Natural killer cells(NK)are important innate immune cells that do not require prior antigen exposure and can directly recognize and attack virus-infected cells and tumor cells.The activation and effector functions of NK cells are regulated by a balance of signals delivered through their surface activating receptors and inhibitory re-ceptors,which bind to ligands on target cells to achieve cytotoxicity via"induced self"and"missing self"recogni-tion models.The killing mechanisms of NK cells primarily include release of cytotoxic granules such as perforin and granzymes to induce target cell lysis,death receptor-mediated apoptosis,secretion of various cytokines,chemokines and growth factors to coordinate with other immune cells in killing tumor cells,thereby generating secondary im-mune responses and antibody-dependent cellular cytotoxicity(ADCC).

Objective To construct a competency-based and functioning-oriented training curriculum system for inclusive education teachers in primary and secondary schools based on World Health Organization International Classification of Functioning,Disability and Health(ICF)and rehabilitation competency framework(RCF).Methods Based on the policy documents of inclusive education from United Nations Educational,Scientific and Cultur-al Organization and the European Union,and aligning with China's national policies such as the 14th Five-Year Plan for Special Education Development and Improvement,this study systematically analyzed the core competen-cies required for primary and secondary inclusive education teachers using ICF and RCF,and developed a compe-tency-based and functioning-oriented training curriculum system.Results The core competencies for primary and secondary school teachers encompassed four dimensions under the con-text of inclusive education.In the dimension of professional identity and ethics,teachers needed to establish in-clusive education values and be able to use ICF to comprehensively understand students'functioning perfor-mance and developmental needs.In the dimension of inclusive teaching and support practices,it was emphasized the ability for inclusive instructional design based on functioning assessment,including applying universal design for learning,creating barrier-free learning environments and implementing multiple assessments.In the dimen-sion of collaboration and communication,it was needed to build home-school-community support networks and possess communication skills for interprofessional teamwork.In the dimension of continuous reflection and pro-fessional development,it was focused on teachers'continuous learning and professional growth.A curriculum system comprising four major modules including concepts and foundations,core skills for teaching and support,collaboration and expansion,and practical reflection and research were constructed based on this competency model.Conclusion Based on ICF and RCF,a competency-based and functioning-oriented training curriculum system has been established,providing a theoretical framework and practical pathway for improving the quality of inclusive edu-cation teachers in China.

Objective To mine and analyze adverse drug events(ADEs)of novel agents for multi-drug-resistant tuberculosis(MDR-TB)based on the FDA Adverse Event Reporting System(FAERS)database,to explore the signals of ADEs,and to provide reference for clinical use.Methods The FAERS database was searched and extracted from Q1 of 2015 to Q4 of 2023,and the ADE reports about bedaquiline,delamanid,and pretomanid were collected.Data mining and analysis were carried out on relevant reports of the drug using the reporting odds ratio(ROR),proportional reporting ratio(PRR),medicines and healthcare products regulatory agency(MHRA),and the Bayesian confidence progressive neural network(BCPNN).Results The number of ADE reports for the target drugs bedaquiline,delamanid,and pretomanid were 2 477,1 630,and 173,respectively.ADE of the target drugs involved multiple organ systems.Positive signals detected by the ROR,PRR,MHRA,and BCPNN methods were 246,246,215,204 for bedaquiline;251,251,224,200 for delamanid;and 25,25,24,22 for pretomanid.Clinically significant high-risk signals include prolonged QT interval on ECG,anemia,liver toxicity,peripheral neuropathy,etc.Conclusions The signal mining of ADEs based on the FAERS database indicates that close attention should be paid to risks such as prolonged QT interval on ECG,anemia,liver toxicity,and peripheral neuropathy during the clinical use of bedaquiline,delamanid,and pretomanid.In addition,monitoring of new potential ADE signals(such as acute heart failure,respiratory failure,acute kidney injury,etc.)should be strengthened,and timely intervention measures should be taken to ensure medication safety.

Objective To construct a competency-based and functioning-oriented training curriculum system for inclusive education teachers in primary and secondary schools based on World Health Organization International Classification of Functioning,Disability and Health(ICF)and rehabilitation competency framework(RCF).Methods Based on the policy documents of inclusive education from United Nations Educational,Scientific and Cultur-al Organization and the European Union,and aligning with China's national policies such as the 14th Five-Year Plan for Special Education Development and Improvement,this study systematically analyzed the core competen-cies required for primary and secondary inclusive education teachers using ICF and RCF,and developed a compe-tency-based and functioning-oriented training curriculum system.Results The core competencies for primary and secondary school teachers encompassed four dimensions under the con-text of inclusive education.In the dimension of professional identity and ethics,teachers needed to establish in-clusive education values and be able to use ICF to comprehensively understand students'functioning perfor-mance and developmental needs.In the dimension of inclusive teaching and support practices,it was emphasized the ability for inclusive instructional design based on functioning assessment,including applying universal design for learning,creating barrier-free learning environments and implementing multiple assessments.In the dimen-sion of collaboration and communication,it was needed to build home-school-community support networks and possess communication skills for interprofessional teamwork.In the dimension of continuous reflection and pro-fessional development,it was focused on teachers'continuous learning and professional growth.A curriculum system comprising four major modules including concepts and foundations,core skills for teaching and support,collaboration and expansion,and practical reflection and research were constructed based on this competency model.Conclusion Based on ICF and RCF,a competency-based and functioning-oriented training curriculum system has been established,providing a theoretical framework and practical pathway for improving the quality of inclusive edu-cation teachers in China.

Objective To mine and analyze adverse drug events(ADEs)of novel agents for multi-drug-resistant tuberculosis(MDR-TB)based on the FDA Adverse Event Reporting System(FAERS)database,to explore the signals of ADEs,and to provide reference for clinical use.Methods The FAERS database was searched and extracted from Q1 of 2015 to Q4 of 2023,and the ADE reports about bedaquiline,delamanid,and pretomanid were collected.Data mining and analysis were carried out on relevant reports of the drug using the reporting odds ratio(ROR),proportional reporting ratio(PRR),medicines and healthcare products regulatory agency(MHRA),and the Bayesian confidence progressive neural network(BCPNN).Results The number of ADE reports for the target drugs bedaquiline,delamanid,and pretomanid were 2 477,1 630,and 173,respectively.ADE of the target drugs involved multiple organ systems.Positive signals detected by the ROR,PRR,MHRA,and BCPNN methods were 246,246,215,204 for bedaquiline;251,251,224,200 for delamanid;and 25,25,24,22 for pretomanid.Clinically significant high-risk signals include prolonged QT interval on ECG,anemia,liver toxicity,peripheral neuropathy,etc.Conclusions The signal mining of ADEs based on the FAERS database indicates that close attention should be paid to risks such as prolonged QT interval on ECG,anemia,liver toxicity,and peripheral neuropathy during the clinical use of bedaquiline,delamanid,and pretomanid.In addition,monitoring of new potential ADE signals(such as acute heart failure,respiratory failure,acute kidney injury,etc.)should be strengthened,and timely intervention measures should be taken to ensure medication safety.

Humans ; alpha-Synuclein/genetics* ; Parkinson Disease/pathology*

A 43-year-old male patient with type 2 diabetes mellitus underwent off-pump coronary artery bypass grafting due to coronary atherosclerotic heart disease. Dapagliflozin was stopped 24 hours before the operation, fasting and discontinuing oral medication started at 8: 00 pm 1 day before the operation. On the day of surgery, blood gas analysis and blood glucose were normal before undergoing cardiopulmonary bypass. Tracheal intubation was successfully removed 7 hours after operation. Blood glucose and anion gap were 11.2 mmol/L and 13 mmol/L, respectively on the 2nd day after operation. The treatments of hypoglycemic, antihypertensive and lipid-regulating drugs and normal diet were restored. On the morning of the 3rd day after operation, the patient developed symptoms such as shallow rapid breathing, poor appetite, excessive urine, and irritability. Blood gas analysis showed pH 7.05, arterial partial pressure of carbon dioxide (PaCO 2) 11 mmHg, base excess -24.5 mmol/L, actual bicarbonate 21.7 mmol/L; blood glucose 10.4 mmol/L, potassium 5.3 mmol/L, and routine urine test showed ketone body (+++) in urine. Treatments such as fluid replacement, electrolyte correction, and acid-base balance, and insulin therapy were given. Ten hours later, the blood gas analysis showed pH 7.44, PaCO 2 32 mmHg, alkali residual -2.5 mmol/L, actual bicarbonate 21.7 mmol/L, anion gap 12 mmol/L, blood glucose was 6.7 mmol/L, and routine urine test showed ketone body (++) in urine. The patient′s symptoms were gradually improved on the 4th day after the operation and then metformin, acarbose, and insulin injection were given for blood glucose management. It was considered that the patient had ketoacidosis, which might be associated with dapagliflozin. Then the hypoglycemic regimen was adjusted to oral metformin 0.85 g twice daily, acarbose 50 mg twice daily, and glimepiride 2 mg twice daily on the 15th day after operation. After that, the fasting blood glucose in the patient was maintained at 8.2-10.6 mmol/L, the postprandial blood glucose was maintained at 8.2-13.1 mmol/L, and the glycosylated hemoglobin was 7.3%. The patient′s ketoacidosis did not recur.

A 43-year-old male patient with type 2 diabetes mellitus underwent off-pump coronary artery bypass grafting due to coronary atherosclerotic heart disease. Dapagliflozin was stopped 24 hours before the operation, fasting and discontinuing oral medication started at 8: 00 pm 1 day before the operation. On the day of surgery, blood gas analysis and blood glucose were normal before undergoing cardiopulmonary bypass. Tracheal intubation was successfully removed 7 hours after operation. Blood glucose and anion gap were 11.2 mmol/L and 13 mmol/L, respectively on the 2nd day after operation. The treatments of hypoglycemic, antihypertensive and lipid-regulating drugs and normal diet were restored. On the morning of the 3rd day after operation, the patient developed symptoms such as shallow rapid breathing, poor appetite, excessive urine, and irritability. Blood gas analysis showed pH 7.05, arterial partial pressure of carbon dioxide (PaCO 2) 11 mmHg, base excess -24.5 mmol/L, actual bicarbonate 21.7 mmol/L; blood glucose 10.4 mmol/L, potassium 5.3 mmol/L, and routine urine test showed ketone body (+++) in urine. Treatments such as fluid replacement, electrolyte correction, and acid-base balance, and insulin therapy were given. Ten hours later, the blood gas analysis showed pH 7.44, PaCO 2 32 mmHg, alkali residual -2.5 mmol/L, actual bicarbonate 21.7 mmol/L, anion gap 12 mmol/L, blood glucose was 6.7 mmol/L, and routine urine test showed ketone body (++) in urine. The patient′s symptoms were gradually improved on the 4th day after the operation and then metformin, acarbose, and insulin injection were given for blood glucose management. It was considered that the patient had ketoacidosis, which might be associated with dapagliflozin. Then the hypoglycemic regimen was adjusted to oral metformin 0.85 g twice daily, acarbose 50 mg twice daily, and glimepiride 2 mg twice daily on the 15th day after operation. After that, the fasting blood glucose in the patient was maintained at 8.2-10.6 mmol/L, the postprandial blood glucose was maintained at 8.2-13.1 mmol/L, and the glycosylated hemoglobin was 7.3%. The patient′s ketoacidosis did not recur.

Humans ; Mitochondria/genetics* ; Mutation/genetics* ; Parkinson Disease/genetics* ; Protein Kinases ; Ubiquitin-Protein Ligases

Humans ; Locomotion ; Mesencephalon ; Midbrain Reticular Formation ; Parkinson Disease