Objective To study the five-year survival status and influencing factors of elderly patients with lung cancer complicated with chronic obstructive pulmonary disease (COPD). Methods A cohort study was conducted to follow up 450 patients with lung cancer and chronic obstructive pulmonary disease who were hospitalized in our hospital from January 2018 to December 2023. The endpoint of the follow-up was the end of a five-year period or death. The Life Tables method was used to calculate survival rates and plot survival curves. The Cox proportional hazards model was used to analyze the influencing factors of five-year survival. Results The results indicated that the overall five-year survival rate of patients was 4.89%, and it decreased year by year. Cox regression analysis showed that age, gender, family functioning, and psychological status significantly influenced patient survival rate (all P<0.05). Stratified analysis found that the smoking status, family functioning, and psychological status of male patients all had an impact on survival rate (all P<0.05), while the psychological status of female patients had a more significant impact on survival (P=0.008). Conclusion This study provides a scientific basis for comprehensive intervention of elderly lung cancer patients with COPD. It is recommended that clinical attention should be paid to psychological and family factors to improve patient prognosis.

AIM:To investigate the expression levels of serum sirtuin 6(Sirt6)and nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2)in patients with primary glaucoma and their correlation with the severity of the disease. METHODS:This study is a cross-sectional study. Patients diagnosed with primary glaucoma at the hospital from August 2022 to June 2025 were enrolled and divided into mild-to-moderate and severe groups based on the mean deviation of visual field defects, along with healthy individuals as a control group. Clinical data were collected, and serum levels of Sirt6 and NOX2 were measured using enzyme-linked immunosorbent assay(ELISA). Correlations between serum Sirt6 and NOX2 levels and clinical parameters were analyzed. Multivariate Logistic regression was used to identify factors influencing disease severity, and the diagnostic efficacy of serum Sirt6 and NOX2 levels was evaluated using receiver operating characteristic(ROC)curves. RESULTS:A total of 120 patients with primary glaucoma(58 males, 62 females, mean age 60.08±8.19 y)and 100 controls(46 males, 56 females, mean age 60.23±8.67 y)were enrolled in this study. There were no statistically significant differences in sex or age between the two groups(both P>0.05). The intraocular pressure and serum NOX2 expression level in the primary glaucoma group were significantly higher than those in the control group, while the Sirt6 level was significantly lower than in the control group(all P<0.001). The AUC values of serum Sirt6 and NOX2 in the diagnosis of primary glaucoma were 0.733 and 0.770, respectively, with optimal cutoff values of 2.35 and 4.25 ng/mL, respectively. The AUC of the combined diagnosis of the two was 0.901, and its efficacy was obviously better than that of a single indicator(Zcombination-Sirt6=5.317, Zcombination-NOX2=4.720, P<0.001).The severe group had lower serum Sirt6 expression levels(P<0.05), and higher NOX2 expression levels(P<0.05)than the mild-to-moderate group. Serum Sirt6 expression levels were prominently negatively correlated with mean intraocular pressure(r=-0.354, P<0.05); NOX2 expression levels were prominently positively correlated with mean intraocular pressure(r=0.240, P<0.05). Multivariate Logistic regression analysis showed that a decrease in serum Sirt6 expression levels(OR=0.229, 95%CI: 0.090-0.581), an increase in serum NOX2 expression levels(OR=2.649, 95%CI: 1.658-4.232), an increase in mean intraocular pressure(OR=1.278, 95%CI: 1.118-1.462)which were risk factors for the progression to severe glaucoma. The AUC values of serums Sirt6 and NOX2 expression levels in diagnosing severe primary glaucoma were 0.794 and 0.800, respectively, the AUC, sensitivity, and specificity of the combined diagnosis of the two were 0.916, 80.00%, and 89.33%, respectively, and the combined diagnostic efficacy was better than that of a single indicator(Zcombination-Sirt6=2.627, P=0.009, Zcombination-NOX2=2.762, P=0.006). CONCLUSION:The decreased serum Sirt6 and increased NOX2 expression levels in patients with primary glaucoma are significantly correlated with disease severity, and the combined detection demonstrates good diagnostic value for primary glaucoma and its severity.

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

AIM:To analyze the influencing factors of visual outcome after vitrectomy for polypoidal choroidal vasculopathy(PCV)combined with vitreous hemorrhage and establish a predictive model.METHODS: A retrospective analysis was conducted on the clinical data of 129 cases(129 eyes)of patients who underwent vitrectomy for PCV combined with vitreous hemorrhage from June 2021 to January 2024 in our hospital. They were divided into elevated group(71 eyes)and non-elevated group(58 eyes)according to visual outcome at early posoperative stage(within 24 mo). Another 30 cases(30 eyes)of PCV with vitreous hemorrhage undergoing vitrectomy were selected as external validation data. The predictive value of the model for the postoperative visual outcomes of both internal and external populations was evaluated.RESULTS: The non-elevated group had a higher proportion of patients aged ≥60 years, diabetes, continuous abnormalities of the ellipsoid zone(EZ)during surgery, bleeding involving the macular fovea, and postoperative retinal scar formation than the elevated group were independent factors affecting postoperative visual acuity(all P<0.05). The AUC of the predictive model for predicting the postoperative visual outcomes of internal and external populations was 0.824(95%CI: 0.750-0.898)and 0.809(95%CI: 0.723-0.865), respectively.CONCLUSION:Patients aged ≥60 years, diabetes, intraoperative continuous abnormalities of EZ, bleeding involving the macular fovea, and postoperative retinal scar formation are influencing factors for visual outcome after vitrectomy in patients with PCV combined with vitreous hemorrhage. A predictive model based on those factors has been established, which has a certain predictive value for postoperative visual outcome.

Objective:To mine risk signals of adverse events (AE) in agalsidase beta therapy for Fabry disease and provide reference for the safe use in clinical practice.Methods:The AE reports with agalsidase beta as the primary suspect drug in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the third quarter of 2024 were collected and the clinical information of patients involved was analyzed descriptively. AEs were standardized and categorized using the preferred term (PT) and system organ class (SOC) in Medical Dictionary for Regulatory Activities version 26.0. Signal mining was performed using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. A PT was defined as the risk signal if the number of reports was ≥3, the lower limit of the 95% confidence interval ( CI) of ROR was >1, and the information component minus two times standard deviation ( IC025) was >0. Descriptive statistical analysis were then conducted on the risk signals. The relative risk of target adverse events in gender subgroups was evaluated using the ROR method. Results:A total of 24 163 AE reports with agalsidase beta as the primary suspect drug were collected, involving 7 763 patients and 2 382 PTs. Severe adverse events accounted for 34.9% (2 712/7 763). A total of 121 risk signals (namely PTs) across 15 SOCs were obtained. The top 5 PTs ranked by number of reports were pyrexia (483 cases), chills (449 cases), infusion related reaction (282 cases), chest pain (221 cases), and cerebrovascular accident (218 cases). The top 5 PTs ranked by signal intensity were cornea verticillata ( ROR=56.44, IC025=4.59), drug specific antibody present ( ROR=54.13, IC025=5.46), cerebral calcification ( ROR=24.82, IC025=3.16), myocardial necrosis marker increased ( ROR=24.14, IC025=3.83), and infusion site rash ( ROR=20.41, IC025=3.46). Among the top 30 PTs ranked by number of reports and signal intensity, there were 4 and 13 PTs not documented in the drug label, respectively. The former included atrial fibrillation, cellulitis, neuralgia, and pallor, while the latter included cornea verticillate, cerebral calcification, auricular swelling, vein discoloration, aortic dilatation, bundle branch block, myocardial fibrosis, cardiac infection, vein rupture, sudden hearing loss, meningitis viral, deafness transitory, and corneal opacity. Subgroup analysis by sex showed that males had higher risks in developing chills, tremor, drug specific antibody detection, renal failure, and renal impairment, while females had higher risks in weight increase and dizziness. Conclusions:The main risk signals of adverse events of agalsidase beta include pyrexia, chills, and infusion related reactions, which are consistent with those documented in package inserts. In addition, potential new risk signals such as atrial fibrillation, cellulitis, neuralgia, cornea verticillate, auricular swelling, and sudden hearing loss were also detected. The relative risks of some target adverse events vary between genders, and it is recommended to strengthen targeted drug monitoring and individualized management in clinical practice.

Objective:To mine risk signals of adverse events (AE) in agalsidase beta therapy for Fabry disease and provide reference for the safe use in clinical practice.Methods:The AE reports with agalsidase beta as the primary suspect drug in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the third quarter of 2024 were collected and the clinical information of patients involved was analyzed descriptively. AEs were standardized and categorized using the preferred term (PT) and system organ class (SOC) in Medical Dictionary for Regulatory Activities version 26.0. Signal mining was performed using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. A PT was defined as the risk signal if the number of reports was ≥3, the lower limit of the 95% confidence interval ( CI) of ROR was >1, and the information component minus two times standard deviation ( IC025) was >0. Descriptive statistical analysis were then conducted on the risk signals. The relative risk of target adverse events in gender subgroups was evaluated using the ROR method. Results:A total of 24 163 AE reports with agalsidase beta as the primary suspect drug were collected, involving 7 763 patients and 2 382 PTs. Severe adverse events accounted for 34.9% (2 712/7 763). A total of 121 risk signals (namely PTs) across 15 SOCs were obtained. The top 5 PTs ranked by number of reports were pyrexia (483 cases), chills (449 cases), infusion related reaction (282 cases), chest pain (221 cases), and cerebrovascular accident (218 cases). The top 5 PTs ranked by signal intensity were cornea verticillata ( ROR=56.44, IC025=4.59), drug specific antibody present ( ROR=54.13, IC025=5.46), cerebral calcification ( ROR=24.82, IC025=3.16), myocardial necrosis marker increased ( ROR=24.14, IC025=3.83), and infusion site rash ( ROR=20.41, IC025=3.46). Among the top 30 PTs ranked by number of reports and signal intensity, there were 4 and 13 PTs not documented in the drug label, respectively. The former included atrial fibrillation, cellulitis, neuralgia, and pallor, while the latter included cornea verticillate, cerebral calcification, auricular swelling, vein discoloration, aortic dilatation, bundle branch block, myocardial fibrosis, cardiac infection, vein rupture, sudden hearing loss, meningitis viral, deafness transitory, and corneal opacity. Subgroup analysis by sex showed that males had higher risks in developing chills, tremor, drug specific antibody detection, renal failure, and renal impairment, while females had higher risks in weight increase and dizziness. Conclusions:The main risk signals of adverse events of agalsidase beta include pyrexia, chills, and infusion related reactions, which are consistent with those documented in package inserts. In addition, potential new risk signals such as atrial fibrillation, cellulitis, neuralgia, cornea verticillate, auricular swelling, and sudden hearing loss were also detected. The relative risks of some target adverse events vary between genders, and it is recommended to strengthen targeted drug monitoring and individualized management in clinical practice.

OBJECTIVE To analyze the potential adverse drug interactions(pADIs)of clarithromycin,and establish refined prescription pre-review rules.METHODS Outpatient prescriptions of clarithromycin in combination with other drugs were collected from January 1,2024 to June 30,2024 through hospital information system of the Third People's Hospital of Bengbu.pADIs were identified and their risk severities were graded according to Lexicomp and Micromedex databases.Then,refined prescription pre-review rules for clarithromycin pADIs-related drugs were established according to the identification and risk level results.RESULTS Among 3 046 clarithromycin combined drug prescriptions,946 cases of pADIs occurred in 812 prescriptions.There were 6,415 and 525 cases classified as"contraindicated","major"and"moderate",respectively.The combination drugs with"contraindicated"levels were tamsulosin,rupatadine,domperidone and ticagrelor,while those with"major"levels were mainly theophylline,dexamethasone and amlodipine.Accordingly,26 refined rules were established,including 4 items of"warning information→prescription interception",11 items of"warning information→prescription double signature"and 11 items of"attention information→prescription approval".CONCLUSIONS There are"contraindicated"and"major"risks associated with clarithromycin and its combination drugs in the hospital,and refined prescription pre-review rules for clarithromycin combined drug prescription have been established successfully.

Objective:To investigate the efficacy and adverse effects of combination therapy containing venetoclax in the treatment of t(11; 14) plasma cell disorders.Methods:A retrospective case series study was conducted. The clinical data of plasma cell disorders patients with t(11; 14) treated with combination therapy containing venetoclax in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 2020 to September 2023 were collected. The general data included baseline clinical characteristics, treatment regimens, treatment responses, survival, and adverse events. The duration of orally administered venetoclax-based treatment regimen was 28 d, and the dose of venetoclax was appropriately adjusted according to the tumor burden and general conditions of patients. Patients were grouped according to drug dosage and treatment regimen. The overall survival (OS) analysis was performed by using Kaplan-Meier method and log-rank test was used for comparison among groups.Results:Among the 14 plasma cell disorders patients with t(11;14), 13 had multiple myeloma (MM) and 1 had primary plasma cell leukemia (pPCL). The median time [ M ( Q1, Q3)] from initial diagnosis to venetoclax treatment was 21 months (8 months, 39 months). The median number of therapy lines was 2 (1, 4); 7 patients had drug resistance to both proteasome inhibitors (PI) and immunomodulators (IMiD), and 5 patients had drug resistance to PI, IMiD and anti-CD38 monoclonal antibodies; 2 patients died after 1 uncompleted course of treatment and they were not enrolled into efficacy evaluation and survival analysis. Among the 11 MM patients evaluable for treatment response, 6 achieved at least partial remission (PR). Of the 4 patients who received the first-line or second-line therapy containing venetoclax, 2 achieved strict complete remission (sCR), 1 achieved very good partial remission (VGPR), and 1 achieved PR. The median course number of therapy lines with venetoclax was 2 (2, 6), and the median acting time was 1.1 months (0.75 months, 1.75 months). Until the last follow-up in May 2024, the median duration of remission of 11 MM patients was 3.3 months (95% CI: 0-7.1 months), and the median OS time was 22.7 months (95% CI: 0-52.5 months). The median OS time was 9.6 months, 31.2 months, respectively in venetoclax combined with PI group (6 cases) and venetoclax combined with daratumumab (Dara) group (4 cases), and the difference in OS between the 2 groups was statistically significant ( P = 0.093); the median duration of remission was 1.7 months and 9.8 months, respectively in venetoclax combined with PI group and venetoclax combined with Dara group, and the difference was statistically significant between the 2 groups ( P = 0.025). The median OS time in high-dose group (maximum dose of venetoclax ≥300 mg, 6 cases) and low-dose group (maximum dose of venetoclax < 300 mg, 5 cases) was 31.2 and 7.5 months, respectively, and the difference in OS was statistically significant ( P = 0.013). The median duration of remission was 9.8 months, 1.6 months, respectively, and the difference was statistically significant ( P = 0.048). Grade ≥3 adverse events of 11 MM patients included neutropenia, lymphopenia, infection, thrombocytopenia, and hypokalemia; 6 patients experienced grade ≥3 adverse events, 2 patients discontinued treatment due to adverse events, and no treatment-related deaths occurred. The pPCL patient received 5 courses of treatment with venetoclax plus DECP (cisplatinum + etoposide + cyclophosphamide + dexamethasone) induction therapy followed by chimeric antigen receptor T cell therapy and then continued venetoclax maintenance, achieving sCR with the duration remission of 18.7 months. During induction, the patient experienced grade 3 neutropenia and infection. Conclusions:The combination therapy containing venetoclax is safe and manageable in MM patients with t(11; 14) and pPCL. The patients receiving early, regular, and adequate-dose treatment with venetoclax have better therapeutic efficacy.

AIM: To investigate the differences in varying stages of non-proliferative diabetic retinopathy(NPDR)using optical coherence tomography angiography(OCTA).METHODS: Cross-sectional study. A total of 77 cases(77 eyes)of diabetic patients were included, and they were divided into non-diabetic retinopathy(NDR; 23 eyes)and non-proliferative diabetic retinopathy(NPDR; 54 eyes)groups, further subdivided into mild NPDR(20 eyes), moderate NPDR(20 eyes), and severe NPDR(14 eyes). Foveal avascular zone(FAZ)area, superficial and deep capillary plexus densities(SSP and DSP), and visual acuity(LogMAR)were compared between NDR and NPDR groups. Furthermore, the visual acuity, FAZ area and levels of SSP and DSP were compared in different degrees of NPDR. Correlation analysis were conducted to elucidate relationships between FAZ area, visual acuity, SSP, DSP, and severity of the disease.RESULTS: Compared with the NDR group, the visual acuity(LogMAR)and macular FAZ area increased, while SSP and DSP were decreased in the NPDR group(P<0.05); there were significant differences in visual acuity, FAZ area and SSP and DSP levels in different degrees of NPDR(P<0.05). Visual acuity(LogMAR)and FAZ area displayed a positive correlation with the severity of disease, while SSP and DSP showed a negative correlation.CONCLUSION: With the progression of NPDR, the visual acuity(LogMAR)and FAZ area increased, and the SSP and DSP decreased.

Objective:To observe the changes of macular structure and microvessels in eyes with diabetes macular ischemia (DMI).Methods:A retrospective case study. From January 2023 to July 2023, 23 patients of 31 eyes diagnosed with DMI at Tangshan Ophthalmological Hospital were included in this study. Among them, there were 14 males with 23 eyes; Female cases with 8 eyes. Age were (59.5±4.6) years old. According to the DMI grading standard formulated by the research group for early treatment of diabetes retinopathy, the patients were divided into mild DMI group, moderate DMI group, and severe DMI group, with 8, 12, and 11 eyes respectively. The blood flow density (VD), perfusion area (FA), small vessel VD (SVD), inner retinal capillary plexus VD, FA, and outer retinal, choroidal, and ganglion cell complex (GCC) thickness within 1 mm of the macular fovea in retinal superficial vascular plexus (SVP)were measured using a scanning frequency light source optical coherence tomography instrument. The changes in macular structure and microvasculature in the affected eyes of different degrees of DMI groups were compared and observed. Inter group comparisons were conducted using one-way ANOVA or Kruskal Wallis H-test. Spearman correlation analysis was used to analyze the correlation between DMI severity and GCC, outer retina, choroid thickness, VD, FA and SVP VD, SVD and FA in inner retina. Results:The GCC ( F=70.670), outer retinal thickness ( H=12.393), VD ( F=105.506), SVD ( H=25.300), FA ( F=107.655), and VD ( H=24.098) and FA ( H=25.300) of the retinal SVP in the mild, moderate, and severe DMI groups were compared, and the differences were statistically significant ( P<0.05). There was no statistically significant difference in choroidal thickness ( H=2.441, P>0.05). Pairwise comparison between groups: VD, SVD, FA of GCC thickness and SVP, and VD of inner retina were statistically significant between severe DMI group and moderate DMI group, and between moderate DMI group and mild DMI group ( P<0.05). The thickness of outer retina was statistically significant between severe DMI group and moderate DMI group ( P<0.05). Inner retinal FA: there were statistically significant differences between severe DMI group, moderate DMI group and mild DMI group ( P<0.05). The correlation analysis results showed that GCC ( r s=-0.918), outer retinal thickness ( r s=-0.448), and inner retinal VD ( r s=-0.894) and FA ( r s=-0.918), as well as VD ( r s=-0.919), SVD ( r s=-0.924), and FA ( r s=-0.939) of retinal SVP, were all negatively correlated with the degree of DMI ( P<0.05). There was no correlation between choroidal thickness and degree of DMI ( r s=-0.081, P>0.05). Conclusion:The thickness of GCC, outer retina and choroid, the VD, SVD, and FA of the retinal SVP, the VD and FA of inner retina are all reduced in eyes with different degrees of DMI, while all of them are negatively correlated with the degree of DMI, except for choroid thickness.