Chronic obstructive pulmonary disease(COPD),as a global health challenge,brings heavy economic and psychological burdens to patients and their families.Accurately identifying the risk factors for COPD and excluding false associations are crucial for understanding its pathogenesis and formulating prevention strategies.Mendelian randomization(MR),as a supplementary method,has shown great potential in reducing the interference of confounding factors,lowering the cost of experimental research,and avoiding experimental ethical issues.This article focuses on MR and its main derivative methods,discusses their basic principles and applicable conditions,and analyzes their application effects and limitations in COPD research in combination with specific cases,enabling MR to be more widely applied in the study of influencing factors of COPD.

PURPOSE: To investigate the regulatory role of nerve injury-induced protein 1 (NINJ1) in the anti-inflammatory function of human umbilical cord mesenchymal stem cells (hUC-MSCs) co-stimulated by interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). METHODS: hUC-MSCs were expanded in vitro using standard protocols, with stem cell characteristics confirmed by flow cytometry and multilineage differentiation assays. The immunomodulatory properties and cellular activity of cytokine-co-pretreated hUC-MSCs were systematically evaluated via quantitative reverse transcription RT-qPCR, lymphocyte proliferation suppression assays, and Cell Counting Kit-8 viability tests. Transcriptome sequencing, Western blotting and small interfering RNA interference were integrated to analyze the regulatory mechanisms of NINJ1 expression. Functional roles of NINJ1 in pretreated hUC-MSCs were elucidated through gene silencing combined with lactate dehydrogenase release assays, Annexin V/Propidium Iodide apoptosis analysis, macrophage co-culture models, and cytokine Enzyme-Linked Immunosorbent Assay. Therapeutic efficacy was validated in a cecal ligation and puncture-induced septic mouse model: 80 mice were randomly allocated into 4 experimental groups (n=20/group): sham group (laparotomy without cecal ligation); phosphate-buffered saline-treated group (cecal ligation and puncture (CLP) + 0.1 mL phosphate-buffered saline); hUC-MSCs (small interfering RNA (siRNA)-interferon-gamma and tumor necrosis factor-alpha co-stimulation (IT))-treated group (CLP + hUC-MSCs transfected with scrambled siRNA); and hUC-MSCs (siNINJ1-IT)-treated group (CLP + hUC-MSCs with NINJ1-targeting siRNA). RESULTS: hUC-MSCs demonstrated compliance with International Society for Cellular Therapy criteria, confirming their stem cell identity. IFN-γ/TNF-α co-pretreatment enhanced the immunosuppressive capacity of hUC-MSCs, accompanied by the reduction of cellular viability, while concurrently upregulating pro-inflammatory cytokines such as interleukin-6 and interleukin-1β. This co-stimulation significantly elevated NINJ1 expression in hUC-MSCs, whereas genetic silencing of NINJ1 effectively suppressed pro-inflammatory cytokine production and attenuated damage-associated molecular patterns release through inhibition of programmed plasma membrane rupture. Furthermore, the NINJ1 interference potentiated the ability of cytokine-pretreated hUC-MSCs to suppress LPS-induced pro-inflammatory responses in RAW264.7 macrophages. In cecal ligation and puncture-induced sepsis model, NINJ1-silenced hUC-MSCs exhibited enhanced therapeutic efficacy, manifested by reduced systemic inflammation and multi-organ damage. CONCLUSION Our findings shed new light on the immunomodulatory functions of cytokine-primed MSCs, offering groundbreaking insights for developing MSC-based therapies against inflammatory diseases via interfering the expression of NINJ1.
Mesenchymal Stem Cells/drug effects* ; Animals ; Interferon-gamma/pharmacology* ; Tumor Necrosis Factor-alpha/pharmacology* ; Humans ; Mice ; Umbilical Cord/cytology* ; Cells, Cultured ; Apoptosis ; Male

Objective:To explore the relationship between medical students' sense of meaning in life and professional commitment, to analyze the mediating role of psychological resilience and the moderating role of social connectedness, and to provide suggestions for medical students' education.Methods:Questionnaires were administered to 899 medical students from four medical colleges and universities in Beijing, China using the Meaning in Life, Professional Commitment, Psychological Resilience, and Social Connectedness scales. Pearson correlation analysis was performed using SPSS 25.0 software, and the mediating role of psychological resilience and the moderating role of social connectedness were tested based on the Process plug-in.Results:The scores of medical students' sense of meaning in life, professional commitment, psychological resilience, and social connectedness were (44.87±8.64), (95.35±18.08), (89.25±15.16), and (28.31±11.25) points, respectively; there was a significant positive correlation between the four variables ( r=0.19-0.71, all P<0.01); the sense of meaning in life significantly and positively predicted medical students' professional commitment ( β=1.48, P<0.05); psychological resilience partially mediated the relationship between the sense of meaning in life and professional commitment, with the mediating effect accounting for 20.41% of the total effect; social connectedness played a moderating role in the "Psychological Resilience-Professional Commitment" pathway. Conclusions:The level of professional commitment of medical students is positively influenced by the factors of sense of meaning in life, psychological resilience, and social connectedness. Colleges and universities should pay attention to the influence of these factors and carry out targeted educational work.

Chronic obstructive pulmonary disease(COPD),as a global health challenge,brings heavy economic and psychological burdens to patients and their families.Accurately identifying the risk factors for COPD and excluding false associations are crucial for understanding its pathogenesis and formulating prevention strategies.Mendelian randomization(MR),as a supplementary method,has shown great potential in reducing the interference of confounding factors,lowering the cost of experimental research,and avoiding experimental ethical issues.This article focuses on MR and its main derivative methods,discusses their basic principles and applicable conditions,and analyzes their application effects and limitations in COPD research in combination with specific cases,enabling MR to be more widely applied in the study of influencing factors of COPD.

Objective:To investigate the effect and safety of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) in treating the chronic pancreatitis (CP) patients with main pancreatic duct (MPD) stones and to analyze the influencing factors of success of lithotripsy.Methods:Clinical data of 132 patients with CP complicated with MPD stones treated with P-ESWL in the Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2022 to December 2023 were retrospectively analyzed, including 103 males and 29 females, aged (50.3±16.9) years. The times of P-ESWL, the success rate of stone fragmentation, the necessity of combining endoscopic retrograde cholangiopancreatograhy (ERCP), clearance rate of MPD stones, and incidence of post-P-ESWL complications (acute pancreatitis, abdominal hematoma, infection, steinstrasse, perforation, etc.) were evaluated. The factors influencing the success rate of lithotripsy were analyzed using univariate and multivariate logistic regression.Results:All patients underwent P-ESWL treatment, with (2.23±0.82) times of P-ESWL per person. The success rate of stone fragmentation was 87.1%(115/132). Of 107 CP patients (81.1%, 107/132) were treated with their first P-ESWL. Of 12 patients (9.1%, 12/132) underwent single P-ESWL, and 120 (90.9%, 120/132) underwent P-ESWL combined with ERCP. There were 95 cases (72.0%, 95/132) with effective removal of stones, and 62 (47.0%, 62/132) with complete removal of stones. Post-P-ESWL complications included eight cases (6.1%, 8/132) of acute pancreatitis, two (7.6%, 2/132) of steinstrasse complicated with acute pancreatitis and one (0.8%, 1/132) of abdominal hematoma. No infection or perforation occurred. Multivariate logistic regression analysis showed that the higher CT value of stones ( OR=1.239, 95% CI: 1.040-1.477, P=0.017) was associated with the lower success rate of stone fragmentation. Conclusion:P-ESWL is safe and effective in treating patients with CP complicated with MPD stones. The CT value of stones is a risk factor for the success rate of P-ESWL.

Objective:To detect adverse reaction risk signals of triazole antifungal agents and provide evidences for their safe use in clinic.Methods:Adverse reaction/event reports with fluconazole, itraconazole, voriconazole, posaconazole, or isavuconazonium as the primary suspect drug were collected from the data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province from January 2004 to June 2024 and the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the second quarter of 2023. Adverse reaction/event terms were standardized using the preferred term (PT) and system organ class in Medical Dictionary for Regulatory Activities 24.0. Risk signals were detected using the reporting odds ratio (ROR) method and the Bayesian confidence propagation neural network (BCPNN) algorithm. A PT was defined as an adverse reaction risk signal if the number of reports was ≥3, the lower limit of the 95% confidence interval ( CI) for ROR was >2, and the lower limit of the 95% CI for the information component ( IC) was >0. Descriptive statistical analysis was performed. Results:A total of 3 988 reports with the above 5 antifungal drugs as the primary suspect drug were collected from data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province, 822 (20.6%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 1 852, 1 395, 703, 27, and 11 cases among the 3 988 reports, and in 591 (31.9%), 149 (10.7%), 59 (8.4%), 18 (66.7%), and 5 (5/11) serious cases among the 822 serious case reports, respectively. A total of 20 066 reports with the above 5 drugs as the primary suspect drug were collected in FAERS database, 9 635 (48.0%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 7 758, 6 180, 2 869, 1 796, and 1 463 cases among the 20 066 reports, and in 4 295 (55.4%), 2 806 (45.4%), 1 191 (41.5%), 828 (46.1%), and 515 (35.2%) serious cases among the 9 635 serious case reports, respectively. Based on the data reported by Shandong Province and in FAERS database, 18 and 207 risk signals of adverse reaction not mentioned in the labels were identified, respectively, and 5 of them were identified in both databases, including fluconazole-induced renal impairment and voriconazole-induced oliguria, delirium, psychiatric disorders, and rhabdomyolysis. In the data reported by Shandong Province and in FAERS database, 13 and 189 reports of muscle-related disorders (rhabdomyolysis, myopathy, and myositis) were identified respectively, involving voriconazole (in 8 and 62 cases), itraconazole (in 4 and 74 cases), and fluconazole (in 1 and 53 cases).Conclusions:Renal impairment induced by fluconazole and oliguria, delirium, psychiatric disorders, and rhabdomyolysis induced by voriconazole are risk signals of adverse reaction not mentioned in the labels for triazole antifungal agents. Voriconazole, itraconazole, and fluconazole may also cause muscle-related disorders, warranting vigilance in clinical practice.

Objective:To establish a standardized code database of adverse drug reactions (ADRs) terms related to linezolid and analyze the common ADRs of linezolid.Methods:Linezolid drug labels, websites (including Side Effect Resource, and the official websites of US Food and Drug Administration, European Medicines Agency and National Medical Products Administration) and scientific literature database (including CNKI, Wanfang, VIP, PubMed, Embase and Web of Science databases) were systematically searched, and ADR terms about linezolid were collected. ADR terms were mapped to the international classification of diseases-10 (ICD-10) code to establish a linezolid adverse reaction database.Results:A total of 117 ADR terms about linezolid were collected and 91 ICD-10 codes were obtained after being mapped to ICD-10. A standardized database was constructed and successfully embedded into the ADR spontaneous reporting system as a specific drug submodule. The gastrointestinal system, skin and subcutaneous tissue system, various nervous systems, blood and lymphatic systems were the most common system organs involved in linezolid-related ADRs under the 91 ICD-10 codes. Among them, ADRs under the gastrointestinal system codes K14.302 (black hairy tongue) and K52.104 (drug-induced gastroenteritis and colitis), the skin and subcutaneous tissue system code L27.005 (drug-induced dermatitis), various nervous system codes G90.800 (other disorders of autonomic nervous system), G62.001 (drug-induced polyneuropathy) and G44.400 (drug-induced headache, not elsewhere classified), the blood and lymphatic system codes D69.502 (drug- induced thrombocytopenia) and D70.x02 (drug-induced granulocytopenia), the metabolic and nutritional codes E87.204 (lactic acidosis), as well as the endocrine system code E16.000 (drug-induced hypoglycaemia without coma) had been reported frequently in the scientific literature. In addition, there were 14 ADR terms related to linezolid under 13 ICD-10 codes not recorded in the drug instructions.Conclusions:It is feasible to use ICD-10 code to standardize ADR terms related to linezolid and establish a database. Common ADRs of linezolid include thrombocytopenia, lactic acidosis, neutropenia, black hairy tongue, gastroenteritis/colitis, hypoglycemia, rash, serotonin syndrome, peripheral neuropathy and headache, which should be paid attention to and researched furtherly.

Objective:To establish a standardized code database of adverse drug reactions (ADRs) terms related to linezolid and analyze the common ADRs of linezolid.Methods:Linezolid drug labels, websites (including Side Effect Resource, and the official websites of US Food and Drug Administration, European Medicines Agency and National Medical Products Administration) and scientific literature database (including CNKI, Wanfang, VIP, PubMed, Embase and Web of Science databases) were systematically searched, and ADR terms about linezolid were collected. ADR terms were mapped to the international classification of diseases-10 (ICD-10) code to establish a linezolid adverse reaction database.Results:A total of 117 ADR terms about linezolid were collected and 91 ICD-10 codes were obtained after being mapped to ICD-10. A standardized database was constructed and successfully embedded into the ADR spontaneous reporting system as a specific drug submodule. The gastrointestinal system, skin and subcutaneous tissue system, various nervous systems, blood and lymphatic systems were the most common system organs involved in linezolid-related ADRs under the 91 ICD-10 codes. Among them, ADRs under the gastrointestinal system codes K14.302 (black hairy tongue) and K52.104 (drug-induced gastroenteritis and colitis), the skin and subcutaneous tissue system code L27.005 (drug-induced dermatitis), various nervous system codes G90.800 (other disorders of autonomic nervous system), G62.001 (drug-induced polyneuropathy) and G44.400 (drug-induced headache, not elsewhere classified), the blood and lymphatic system codes D69.502 (drug- induced thrombocytopenia) and D70.x02 (drug-induced granulocytopenia), the metabolic and nutritional codes E87.204 (lactic acidosis), as well as the endocrine system code E16.000 (drug-induced hypoglycaemia without coma) had been reported frequently in the scientific literature. In addition, there were 14 ADR terms related to linezolid under 13 ICD-10 codes not recorded in the drug instructions.Conclusions:It is feasible to use ICD-10 code to standardize ADR terms related to linezolid and establish a database. Common ADRs of linezolid include thrombocytopenia, lactic acidosis, neutropenia, black hairy tongue, gastroenteritis/colitis, hypoglycemia, rash, serotonin syndrome, peripheral neuropathy and headache, which should be paid attention to and researched furtherly.

Objective:To detect adverse reaction risk signals of triazole antifungal agents and provide evidences for their safe use in clinic.Methods:Adverse reaction/event reports with fluconazole, itraconazole, voriconazole, posaconazole, or isavuconazonium as the primary suspect drug were collected from the data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province from January 2004 to June 2024 and the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the second quarter of 2023. Adverse reaction/event terms were standardized using the preferred term (PT) and system organ class in Medical Dictionary for Regulatory Activities 24.0. Risk signals were detected using the reporting odds ratio (ROR) method and the Bayesian confidence propagation neural network (BCPNN) algorithm. A PT was defined as an adverse reaction risk signal if the number of reports was ≥3, the lower limit of the 95% confidence interval ( CI) for ROR was >2, and the lower limit of the 95% CI for the information component ( IC) was >0. Descriptive statistical analysis was performed. Results:A total of 3 988 reports with the above 5 antifungal drugs as the primary suspect drug were collected from data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province, 822 (20.6%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 1 852, 1 395, 703, 27, and 11 cases among the 3 988 reports, and in 591 (31.9%), 149 (10.7%), 59 (8.4%), 18 (66.7%), and 5 (5/11) serious cases among the 822 serious case reports, respectively. A total of 20 066 reports with the above 5 drugs as the primary suspect drug were collected in FAERS database, 9 635 (48.0%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 7 758, 6 180, 2 869, 1 796, and 1 463 cases among the 20 066 reports, and in 4 295 (55.4%), 2 806 (45.4%), 1 191 (41.5%), 828 (46.1%), and 515 (35.2%) serious cases among the 9 635 serious case reports, respectively. Based on the data reported by Shandong Province and in FAERS database, 18 and 207 risk signals of adverse reaction not mentioned in the labels were identified, respectively, and 5 of them were identified in both databases, including fluconazole-induced renal impairment and voriconazole-induced oliguria, delirium, psychiatric disorders, and rhabdomyolysis. In the data reported by Shandong Province and in FAERS database, 13 and 189 reports of muscle-related disorders (rhabdomyolysis, myopathy, and myositis) were identified respectively, involving voriconazole (in 8 and 62 cases), itraconazole (in 4 and 74 cases), and fluconazole (in 1 and 53 cases).Conclusions:Renal impairment induced by fluconazole and oliguria, delirium, psychiatric disorders, and rhabdomyolysis induced by voriconazole are risk signals of adverse reaction not mentioned in the labels for triazole antifungal agents. Voriconazole, itraconazole, and fluconazole may also cause muscle-related disorders, warranting vigilance in clinical practice.