AIM: To explore the impacts of wearing orthokeratology lenses on the ocular surface and meibomian gland of children and adolescents in high-altitude areas.METHODS: Retrospective study. Myopic children and adolescents who visited at the ophthalmology department and received orthokeratology lens from June 2023 to December 2023 were selected as orthokeratology group, and those who visited and wore regular spectacle group during the same period were selected as regular spectacle group. Then the ocular surface disease index(OSDI)score, tear meniscus height, non-invasive breakup time(NIBUT)[first NIBUT(fNIBUT), average NIBUT(avNIBUT)], and meibomian gland score were compared between the two groups before wearing lenses, and at 1, 3, 6, and 12 mo after wearing lenses.RESULTS: A total of 80 children(160 eyes)with myopia were included in this study. Among them, 40 cases(80 eyes)were in the orthokeratology lens group, with 25 males and 15 females and an average age of 11.33±2.76 years old, and 40 cases(80 eyes)were in the regular spectacle group, with 23 males and 17 females and an average age of 11.58±2.94 years old. The OSDI scores and tear meniscus heights showed no clear difference between two groups at various time points before and after wearing glasses(all P>0.05). The fNIBUT and avNIBUT of the orthokeratology lens group decreased compared with the regular spectacle group at 6 and 12 mo after wearing lenses, and meibomian gland score of the orthokeratology group was higher than that of the regular spectacle group at 12 mo after wearing lenses(all P<0.001). Among them, the fNIBUT and avNIBUT of the orthokeratology lenses group at 3, 6, and 12 mo after wearing glasses were lower than those before wearing glasses(all P<0.05). Moreover, the meibomian gland scores of the orthokeratology lenses group at 12 mo after wearing glasses were higher than those before wearing glasses, and 1, 3, and 6 mo after wearing glasses(all P<0.05), while there was no statistical difference in fNIBUT, avNIBUT, and meibomian gland score at each time point in the regular spectacle group(all P>0.05).CONCLUSION: Long term wearing of orthokeratology lenses can shorten the NIBUT of myopic children and adolescents in high-altitude areas, and have a certain impact on their meibomian gland function.

Objective To explore the predictive performance of machine learning models integrating clinico-pathological features and inflammatory markers for lymphovascular invasion (LVI) before gastric cancer surgery. Methods A retrospective cohort of 193 gastric cancer patients from The First Hospital of Lanzhou University (training set) and 185 patients from Zhongshan Hospital, Fudan University (validation set) was included. Preoperative clinical pathological characteristics, tumor markers, and inflammatory markers were collected to identify independent risk factors for LVI. Six machine learning models were established in the training set. Model performance was evaluated using area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, decision curve analysis (DCA), and Brier scores. Shapley additive explanations (SHAP) was applied for model interpretability. Results The multivariate logistic regression showed increased tumor invasion depth (T-stage), lymph node metastases (N-stage), and the systemic immune-inflammation index (SII) were independent risk factors for gastric cancer LVI (P＜0.05). Using these three indicators, 6 machine learning models were developed, all of which demonstrated favorable predictive performance, with 0.79 and 0.76 of minimum AUC values in the training set and the validation set, respectively. Among them, the light gradient boosting machine (LightGBM) model exhibited the best overall performance, achieving AUCs of 0.83 and 0.82 in the training set and the validation set, along with Brier scores of 0.163 and 0.187, respectively. Calibration and DCA curves further confirmed that the model possesses strong predictive accuracy and application value. SHAP analysis showed the feature importance in LightGBM model, identifying the N-stage as the top contributor, followed by the T-stage and the SII. Conclusion The machine learning models incorporating clinical pathological features and inflammatory indicators can effectively predict LVI status in gastric cancer, with the LightGBM model demonstrating optimal performance.

To investigate the potential protective effect of thalidomide (THD) on diabetic nephropathy (DN) and its underlying mechanisms. Twenty-four C57BL/6J mice were randomly divided into control, DN and DN+THD200 groups by random number table method. The DN mouse model was established via intraperitoneal injection of streptozotocin. The DN+THD200 group received THD treatment (200 mg·kg -1·d -1) for 8 weeks. Blood and urine biochemical parameters, as well as renal histopathological changes, were compared among the three groups. For in vitro experiments, a high glucose (HG)-induced injury model was established in mouse glomerular podocytes (MPC5). Cells were divided into control (NG), HG, HG+DMSO, HG+THD100 (100 μg/ml), and HG+THD200 (200 μg/ml) groups. THD-treated cells were exposed to THD for 24 h. Western blotting and real-time quantitative PCR were performed to respectively detect protein and mRNA expression levels of ferroptosis-related molecules, including nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO-1), and glutathione peroxidase 4 (GPX4). Immunofluorescence was used to evaluate the expression of solute carrier family 7 member 11 (SLC7A11) and 4-hydroxynonenal (4-HNE). The results showed that, compared with control group, DN group exhibited significantly lower blood urea nitrogen, serum creatinine and 24 h urinary albumin levels (all P<0.05). Compared with DN group, DN+THD200 group exhibited significantly lower blood urea nitrogen, serum creatinine and 24 h urinary albumin levels (all P<0.05). Histopathological examination revealed glomerular expansion, mesangial widening, and basement membrane thickening in DN group compared to control group, which were markedly ameliorated by THD treatment. In vitro, HG group showed significantly decreased protein and mRNA expression levels of GPX4, NRF2 and HO-1 compared to NG group. Both HG+THD100 and HG+THD200 groups exhibited upregulated expression levels of these proteins and corresponding mRNA compared to HG group (all P<0.05). Immunofluorescence demonstrated HG group had enhanced 4-HNE fluorescence intensity and reduced SLC7A11 fluorescence intensity, which were reversed by THD treatment. THD alleviates renal injury in DN mice and mitigates HG-induced ferroptosis in MPC5 cells, potentially via activation of NRF2-HO-1-GPX4 signaling pathway.

To effectively exploit the tumor microenvironment (TME), TME-responsive nanocarriers based on cascade reactions have received much attention. In this study, we designed a novel nanoparticle PB@SiO₂@MnO₂@P-Arg (PMP) to construct a cascade reaction nanoplatform. While using biosafety Prussian blue (PB) for photothermal therapy (PTT), this nanoplatform uses silica (SiO₂) as an intermediate layer to assemble Prussian blue and manganese dioxide (MnO₂) into a core-shell structure, which effectively enhances the response of the nanoplatform to TME and promotes the effect of chemodynamic therapy (CDT) resulting from glutathione (GSH) depletion and Fenton-like reaction. The released Mn²⁺ can also be used for magnetic resonance imaging (MRI). Through the cascade reaction, poly-l-arginine (P-Arg) coated on the surface of the nanoparticles can react with hydroxyl radical (•OH) obtained from the Fenton-like reaction to release nitric oxide (NO), which further reacts with O₂•^- to produce the more toxic peroxynitrite anion (ONOO^-). The photothermal effect of PB further enhances the effect of the cascade reaction while reducing the amount of heat required for treatment. In vitro and in vivo studies confirmed the antitumor effects of cascade reaction-based nanoplatforms in combined photothermal/chemodynamic/gas cancer therapies, providing new strategies for the design and fabrication of multifunctional nanoplatforms that integrate diagnostic and therapeutic functions, as well as the application of cascade reactions in multimodal synergistic therapy.

AIM:To elucidate the pharmacody-namic and network pharmacological mechanisms of total flavonoids of Carthamus tinctorius L.,to ex-plore their key targets and related pathways,and to clarify their mechanism of action against hepatic fibrosis.METHODS:The total flavonoids of Cartha-mus tinctorius L.were determined by LC-MS/MS and analysed for their compositions;the active in-gredients were screened by TCMSP database,SWISS ADME database and literature search;the targets related to total flavonoids of Carthamus tinctorius L.were screened by Swiss Target Predic-tion database;and the targets related to hepatic fi-brosis were screened by GeneCards database;the anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained by taking the intersection of Venny.2.1.0;the protein interac-tions were analysed by STRING database;the visu-alization analysis was carried out by Cytoscape soft-ware;the GO function and KEGG pathway analysis was carried out by Metascape platform;and molec-ular docking was verified by using AutoDock soft-ware for the core targets and active ingredients.The mechanism of anti-hepatic fibrosis of total fla-vonoids of Carthamus tinctorius L.was verified by animal model and in vitro cell experiments.RE-SULTS:A total of 41 flavonoid components were identified in Carthamus tinctorius L.Through the network pharmacological analysis,149 anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained,including 23 core tar-gets.The GO enrichment analyses involved a total of three aspects,namely,biological process(BP),cellular component(CC),and molecular function(MF).KEGG enrichment results showed that PI3K/Akt and MAPK are pathways involved in the devel-opment of hepatic fibrosis.Molecular docking veri-fied that the active ingredients Quercetin,Acacetin and Glabridin were tightly bound to Akt1 and HI-FIA,respectively.In animal model experiments,it was observed by HE and Masson staining that fibro-plasia was reduced,collagen deposition was re-duced,inflammatory cell infiltration was reduced,and fibrotic liver tissues were improved in total fla-vonoids of Carthamus tinctorius L.administration group.In isolated cell experiments:Western blot-ting results suggested that total flavonoids of Car-thamus tinctorius L.could decrease the hepatic fi-brosis marker factor α-SMA,Collagen1(P＜0.01)and PI3K,Akt protein expression(P＜0.01).CONCLU-SION:Total flavonoids of Carthamus tinctorius L.ex-erted anti-hepatic fibrosis effects through multi-components,multi-targets and multi-pathways,and their mechanism of action may be achieved by regulating the PI3K/Akt signalling pathway.

Objective To explore the correlation between serum angiotensin-converting enzyme(SACE),matrix metalloproteinase-9(MMP-9)and haptoglobin(HPT)with pulmonary infection in patients with schizophrenia.Methods A total of 83 patients with schizophrenia were selected and divided into the infected group(40 cases)and the non-infected group(43 cases)according to whether they had pulmonary infection.Data of antipsychotic drugs,length of hospital stay,course of disease and electroconvulsive therapy were collected.Serum SACE,MMP-9 and HPT levels were detected by enzyme-linked immunosorbent assay.Spearman correlation analysis was used to determine serum SACE,MMP-9 and HPT and pulmonary infection in patients with schizophrenia.Logistic regression was used to analyze risk factors for pulmonary infection in patients with schizophrenia,and receiver operating characteristic(ROC)curves were used to evaluate the predictive value of serum SACE,MMP-9 and HPT in patients with pulmonary infection.Results Before treatment,the types of antipsychotic drugs≥2,the proportion of electroconvulsive therapy,serum SACE,MMP-9 and HPT levels were higher in the infected group than those in the non-infected group(P＜0.05).After treatment,there were no significant differences in serum SACE,MMP-9 and HPT levels between the infected group and the non-infected group(P＞0.05).Serum SACE,MMP-9 and HPT were positively correlated with pulmonary infection in patients with schizophrenia(P＜0.05).More than 2 types of antipsychotic drugs,electroconvulsive therapy and elevated SACE,MMP-9 and HPT were risk factors for pulmonary infection in schizophrenia patients(P＜0.05).The ROC curve analysis showed that the combined serum SACE,MMP-9 and HPT for pneumonia in schizophrenic patients were better than each of these indicators alone in predicting pulmonary infection in patients with schizophrenia.Conclusion Serum SACE,MMP-9 and HPT are related with pulmonary infection in patients with schizophrenia,and which can be used as potential indicators for predicting pulmonary infection in patients with schizophrenia.

To investigate the potential protective effect of thalidomide (THD) on diabetic nephropathy (DN) and its underlying mechanisms. Twenty-four C57BL/6J mice were randomly divided into control, DN and DN+THD200 groups by random number table method. The DN mouse model was established via intraperitoneal injection of streptozotocin. The DN+THD200 group received THD treatment (200 mg·kg -1·d -1) for 8 weeks. Blood and urine biochemical parameters, as well as renal histopathological changes, were compared among the three groups. For in vitro experiments, a high glucose (HG)-induced injury model was established in mouse glomerular podocytes (MPC5). Cells were divided into control (NG), HG, HG+DMSO, HG+THD100 (100 μg/ml), and HG+THD200 (200 μg/ml) groups. THD-treated cells were exposed to THD for 24 h. Western blotting and real-time quantitative PCR were performed to respectively detect protein and mRNA expression levels of ferroptosis-related molecules, including nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO-1), and glutathione peroxidase 4 (GPX4). Immunofluorescence was used to evaluate the expression of solute carrier family 7 member 11 (SLC7A11) and 4-hydroxynonenal (4-HNE). The results showed that, compared with control group, DN group exhibited significantly lower blood urea nitrogen, serum creatinine and 24 h urinary albumin levels (all P<0.05). Compared with DN group, DN+THD200 group exhibited significantly lower blood urea nitrogen, serum creatinine and 24 h urinary albumin levels (all P<0.05). Histopathological examination revealed glomerular expansion, mesangial widening, and basement membrane thickening in DN group compared to control group, which were markedly ameliorated by THD treatment. In vitro, HG group showed significantly decreased protein and mRNA expression levels of GPX4, NRF2 and HO-1 compared to NG group. Both HG+THD100 and HG+THD200 groups exhibited upregulated expression levels of these proteins and corresponding mRNA compared to HG group (all P<0.05). Immunofluorescence demonstrated HG group had enhanced 4-HNE fluorescence intensity and reduced SLC7A11 fluorescence intensity, which were reversed by THD treatment. THD alleviates renal injury in DN mice and mitigates HG-induced ferroptosis in MPC5 cells, potentially via activation of NRF2-HO-1-GPX4 signaling pathway.

Objective:To analyze the epidemiological and clinical characteristics of pertussis in children and the antimicrobial resistance pattern of Bordetella pertussis isolates in Anhui province in 2024. Methods:Prospective observational study. The demographic information of 4 233 cases of pertussis confirmed by nucleic acid testing in Anhui Provincial Children′s Hospital in 2024 and the clinical data of hospitalized cases were collected. The annual epidemic trend of pertussis in children, the clinical characteristics of hospitalized cases, and the vaccination status were analyzed. Bordetella pertussis isolates were recovered from nasopharyngeal swabs obtained from hospitalized children and their family caregivers during the outbreak period and antimicrobial susceptibility was tested. Results:Among the 4 233 children, 2 330 were male and 1 903 were female. A total of 4 059 cases (95.9%) occurred from March to September, with the peak of the disease from April to July (3 364 cases (79.5%)).There were 4 075 cases (96.3%) aged 9 years and under, among which 718 cases (17.0%) were under 1 year old and 2 494 cases (58.9%) were aged 4 to 7 years. During the outbreak period, there were a total of 301 hospitalized children (7.1%), with an average age of 4.4 (2.8, 16.5) months. Among them, 61 cases (20.3%) received the full course of vaccination (4 doses), 64 cases (21.3%) received partial doses of the vaccine, and 176 cases (58.5%) were unvaccinated. Among the unvaccinated children, 79.6% (172/216) were under 1 year old, 8.7% (2/23) were between 1 and 3 years old, and 3.2% (2/62) were 3 years old or older. None of the 20 cases (6.6%) of severe pertussis received pertussis vaccine.Among the 301 hospitalized children, 298 cases (99.0%) presented with typical paroxysmal spasmodic cough, 94 cases (31.2%) had vomiting after coughing, 82 cases (27.2%) had whooping sounds, and 54 cases (17.9%) had cyanotic attacks. There were 228 cases (75.7%) complicated with pneumonia and 5 cases (1.7%) with pertussis encephalopathy. The infection rate among the accompanying family members who underwent screening was 77.1% (371/481). Based on the minimum inhibitory concentration testing of 186 Bordetella pertussis isolates, the minimum inhibitory concentration 90 of azithromycin and trimethoprim-sulfamethoxazole were >256.000 and 0.050 mg/L, respectively. Conclusions:The peak of pertussis cases in Anhui region in 2024 occurred from April to July. Children aged ≤9 years were the major affected population. Infants and preschool children were most susceptible to pertussis. The intrafamily transmission rate of pertussis is high. Empirical use of macrolides for the treatment of pertussis is not recommended. Trimethoprim-sulfamethoxazole can be used as the preferred antibiotic for pertussis in children aged 2 months and above.

Objective:To observe and analyze the subtype-specific prognostic factors for visual recovery in patients with demyelinating optic neuritis (DON) after glucocorticoid pulse therapy.Methods:A retrospective cohort study. A total of 195 patients (249 eyes) with DON diagnosed by ophthalmology examination at Department of Ophthalmology, Xi'an People's Hospital (Xi'an Fourth Hospital) from January 2021 to December 2024 were included in the study. According to the results of serum antibody detection and clinical diagnostic criteria, the patients were divided into the neuromyelitis optica spectrum disorder (NMOSD)-associated optic neuritis (ON) (NMOSD-ON) group, the myelin oligodendrocyte glycoprotein antitide-associated ON (MOG-ON) group, and the double antibody negative ON group. They were 51 cases (58 eyes), 72 cases (103 eyes), and 72 cases (88 eyes) respectively. Baseline clinical data, imaging characteristics, and treatment protocols were collected. The primary endpoints were complete visual recovery [best-corrected visual acuity (BCVA) ≥ 1.0] and moderate recovery (BCVA ≥0.5) at 3 months post-onset. Multivariate logistic regression was used to identify independent prognostic factors for visual outcomes within each subtype.Results:At 3 months post-onset, complete recovery rates were 9 (15.5%, 9/58) in the NMOSD-ON group, 64 (62.1%, 64/103) in the MOG-ON group, and 31 (35.2%, 31/88) in the double-seronegative ON group. The results of multivariate regression analysis showed that age [odds ratio ( OR) =0.901, 95% confidence interval ( CI) 0.854-0.950, P<0.001] and peak visual acuity ( OR=0.311, 95% CI 0.147-0.660, P=0.002) and the involvement of optic nerve length ≥1/2 ( OR=3.849, 95% CI 1.083-13.682, P=0.037) were the influencing factors for the complete recovery of visual acuity in the affected eyes of the double antibody negative ON group. Age ( OR=0.958, 95% CI 0.933-0.983, P=0.001) was the only influencing factor for the complete recovery of visual acuity in the affected eyes of the MOG-ON group. Peak visual acuity ( OR=0.288, 95% CI 0.090-0.927, P=0.037) and optic nerve involvement length ≥1/2 ( OR=19.974, 95% CI 1.905-209.559, P=0.013) were the influencing factors for the complete recovery of visual acuity in the affected eyes of the NMOSD-ON group. Age ( OR=0.936, 95% CI 0.890-0.983, P=0.009), time from onset to intravenous infusion of methylprednisolone sodium succinate intervention ( OR=0.854, 95% CI 0.759-0.961, P=0.009), optic disc edema ( OR=4.405, 95% CI 1.108-17.512, P=0.035) and peak visual acuity ( OR=0.13, 95% CI 0.046-0.365, P<0.001) were the influencing factors for the moderate recovery of visual acuity in the affected eyes of the double antibody negative ON group. Peak visual acuity was the only influencing factor for the moderate recovery of visual acuity in the MOG-ON group ( OR=0.060, 95% CI 0.010-0.352, P=0.002) and the NMOSD-ON group ( OR=0.163, 95% CI 0.053-0.500, P=0.001). Conclusions:The prognostic factors for visual recovery in patients with DON after glucocorticoid pulse therapy are subtype-specific. Peak visual acuity is a common predictor for all subtypes. For NMOSD-ON and double antibody-negative ON, attention should be paid to the length of optic nerve lesions. MOG-ON is age-related. Early intravenous infusion of methylprednisolone sodium succinate for double antiantibody negative ON is more likely to achieve moderate vision recovery.

Objective:To conduct a survey on the influence of personality trait on depres-sive symptom and obesity in patients before bariatric and metabolic surgery.Methods:The retros-pective cross-sectional investigation study was conducted. Patients who underwent bariatric and metabolic surgery in The Third Xiangya Hospital of Central South University and The First Affiliated Hospital of Ji′nan University from January 1 to June 1,2024 were recruited. The survey was conducted in electronic format using the general information survey questionnaire, the patient health question-naire-9 (PHQ-9), and the Chinese big five personality inventory brief version (CBF-PI-B). Observa-tion indicators: (1) results of the questionnaire; (2) general data of patient; (3) personality trait scores for patient with different subtypes of obesity; (4) depression symptom scores for patient with different subtypes of obesity; (5) correlation analysis for patient personality trait, depressive symptom and body mass index (BMI). Comparison of measurement data with normal distribution between groups was conducted using the independent t test, and one-way analysis of variance was used for comparison among multiple groups. LSD test was used for pairwise comparison. Comparison of measurement data with skewed distribution among multiple groups was conducted using the Kruskal-Wallis H test, and Dunn Bonferroni test was used for pairwise comparison. The Spearman correlation analysis and Pearson correlation analysis were used for correlation analysis, and the mediation effect analysis was conducted using the Process 4.0 model and the Bootstrap test. Results:(1)Results of the questionnaire. A total of 146 questionnaires were distributed and collected, including 83 questionnaires from The Third Xiangya Hospital of Central South University and 63 questionnaires from The First Affiliated Hospital of Ji′nan University. Of 146 questionnaires, 137 questionnaires were valid, yielding an effective response rate of 93.836%(137/146). (2)General data of patient. Of the 137 patients who completed valid questionnaires, 52 were male with BMI of (41±5)kg/m 2, 85 were female with BMI of (38±6)kg/m 2, showing a significant difference between them ( t=2.586, P<0.05). There were 40 patients aged ≤25 years, with BMI of (42±5)kg/m 2, 28 patients aged 26-30 years, with BMI of (39±5)kg/m 2, 49 patients aged 31-40 years, with BMI of (38±6)kg/m 2, 14 patients aged 41-50 years, with BMI of (38±7)kg/m 2, 6 patients aged >50 years, with BMI of (37±3)kg/m 2. There were significant differences in BMI of patients of different age groups ( F=2.697, P<0.05). (3)Persona-lity trait scores for patient with different subtypes of obesity. Of the 137 patients who completed valid questionnaires, there were 15 patients of mild obesity, with personality trait neuroticism score of 19.0(14.0,24.0), personality trait strictness score of 32.5±5.2, personality trait extroversion score of 30.0(24.0,40.0), 36 patients of moderate obesity, with personality trait neuro-ticism score of 26.5(22.3,28.8), personality trait strictness score of 32.6±5.9, personality trait extro-version score of 34.0(26.3,39.0), 81 patients of severe obesity, with personality trait neuroticism score of 35.0(29.5,41.0), personality trait strictness score of 26.8±7.4, personality trait extroversion score of 28.0(20.5,35.0), 5 patients of extreme obesity, with personality trait neuroticism score of 28.0(26.5,44.0), personality trait strictness score of 19.6±3.4, personality trait extroversion score of 22.0(18.5,25.0). There were significant differences in personality trait neuroticism, strictness and extroversion among patients of different subtypes of obesity ( H=50.316, F=10.774, H=14.446, P<0.05). (4)Depression symptom scores for patient with different subtypes of obesity. Of the 137 pati-ents who completed valid questionnaires, the depressive symptom score were 4.0(2.0,9.0) for 15 pati-ents of mild obesity, 5.0(3.0,7.0) for 36 patients of moderate obesity, 13.0(8.5,17.0) for 81 patients of severe obesity, and 18.0(9.5,22.0) for 5 patients of extreme obesity, respectively, showing a significant difference among them ( H=50.129, P<0.05). (5) Correlation analysis for patient personality trait, depressive symptom and BMI. Results of Spearman correlation analysis showed that personality trait neuroticism were positively correlated with depressive symptoms and BMI ( r=0.780, 0.557, P<0.05), personality trait strictness was negatively correlated with depressive symptoms ( r=-0.523, P<0.05), personality trait extroversion were negatively correlated with depressive symptoms and BMI ( r=-0.448, -0.323, P<0.05), and depressive symptoms was positively correlated with BMI ( r=0.568, P<0.05). Results of Pearson correlation analysis showed that personality trait strictness was negatively correlated with BMI ( r=-0.489, P<0.05). Conclusion:Preoperative personality trait of patients undergoing bariatric and metabolic surgery can influence their depressive symptom and BMI.