibited notable antibacterial activity against the fish pathogenic bacterium Streptococcus parauberis FP KSP28,with an MIC90 value of 0.0472 μg·mL-1.

Objectives:To investigate the association between social determinants of health(SDOH)and incident stroke and analyze the main risk factors for stroke among resident with different SDOH levels. Methods:From 2012 to 2015,30 036 residents(≥35 years old)from 30 districts in 14 provincial-level administrative divisions in China were enrolled this study based on stratified multi-stage-random-sampling method.The prevalence of cardiovascular diseases and related risk factors were investigated,and stroke events were followed up in 2018 to 2019.Principal component analysis was performed to establish SDOH scores based on 9 indicators related to socioeconomic and healthcare resources,participants were divided into low SDOH group(n=8 343)when it was≥-2.01 to<-1.14,middle SDOH group(n=7 257)when it was≥-1.14 to<0.10,and high SDOH group(n=8 457)when it was≥0.10 to≤5.79.Multivariate Cox regression was applied to estimate the association of SDOH levels with incident stroke.The random survival forest method was used to analyze the major risk factors in different SDOH levels. Results:A total of 24 057 participants were finally included,669(2.8%)participants developed stroke during a mean of(4.7±0.8)years follow-up.The incidence densities of stroke in the low,medium,and high SDOH groups were 468.39,628.85,and 700.39/100 000 person-years,respectively(Pdifference<0.05,Ptrend=0.01).Compared with individuals with low SDOH level group,fully HR for incident stroke among those with medium and high were 1.91(95%CI:1.54-2.36)and 1.59(95%CI:1.30-1.95),respectively(Ptrend<0.001).Advanced age is the primary risk factor for stroke in the population,especially in districts with high SDOH level.In districts with medium SDOH level,diabetes is an important risk factor for stroke.High blood pressure and alcohol consumption are important modifiable risk factors in low SDOH level districts. Conclusions:Present study shows that higher levels of SDOH are associated with increased risk of stroke.The main risk factors for stroke differ among participants with different SDOH level districts.Targeted interventions should be implemented to improve the prevention and treatment of stroke in populations with different levels of SDOH.

Objective:To investigate the efficacy and safety of separated R-CHOP in older patients with newly diagnosed diffuse large B-cell lymphoma(DLBCL).Methods:A total of 137 patients aged 65-80 years newly diagnosed with DLBCL between April 2013 and September 2022 at The First Affiliated Hospital of Zhengzhou University were enrolled.The patients were assigned into separated R-CHOP,full-dose R-CHOP,and reduced R-CHOP-like groups based on their different chemotherapy regimens.All individuals were treated in 21-day cycles for 4-8 cycles.The short-term and long-term efficacies and adverse reactions of the treatments were compared among the three groups,and factors influencing progression-free survival(PFS)and overall survival(OS)were analyzed.Results:The overall response rates(ORR)of patients in the separated R-CHOP,full-dose R-CHOP,and reduced R-CHOP-like groups were 89.7%,90.3%,and 86.1%,respectively,with no significant differences among them.The complete respond rate(CRR)of the separated R-CHOP group(64.1%)was significantly higher than that of the reduced R-CHOP-like group(33.3%)(P=0.008)but not significantly different from that of the full-dose R-CHOP group(66.1%).Survival curve analysis revealed no significant differences in PFS and OS between the separated and full-dose R-CHOP groups.Although the separated R-CHOP group showed improved PFS compared with the reduced R-CHOP-like group(P=0.036),there was no statistical difference in OS between these two groups.Multivariate analysis revealed that the international prognostic index(IPI)and separated R-CHOP had significant effects on PFS in patients with DLBCL(all P<0.05),whereas only IPI had a significant effect on OS(P<0.001).The incidence of leukopenia and grade 3-4 leukopenia in the separated R-CHOP group was significantly lower than that in the full-dose R-CHOP group(P=0.007,P=0.012),but there was no significant difference with the reduced R-CHOP-like group in this regard.Conclusions:In older patients with newly diagnosed DLBCL,separated R-CHOP showed good efficacy both in the short and long terms and had acceptable safety and tolerability profiles.