AIM:To investigate the effect of apoptosis stimulation protein 2(ASPP2)on the development of traumatic proliferative vitreoretinopathy(PVR)in a rabbit model.METHODS:A total of 30 New Zealand white rabbits were selected, and the right eyes of all rabbits were inflicted with a scleral penetrating wound of approximately 6 mm. Then rabbits were randomly and evenly divided into experimental and control group. The experimental group received an intravitreal injection of 0.1 mL of ARPE-19 cell suspension transfected with lentivirus-ASPP2, while the control group received an intravitreal injection of 0.1 mL of ARPE-19 cell suspension transfected with negative control lentivirus. At 1, 2, 3, and 4 wk after PVR modeling, a handheld tonometer was used to measure the intraocular pressure. Moreover, fundus photography and ocular ultrasound examination were performed to detect the retinal proliferation. At 4 wk after modeling, hematoxylin-eosin staining was used to observe the morphological retinal changes, and Western blot was used to determine the protein expressions of ASPP2 and the epithelial-mesenchymal transition(EMT)marker Vimentin in the rabbit retinas.RESULTS:At 1, 2, 3, and 4 wk after modeling, there were no significant changes in intraocular pressure within the experimental and control group of rabbit eyes, either before or after PVR modeling, the success rate of PVR modeling in the experimental group was lower than that in the control group(P<0.05), and the retinal proliferation and structural disorder was less severe in the experimental group. At 4 wk after modeling, the retinal protein expression level of ASPP2 in the experimental group was significantly higher than that in the control group(t=3.193, P=0.033), while the Vimentin protein expression level was significantly lower in the experimental group(t=-3.599, P=0.023).CONCLUSION:ASPP2 may be involved in regulating the process of EMT in retinal pigment epithelial cells, thereby delaying the development and progression of traumatic PVR in rabbit eyes.

AIM:To evaluate the effects of periocular injection of triamcinolone acetonide combined with dexamethasone on ocular surface function and tear dynamics in patients with thyroid-associated ophthalmopathy(TAO).METHODS: In this single-center retrospective study, 26 TAO patients(52 eyes)treated between September 2020 and September 2023 received periocular injections of triamcinolone acetonide(20 mg)and dexamethasone(2.5 mg). Clinical parameters, including clinical activity score(CAS), ocular surface disease index(OSDI), Schirmer I test(SⅠt), tear film breakup time(BUT), tear meniscus height(TMH), corneal fluorescein staining(FL), meibomian gland loss, and lipid secretion score, were assessed at baseline, 1 wk, and 1 mo post-injection.RESULTS: There were statistically significant differences in CAS, OSDI, SⅠt, BUT, TMH, FL score, and meibomian gland secretion score before and after injection in the included patients(all P<0.05). At 1 wk after injection, there were differences in CAS, OSDI, SⅠt, BUT, TMH, FL score, and meibomian gland secretion score compared with those before injection(all P<0.0167). At 1 mo after injection, there were differences in CAS, OSDI, SⅠt, BUT, TMH, FL score, and meibomian gland secretion score compared with those at 1 wk after injection(all P<0.0167). At 1 mo after injection, there were no differences in CAS, OSDI, SⅠt, BUT, TMH, FL score, and meibomian gland secretion score compared with those before injection(all P>0.05). There was a difference in meibomian gland dropout score before and after injection in the included patients(P<0.05), but pairwise comparisons showed no differences(P=0.900, 0.306). During the treatment period, 1 patient experienced transient elevation of intraocular pressure(25 mmHg), which was alleviated after control with intraocular pressure-lowering medication, and no cases of secondary glaucoma occurred.CONCLUSION: Periocular injection of triamcinolone acetonide combined with dexamethasone provides short-term improvement in ocular surface symptoms, tear film stability and secretion in TAO patients. However, efficacy diminishes over time and does not reverse structural damage. Long-term maintenance therapy is recommended.

Objective: To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials. Methods: The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group Results: The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group. Conclusion The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.

Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (⁹⁰Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent ⁹⁰Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of ⁹⁰Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (^99mTc-MAA) perfusion test and received the ⁹⁰Y-SIRT; one patient received ⁹⁰Y-SIRT after the second ^99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of ⁹⁰Y-SIRT for treating malignant liver tumors are mild, indicating good safety.

ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

ObjectiveTo explore the mechanism of Yishen Huashi granules in alleviating renal tubular epithelial cell injury and relieving diabetic kidney disease by regulating the mitogen-activated protein kinase （MAPK） signaling pathway. MethodsThe db/db mice of 12 weeks old were randomly assigned into model ， dapagliflozin （1.6 mg·kg^-1）， and Yishen Huashi granules （4.7 g·kg^-1）， and db/m mice were used as the control group. The general conditions of mice were observed， and fasting blood glucose and 24-h urinary protein and albumin-to-creatinine ratio （ACR） were measured at weeks 0 and 12 of administration. After 12 weeks of treatment， the levels of serum creatinine （SCr）， blood urea （UREA）， triglycerides （TG）， total cholesterol （TC）， and low density lipoprotein （LDL） were measured. The pathological changes in the renal tissue were observed by hematoxylin-eosin （HE） staining， Periodic acid-Schiff （PAS） staining， Mallory staining， and transmission electron microscopy. Real-time PCR was employed to determine the mRNA levels of monocyte chemotactic protein-1 （MCP-1） and CC chemokine receptor-2 （CCR2） in the renal tissue of mice. The immunohistochemical assay was employed to examine the expression of p38， phospho-p38 （p-p38）， MCP-1， and CCR2 in the renal tissue of mice. Western blotting was employed to measure the protein levels of p-p38， p38， MCP-1， and CCR2 in the renal tissue of mice.HK-2 cells cultured in vitro were grouped as follows： negative control， high glucose（30 mmol·L^-1）， Yishen Huashi granule-containing serum， and SB203580. After 48 h of cell culture in each group， RNA were extracted and the levels of MCP-1， and CCR2 mRNA were determined by Real-time PCR，proteins were extracted and the levels of p38， p-p38， MCP-1， and CCR2 were determined by Western blot. ResultsThe in vivo experiments showed that before treatment， other groups had higher body weight， blood glucose level， 24 h urinary protein， and ACR than the control group （P<0.05，P<0.01）. After 12 weeks of treatment， compared with the model group， the Yishen Huashi granules group showed improved general conditions， a decreasing trend in body weight， lowered levels of blood glucose， 24-h urinary protein， and ACR （P<0.01）， reduced SCr and UREA （P<0.01）， and declined levels of TC， TG， and LDL （P<0.05，P<0.01）. Compared with the model group， the Yishen Huashi granules group showed alleviated damage and interstitial fibrosis in the renal tissue as well as reductions in glomerular foot process fusion and basement membrane thickening. Moreover， the Yishen Huashi granules group showed down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01）， reduced positive expression of p-p38， MCP-1， and CCR2 （P<0.01）， and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2 （P<0.05） in the renal tissue. The cell experiment showed that compared with the high glucose group， the Yishen Huashi granule-containing serum group showcased down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01） and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2（P<0.05，P<0.01）. ConclusionYishen Huashi granules can regulate glucose-lipid metabolism， reduce 24 h urinary protein and ACR， improve the renal function， alleviate the renal tubule injury caused by high glucose， and protect renal tubule epithelial cells in db/db mice by reducing MCP-1/CCR2 activation via the p38 MAPK signaling pathway.

Objective To analyze the characteristics of postoperative hospital-acquired infections and drug sensitivity in lung transplant recipients over the past 5 years in a single center. Methods A total of 724 lung transplant recipients at Wuxi People's Hospital from January 2019 to December 2023 were selected. Based on the principles of hospital-acquired infection diagnosis, a retrospective analysis was conducted on the hospital infection situation and infection sites of lung transplant recipients, and an analysis of the distribution of hospital-acquired infection pathogens and their antimicrobial susceptibility test status was performed. Results Among the 724 lung transplant recipients, 275 cases of hospital-acquired infection occurred, with an infection rate of 38.0%. The case-time infection rate decreased from 54.2% in 2019 to 22.8% in 2023, showing a downward trend year by year (Z=30.98, P<0.001). The main infection site was the lower respiratory tract, accounting for 73.6%. The pathogens were mainly Gram-negative bacteria, with the top four being Acinetobacter baumannii (37.1%), Pseudomonas aeruginosa (17.3%), Klebsiella pneumoniae (13.7%), and Stenotrophomonas maltophilia (13.4%), with imipenem resistance rates of 89%, 53%, 58% and 100%, respectively. Gram-positive bacteria were mainly Staphylococcus aureus (3.6%), with a methicillin resistance rate of 67%. Conclusions Over the past 5 years, the hospital-acquired infections in lung transplant recipients have shown a downward trend, mainly involving lower respiratory tract infections, with the main pathogens being Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae, all of which have high resistance rates to imipenem.

Brain’s neural activities encompass both periodic rhythmic oscillations and aperiodic neural fluctuations. Rhythmic oscillations manifest as spectral peaks of neural signals, directly reflecting the synchronized activities of neural populations and closely tied to cognitive and behavioral states. In contrast, aperiodic fluctuations exhibit a power-law decaying spectral trend, revealing the multiscale dynamics of brain neural activity. In recent years, researchers have made notable progress in studying brain aperiodic dynamics. These studies demonstrate that aperiodic activity holds significant physiological relevance, correlating with various physiological states such as external stimuli, drug induction, sleep states, and aging. Aperiodic activity serves as a reflection of the brain’s sensory capacity, consciousness level, and cognitive ability. In clinical research, the aperiodic exponent has emerged as a significant potential biomarker, capable of reflecting the progression and trends of brain diseases while being intricately intertwined with the excitation-inhibition balance of neural system. The physiological mechanisms underlying aperiodic dynamics span multiple neural scales, with activities at the levels of individual neurons, neuronal ensembles, and neural networks collectively influencing the frequency, oscillatory patterns, and spatiotemporal characteristics of aperiodic signals. Aperiodic dynamics currently boasts broad application prospects. It not only provides a novel perspective for investigating brain neural dynamics but also holds immense potential as a neural marker in neuromodulation or brain-computer interface technologies. This paper summarizes methods for extracting characteristic parameters of aperiodic activity, analyzes its physiological relevance and potential as a biomarker in brain diseases, summarizes its physiological mechanisms, and based on these findings, elaborates on the research prospects of aperiodic dynamics.

Objective To construct a recombinant M13 phage vaccine targeting the outer membrane protein P6 of nontypeable Haemophilus influenzae(NTHi) and evaluate its immunogenicity in order to provide new ideas for further development of NTHi vaccines. Methods The NTHi P6 gene was fused with the vector pMECS Phagemid by gene recombination technique.After packaging and purification, the obtained recombinant P6-M13 phage was prepared into recombinant P6-M13 phage vaccine. The expression of P6-M13 PⅢ fusion protein in the vaccine was detected by Western blot, the vaccine titer was determined by double-layer agar plate method, and the recombinant P6-M13 phage morphology was observed under transmission electron microscope. Ninety 5-week-old BALB/c female mice were randomly divided into PBS group, M13 phage group and recombinant P6-M13 phage vaccine group, 30 for each, and intraperitoneally injected with PBS(500 μL/mouse), M13 phage[1 × 10~(12)pfu/(500 μL·mouse)]and recombinant P6-M13 phage vaccine[1 × 10~(12)pfu/(500 μL·mouse)]on the 0, 14th and28th day, separately. Two weeks after the last immunization, the levels of specific IgG in serum and IFNγ, IL-2, IL-4, IL-5and IL-17A in spleen lymphocyte culture supernatant were detected by ELISA, and the proliferation of spleen lymphocytes was analyzed by CCK-8. Three weeks after the last immunization, the mice were challenged with 1. 5 × 108cfu/mL NTHi through the nasal cavity. After one week of challenge, the pathological changes of nasal mucosa and lung tissue were observed by HE staining. Four weeks after the last immunization, the heart, liver, spleen, lung and kidney of mice were weighed, the organ coefficients were calculated, and histopathological sections were prepared for pathological observation.Results The recombinant P6-M13 phage could correctly express P6-M13 PⅢ fusion protein with a titer of 5. 5 × 10~(14) pfu/mL,and the recombinant P6-M13 phage with regular morphology was observed under microscope. Compared with M13 phage group and PBS group, the level of serum specific antibody IgG in mice of recombinant P6-M13 phage vaccine group was significantly higher(F = 71. 489, P < 0. 05); the levels of IFNγ, IL-2, IL-4 and IL-5 secreted by mouse spleen cells decreased significantly(F = 8. 315, 16. 986, 39. 204 and 6. 291, respectively, each P < 0. 05), while there was no significant difference in IL-17 level among the three groups(F = 0. 863, P > 0. 05); the spleen cell stimulation index increased significantly(F =22. 952, P < 0. 05). After challenge, the nasal mucosa and lung tissue structures of mice in PBS group and M13 phage group were seriously damaged, and inflammatory cells increased, while in the recombinant P6-M13 phage vaccine group, the structures of nasal mucosa and lung tissue were normal with few inflammatory cells. There was no significant difference in the organ coefficients of heart, liver, spleen, lung and kidney of mice in each group(F = 1. 012, 1. 642, 0. 300, 2. 079, and 0. 405, respectively,each P > 0. 05), and no pathological changes were found in the general color morphology and pathological sections of the main organs. Conclusion The constructed recombinant P6-M13 phage vaccine targeting NTHi outer membrane protein P6 can induce effective humoral and cellular immunity in mice with certain immune protection ability and good safety.

Objective: To explore the types of medication adherence and their influencing factors among inpatients with chronic diseases based on latent profile analysis, so as to provide the basis for improving medication adherence among patients with chronic diseases. Methods: The inpatients with chronic diseases admitted to the Second Affiliated Hospital of Hainan Medical University were selected as the study subjects. Demographic information, chronic disease status, and health education were collected through questionnaire surveys. Medication adherence was assessed using the Medication Adherence Scale and categorized based on the scores of its eight items through latent profile analysis. Factors affecting medication adherence among inpatients with chronic diseases were analyzed using a multinomial logistic regression model. Results: Totally 290 valid questionnaires were recovered, with an effective recovery rate of 97.64%. There were 157 males (54.14%) and 133 females (45.86%), with a median age of 61 (interquartile range, 21) years. The median score of medication adherence was 4.75 (interquartile range, 4.50). Based on latent profile analysis, medication adherence was categorized into three types: subjective neglect with poor adherence (38.97%), subjective confidence with fluctuating adherence (28.28%), and self-reflective with good adherence (32.76%). Multinomial logistic regression analysis showed that compared to the subjective confidence with fluctuating adherence, family monthly income (5 000-10 000 yuan, OR=2.981, 95%CI: 1.055-8.429), comorbidity of chronic diseases (OR=3.478, 95%CI: 1.579-7.661), number of health education sessions received in the past year (≤1 session, OR=0.329, 95%CI: 0.120-0.907; 2 sessions, OR=0.363, 95%CI: 0.138-0.950), and health information literacy scores (<60 points, OR=2.596, 95%CI: 1.209-5.573) were statistically associated with subjective neglect with poor adherence (all P<0.05). Conclusion Subjective neglect with poor medication adherence among inpatients with chronic diseases is associated with family monthly income, comorbidity of chronic diseases, the number of health education sessions received, and health information literacy.