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.

In recent years,in order to meet urgent clinical needs alleviate the shortage of rare disease drugs in China,a series of policies encouraging the research and development of rare disease drugs has been introduced.Enzyme replacement therapy(ERT)is a standard treatment for rare congenital metabolic disorders,especially for enzyme deficiency diseases.Due to the complexity and heterogeneity of drug molecules for rare enzyme replacement therapy,the evaluation of animal models is a major challenge in non-clinical development and evaluation.This article introduces the latest research progress in the development of rare enzyme replacement therapy drugs at home and abroad,put forward some thoughts and suggestions on the non-clinical evaluation(pharmacology,pharmacokinetics,and toxicology)of such products based on representative literature,combined with review practice.

Objective:To investigate the prognostic value of early serum lactate, albumin, and lactate/albumin ratio (L/A) on the 28-day prognosis of adult patients with sepsis.Methods:A retrospective cohort study was conducted among adult patients with sepsis admitted to the First Affiliated Hospital of Xinjiang Medical University from January to December in 2020. Gender, age, comorbidities, lactate within 24 hours of admission, albumin, L/A, interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) and 28-day prognosis were recorded. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of lactate, albumin and L/A for 28-day mortality in patients with sepsis. Subgroup analysis of patients was performed according to the best cut-off value, Kaplan-Meier survival curves were drawn, and the 28-day cumulative survival of patients with sepsis was analyzed.Results:A total of 274 patients with sepsis were included, and 122 patients died at 28 days, with a 28-day mortality of 44.53%. Compared with the survival group, the age, the proportion of pulmonary infection, the proportion of shock, lactate, L/A and IL-6 in the death group were significantly increased, and albumin was significantly decreased [age (years): 65 (51, 79) vs. 57 (48, 73), pulmonary infection: 75.4% vs. 53.3%, shock: 37.7% vs. 15.1%, lactate (mmol/L): 4.76 (2.95, 9.23) vs. 2.21 (1.44, 3.19), L/A: 0.18 (0.10, 0.35) vs. 0.08 (0.05, 0.11), IL-6 (ng/L): 337.00 (97.73, 2 318.50) vs. 55.88 (25.26, 150.65), albumin (g/L): 27.68 (21.02, 33.03) vs. 29.62 (25.25, 34.23), all P < 0.05]. The area under the ROC curve (AUC) and 95% confidence interval (95% CI) of lactate, albumin, and L/A were 0.794 (95% CI was 0.741-0.840), 0.589 (95% CI was 0.528-0.647), 0.807 (95% CI was 0.755-0.852) for predicting 28-day mortality in sepsis patients. The optimal diagnostic cut-off value of lactate was 4.07 mmol/L, the sensitivity was 57.38%, the specificity was 92.76%. The optimal diagnostic cut-off value of albumin was 22.28 g/L, the sensitivity was 31.15%, the specificity was 92.76%. The optimal diagnostic cut-off of L/A was 0.16, the sensitivity was 54.92%, and the specificity was 95.39%. Subgroup analysis showed that the 28-day mortality of sepsis patients in the L/A > 0.16 group was significantly higher than that in the L/A ≤ 0.16 group [90.5% (67/74) vs. 27.5% (55/200), P < 0.001]. The 28-day mortality of sepsis patients in the albumin ≤ 22.28 g/L group was significantly higher than that in the albumin > 22.28 g/L group [77.6% (38/49) vs. 37.3% (84/225), P < 0.001]. The 28-day mortality in the group with lactate > 4.07 mmol/L was significantly higher than that in the group with lactate ≤ 4.07 mmol/L [86.4% (70/81) vs. 26.9% (52/193), P < 0.001]. The three were consistent with the analysis results of Kaplan-Meier survival curve. Conclusion:The early serum lactate, albumin, and L/A were all valuable in predicting the 28-day prognosis of patients with sepsis, and L/A was better than lactate and albumin.

Objective:To explore the expression and importance of Piezo1, E-cadherin, and Vimentin in nasal polyps patients. Methods:Thirty-five patients undergoing endoscopic sinus surgery under general anesthesia were streamed into 20 cases of nasal polyps（NP group） and 15 cases of simple septoplasty without any sinus disease（Control group）. Immunofluorescence staining and Western Blot were applied to detect the protein level of Piezo1, E-cadherin, and Vimentin in NP tissues and nasal polyp-derived primary human nasal epithelial cells（pHNECs）. Also, BEAS-2B cell lines were treated with human TGF-β1 protein to establish epithelial mesenchymal transition（EMT） model in vitro and quantitative real-time polymerase chain reaction were used to calculate Piezo1 and above biomarkers in the model. Results:Compared with control group, Piezo1 and Vimentin showed higher level while E-cadherin was lower in NP tissues and pHNECs.In EMT model in vitro, Piezo1 and Vimentin were demonstrated higher expression with decreased level of E-cadherin. Conclusion:The tendency of Piezo1 is consistent with the mesenchymal-related biomarker Vimentin, going against with epithelial-related biomarker E-cadherin, implying its involvement with EMT process in nasal polyps.
Humans ; Biomarkers/metabolism* ; Cadherins/metabolism* ; Chronic Disease ; Epithelial-Mesenchymal Transition ; Nasal Polyps/metabolism* ; Rhinosinusitis ; Sinusitis ; Transforming Growth Factor beta1/metabolism* ; Vimentin/metabolism*

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

OBJECTIVE To study the mechanism of Compound zaoren granule in improving insomnia. METHODS Forty-nine mice were divided into blank group， model group， positive control group 1 （Estazolam tablets 0.5 mg/kg），control group 2 （Shumian capsule 0.6 g/kg）， Compound zaoren granule low-dose， medium-dose and high-dose groups （2.5， 5， 10 g/kg）， with 7 mice in each group. The insomnia model was established by chronic unpredictable mild stress combined with 4-chloro-DL- phenylacetic acid. The behavioral changes of mice were investigated through open field test and pentobarbital sodium synergistic hypnosis experiment， as well as the pathomorphology of mice hypothalamus tissue was observed by HE staining. The metabonomics analysis and multivariate statistical analysis of serum in mice were performed by UHPLC-Q-TOF-MS/MS， and the differential metabolites were screened out； the metabolic pathway analysis was conducted based on MetaboAnalyst 5.0 database. RESULTS Compared with blank group， the total travelling distance， the number of entering the central region and the moving distance in the central region of the model group were significantly reduced （P＜0.05）， the proportion of total rest time was significantly increased （P＜0.05）， the sleep duration of mice was significantly shortened （P＜0.05）， and hypothalamic nerve cells damaged and severely vacuolated. Compared with model group， the total travelling distance of Compound zaoren granule low-dose and medium-dose groups were increased significantly and the proportions of total rest time of those groups were decreased significantly （P＜0.05）， and the sleep duration of mice in Compound zaoren granule high-dose group was prolonged significantly （P＜0.05）； the hypothalamic nerve cells of mice in each administration group recovered to varying degrees， and the hypothalamus histiocytes of mice in the Compound zaoren granules high-dose group were closer to those in the blank group. A total of 18 differential metabolites （such as phenylalanine， taurine， norvaline， methionine） and 4 important amino acid metabolic pathways （L-phenylalanine， tyrosine and tryptophan biosynthesis； taurine and hypotaurine metabolism； L-phenylalanine metabolism； cysteine and methionine metabolism） were identified through metabolomics analysis. CONCLUSIONS Compound zaoren granules can normalize the disordered metabolism in vivo by regulating differential metabolites such as phenylalanine， taurine， and four amino acid metabolic pathways， so as to improve insomnia.

OBJECTIVE To explore the mechanism of Kuaisong yin in the prevention and treatment of constipation. METHODS Slow transit constipation （STC） model was established with Compound difenoxylate tablet in mice and rats. Two batches of mice were divided into blank group， model group， positive control group （Maren soft capsule， 0.64 g/kg）， Kuaisong yin low-dose， medium-dose and high-dose groups （3.2， 6.4， 12.8 g/kg）， with 10 mice in each group. The effect of Kuaisong yin on constipation in mice was evaluated by intestinal propulsion experiment and defecation experiment. Rats were divided into blank group， model group， positive control group （Maren soft capsule，0.36 g/kg）， Kuaisong yin low-dose and high-dose groups （2.4， 4.8 g/kg）， with 7 or 8 rats in each group. They were given relevant medicine once a day for 1 week. The metabonomics of serum and urine of rats were analyzed by UPLC-Q-TOF-MS/MS technology. RESULTS Compared with model group， the ink propulsion rate and 5 h defecation volume of mice in Kuaisong yin high-dose group were significantly increased （P＜0.05）； the first defecation time of mice in Kuaisong yin medium-dose and high-dose groups was significantly shortened， and the quality of defecation was significantly reduced within 5 h （P＜0.05 or P＜0.01）. Serum metabonomics screened 16 compounds （such as proline， propionylcarnitine， hemolytic phosphatidylcholine， etc.） and 6 metabolic pathways （such as sphingomyelin metabolism， arginine and proline metabolism， sphingolipid biosynthesis-lactose and neolactone series）. Urine metabonomics screened 20 different metabolites （such as prostaglandin A2， L-valine， phosphatidylcholine， sphingomyelin， etc.） and 8 metabolic pathways （such as valine， leucine and isoleucine biosynthesis， sphingomyelin metabolism， pyruvate metabolism， etc.）. CONCLUSIONS Kuaisong yin can play a role in improving constipation by regulating different metabolites such as hemolytic phosphatidylcholine， phosphatidylcholine， prostaglandin A2， L-valine， proline， and regulating metabolic pathways such as multiple amino acid metabolism， sphingomyelin metabolism， etc.

Objective:To describe the epidemiological features and temporal trends of colorectal cancer in urban Shanghai from 1973 to 2017. Methods:Data on colorectal cancer in urban Shanghai was obtained through Shanghai Cancer Registry and Vital Statistics System.Joinpoint analysis was used to describe the temporal trends and annual percent change(APC)and age-period-cohort analysis was used to estimate the association between age,period and birth cohort and colorectal cancer. Results:A total of 105 847 cases and 60 447 deaths of colorectal cancer were diagnosed in urban Shanghai over the 45-year study period.Both the number of new cases and the number of deaths showed an increasing trend.In the same period,the age-standardized incidence of colorectal cancer in urban areas of Shanghai increased significantly from 14.1/100 000 in 1973 to 27.7/100 000 in 2017,while the age-standardized mortality rate increased from 8.2/100 000 to 10.7/100 000.The overall average annual age-standardized incidence and mortality rates were 20.4/100 000 and 11.0/100 000,respectively.With the increase of age,the age-standardized morbidity and mortality of colorectal cancer showed an obvious upward trend.Taking 1993-1997 as reference,the risk of colorectal cancer in Shanghai reached the highest in 2013-2017,and the corresponding relative risk was 1.2(95％confidence interval:1.2-1.3),while the lowest was 0.9(95％confidence interval:0.8-1.0)during 1973-1977.Mortality risk,on the contrary,decreased with the increase of time.Before 1953-1957,the risk of colorectal cancer in urban Shanghai increased with the increase of birth cohort time,and then showed a downward trend.There was a corresponding decline in the risk of colorectal cancer death among people born after 1957. Conclusion:The incidence and mortality of colorectal cancer in Shanghai showed an increasing trend from 1973 to 2017,but the prevalence trend of colorectal cancer is still different among different populations.

Objective:To investigate the application value of standardized outcomes in nephrology hemodialysis (SONG-HD) scale in evaluating the fatigue level of patients undergoing maintenance hemodialysis (MHD) patients and the factors that affect fatigue.Methods:A total of 201 patients undergoing regular MHD who received treatment in the Department of Nephrology, The First Affiliated Hospital of Xiamen University in April 2021 were included in April, 2021. The SONG-HD scale was used to evaluate patient's fatigue level. Fatigue was assessed using face-to-face interview questionnaire. Clinical and laboratory indicators were analyzed. Univariate logistic regression analysis and multivariate logistic regression analysis were performed to analyze the factors that affect fatigue of patients undergoing MHD.Results:Among the 201 MHD patients, 73.1% (147/201) had fatigue. The high-sensitivity C-reactive protein and parathyroid hormone levels in patients with fatigue were 0.91 (0.30, 3.63) mg/L and 216.00 (141.00, 347.00) ng/L, respectively, which were significantly higher than 0.40 (0.30, 2.01) mg/L and 153.00 (96.73, 308.50) ng/L in patients who had no fatigue ( Z = 2.12, 2.17, both P < 0.05). The pre-dialysis carbon dioxide binding capacity and blood albumin levels in patients who had fatigue were (21.03 ± 2.65) mmol/L and (36.76 ± 3.20) g/L, respectively, which were significantly lower than (22.68 ± 3.01) mmol/L and (38.61 ± 2.85) g/L in patients who had no fatigue ( t = 3.77, 3.73, both P < 0.05). Univariate logistic regression analysis showed that high-sensitivity C-reactive protein, pre-dialysis carbon dioxide binding capacity, serum albumin level, and parathyroid hormone level were related to the occurrence of fatigue in patients undergoing MHD ( Wald = 4.32, 12.39, 12.23, 4.66, all P < 0.05). Additionally, in a multivariate model adjusted for confounding factors, the independent risk factors for fatigue in patients undergoing MHD were relatively low pre-dialysis carbon dioxide binding capacity and serum albumin level ( Wald = 12.41, 11.67, both P < 0.05). Conclusion:The incidence of fatigue is high in patients undergoing MHD. The SONG-HD scale is convenient to use in assessing the fatigue level of patients undergoing MHD. After adjusting for confounding factors, fatigue in patients undergoing MHD is associated with reduced levels of pre-dialysis carbon dioxide binding capacity and serum albumin.

Objective:To correlate peripheral blood neutrophil-to-lymphocyte ratio with the occurrence of restless legs syndrome (RLS) in patients undergoing maintenance hemodialysis (MHD).Methods:This is a cross-sectional study. A total of 203 patients who underwent long-term MHD at the Blood Purification Center, Department of Nephrology, The First Affiliated Hospital of Xiamen University from May to June 2021 were included in this study. The counts of peripheral blood neutrophils and lymphocytes were determined and the neutrophil-to-lymphocyte ratio was calculated. These patients were divided into a RLS group and a non-RLS group according to whether they developed RLS. RLS-related factors were evaluated using face-to-face interview questionnaires. Various clinical and laboratory parameters were analyzed. The influential factors of RLS in patients undergoing MHD were analyzed through univariate regression analysis and multivariate logistic regression analysis.Results:A total of 203 patients undergoing MHD were enrolled, 30 individuals were determined as current RLS cases (14.78%). The levels of NLR and PTH in the RLS group were 4.86 (3.39, 5.82) L/L and 244.50 (143.25, 406.50) ng/L, respectively, which were significantly higher than those in the normal group [3.51 (2.60, 5.24) L/L, 147.00 (94.80, 263.50) ng/L, Z = -3.38, -2.64, both P < 0.05]. Univariate logistic regression analysis showed that NLR, PTH, uric acid, and neutrophil count were correlated with RLS (Wald χ2 = 7.96, 4.99, 4.76, 8.33, all P < 0.05). NLR was the independent risk factor of RLS (Wald χ2 = 6.14, P < 0.05) in multivariate models adjusting for confounding factor. Conclusion:The prevalence of RLS is high in patients undergoing MHD. RLS is assicuated with NLR among patients undergoing MHD after adjusting for confounding factor. RLS is likely associated with systemic inflammatory diseases.