Driven by the growing practical need to accelerate drug development and the continuous innovation of trial design in recent years， the number of protocol amendments during clinical trials have gradually increased， and the changed contents have become more flexible and complex， which significantly heightens the difficulty of ethical review on amendments. Against this backdrop， it is of great importance to fully leverage the role and responsibilities of ethics committees， effectively control clinical trial risks， and ensure subject safety. This paper analyzed development trends of protocol amendments in recent years， sorted out requirements for protocol amendments in Chinese regulations and guiding principles， and examined difficulties of amendment ethical review in practical work. Based on these， targeted strategies and recommendations were proposed， namely， strengthening the integration with scientific review， enhancing the formal review， adjusting the scope of review according to approval notifications， and adopting appropriate review methods， with a view to providing insights and references for the management of the amendment ethical review in drug clinical trials.

OBJECTIVE To investigate the reversal effect of Qingfei huayu jiedu formula （QFHYJDF） on drug resistance in non-small cell lung cancer （NSCLC） cells based on the microRNA-641 （miR-641）/extracellular signal-regulated kinase （ERK） signaling pathway. METHODS The human parental NSCLC cell line A549 was used to establish gefitinib-resistant cells A549/GR by combining concentration gradient increment with high-concentration pulse strategy. After screening for optimal intervention concentration and duration， the resistant cells were divided into a control serum group （treated with 20% blank serum for 48 h）， QFHYJDF-containing serum group （treated with 20% QFHYJDF-containing serum for 48 h）， and the normally cultured group （normally cultured for 48 h）. The cell relative viability， total apoptosis rate， as well as the expression levels of miR-641， neurofibromin 1 （NF1）， ERK1/2， and phosphorylated ERK1/2 （p-ERK1/2）， were assessed in each group. RESULTS Compared with the normally cultured group and the control serum group， the QFHYJDF-containing serum group exhibited significantly decreased cell relative viability and significantly increased total apoptosis rate （ P ＜0.05）. Moreover， the expression of NF1 protein was significantly up-regulated， while the expression levels of miR-641 and p-ERK1， p-ERK2 proteins were significantly down-regulated in the QFHYJDF-containing serum group （ P ＜0.05）. CONCLUSIONS QFHYJDF can inhibit proliferation and promote apoptosis of gefitinib-resistant lung cancer cells， which may be associated with up-regulating NF1 protein expression， down-regulating miR-641 expression， and inhibiting the activity of the ERK signaling pathway.

Objective:To obtain a polyvalent single-chain variable fragment（scFv）against West Nile virus through PEGylation in order to improve its antigen-binding ability and neutralizing activity.Methods:A scFv carrying a C-terminal cysteine residue（scFvC）was constructed by introducing Cys into the C-terminal of scFv against West Nile virus. Then the multimerization of scFvC was achieved by targeting the thiol group of Cys with maleimide-activated polyethylene glycol. ELISA was used to detect the antigen-binding activity of the multivalent scFvC. Pseudovirus-based neutralization assay was used to evaluate the neutralizing activity of the multivalent scFvC in vitro. One-way analysis of variance was used for statistical analysis. Results:The PEGylated scFvC multimers showed higher antigen-binding ability than the monomeric scFvC. In the pseudovirus-based neutralization assay，both monomeric scFvC and PEGylated scFvC multimers showed good neutralizing activity compared with the control group（ P<0.000 1）. Moreover，the PEGylated scFvC multimers showed a more effective ability to block the pseudovirus infection in target cells（ P<0.05），suggesting that the PEGylated scFvC multimers could enhance their function in vitro through avidity effect. Conclusion:In this study，a scFvC targeting West Nile virus is successfully constructed and its polyvalent form is generated through PEGylation，which improves the antigen-binding and neutralizing activity of the parental scFv.

Objective:To obtain a polyvalent single-chain variable fragment（scFv）against West Nile virus through PEGylation in order to improve its antigen-binding ability and neutralizing activity.Methods:A scFv carrying a C-terminal cysteine residue（scFvC）was constructed by introducing Cys into the C-terminal of scFv against West Nile virus. Then the multimerization of scFvC was achieved by targeting the thiol group of Cys with maleimide-activated polyethylene glycol. ELISA was used to detect the antigen-binding activity of the multivalent scFvC. Pseudovirus-based neutralization assay was used to evaluate the neutralizing activity of the multivalent scFvC in vitro. One-way analysis of variance was used for statistical analysis. Results:The PEGylated scFvC multimers showed higher antigen-binding ability than the monomeric scFvC. In the pseudovirus-based neutralization assay，both monomeric scFvC and PEGylated scFvC multimers showed good neutralizing activity compared with the control group（ P<0.000 1）. Moreover，the PEGylated scFvC multimers showed a more effective ability to block the pseudovirus infection in target cells（ P<0.05），suggesting that the PEGylated scFvC multimers could enhance their function in vitro through avidity effect. Conclusion:In this study，a scFvC targeting West Nile virus is successfully constructed and its polyvalent form is generated through PEGylation，which improves the antigen-binding and neutralizing activity of the parental scFv.

【Objective】 To analyze the overall situation and main influencing factors of adverse reactions of blood donation of apheresis platelet donors in China by systematic review, and to provide basis for preventing and controlling adverse reactions of platelet donation and improving the quality of blood donation service. 【Methods】 CNKI, VIP, Wanfang Data, Pubmed and Embase databases were searched to collect cross-section studies on adverse reactions of platelet donation in China. The observation period was ≥6 months, and the retrieval time was from 1998 to March 2023. The studies were independently screened by 2 evaluators according to the inclusion and exclusion criteria. Data extraction and literature quality evaluation were carried out, and meta analysis was performed by Stata 14.0 software. 【Results】 A total of 91 literature involving 585 769 apheresis platelet donors were included, and 9 102 of them had adverse reactions. Random effect model meta-analysis showed that the total incidence of adverse reactions of platelet donation was 2.65% [95% CI(2.04, 3.45), P<0.000 1]. Subgroup analysis showed that the incidence of platelet donation adverse reactions in the eastern, central and western regions were 2.63% [95% CI(1.94, 3.58)], 2.32% [95% CI(1.29, 4.16)] and 4.10% [95% CI(1.90, 8.83)], respectively, with regional differences (P<0. 000 1). The incidence of adverse reactions of different degrees was 3.62% [95% CI (2.69, 4.86)] for non-severe and 0.28% [95% CI(0.18, 0.45)] for severe. The incidence of adverse reactions of blood donation was also different among different apheresis instruments (P<0. 000 1): Amicus 2.73% [95% CI(1.23, 6.06)], CS3000 series 3.59% [95% CI(2.64, 4.89)], MCS+ series 3.42% [95% CI(2.23, 5.25)], Trima 4.86% [95% CI(3.08, 7.66)], other groups 1.71% [95%CI (0.15, 20.02)]. In addition, the incidence of adverse reactions was 4.80% [95% CI(3.05, 7.55)] in females and 1.39% [95% CI(0.90, 2.15)] in males, with the incidence in females higher than that in males (P<0.000 1). The adverse reactions of platelet donors under 30 years old and over 30 years old were 2.31% [95% CI(1.34, 3.98)] and 1.95% [95% CI(1.19, 3.20)], respectively, and there was no statistically significant difference (P>0.01). The incidence of adverse reactions of blood donation for first-time donors and repeat donors was 2.16% [(95%CI (1.18, 3.95)] and 1.12% [(95% CI(0.35, 3.58)], with the former higher than the latter(P<0.000 1). The incidence of adverse reactions for single and double platelet collection was 1.67% [95% CI(0.57, 4.89)] and 3.13% [95% CI(1.11, 8.86)] respectively, with no significant difference(P>0.01). 【Conclusion】 It′s suggested to unify the monitoring standards of adverse reactions of apheresis platelet donation, understand and master the factors that affect the adverse reactions of apheresis platelet donors, so as to improve the quality of apheresis platelet donation service and ensure the safety of donations.

OBJECTIVE To systematically review the efficacy and safety of ticagrelor versus clopidogrel in CYP2C19 loss-of-function carriers with mild ischemic stroke or transient ischemic attack(TIA). METHODS Databases such as PubMed, Embase, the Cochrane Library, CNKI, and Wanfang were systematically searched, and the search period was from database establishment to June 2022. Two reviewers independently screened literature, extracted data, and evaluated the methodological quality of the included studies. Meta-analysis was performed using RevMan 5.3 software. RESULTS A total of 2 studies with 7 087 patients were included. Compared with clopidogrel, ticagrelor reduced the incidence of stroke[RR=0.78, 95%CI(0.66−0.93), I2=0%, P=0.007] and vascular event[RR=0.78, 95%CI(0.66−0.91), I2=0%, P=0.002] in patients with mild ischemic stroke or TIA carrying the CYP2C19 loss-of-function allele. The incidence of any bleeding[HR=2.18, 95%CI(1.66−2.85)] and minor bleeding[HR=2.41, 95%CI (1.81−3.20)] in the ticagrelor-aspirin group was higher than that in the clopidogrel-aspirin group, and dyspnea (1.2% vs 0.2%, P<0.001) and arrhythmias(1.7% vs 0.8%, P=0.001) were more common in the ticagrelor-aspirin group than in the clopidogrel-aspirin group. There was no significant difference in the incidence of severe bleeding between the two groups. CONCLUSION Compared with clopidogrel, ticagrelor reduces the incidence of stroke and vascular events in patients with mild ischemic stroke or TIA carrying the CYP2C19 loss-of-function allele, and did not increase the risk of severe bleeding. However, the ticagrelor group had a higher incidence of minor bleeding, dyspnea and arrhythmias.

Objective:To evaluate the efficacy and safety of Qingxuan Zhike granules in improving cough symptoms and shortening the course of influenza (wind-heat invading lung) in children.Methods:In this multicenter, randomized, controlled clinical trial, a total of 240 outpatient influenza patients from 7 hospitals, including the First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, from April 2023 to December 2023 were collected.The subjects were randomly divided into the control group and the experimental group via SAS software using the block randomization method.The differences between two groups were compared with t test, corrected t test and χ2 test.Subjects in the control group were given Oseltamivir phosphate granules, orally, twice a day (weight ≤15 kg, 30 mg/time; weight >15-23 kg, 45 mg/time; weight >23-40 kg, 60 mg/time; weight >40 kg, 75 mg/time; age≥13 years, 75 mg/time).In addition to Oseltamivir phosphate granules, subjects in the experimental group were also given Qingxuan Zhike granules, orally, 3 times a day (1-3 years old, 1/2 bag each time; >3-6 years old, 3/4 bag each time; >6-14 years old, 1 bag each time).After 5 days of treatment, the medication was suspended for 2 days.The effect of cough, antipyretic effect, clinical recovery rate, clinical recovery time, Canadian Acute Respiratory Illness and Flu Scale (CARIFS) score, traditional Chinese medicine (TCM) syndrome effect, complication rate, and adverse reactions were evaluated between the two groups. Results:Finally, 232 cases were included in the study, including 115 cases in the experimental group and 117 cases in the control group.Before and after treatment, there were no significant difference in CARIFS cough score between the experimental group and the control group (all P>0.05).After treatment, the change in CARIFS cough score in the experimental group [(-1.00±0.91) scores]was significantly higher than that in the control group [(-0.75±0.98) scores] ( t=-1.995, P=0.047).After treatment, the change in TCM syndrome cough score in the experimental group [(-1.69±1.51) scores] was significantly higher than that in the control group [(-0.97±1.63) scores] ( t′=-0.035, P=0.001).The time of complete regression of fever in the experimental group [(44.82±22.72) h] was shorter than that in the control group [(51.35±27.07) h], and the difference between the two groups was statistically significant ( t=-1.966, P=0.050).The fever score showed that the area under the curve between the CARIFS symptom fever score and time in the experimental group was 4.40±2.42, while that in the control group was 5.12±2.44, and the difference between the two groups was statistically significant ( t=-2.252, P=0.025).The clinical recovery rate was 93.91%(108/115) in the experimental group and 92.31%(108/117) in the control group, and there was no significant difference between the two groups ( χ2=0.233, P>0.05).The clinical recovery time in the experimental group [(2.93±1.21) d] was shorter than that in the control group [(3.29±1.15) d], and the difference between the two groups was statistically significant ( t=-2.279, P=0.024).After treatment, there was a significant difference in TCM syndrome score variation between the experimental group [(-12.00±4.13) scores] and the control group [(-10.85±4.31) scores] ( t′=-2.067, P=0.040).No complication occurred in both groups, and there was no significant difference in the incidence of adverse events between the two groups ( χ2=1.299, P>0.05). Conclusions:Qingxuan Zhike granules combined with Oseltamivir phosphate can effectively improve the cough symptoms associated with influenza in children, shorten the time and course of fever, and improve the TCM syndrome score; thus, they are safe in clinical application.

Abstract Blood donation institutions mainly rely on manual identification for pre-donation health screening of blood donors. To further ensure the safety of blood donation and minimize the participation of unqualified donors, Ningbo Central Blood Station developed and launched a pre-blood donation health screening software as a supplement to the manual identification in May 2023. The software establishes preset rules based on the conditions of donors who are ineligible or temporarily ineligible to donate blood in Whole Blood and Component Donor Selection Requirements (GB 18467-2011), retrieves the health records of blood donors from the Ningbo National Health Information System and compares with the preset rules. When a preset rule is triggered, the medical examiner receives a warning. The pre-donation health screening software effectively enhances the capabilities of blood donation institutions in identifying unqualified donors. It is conducive to promoting the standardization of the pre-donation health screening process, the intelligence of blood donation services and blood management, and the establishment of a more scientific and efficient pre-donation health screening procedure.

In recent years,with the gradual maturity of achievable remote collection of digital health technology,more and more clinical research have applied this technology to improve the quality of data collection and reduce the burden on subjects.However,its technological characteristics of detachment from the diagnostic and treatment environment and real-time transmission of sensitive information also pose corresponding risks to the protection of subjects'rights and interests and data standardization management,among which personal information protection and data control permissions are more prominent issues.Based on risk analysis and regulatory review,this paper explored the responsibilities of multiple parties,including the sponsors,researchers,clinical trial institutions,and ethics committee,as well as proposed five elements of special concern for ethical review,with a view to providing a reference for promoting the standardized development of digital health technology in clinical research.

Objective:To examine the treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations.Methods:This is a retrospective case series study. Clinic data from 24 children with tracheal stenosis who underwent surgical treatment in the Department of Cardiac Surgery, Children′s Hospital Affiliated to Shandong University from February 2017 to March 2023 were retrospectively collected. There were 16 males and 8 females, aged ( M(IQR)) 6.5 (19.6) months (range: 2.2 to 66.3 months) and weighted 5.95 (4.76) kg (range: 3.2 to 20.0 kg). All patients had obvious respiratory symptoms. Eighteen patients underwent cardiac malformation correction and tracheoplasty at the same time (simultaneous group). Six patients in the staged operation group were treated with cardiac malformation correction in the first stage operation and tracheoplasty in the second stage operation due to missed diagnosis or delayed diagnosis of tracheal stenosis or no condition for tracheoplasty. Slide tracheoplasty was used to correct tracheal stenosis in both groups. The recovery of the children was followed. Wilcoxon sign rank test was used for comparison between the two groups. Results:There was no death during the perioperative period and hospitalization. In the simultaneous group, 1 case with delayed chest closure underwent bedside chest closure after 52 hours, 2 cases were intubated again after operation, and 1 case was implanted with an endotracheal stent. The duration of mechanical ventilation was 40.5 (39.6) hours (range: 19.0 to 438.8 hours). In the staged group, there was 1 case of re-intubation after operation, combined with left vocal cord paralysis and respiratory multidrug-resistant bacterial infection ( Acinetobacter baumanii). One patient underwent 3 times of bronchoscopic balloon dilatation of the right middle bronchus, and heart rate returned to normal range. The duration of mechanical ventilation was 19.0 (21.4) hours (range: 17.1 to 96.7 hours). During follow-up, a patient in the simultaneous group was prone to respiratory infection and had good exercise tolerance, 1 case in the staged group still had sputum stridor in the throat 3 months after the operation, and symptoms improved significantly 6 months after the operation. The other children didn′t have obvious respiratory symptoms. Conclusions:The diagnosis of tracheal stenosis may be delayed or missed when tracheal stenosis is complicated by non-vascular ring cardiac malformations. One-stage correction of tracheal stenosis and cardiac malformation can achieve a good outcome.