Artificial intelligence (AI) has emerged as a transformative force in healthcare, with applications spanning diagnostics to drug development. However, its integration into drug regulation remains nascent, with varying degrees of adoption and implementation across different regulatory bodies worldwide. This review aims to provide a comprehensive overview of the current state of AI in drug regulation, encapsulating AI-related policies, initiatives, and its practical application in regulatory agencies globally. It further discusses the challenges and future prospects of AI in this field. The findings reveal that numerous agencies have launched action plans and initiatives to incorporate AI, aiming to streamline regulatory processes and enhance data-driven regulatory decision-making. Moreover, AI's deployment in safety surveillance, workflow optimization, and regulatory science research is expanding, highlighting its increasing impact on drug regulation. Nonetheless, key challenges persist, such as data quality and reliability, technical limitations, talent shortage and the absence of standards. The review concludes that interdisciplinary collaboration is crucial to harness AI's full potential in drug regulation and overcoming its current limitations. In the future, AI may become a pivotal catalyst in drug regulation, promising a new era of enhanced scrutiny, efficiency, and innovation that will benefit public health on a global scale.

Rare diseases are a collective term for diseases with extremely low prevalence and incidence rates.Up to now,China has released two lists identifying a total of 207 rare diseases.Given that most rare diseases do not have drugs with corresponding indications,physicians frequently resort to using off-label drugs when treating patients with rare diseases.However,there is currently no systematic guideline or expert consensus for the use of off-label medications in China.To comprehensively collect existing evidence of off-label drug use for rare diseases,fully analyze and evaluate the rationality of off-label drug use for rare diseases,and standardize the management of off-label drug use for rare diseases,the Rare Disease Branch of Beijing Medical Association,Chinese Pharmaceutical Association,Beijing Pharmaceutical Association,and the School of Public Health,Peking University have jointly initiated the drafting of the Expert Consensus on Off-label Use of Drugs for Rare Diseases.This consensus refer to the WHO Handbook for Guideline Development,the Guidelines for Developing/Revising Clinical Diagnostic and Treatment Guidelines in China(2022 Edition),the AGREE Ⅱ and the STAR tools.This protocol outlines the background and purpose of consensus,as well as the comprehensive framework for consensus development,encompassing panel formation,clinical issue identification,evidence retrieval,data extraction,and evidence-based recommendation formulation.

Rare diseases are a collective term for diseases with extremely low prevalence and incidence rates.Up to now,China has released two lists identifying a total of 207 rare diseases.Given that most rare diseases do not have drugs with corresponding indications,physicians frequently resort to using off-label drugs when treating patients with rare diseases.However,there is currently no systematic guideline or expert consensus for the use of off-label medications in China.To comprehensively collect existing evidence of off-label drug use for rare diseases,fully analyze and evaluate the rationality of off-label drug use for rare diseases,and standardize the management of off-label drug use for rare diseases,the Rare Disease Branch of Beijing Medical Association,Chinese Pharmaceutical Association,Beijing Pharmaceutical Association,and the School of Public Health,Peking University have jointly initiated the drafting of the Expert Consensus on Off-label Use of Drugs for Rare Diseases.This consensus refer to the WHO Handbook for Guideline Development,the Guidelines for Developing/Revising Clinical Diagnostic and Treatment Guidelines in China(2022 Edition),the AGREE Ⅱ and the STAR tools.This protocol outlines the background and purpose of consensus,as well as the comprehensive framework for consensus development,encompassing panel formation,clinical issue identification,evidence retrieval,data extraction,and evidence-based recommendation formulation.

AIM:To evaluate the bioequivalence of the two rivaroxaban tablets in Chinese healthy subjects.METHODS:Twenty-eight subjects under fasting status and twenty-eight subjects under fed status were enrolled in the study.This study was designed as a four period,fully repetitive,cross-over study.All subjects were administered test(T)and reference(R)rivaroxaban tablets(10 mg)un-der fasting and fed condition respectively.Liquid chromatography-tandem mass spectrometry was used to detect the concentrations of rivaroxaban in plasma.WinNonlin 7.0 was used to calculate the main pharmacokinetic parameters(PK)and to eval-uate the bioequivalence.RESULTS:In fasting group,the main pharmacokinetic parameters of T and R preparation were as follows:Cmax were(186.57±56.41)and(187.61±50.89)ng/mL;AUC0-t were(1 156.21±335.85)and(1 177.59±343.72)h·ng·mL-1;AUC0-∞ were(1 235.77±384.03)and(1223.53±392.10)ng·h·mL-1.The 90％confidential interval(CI)of the three main parameters were 90.81％-105.67％,92.83％-103.85％and 95.04％-107.13％.The upper limit of the 90％CI for the test-to-reference ratio of the within-subject of Cmax,AUC0-t and AUC0-∞ were 1.56,1.41 and 1.73.In fed group,the main pharmacokinetic parameters of T and R preparation were as follows:Cmax were(207.81±45.26)and(211.04±36.62)ng/mL;AUC0-t were(1 271.26±260.92)and(1 233.23±201.85)h·ng·mL-1;AUC0-∞ were(1 290.76±264.90)and(1251.68±203.73)ng·h·mL-1.The 90％CI of the three main parameters were 92.82％-102.28％,97.68％-106.68％and 97.71％-106.68％.The upper limit of the 90％CI for the test-to-reference ratio of the within-subject of Cmax,AUC0t and AUC0-∞were 1.76,1.47 and 1.47.CONCLUSION:The two preparations of rivaroxaban tablets were bioequiva-lent.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

AIM:To evaluate the bioequivalence of the two rivaroxaban tablets in Chinese healthy subjects.METHODS:Twenty-eight subjects under fasting status and twenty-eight subjects under fed status were enrolled in the study.This study was designed as a four period,fully repetitive,cross-over study.All subjects were administered test(T)and reference(R)rivaroxaban tablets(10 mg)un-der fasting and fed condition respectively.Liquid chromatography-tandem mass spectrometry was used to detect the concentrations of rivaroxaban in plasma.WinNonlin 7.0 was used to calculate the main pharmacokinetic parameters(PK)and to eval-uate the bioequivalence.RESULTS:In fasting group,the main pharmacokinetic parameters of T and R preparation were as follows:Cmax were(186.57±56.41)and(187.61±50.89)ng/mL;AUC0-t were(1 156.21±335.85)and(1 177.59±343.72)h·ng·mL-1;AUC0-∞ were(1 235.77±384.03)and(1223.53±392.10)ng·h·mL-1.The 90％confidential interval(CI)of the three main parameters were 90.81％-105.67％,92.83％-103.85％and 95.04％-107.13％.The upper limit of the 90％CI for the test-to-reference ratio of the within-subject of Cmax,AUC0-t and AUC0-∞ were 1.56,1.41 and 1.73.In fed group,the main pharmacokinetic parameters of T and R preparation were as follows:Cmax were(207.81±45.26)and(211.04±36.62)ng/mL;AUC0-t were(1 271.26±260.92)and(1 233.23±201.85)h·ng·mL-1;AUC0-∞ were(1 290.76±264.90)and(1251.68±203.73)ng·h·mL-1.The 90％CI of the three main parameters were 92.82％-102.28％,97.68％-106.68％and 97.71％-106.68％.The upper limit of the 90％CI for the test-to-reference ratio of the within-subject of Cmax,AUC0t and AUC0-∞were 1.76,1.47 and 1.47.CONCLUSION:The two preparations of rivaroxaban tablets were bioequiva-lent.

AIM: To evaluate the risk of drug-related dysphagia in elder people based on the FDA Adverse Event Reporting System (FAERS). METHODS: We collected the reports of dysphagia in elder people (Age≥65) from 2004 quarter 1 through 2022 quarter 2 of FAERS by Open Vigil 2.1 database. The reported odds ratio (ROR) and the proportional reported ratio (PRR) were calculated to detect the adverse reaction signal of drug-induced dysphagia in elder people. Signal generation standard of ROR: number of reports≥3 with the lower limit of 95% confidence interval (CI) of the ROR value>1, PRR≥2 and c

Objective:To investigate the diagnostic value of ultrasound contrast agent enema (UCAE) for anastomotic leakage (AL) after rectal cancer surgery.Methods:From January 2020 to December 2022, a total of 95 patients with presacral fluid collection after rectal cancer surgery in the Sixth Affiliated Hospital of Sun Yat-sen University who received perineal ultrasound (PNUS) and UCAE were retrospectively selected. Among them, 70 patients (73.3%) were diagnosed with AL.After PNUS scanning, all patients received a diluted ultrasound contrast agent administered through the rectum. Receiver operating characteristic (ROC) curve were used to compare the accuracies of PNUS, UCAE, CT, MRI and water-soluble contrast enema in the diagnosis of AL. Factors that may have impacts on the sensitivity of UCAE were thoroughly analyzed.Results:UCAE improved the consistency (Kappa value: 0.757 vs 0.292, P<0.001) and accuracy (AUC: 0.893 vs 0.693, P<0.001) of PNUS in the diagnosis of AL, and its diagnostic accuracy was comparable to that of CT (AUC 0.807), MRI (AUC 0.811) and water-soluble contrast enema (AUC 0.923) (all P>0.05). For mid-to-high AL (anastomotic stoma distance ≥70 mm) and tiny AL (≤3 mm), the sensitivity of UCAE decreased significantly (anastomotic stoma position: 25.0% vs 85.5%, P=0.001; anastomotic leak diameter: 42.9% vs 87.5%, P=0.002). Conclusions:UCAE can significantly improve the diagnostic accuracy and consistency of PNUS for AL after rectal cancer surgery, and its diagnostic sensitivity is affected by the anastomotic stoma distance and the diameter of the leak.

Objective:To evaluate the efficacy of high-flow nasal cannula (HFNC) oxygen therapy in optimizing painless transesophageal echocardiography in elderly patients.Methods:Sixty American Society of Anesthesiologists Physical Status classification Ⅱ patients, regardless of gender, aged 60-75 yr, with body mass index of 18.5-23.9 kg/m 2, were randomized into 2 groups ( n=30 each) by a random number table method: group HFNC and conventional ventilation group (group C). Pure oxygen 10 L/min was inhaled for 3 min preoxygenation using the HFNC device in group HFNC. Group C inhaled pure oxygen at 6 L/min for 3 min preoxygenation via a nasal cannula. Sufentanil 0.1 μg/kg and remazolam 0.25-0.30 mg/kg were intravenously injected in turn. Group HFNC was connected to a high-flow humidification oxygen therapy device and inhaled pure oxygen at 60 L/min (37℃, FiO 2 100%). The flow rate of pure oxygen was maintained at 6 L/min (FiO 2 100 %) in group C. The patients were placed in left lateral decubitus position, esophageal ultrasound was performed after the eyelash reflex disappeared, and remazolam 0.1 mg/kg was intravenously injected intermittently when bucking and body movement were induced by operation stimulation. The occurrence of hypoxia-related adverse events, mandibular intervention and ventilation-related adverse events was observed during examination. The operation time, time of emergence from anesthesia and consumption of remazolam were recorded. Results:Compared with group C, the incidence of severe hypoxia and rate of mandibular intervention were significantly decreased (7%/0 and 53%/17%, P<0.05), the lowest intraoperative SpO 2 was increased ( P<0.05), and no significant change was found in the operation time, time of emergence from anesthesia and consumption of remazolam in group HFNC ( P>0.05). No ventilation-related adverse events occurred in both groups. Conclusions:HFNC can markedly optimize the ventilation management of elderly patients undergoing painless transesophageal echocardiography.

Objective:To investigate the clinical and electrophysiological characteristics of facial onset sensory motor neuronopathy (FOSMN) syndrome.Methods:Ten patients diagnosed with FOSMN syndrome in Peking Union Medical College Hospital from January 2012 to December 2022 were included. The clinical and electrophysiological characteristics of patients were analyzed and summarized, and the genetic testing was also performed in these patients.Results:The age of onset was (56.6±6.5) years, and the longest survival duration of disease was 10 years. All patients had numbness around the face and mouth as the first symptom and abnormal blink reflex. A total of 52 sensory nerve conduction nerves were detected, among which 2 median nerves and 2 μlnar nerves showed decreased amplitude of sensory nerve action potential. Needle electromyography showed neurogenic lesions, with both progressive and chronic denervation. Whole exome sequencing identified the heterozygous variant c.272A>C in the exon 4 of the SOD1 gene resulting in the amino acid change p.Asp90Ala in 1 patient. In all patients, the disease progressed relentlessly and eventually led to involvement of respiratory muscle. Conclusion:FOSMN syndrome is characterized by abnormal blink reflex and sometimes abnormal sensory nerve conduction may be shown on electrophysiologic testing.