Malignant lymphoma (ML) is a heterogeneous malignant tumor in the hematological system, the existing treatment methods can not meet the clinical needs, and the rapid rise of new treatment schemes has improved the survival benefits of patients with recurrent or refractory ML. Antibody-drug conjugate (ADC), as a new type of highly effective anti-tumor drug composed of monoclonal antibodies specifically targeting tumor cell surface antigens, coupled with small molecular cytotoxic loads through chemical connectors, has attracted much attention in the application prospect of malignant lymphoma. Several ADCs have been approved for the treatment of ML, including brentuximab vedotin, inotuzumab ozogamicin, moxetumomab pasudotox, polatuzumab vedotinands, loncastuximab tesirine, etc. These drugs can exert anti-tumor effects by targeting CD30, CD22, CD79b, CD19, etc. on the surface of tumor cells with good efficacy and safety.

Alzheimer’s disease (AD) is a progressive degenerative disease of the central nervous system. Lecanemab is a humanized IgG1 monoclonal antibody that preferentially targets soluble amyloid β-protein aggregates and can slow down the progression of AD. In January 2023, the U.S. Food and Drug Administration approved lecanemab to treat AD patients with mild cognitive impairment or mild dementia stage of disease. The common adverse drug reactions of lecanemab were infusion-related reactions, headache, and amyloid-related imaging abnormalities with edema. The mechanism of action, pharmacokinetics, clinical research, economic evaluation, and safety evaluation of lecanemab were reviewed in this article, so as to provide reference for rational clinical drug use.

To explore the daily regulatory strategies of regulatory authorities after the implement of filing system of drug clinical trial institutions. From the perspective of administrative law, this article analyzes the differences between the qualification recognition and filing management of drug clinical trial institutions, as well as the characteristics of filing management, and explore the adjustments and response measures for regulatory authorities of drug clinical trial institutions under the current filing system through practice. The filing system simplifies the time limit for drug clinical trial institutions to obtain qualifications, refines the admission standards for drug clinical trial institutions, highlights the qualification requirements and main responsibilities of institutions and researchers, and puts forward higher requirements for post-supervision. The update of regulatory requirements and the increase in regulatory quantity require regulatory authorities to strictly inspect standards, transform law enforcement concepts, innovate regulatory methods, strengthen risk control, and continuously improve regulatory levels, thereby to help China build high-quality drug clinical trial institutions.

To accelerate the development and market launch of new drugs that address unmet clinical needs, the European Medicines Agency (EMA) launched the “priority medicines (PRIME)” scheme in 2016. A range of supportive measures have been provided to drugs granted this qualification at various stages of development, including the appointment of dedicated personnel from EMA to assist applicants, multiple opportunities for applicants to engage in dialogue with regulatory authorities at key developmental stages, assistance in formulating or adjusting drug development plans and regulatory strategies, and facilitating the transition from drug development to market authorization review, thereby expediting the approval process for drug market applications. As of the first half of 2021, EMA had received a total of 384 PRIME qualification applications, of which 95 were approved, covering 19 therapeutic areas including antineoplastic medications, hematological medications, neurological medications, etc. It is suggested that relevant departments in China may draw on the practices of EMA to strengthen the construction in project management, management of communication and exchange meetings, utilization of review resources, and quality management of the review process, in order to improve the system for breakthrough therapeutic drugs in China.

AIM To evaluate the anesthetic effect of esketamine combined with remimazolam in elderly patients undergoing gastroenteroscopy, as well as the influence on oxygen desaturation saturation and hemodynamics. METHODS A total of 160 elderly patients scheduled to undergo gastroenteroscopy in our hospital from September 2021 to October 2023 were included, and randomly equally divided into remimazolam group (R group) or esketamine combined remimazolam group (E+R group). Both two groups received intravenous injection of sufentanil 0.1 μg·kg^-1 and remimazolam 0.2 mg·kg^-1 for anesthesia induction. The E+R group additionally was given intravenous esketamine 0.25 mg·kg^-1. The primary outcomes during the examination include occurrence of desaturation and hypotension. Secondary outcomes include hemodynamic parameters during the examination, rescue sedation, time to loss of consciousness, time to recovery of consciousness, and PACU stay time. The MAP and HR are recorded at different time points: before anesthesia induction (T₀), immediately after anesthesia induction (T₁), immediately after the placement of gastroscopy (T₂), immediately after the placement of colonoscopy (T₃), and immediately after the surgery (T₄). The PACU outcome include nausea/vomiting, dizziness/headache, delayed awakening, emergence agitation, and patient satisfaction scores. RESULTS There were 78 and 80 patients included eventually in the E+R group and the R group, respectively. The rates of deoxygenation saturation, hypotension and remedial sedation ≥2 times in the E+R group were significantly lower than those in the R group (P<0.05). The loss time of consciousness, recovery time of consciousness and PACU residence time in the E+R group were significantly shorter than those in the R group (P<0.05). MAP and HR of T₁-T₃ time points in the E+R group were significantly higher than those in the R group (P<0.05). The MAP and HR of T₂ and T₃ were significantly higher than those of T₁ in the R group (P<0.05), but there was no significant difference between MAP and HR of T₂ or T₃ and those of T₁ in the E+R group (P>0.05). There were no significant differences in PACU nausea and vomiting, dizziness/headache, delayed recovery, emergence agitation and satisfaction scores between the two groups (P>0.05). CONCLUSION Compared with remimazolam, esketamine combined with remimazolam can shorten the recovery time, reduce the incidence of desaturation and hypotension in elderly patients undergoing gastroenteroscopy, and contribute to maintain hemodynamic stability without increasing adverse reactions during recovery.

AIM To analyze the effects of different doses of ciprofol on general anesthesia induction in elderly patients, and the influence on hemodynamics during general anesthesia induction. METHODS One hundred and twenty elderly patients undergoing elective surgery were randomly included in ciprofol 0.2 mg·kg^-1 group (C_0.2 group), ciprofol 0.3 mg·kg^-1 group (C_0.3 group) and ciprofol 0.4 mg·kg^-1 group (C_0.4 group), with 40 cases in each group. The corresponding dose of ciprofol was injected intravenously according to the group, and the injection time was 30 s. And all patients induced by rocuronium 0.6 mg·kg^-1 and sufentanil 0.5 μg·kg^-1 were injected intravenously, followed by ciprofol 0.8-2.4 mg·kg^-1·h^-1, remifentanil 8-15 μg·kg^-1·h^-1 was injected intravenously and 1% sevoflurane was inhaled for anesthesia maintenance. The bispectral index (BIS) was maintained 40~60 during the operation. The mean arterial pressure (MAP), heart rate (HR) and BIS of the patients were monitored, the success rate of anesthesia induction, the number of cases of remedial sedation and the time of loss of consciousness were recorded, and the occurrence of adverse reactions were observed. RESULTS The MAP, HR and BIS of the three groups immediately after anesthesia induction (T₁), 10 s after tracheal intubation (T₂) and 3 min after tracheal intubation (T₃) were significantly lower than those of the same group at the time of entering the operating room (P<0.05), and the MAP and HR of T₁-T₃ in the C_0.4 group were significantly lower than those in the C_0.2 group and C_0.3 groups (P<0.05). There were no significant differences in MAP and HR of T₁-T₃ between the C_0.3 group and C_0.2 group (P>0.05). There were no significant differences in the success rate of anesthesia induction among the three groups (P>0.05). The rate of remedial sedation in the C_0.2 group was significantly higher than that in the C_0.3 group and C_0.4 group (P<0.05), and the time of consciousness loss was significantly longer than that in the C_0.3 group and C_0.4 group (P<0.05). There was no significant difference in rate of remedial sedation and consciousness loss time between the C_0.3 group and C_0.4 group (P>0.05). The incidence of hypotension and bradycardia in the C_0.4 group was significantly higher than that in the C_0.2 group and C_0.3 group (P<0.05), but there was no significant difference in the incidence of hypotension and bradycardia between the C_0.3 group and C_0.2 group (P>0.05). CONCLUSION Ciprofol 0.3 mg·kg^-1 has good safety and efficacy for general anesthesia induction in elderly patients.

AIM To explore the clinical efficacy of Jia Wei Jingui Shengqi Pill (JWJSP) as a novel prophylaxis regimen for haemorrhagic cystitis (HC) in patients undergoing haploidentical hematopoietic stem cell transplantation. METHODS A prospective cohort analysis was conducted on 65 patients with hematological malignancies who underwent haploidentical hematopoietic stem cell transplantation from January 2020 to October 2023. Patients were divided into a JWJSP group (31 cases) and a control group (34 cases). The JWJSP group was administered JWJSP 5 g orally twice daily, while the control group received no specific prophylactic measures. The cumulative incidence of HC, clinical characteristics, and the positive rate of viruria in both groups were compared. The median follow-up duration was 277 (65, 624) days. RESULTS The cumulative incidence of HC in the JWJSP group was (29±3) %, significantly lower than that in the control group (53±3) % (P<0.01). There was no significant difference in the median onset time and duration of HC between the two groups (P>0.05). The median onset time of HC in the two groups of patients was 26 (20, 32) days and 37 (25, 45) days after transplantation, respectively, and the median duration was 13 (10, 24) days and 16 (14, 53) days, respectively, with no significant difference (P>0.05). The positive rate of BKV viruria in the JWJSP group after transplantation was 42%, significantly lower than that in the control group (68%) (P<0.05). CONCLUSION Prophylaxis with JWJSP may decrease the infection rate of BKV in urine and the overall incidence of HC in patients undergoing haploidentical hematopoietic stem cell transplantation.

AIM To explore the risk factors of drug-induced liver injury (DILI) of compound sulfamethoxazole (sulfamethoxazole-trimethoprim, SMZ-TMP) in acquired immunodeficiency syndrome (AIDS) patients and provide reference for clinical pharmacovigilance and rational drug use. METHODS The data of AIDS patients treated with SMZ-TMP in our hospital from December 2020 to December 2022 were collected retrospectively. The general information of patients with DILI after taking SMZ-TMP was compared with that of patients without DILI, and binary logistic regression equation was constructed to screen out the risk factors of DILI in AIDS patients induced by SMZ-TMP. RESULTS Totally 271 AIDS patients were involved, and 29 patients had DILI, all of whom were male. Among them, 27 patients were of hepatocellular injury pattern and 2 patients were of cholestatic injury pattern. All DILI patients were cured or improved after symptomatic treatment. Relevant factor analysis showed that, allergy history (OR=15.334，95%CI: 3.147 to 74.710), no receiving antiviral treatment or tenofovir+lamivudine+lopinavir/ritonavir (TDF+3TC+LPV/r) regimen (OR=56.123, 95% CI: 10.797 to 291.719), daily dose of SMZ-TMP ≥ 12 tablets (OR=52.809, 95% CI: 9.894 to 281.868), alanine transaminase (ALT) ≥ 23 U·L^-1 (OR=18.514, 95% CI: 3.993 to 85.843), CD4⁺ T cell ≤110·µL^-1 (OR=40.586，95%CI：6.625 to 248.634), and CD8⁺ T cell ≤ 920·µL^-1 (OR=135.978，95%CI：11.190 to 1 652.303) can increase the risk of SMZ-TMP related DILI in AIDS patients (P<0.05). CONCLUSION The incidence of SMZ-TMP related DILI is relatively high in AIDS patients. Allergy history, selection of antiviral treatment regimens, dose of SMZ-TMP, ALT level, and CD4⁺ and CD8⁺ T lymphocyte counts are the independent risk factors for SMZ-TMP related DILI in AIDS patients. Monitoring of high-risk population should be strengthened and early intervention measures should be taken.

AIM To investigate the efficacy of combined use of sodium oligomannate on psychological and behavioral symptoms in patients with mild to moderate Alzheimer’s disease (AD). METHODS Mild to moderate AD patients with behavioral and psychological symptoms of dementia (BPSD) who visited the outpatient department and inpatient department of our hospital from January 2021 to June 2022 were randomly divided into two groups. The control group was orally administered with donepezil at an initial dose of 5 mg·d^-1, which increased to 10 mg·d^-1 after 4 weeks. On the basis of taking donepezil, the study group combined the use of sodium oligomannate, 450 mg each time, twice a day. The two groups were all treated for 8 weeks. The mini-mental state examination (MMSE) and neuropsychiatric inventory (NPI) were assessed and compared between the two groups at baseline and after 4 and 8 weeks of treatment. The general linear model was used to analyze the effect of combined use of sodium oligomannate on the improvement of NPI scores after the 8-week treatment. RESULTS Finally, 60 patients completed the clinical study, with 30 in each group. The total score of NPI in two groups was significantly decreased compared with baseline after 4 weeks and 8 weeks of treatment (P<0.05), and the decrease was more significant in the study group with significant difference between groups (P<0.05). Compared with the baseline, the scores of apathy, depression, anxiety, and irritability in the study group were significantly decreased at the end of 4 weeks (P<0.05), and agitation and delusion scores were also significantly decreased at the end of 8 weeks (P<0.05). Compared with the control group, the study group showed a more significant decrease in depression, anxiety, agitation, irritability, and appetite scores compared to baseline after 4 weeks of treatment (P<0.05), and a more significant decrease in emotional apathy score after 8 weeks of treatment (P<0.05). The MMSE scores of the two groups were significantly higher than those of the baseline at the end of 4 and 8 weeks (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). CONCLUSION Combined use of sodium oligomannate can not only improve the cognitive function of AD patients, but also improve their BPSD, especially emotional problems such as anxiety, depression, agitation, and irritability, without obvious adverse reactions.

AIM To evaluate the effectiveness, safety and economy of lorlatinib in anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients, and provide evidence for clinical treatment. METHODS Databases such as PubMed, Cochrane Library, CNKI, Wanfang Data, and VIP and Health Technology Assessment (HTA) related websites were searched to collect HTA reports, systematic evaluation/meta-analysis and pharmacoeconomic evaluation of loratinib for ALK positive NSCLC. Select the literature according to the inclusion and exclusion criteria, extract the data, and evaluate the literature quality. Qualitative description was performed. RESULTS A total of 16 literatures were included, involving 11 systematic review/meta-analysis and 5 pharmacoeconomic evaluation. In terms of effectiveness，compared with other ALK-tyrosine kinase inhibitors (TKIs) and chemotherapy as first-line treatment, lorlatinib significantly prolonged the progression free survival (PFS) in ALK positive NSCLC patients. Compared with chemotherapy as a second- or third-line treatment, lorlatinib significantly prolonged PFS and overall survival. In terms of safety, there was no statistical difference among the ALK-TKIs and chemotherapy in the incidence of adverse events (AEs) of grade≥3, but the incidence of lorlatinib was relatively high. In regards to the serious AEs and AEs leading to treatment discontinuation, lorlatinib was the lowest. In terms of economy, lorlatinib was not cost-effectiveness compared to ensartinib and crizotinib in China, but lorlatinib was cost-effectiveness compared to chemotherapy as a second- or third-line treatment in Greece and Sweden. CONCLUSION Lorlatinib shows good efficacy and safety for ALK positive NSCLC, but its cost-effectiveness after price reduction in China needs further evaluation.