Innovative biologics are the most powerful tools for preventing and treating infectious diseases. During the containment of major public health emergencies, ensuring the production and supply of clinically urgent medications through post-approval changes carries dual requirements of compliance and urgency. This study was conducted from the perspective of enhancing prevention and control of public health emergencies. The needs and difficulties of emergency changes were analyzed, with a focus on how marketing authorization holders can efficiently carry out emergency changes to expand production capacity and accelerate release testing. Based on the analysis, relevant recommendations were proposed, such as conducting pre-research on changes, building “dual-use for routine and emergency” capabilities, implementing graded and categorized management, optimizing registration testing, and promoting the rapid microbiological methods and AI.

Gene therapy products may accidentally leak or shed during clinical use, thereby integrating the genetic material they carry into other non-patient populations or plants and animals, with adverse effects on ecosystems and human health. In order to reduce the environmental risks of gene therapy products, the United States and the European Union have formulated relevant laws and regulations and issued special guidelines, which stipulate the environmental risk assessment conduct, review and specific steps in the clinical trials and marketing registration of gene therapy products. At present, there are no specific regulations on the environmental risks of gene therapy products in China, it is suggested that China can learn from the relevant practices of the Europe and the USA, establishing gene therapy products environmental risk supervision laws and regulations system, and clarify the specific steps of environmental risk assessment; harmonizing the regulatory agencies and review procedures for gene therapy products registration and environmental risk assessment; establishing a scientific and reasonable basis for consideration of gene therapy products environmental risk assessment and take different regulatory measures according to the level of environmental risk of the product.

N6-methyladenosine（m6A） methylation is involved in the whole process of mRNA biological behavior and plays an important role in the malignant progression of cancer. This article reviewed the invasion and metastasis of m6A methylation in hepatocellular carcinoma （HCC）, its regulation with non-coding RNA, and the effect of immunotherapy. It is very important to find that m6A methylated regulatory proteins are involved in the development and prognosis of HCC.m6A methylation is closely related to the regulation of non-coding RNA on the proliferation, metastasis and drug resistance of HCC. In terms of immunotherapy, circRHBDD1 and BTBD10 participate in m6A methylation modification to regulate cell metabolism and inhibit the immune escape of cancer cells, which can be used for the HCC diagnosis and innovative drug discovery in the future.

Migraine is a recurrent neurological disorder recognized by the World Health Organization as the second leading cause of disability. Currently, most available pharmacological interventions for migraine prevention and treatment are either non-specific or associated with contraindications and serious adverse reactions. Recent research has focused on calcitonin gene-related peptide （CGRP）, which plays a pivotal role in the pathophysiological mechanisms underlying migraine. Targeted CGRP pathway inhibitors have been developed, including CGRP receptor antagonists （gepants） and anti-CGRP monoclonal antibodies. Current studies indicate that these agents demonstrate favorable safety profiles, efficacy,and tolerability. This paper reviewed relevant clinical trials and research findings of targeting the CGRP pathway, aiming to provide a foundation for future selection of domestic migraine therapeutics.

Alzheimer’s disease （AD） is a slowly progressive degenerative disease of the central nervous system, and its incidence, prevalence and mortality are increasing year by year. At present, there is no cure for AD, mainly sympotomatic treatment with drugs, including cholinesterase inhibitors and megaline, but these drugs can only relieve clinical symptoms,but can not stop or reverse the development of AD. Aducanumab and lecanemab are targeted drugs developed for amyloid β-protein （Aβ） plaques in the brain in recent years, but they have not been fully popularized, and the safety and effectiveness of drugs need to be further verified. Sodium oligomannate is an innovative drug developed in China for the treatment of mild to moderate AD patients. It mainly improves cognitive function by regulating gut microbiota-brain axis. Other possible mechanisms include reducing brain Aβ deposition and tau protein phosphorylation, activating intestinal endocrine cell-vagus afferent pathway, inhibiting intracranial neuritidine, etc. With the clinical application of sodium oligomannate, more evidence shows that sodium oligomannate can not only improve the cognitive function of AD patients, but also have certain effects on the behavioral and psychiatric symptoms and daily living ability of patients. Combined treatment with other drugs may improve the clinical efficacy and reduce adverse reactions.

AIM To observe the efficacy and safety of bendamustine combined with chemotherapy for relapsed and refractory multiple myeloma（RRMM）. METHODS A retrospective analysis was conducted on 32 RRMM patients treated with bendamustine combined with chemotherapy in the Department of Hematology and Oncology, Shijingshan Campus of Beijing Chaoyang Hospital, Capital Medical University from August 2019 to September 2022. The efficacy, adverse reactions and survival conditions were observed. RESULTS Thirty-two patients completed 3（1, 8） treatment courses. The overall response rate（ORR） was 38%（11/29） for 29 patients who completed ≥2 treatment courses, and the ORR was 73%（11/15）for 15 patients who completed≥4 treatment courses. The ORR was 26%（5/19） for 19 patients with extramedullary diseases,and the disease control rate was 53% （10/19）. The estimated median progression-free survival was 11 months, and the estimated median overall survival was 25 months for the 32 RRMM patients. Sixteen patients experienced adverse reactions of decreased white blood cell count with the grade from 1 to 3. CONCLUSION Bendamustine combined with chemotherapy has the advantages of good therapeutic response and good tolerance in the treatment of RRMM, and can be used as one of the treatment options for RRMM patients, especially for those with extramedullary diseases.

AIM To evaluate the efficacy and safety of oxycodone in acute heart failure （AHF）. METHODS In this prospective randomized controlled trial, 50 AHF patients admitted to the ICU between January 2022 and December 2023 were allocated to morphine group （n=25） or oxycodone group （n=25） using random number table, received intravenous injection of 5 mg morphine or oxycodone based non-invasive ventilation, respectively. Effectiveness outcomes （comfort score,NT-proBNP, oxygenation index （OI）, ICU length of stay, non-invasive ventilation duration, and hospitalization outcomes）and safety parameters （mean arterial pressure （MAP）, heart rate （HR）, respiratory rate （RR）, minute ventilation （MV）,intubation rate, and respiratory depression） were assessed at baseline （T₀）, 10 min （T₁）, 20 min （T₂）, 30 min （T₃）,and 24 h （T₄） post-treatment in the two groups. RESULTS Both groups showed significant reduction in comfort scores at T₃ and increased OI at T₄ compared with those of T₀ （P<0.01）, and the oxycodone group demonstrated significantly lower NT-proBNP at T₄ （P<0.05）, with no significant differences between the two groups（P>0.05）. No between-group differences were observed in ICU stay or ventilation duration. MAP decreased transiently in both groups: the morphine group maintained lower MAP in T₁-T₃ than T₀（P<0.05）, whereas the oxycodone group only showed reductions at T₁ and T₂ （P<0.05）,with significantly higher MAP than the morphine group during T₁-T₃ （P<0.05）. HR exhibited biphasic changes while RR and MV progressively declined. The morphine group showed sustained RR reduction in T₁-T₃ than T₀（P<0.05）, and the oxycodone group showed reduction at T₂ and T₃ （P<0.05）. Neither group required intubation or developed respiratory depression. CONCLUSION Oxycodone demonstrates favorable hemodynamic stability and potential prognostic benefits in AHF management, suggesting its promise as a novel therapeutic option.

AIM To explore the effect of Ginkgo biloba diterpene lactone glucamine injection on inflammation and oxidative indicators and proteins related to the phosphatidylinositol 3-kinase （PI3K）/serine-threonine protein kinase（Akt） signaling pathway in the blood of patients with post-stroke epilepsy. METHODS A total of 150 patients with post-stroke epilepsy in our hospital form May 2021 to April 2023 were randomly divided into two groups, each containing 75 cases. The control group was given sodium valproate for 3 months, and on this basis, the observation group was given Ginkgo biloba diterpene lactone glucamine injection for 2 weeks. The clinical efficacy and adverse reactions of the two groups were compared, as well as seizure number, duration, serum interleukin-1β （IL-1β）, matrix metalloproteinase-9 （MMP-9）,superoxide dismutase （SOD）, tumor necrosis factor-alpha （TNF-α）, glutathione peroxidase （GSH-Px）, malondialdehyde（MDA）, and protein expression related to PI3K/Akt signaling pathway before and after the treatment. RESULTS The total clinical effective rate of the observation group was 92%, which was higher than 72% of the control group （P<0.05）. After 3 months of treatment, the number of seizures and seizure duration in the observation group were less than those in the control group （P<0.05）. After 2 weeks and 3 months of treatment, the levels of IL-1β, MMP-9, MDA, TNF-α, and the expression of PI3K and Akt proteins in the observation group were lower than those in the control group, while the activities of SOD and GSH-Px were higher than those in the control group （P<0.05）. There was no significant difference in the incidence of adverse reactions between the two groups （P>0.05）. CONCLUSION Ginkgo biloba diterpene lactone glucamine injection can reduce the inflammatory level and oxidative stress response in patients with epilepsy after stroke, and regulate the PI3K/Akt signaling pathway, thereby effectively controlling seizures, with significant effects.

AIM To evaluate the effectiveness, safety and economy of mepolizumab so as to provide evidence-based references for selection and clinical rational usage of drugs. METHODS Chinese and English literature and clinical trials were systematically retrieved, including health technology assessment （HTA） reports, systematic reviews/meta-analysis and pharmacoeconomic studies on mepolizumab versus placebo or other drugs for eosinophilic asthma. The literature was screened according to inclusion and exclusion criteria, the quality of the literature and extract data were evaluated,and a summary analysis was conducted. RESULTS A total of 1 HTA report, 11 systematic reviews/meta-analyses and 4 pharmacoeconomic studies were included. The results showed that mepolizumab had the same efficacy and safety as other IL-5/IL-4 and IgE antagonism, with no difference in safety compared to placebo. Meanwhile, it could significantly reduce asthma exacerbation and eosinophil counts in sputum or blood, significantly reduce the use of oral glucocorticoids and rescue drugs, improve lung function to a certain extent, and subsequently control asthma symptoms, and improve patients’ quality of life. However, it did not meet the minimum of clinical significant improvement. In terms of economy, due to the current price,the conclusions on economics were not consistent. CONCLUSION Mepolizumab in the treatment of eosinophilic asthma has the same efficacy, safety and economy as other monoclonal antibodies, but due to the current price, it does not have a clear economic advantage over standard treatment. As a result, further economic research on the Chinese population needs to be carried out.

AIM To analyze the potential adverse drug interactions （pADIs） of non-vitamin K antagonist oral anticoagulants （NOAC）, and to promote rational drug use. METHODS Outpatient prescriptions of using NOAC in combination with other drugs were surveyed from January 1, 2024 to May 31, 2024 through the information system of the third people's hospital of Bengbu, and pADIs were identified and their severities were graded. Refined prescription pre-review rules were developed by rational drug software. RESULTS Among 1 153 NOAC combined prescriptions, 406 prescriptions had 511 cases of pADIs, including 180 cases of dabigatran etexilate, 288 cases of rivaroxaban and 43 cases of apixaban.The combined drugs involved antiepileptic, antiplatelet, Chinese medicines containing salvia/ginseng/ginkgo biloba and antiarrhythmic drugs. Rivaroxaban + phenobarbital severity classification was contraindicated. Refined rules included 1 interception rule and 10 alert information + double-signature rules and 8 attention information rules. CONCLUSION There are pADIs between NOAC and other drugs in the hospital. The medication risks can be prevented through targeted intervention based on evidence-based refined prescription pre-review rules.

AIM To evaluate the cost-effectiveness of insulin degludec-liraglutide（iDegLira） versus insulin glargine-lixisenatide （iGlarLixi） in Chinese adult type 2 diabetes mellitus （T2DM） patients. METHODS From the perspective of China’s health system, a Markov model was developed. Quality-adjusted life years （QALY） were used as the health output indicator, and three times 2023 gross domestic product （GDP） per capita of China was used as the willingness-to-pay （WTP） threshold. The model simulates the health output and medical costs over 30 years, evaluates the economics of the two treatment options using the incremental cost-effectiveness ratio （ICER） as an evaluation metric, and performs sensitivity and contextual analyses to test the uncertainty of the results. RESULTS Compared with the iGlarLixi scheme,iDegLira scheme had an incremental cost of 46 142.61 yuan, an incremental utility of 0.014 QALY. The ICER was 3 258 162.70 yuan·QALY^-1, which was much larger than the WTP threshold （268 074 yuan·QALY^-1） and was not cost-effectiveness. The results of the sensitivity analysis show that the underlying analysis was relatively robust. The results of the contextual analysis showed that the cost-effectiveness of the two schemes was comparable when the price was reduced by 31% at the current WTP threshold. CONCLUSION For Chinese adult T2DM patients with poor glycemic control despite receiving basal insulin in combination with oral hypoglycemic agents, iDegLira scheme has a lower probability of being economical at current prices compared with the iGlarLixi scheme.

AIM To analyze the clinical characteristics and influencing factors of dextromethorphan-induced 5-hydroxytryptamine syndrome （5-HTS）. METHODS Relevant cases of dextromethorphan-induced 5-HTS in PubMed,Embase, Cochrane Library, CINAHL, PsycINFO, CNKI, WanFang database, SinoMed, and VIP database were retrieved,and clinical data were summarized and analyzed. RESULTS A total of 16 cases of 5-HTS were collected, including 11 males and 5 females. Dextromethorphan could cause 5-HTS at both normal and excessive doses, and the majority （88%）of patients were co-administered with other 5-hydroxytryptamine drugs. The onset of 5-HTS occurred between 4 hours and 6 weeks after dextromethorphan administration, with symptoms including myoclonus, tachycardia, and fever. After discontinuation of dextromethorphan and other serotonergic drugs, along with supportive therapy, all patients improved.The mean duration of 5-HTS was 26 hours. Patients treated with cyproheptadine had a shorter duration of 5-HTS, averaging 21.6 hours. CONCLUSION Dextromethorphan-induced 5-HTS most often occurs when used in combination with other serotonergic drugs. It is recommended to strengthen management to reduce the abuse of dextromethorphan and unnecessary co-administration, as well as to improve the ability of physicians and pharmacists to recognize and monitor 5-HTS.