ObjectiveTo sort out the pre-ethical review status of drug clinical trials in a tertiary A hospital， summarize practical experience， and provide references for pre-ethical review. MethodA retrospective analysis was conducted on the ethical review of pre-ethical projects in a tertiary A hospital from 2018 to 2023. ResultsFrom 2018 to 2023， a total of 285 pre-ethical projects were reviewed in this tertiary hospital， including 79 projects where it served as the leading unit. Among these， 279 clinical trials ultimately received approval of the ethical review committee， while 6 projects were not approved due to sponsors’ refusal to modify study protocols. In terms of trial phases， phase III clinical trials constituted the largest proportion， and the oncology center was the department with the highest number of projects. In 2023， the average time for pre-ethical review projects from submission to approval was 43 calendar days， 3 days longer than for other project types. In 2023， this hospital reviewed 75 pre-ethical review projects， including 58 where it served as a participating unit. Among these， 42 projects received approval later than the leading unit， while 9 projects were approved earlier than the leading unit’s ethical approval date. Among the pre-ethical review projects applied in 2023， 70 projects obtained drug clinical trial notifications from the National Medical Products Administration， while 5 projects had unknown notification status due to the lack of ethical approval or discontinuation. Of the projects receiving approval notifications， 16 were annotated with matters requiring enhanced attention during clinical trials， and 7 necessitated protocol improvements. ConclusionThis tertiary A hospital has implemented multiple measures to optimize the management of pre-ethical review. This ethical review model does not compromise the quality of ethical review and contributes to accelerating the initiation of clinical trials. Notably， it is crucial to construct a patient-centered drug development system. Clinical trials guided by this concept align with ethical values， laying the foundation for the smooth conduct of clinical trials， assisting in the drug development process， and safeguarding patients’ medication needs.

Background Co-exposure to noise and microwave radiation occurs frequently. The central nervous system has been identified as a sensitive target organ for both noise and microwave exposure individually, and the underlying mechanisms remain poorly understood. The specific biological effects resulting from co-exposure to these two factors have yet to be fully elucidated. Objective To clarify the effects of co-exposure to noise and microwave on neurobehavior and hippocampal tissue structure, and to explore the underlying mechanism through the assessment of serum cytokines. Methods C57BL/6N mice were selected and randomly assigned to a blank control group, a noise group, a microwave group, and a combined noise & microwave exposure group. To establish the exposure models, the noise group was subjected to broadband noise at 100 dB for 2 h, while the microwave group received radiation at a central frequency of 9.375 GHz with an average power density of 12 mW·cm⁻² and a specific absorption rate of 2.58 W·kg⁻¹ for 15 min. Open field and tail suspension tests assessed anxiety-like emotional behaviour; novel object recognition and Y-maze tests evaluated cognitive function. Histological changes in hippocampal tissue were examined using haematoxylin and eosin (HE) staining, and Nissl staining under light microscopy. Serum cytokine levels were measured using radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). Results After 3 d of exposure, the noise, microwave, and combined exposure groups showed significant reductions in exploration frequency, duration, and distance within the central zone of the open field test compared to the control group (P < 0.01); the combined exposure group exhibited increased ratios of peripheral-to-central exploration time and distance (P < 0.05). After 7 d of exposure, compared with the control group, the noise group maintained a decrease in central zone exploration time (P < 0.01), while the combined exposure group showed persistent decline across all central zone metrics (P < 0.05) and elevated peripheral-to-central ratios (P < 0.05); compared to the microwave group, the combined exposure group showed significant less time in the central zone (P < 0.05) and higher peripheral-to-central ratios (P < 0.05). Regarding behaviour and cognition, compared with the control group, the combined exposure group showed increased immobility time in the tail suspension test after 3 d of exposure (P < 0.01). At this interval, all exposure groups demonstrated reduced frequency and duration of novel object recognition (P < 0.05), with the combined exposure group showing a marked decrease in novel arm exploration time (P < 0.01). After 7 d of exposure, compared with the control group, the noise group showed reduced novel object recognition frequency (P < 0.05), and both the noise and microwave groups exhibited decreased novel arm exploration time (P < 0.05). Pathological alterations including an increased number of hyperchromatic nuclei and depleted Nissl bodies were observed in the CA3 and DG regions across all exposure groups with the most severe lesions observed in the combined exposure group. Serum levels of central nervous system-specific protein β (S-100β), glial fibrillary acidic protein (GFAP), and corticosterone (CORT) were significantly elevated in all exposure groups compared with the control group (P < 0.05). Aquaporin-4 (AQP4) levels increased in the combined exposure group (P < 0.05), while CXC chemokine ligand 10 (CXCL10) levels rose in both the noise and combined groups compared with the control group (P < 0.05). Specifically, S-100β and CXCL10 levels in the combined exposure group were higher than those in the microwave group (P < 0.05); moreover, levels of S-100β, GFAP, CORT, AQP4, and CXCL10 in the combined exposure group were significantly higher than those in the noise group (P < 0.05). Conclusion Combined exposure to noise and microwave radiation induces pathological changes in the hippocampus of mice, increases levels of serum stress hormones and neuro-specific biomarkers. These impairments are more severe than those observed following single-factor exposure. The underlaying mechanism may be related to systemic stress response, neuronal damage, astrocyte activation, and changes in blood-brain barrier permeability, leading to emotional behavioral abnormalities and cognitive decline.

[摘 要] 目的：探讨DNA甲基转移酶1（DNMT1）通过稳定zeste基因增强子同源物2（EZH2）促进结直肠癌（CRC）HCT8细胞增殖与迁移的机制。方法：利用生物信息学方法分析DNMT1在CRC组织中的表达水平。WB法检测DNMT1在CRC细胞HCT8、SW620和正常结肠上皮细胞NCM460中的表达。通过siRNA或慢病毒载体转染HCT8细胞，分为siNC组、siDNMT1组、Vector组、DNMT1-OE组、siTRAF6组、siEZH2组、siEZH2 + DNMT1-OE组。采用克隆形成实验、CCK-8法、Transwell实验和划痕愈合实验检测敲低或过表达DNMT1对HCT8细胞增殖与迁移的影响，WB和qPCR法检测EZH2蛋白和mRNA水平，免疫沉淀（IP）法检测EZH2泛素化水平，免疫荧光双染检测肿瘤坏死因子受体相关因子6（TRAF6）与EZH2的细胞内共定位情况，克隆形成和划痕愈合实验验证EZH2对DNMT1功能的逆转作用。收集2022—2025年间郑州大学附属洛阳中心医院手术切除的12例CRC患者的癌及癌旁组织标本，采用免疫组化法检测CRC组织中DNMT1、TRAF6和EZH2的表达水平。结果：DNMT1在CRC组织中表达显著高于癌旁组织（P < 0.01），且在CRC细胞中表达上调（P < 0.05）；DNMT1敲低显著抑制HCT8细胞增殖及迁移（均P < 0.01），过表达则相反（均P < 0.01）。DNMT1正向调控EZH2的蛋白水平（P < 0.01），而mRNA水平不变（P > 0.05）。MG132可恢复siDNMT1组的EZH2蛋白表达（P < 0.01），且siDNMT1组EZH2泛素化水平升高。DNMT1负向调控TRAF6的表达（P < 0.01），且TRAF6与EZH2在细胞质中共定位，IP证实两者直接结合。敲低TRAF6可减弱EZH2的泛素化水平，敲低EZH2可逆转DNMT1对HCT8细胞增殖、迁移的促进作用（均P < 0.01）。DNMT1和EZH2在CRC组织中呈高表达（P < 0.01），TRAF6在CRC组织中表达显著低于癌旁组织（P < 0.05）。结论：DNMT1通过抑制TRAF6稳定EZH2促进CRC细胞的增殖和迁移，DNMT1、TRAF6和EZH2可能是CRC治疗的潜在靶点。

ObjectiveTo analyze the epidemiological and clinical characteristics of pertussis in Taizhou City, Zhejiang Province, 2024, and to provide a scientific basis for formulating local prevention and control strategies. MethodsCase data and population data were obtained from the China Disease Prevention and Control Information System. Epidemiological case investigation data were collected from the Zhejiang Vaccine Clinical Research and Application Effectiveness Evaluation System and the Immunization Service Information System. Descriptive epidemiological methods were used to analyze the temporal, spatial and demographic distributions, and SaTScan 9.7 software was applied for spatiotemporal cluster scanning. ResultsIn 2024, a total of 3 090 pertussis cases were reported in Taizhou City, with no deaths. The number of reported cases increased significantly compared with those in previous years, and the peak occurred in April. Spatiotemporal scanning identified three clusters: a most likely cluster centered around Tantou Town in Tiantai County, covering 16 streets/towns, a second most likely cluster centered around Taiping Subdistrict in Wenling City, covering 11 streets/towns, and a third most likely cluster centered around Ganjiang Town in Yuhuan City, covering 6 streets/towns. The three clusters together accounted for 31.04% of the total scanned cases.The majority of cases were in the 6‒10 years age group (55.02%), and students accounted for the highest proportion by occupation (44.17%). Among 2 929 epidemiological investigation cases, the most common clinical manifestations were cough (97.58%) and aggravated nocturnal cough (52.10%), while typical symptoms (including paroxysmal spasmodic cough and post-tussive vomiting, etc.) were less frequent. Among the cases, 82.49% had completed the full 4-dose vaccination schedule, and their complication rate (10.47%) was lower than that of the unvaccinated group (20.56%). ConclusionThe number of reported pertussis cases surged in Taizhou City in 2024, showing significant spatiotemporal clustering, with school‑aged children being the high‑risk group. Vaccination could reduce the risk of complications. It is recommended to further enhance surveillance sensitivity, with a focus on strengthening immunization strategies for high-risk groups such as school-aged children aged 6‒10 years, and to reinforce targeted protection for infants under 1 year old who have not completed primary vaccination, along with their families. In addition, prevention and control resources should be deployed in advance for the cluster areas identified through spatiotemporal analysis and for the spring peak season,to interrupt local transmission chains.

OBJECTIVE To investigate the cognition， attitudes， and current practices of Chinese physicians regarding biosimilars and their clinical switching， so as to provide a basis for the rational clinical application of biosimilars in China and the improvement of related policies.METHODS A national cross-sectional online questionnaire survey was conducted in 2025. Quota sampling was adopted， with quotas based on physicians’ sex， city tier， and specialty. Questionnaire invitations were distributed to licensed physicians， and physicians who had prescribed monoclonal antibody biosimilars were included for analysis. The questionnaire covered their familiarity with biosimilars， attitudes， clinical switching practices， and reasons. Data were processed using reliability and validity tests， dispersion analysis， and cross-tabulation analysis.RESULTS The questionnaire scale showed good reliability and validity， with Cronbach’s α coefficient ＞0.7 and KMO value ＞0.6. A total of 2 071 survey invitations were distributed， and 300 valid questionnaires were returned， with an effective response rate of 14.5%. Among the respondents， 75.3% had prescribed 3-5 types of monoclonal antibody biosimilars； only 35.3% were aware that China currently has no clear regulatory provisions on biosimilar switching； 46.3% and 47.3% of respondents believed that there was no difference in safety and efficacy， respectively， between biosimilars and originator products； 63.0% of respondents were concerned about the immunogenicity risk of long-term switching between originator drugs and biosimilars. A total of 92.3% of respondents had experience with biosimilar switching， 87.7% of which involved switching from originator products to biosimilars， and 28.2% of respondents had completed three or more switches in the same patient. Among the primary reasons for switching， non-medical factors accounted for 57.4%， higher than medical factors at 42.6%； “lower treatment cost after switching” was the most important reason for switching； 95.3% of respondents believed that informed consent should be obtained from patients before switching.CONCLUSIONS The surveyed physicians had basic knowledge of biosimilars， but their understanding of the relevant regulations of the national drug regulatory authority was insufficient. Although most physicians were concerned about the risks of non-medical switching， clinical switching was mostly driven by non-medical factors. It is recommended to strengthen policy education for medical professionals and standardize clinical switching behavior. The National Medical Products Administration should also promptly improve the interchangeability review standards and post-marketing surveillance system for biosimilars, so as to promote the rational use of biosimilars.

To summarize the nursing experience of a patient with uremia on maintenance hemodialysis complicated by recurrent ventricular tachycardia and treated with transcatheter radiofrequency ablation.Key nursing interventions included:dynamically assessing the patient's coagulation and bleeding status,being vigilant against the occurrence of deep vein thrombosis,and preventing local and major organ bleeding;implementing goal-oriented volume management strategies to prevent electrolyte disorders;the strengthened management of vascular access to reduce risks of stenosis or occlusion in the arteriovenous fistula;conducting precise assessment and comprehensive intervention to reduce the patient's psychological and mental burden.After careful treatment and nursing care,the patient was stable and discharged on the 6th postoperative day.During the 2-month outpatient follow-up,cardiac function indicators were normal,and the fistula was unobstructed,and the patient recovered well.

[Purpose]To analyze the epidemiology and disease burden of gastric cancer in China,Japan and Republic of Korea from 1990 to 2021 and to predict changing trends from 2022 to 2031.[Methods]Data were obtained from the Global Burden of Disease(GBD)database.Age-stan-dardized incidence rate(ASIR),age-standardized mortality rate(ASMR),crude incidence rate(CIR),crude mortality rate(CMR),and disability-adjusted life years(DALY)rate for China,Japan and Republic of Korea from 1990 to 2021 were analyzed.Joinpoint regression software was used to analyze trends and calculate annual percentage changes.The autoregressive integrated moving average(ARIMA)model was applied to predict incidence and mortality from 2022 to 2031.[Results]In 2021,China had 611 799 new gastric cancer cases and 445 013 deaths,with an ASIR of 29.05/105 and an ASMR of 21.51/105,both significantly higher than those in Japan and Republic of Korea.Among men in China,both the ASIR(44.48/105)and ASMR(32.61/105)were the highest among the three countries,exceeding those in Japan(38.77/105,20.26/105)and Re-public of Korea(38.98/105,20.50/105).Among women,China had the highest number of new cases,but its ASIR(15.23/105)was slightly lower than Republic of Korea's(15.57/105)and higher than Japan's(14.66/105).However,China's ASMR among women(12.02/105)remained significantly higher than Japan's(7.64/105)and Republic of Korea's(8.08/105).From 1990 to 2021,ASIR,ASMR and DALY rates for gastric cancer declined in all three countries,but the reduction in China was significantly smaller than that in Japan and Republic of Korea,with Republic of Korea showing the steepest declines across all indicators.ARIMA model predictions indicated significant differences in disease burden among the three countries from 2022 to 2031.ASIR is projected to continue declining in China and Republic of Korea,reaching 22.87/105 and 12.45/105,respectively by 2031,while in Japan it is predicted to rise to 26.55/105.ASMR is projected to decline in all three countries,reaching 13.71/105(China),10.44/105(Japan),and 9.08/105(Republic of Korea)in 2031.[Conclusion]Among China,Japan and Republic of Korea,China had the highest ASIR and ASMR of gastric cancer in 2021.Moreover,from 1990 to 2021,the reductions in ASIR,ASMR and DALY rates for gastric cancer were the smallest in China compared to Japan and Republic of Korea.These findings suggest that the disease burden of gastric cancer remains substantial in China,high-lighting the need for increased efforts in gastric cancer screening and early diagnosis and treatment.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

To summarize the nursing experience of a patient with uremia on maintenance hemodialysis complicated by recurrent ventricular tachycardia and treated with transcatheter radiofrequency ablation.Key nursing interventions included:dynamically assessing the patient's coagulation and bleeding status,being vigilant against the occurrence of deep vein thrombosis,and preventing local and major organ bleeding;implementing goal-oriented volume management strategies to prevent electrolyte disorders;the strengthened management of vascular access to reduce risks of stenosis or occlusion in the arteriovenous fistula;conducting precise assessment and comprehensive intervention to reduce the patient's psychological and mental burden.After careful treatment and nursing care,the patient was stable and discharged on the 6th postoperative day.During the 2-month outpatient follow-up,cardiac function indicators were normal,and the fistula was unobstructed,and the patient recovered well.

Objective:To observe the effect of isokinetic sensorimotor training on the hand function of stroke survivors.Methods:Forty-two stroke survivors with hand dysfunction were randomly divided into an isokinetic group of 22 and a control group of 20. Both groups were given sensorimotor training in addition to routine drug treatment and rehabilitation therapy, but the isokinetic group was additionally provided with sensorimotor training based on isokinetic techniques for 45 minutes daily, 5 days a week for 4 consecutive weeks. Before and after the intervention, both groups were evaluated using the Semmes-Weinstein monofilament examination (SWME), their two-point discrimination (2-PD) was documented, proprioception of their wrist joints was quantified, and the Fugl-Meyer upper extremity assessment (FMA-UE) and the simplified upper limb function assessment (STEF) were applied.Results:In both groups after treatment, there was a significant improvement in the SWME scores and 2-PD distance of the index finger and the thenar, and there was a significant decrease in the angle of motion perception (at 30° of flexion). The average FMA-UE and STEF scores of both groups had improved. After the treatment, the SWME scores of the index finger and the thenar, as well as well as the average FMA-UE and STEF scores of the isokinetic group were significantly higher than the control group′s averages. Angle of motion perception was also significantly superior.Conclusions:Sensorimotor training based on isokinetic techniques can significantly improve touch, motion sense, gross motor function and the fine motor ability of stroke survivors.