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.

ObjectiveTo investigate the fluctuations in serum uteroglobin-related protein 1（UGRP1） levels in Hashimoto’s thyroiditis （HT） patients before and after pregnancy， and to analyze the influencing factors. MethodsTen healthy individuals and ten HT patients were enrolled. Thyroid fine needle aspiration cytology combined with immunohistochemistry was used to detect the expression of UGRP1 protein in thyroid cells between the two groups. A total of 30 healthy women were enrolled as the control group， and 149 HT patients were recruited， including 36 non-pregnant HT patients， 77 pregnant HT patients and 36 post-partum HT patients. According to levothyroxine sodium （L-T4） administration status， the pregnant HT group was further subdivided into the non-L-T4 subgroup （n=36） and the L-T4 subgroup （n=41）. Kruskal-Wallis H test was used to compare the general clinical data， thyroid-related indicators and serum UGRP1 levels among groups. Spearman correlation analysis and univariate linear regression analysis were performed to explore the influencing factors of serum UGRP1 levels in HT patients. ResultsUGRP1 expression was negative in thyroid cells of all healthy individuals， while 80% of HT patients exhibited positive expression. The serum UGRP1 levels in the control group， non-pregnant HT group， pregnant HT group， and post-partum HT group were 359.52 （297.84， 440.60）， 695.77 （518.55， 865.04）， 207.96 （173.82， 264.91）， and 582.08 （280.83， 735.87） pg/mL， respectively， with statistically significant differences among groups （P<0.001）. Correlation analysis showed no significant correlation between serum UGRP1 levels and thyroid-related indicators or gestational age in pregnant HT patients. Univariate linear regression analysis revealed that pregnancy status was negatively correlated with serum UGRP1 levels in HT patients （β= -424.457， P<0.001）， while L-T4 administration had no statistically significant effect on serum UGRP1 levels in pregnant HT patients （P=0.890）. ConclusionSerum UGRP1 levels are significantly higher in HT patients than in healthy individuals. Pregnancy is an important factor affecting serum UGRP1 levels in HT patients， which can lead to a decrease in UGRP1 levels， while L-T4 administration has no significant effect on serum UGRP1 levels.

Physical function maintenance in brain-dead pregnancy refers to a medical technology that， after a pregnant woman being brain-dead， sustains her uterine and related physiological functions through medical intervention， creates conditions for the normal development of the embryo （fetus）， and performs a cesarean section at an appropriate gestational week to achieve live birth. The implementation of the physical function maintenance technologies in brain-dead pregnancy breaks through the existing procreation paradigm， bearing clinical significance in protecting the life potential of the fetus and alleviating the emotional impact on kinship ethics. Meanwhile， it also faces restrictions by ethical and legal dilemmas and urgently necessitates the “responsive” support of bioethics law. The tension between dignity in death and the protection of potential life， the lack of opportunities for autonomous consent， the ambiguity of surrogate consent rules， and conflicts with traditional Chinese bioethical concepts collectively reflect the ethical concerns over the implementation of physical function maintenance technologies in brain-dead pregnancy. However， the bioethical and legal status of fetal potential life， as well as presumed consent and surrogate consent as permissible forms of informed consent under special conditions， validates the legitimate basis of maternal physiologic support after brain death. In terms of countermeasures， it is essential to adhere to the disputable approach of “case-by-case deliberation” in bioethics law. Based on the specific circumstances of individual clinical cases， it is also necessary to balance and consider multiple ethical evaluation factors， including the clear prior will expression of the parties concerned， fetal development and survival possibility， and the decision-making results of surrogate consent.

ObjectiveGliomas in the motor functional area can damage the corticospinal tract (CST), leading to motor dysfunction. Currently, there is a lack of unified methods for evaluating the extent of CST damage, especially in patients with high surgical risk where the minimum distance from the lesion to the CST is less than 10 mm. This study aims to further clarify the classification method and clinical significance of CST morphological changes in these patients. MethodsThis retrospective study analyzed 109 high-risk functional area glioma patients who underwent neurosurgical treatment with preoperative diffusion tensor imaging (DTI) imaging and intraoperative neurostimulation guidance between 2014 and 2024. All patients had a lesion-to-tract distance (LTD) of less than 10 mm between the CST and the lesion. Preoperative DTI evaluation of CST involvement-induced morphological changes were reviewed. Patients were divided into 3 groups: 17 cases (15.6%) with symmetric CST morphology compared to the healthy side (CST symmetry), 48 cases (44.0%) with significant CST morphology changes compared to the healthy side (CST deformation), and 44 cases (40.4%) with CST overlap with the tumor (CST overlap). Then we classified patients according to preoperative assessment of tumor-induced morphological changes, and analyze postoperative motor function for each category. ResultsPostoperative pathology showed a significantly higher proportion of high-grade gliomas (HGG) in the CST overlap group compared to the other two groups (P=0.001). Logistic regression analysis showed that CST overlap was a predictor of HGG (P=0.000). The rate of total tumor resection in the CST deformation group and overlap group was lower than in the CST symmetric group (P=0.008). There was a total of 41 postoperative hemiplegic patients, with 4 cases (23.5%) in the CST symmetric group, 11 cases (22.9%) in the CST deformation group, and 26 cases (59.1%) in the CST overlap group. CST overlap with the tumor predicted postoperative hemiplegia (P=0.016). Two-way ANOVA analysis of the affected/healthy side and CST morphology groups showed significant main effects of CST grouping and healthy-affected side (P=0.017 and P=0.010), with no significant interaction (P=0.31). The fractional anisotropy (FA) value in the CST overlap group and the affected side was lower. A decrease in the FA value on the affected side predicted postoperative hemiplegia (sensitivity 69.2%, specificity 71.9%). ConclusionWe have established a method to predict postoperative hemiplegia in high-risk motor functional area glioma patients based on preoperative CST morphological changes. CST overlap leads to a decrease in CST FA values. This method can be used for precise patient management and aid in accurate preoperative surgical planning.

ObjectiveTo explore the process and guidelines for ethical review in decentralized drug clinical trials， promote clinical trial progress， and ensure drug development progress. MethodsThe key points of the ethical review were summarized by studying the relevant laws and regulations on decentralized drug clinical trials， analyzing the advantages and challenges of decentralized drug clinical trials， and combining the experience of the ethics committee of the institution in reviewing decentralized drug clinical trials. ResultsRelevant laws and regulations were the basis for the ethical review， and the ethics committee should adopt appropriate review methods based on regulations and hospital ethical standard operating procedures. The ethics committee should focus on the feasibility， applicability， and rationality， the adequacy of informed consent， the protection of rights and interests and privacy of subjects， as well as the qualification and standard operating procedures of electronic platforms for conducting decentralized drug clinical trials. ConclusionDecentralized drug clinical trials are in their early stages and urgently require guidance from relevant laws and regulations. Ethical review is also constantly being refined through exploration. It is necessary to supervise the implementation of responsibilities by all parties， pay attention to the rights and interests of subjects， and gradually promote the implementation of decentralized drug clinical trials.

Objective:This study aims to improve the management level and quality of horizontal scientific research contracts in hospitals, reduce the risk of contract management, and explore an efficient mode of information management of horizontal scientific research contract management.Methods:Taking a Tertiary Grade A hospital as an example, this study described and summarized the management status of horizontal scientific research contracts from 2018 to 2022, sorted out the potential risks and prevention and control nodes of the review, signing, performance, and archiving of horizontal scientific research contracts in the whole cycle management process, and designed an information management model according to the relevant elements of risk prevention and control and the standardized requirements of contract management, thereby developing information platform related functions.Results:The horizontal research contract management function of the clinical research platform based on the integration concept was available to meet the requirements of risk prevention and control of horizontal research contracts, and the contract review and signing cycle of the information management mode was shortened by 33.33% and 31.95% respectively compared with the traditional management mode. The platform realized a standardized whole process management of contract submission, review, repair and revision, signing, performance, and filing.Conclusions:Information management can effectively reduce the risk of horizontal scientific research contract management. It is necessary to strengthen the docking and interaction function with other information platforms and further explore the information auxiliary function to improve the refined management effect of horizontal scientific research contracts.

Objective:To explore the management strategies of conflicts of interest(COI) by analyzing the definition, manifestations, and implications of COI related to clinical research.Methods:This study summarized the definitions and types, manifestations, and implications of different groups of COI in clinical research. It explored the management response of medical institutions to the COI related to clinical research.Results:Conflicts of Interest could be divided into economic and non-economic conflicts of interest, showing different manifestations in different groups. COI occurs in a variety of links involved in clinical research, and the overall disclosure ratio of COI is low, which might have adverse effects on institutions, investigators, clinical research quality, and subjects.Conclusions:COI management should be implemented by strengthening the construction of the COI management system, strictly following the principle of public disclosure, and strengthening education and training, to improve the quality and credibility of clinical research.

Objective:To investigate the effects of 10° head up tilt bed rest (HUT) on human cardiac function via 3D speckle tracking echocardiography (3D-STE), and to study the difference in cardiac function under the submaximal exercise load between the horizontal position and 10° HUBR.Methods:Thirty young healthy volunteers were recruited as the subjects, who were randomly divided into an 10° HUT exercise group and horizontal exercise group with 15 subjects in each. Subjects in both groups were asked to ride the bicycle ergometer in the 10° HUBR position and supine position respectively. The load started with 50 W and was increased by 25 W every 3 min until it reached the maximum of 125 W. Before the exercise (resting state), 1 min after the load was increased each time, and 3 min after exercise (recovery period), the following indices were collected: ①basic cardiac function indices: heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), ②conventional cardiac ultrasound indices: left ventricular ejection fraction (LVEF), stroke volume (SV) and cardiac output (CO), ③left ventricular strain indices: global longitudinal strain (GLS), global circumferential strain (GCS), and global area strain (GAS) measured by 3D-SET. The changes of these indices in the 2 groups of subjects under different exercise loads were observed.Results:The differences in the major effect of the basic heart indices (HR, SBP and DBP), conventional cardiac ultrasound indices (LVEF, SV and CO) and left ventricular strain indices (GLS, GCS and GAS) in response to the exercise load were statistically significant ( F=194.90, 113.66, 17.19, P=0.017, 0.018, 0.001). With the increase of the exercise load, the basic heart indices and conventional cardiac ultrasound indices kept rising, the left ventricular strain indices reached the minimum under a moderate exercise load (75 W), HR, SBP and CO were higher than those of the resting state ( P<0.05 or 0.01). Both LVEF under exercise loads of 75, 100, 125 W and during recovery, and SV under exercise loads of 100, 125 W and during recovery were significantly higher than those of the resting state ( P<0.05 or 0.01), while GLS and GCS under exercise loads of 50, 75, 125 W ( P<0.05 or 0.01), and GAS under exercise loads of 50, 75 W ( P<0.01) were significantly lower. There were statistically significant differences not only in GCS across the groups ( F=4.60, P=0.026) but also in DBP due to the interactions between the grouping and exercise loads ( F=3.13, P=0.031). DBP was higher than that of the resting state when the exercise load was 125 W in both groups. Conclusions:During submaximal exercise, myocardial contractility shows sustained enhancement with the increase of the exercise load. The results of GLS, GCS and GAS indicate that myocardial strain reaches its lowest value under a moderate exercise load, suggesting that moderate exercise can be used to evaluate cardiac function via 3D-SET. Under a simulated lunar gravity of 10° HUT, there is less deformation in the short axis direction of the myocardium, indicating that GCS can be used as a sensitive indicator to detect changes in cardiac function under different gravities.

AIM:This study aims to investigate the impact of TWIK-1 channels on abnormal pacemaker activi-ties induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:The gene sequences encoding hu-man TWIK-1,specific TWIK-1 shRNA and TWIK-1-T118i mutant were synthesized and subsequently subcloned into lenti-viral vectors.To knock down the TWIK-1 gene in human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs),the cells were transduced with lentivirus carrying the specific TWIK-1 shRNA sequences.For the overexpression of TWIK-1 or the TWIK-1-T118i mutant in HL-1 mouse cardiomyocytes,the cells received lentiviral transduction containing the respective gene sequences.Patch-clamp techniques were employed to assess the effects of 1 mmol/L extracellular K+on the membrane potentials and whole-cell currents of the cardiomyocytes.RESULTS:Under conditions of 1 mmol/L extra-cellular K+,depolarization of membrane potentials was observed in the hiPSC-CMs and the HL-1 mouse cardiomyocytes ex-pressing human TWIK-1 channel,leading to the induction of abnormal pacemaker activities.This phenomenon could be reversibly abolished by the removal of extracellular Na+or inhibited through TWIK-1 knockdown.In contrast,the mem-brane potentials of HL-1 mouse cardiomyocytes expressing human TWIK-1-T118i mutant hyperpolarized,with no occur-rence of abnormal pacemaker activities.The hiPSC-CMs exhibiting abnormal pacemaker activities at 1 mmol/L extracellu-lar K+demonstrated TWIK-1-like Na+leak currents,which were blocked by quinine,a non-selective blocker of TWIK-1.CONCLUSION:The TWIK-1 channels play a critical role in the development of hypokalemia-induced abnormal pace-maker activities in human cardiomyocytes by facilitating Na+leak currents.

Objective:To investigate the effects of psychosocial factors on early puberty and its sex specific differences.Methods:Bengbu Yuhui Longitudinal Study of Children Development Cohort, consisting of 1 162 students in grades 1-3 (524 girls) and their parents, was established in April 2021 in Bengbu, Anhui Province. The parents were surveyed by questionnaire to collect the information about their children's 56 items of psychosocial factor exposures, including 5 dimensions: major life events, early life adversity, interpersonal/relational conflict, family economic status and daily life troubles. Pubertal growth and physical examinations were conducted by trained professionals at baseline, the 1 st (May 2022), 2 nd (October 2022), 3 rd (May 2023), and 4 th (October 2023) follow-up surveys. In this study, the pubertal development status data were from the 4 th follow-up examination. Fianally, the valid data on pubertal development of 1 105 children were obtained, including the data from 510 girls (46.15%). Multinomial logistic regression model was used to analyze the association between psychosocial factors and early puberty, and the final predictors of early puberty were explored by using four models [least absolute shrinkage and selection operator (LASSO), multiple logistic regression, ridge regression, and Bayesian]. Results:The detection rates of early puberty in boys and girls were 13.60% and 16.30%, respectively. The median of intra-group absolute correlation of psychosocial factor exposure (0.042-0.066) was generally higher than that of inter-group among girls (0.031-0.059), while no similar diference was found among boys. LASSO model showed that moving house, being raised by someone other than parents, sexual abuse, peer conflict, high monthly household income, and high exposure to electronics on school days were predictors of early puberty in girls, while moving house and high monthly household income were the predictors of early puberty in girls in all four models (LASSO, multiple logistic regression, ridge regression, and Bayesian). Among boys, only a transient loss from family was a predictor of early puberty.Conclusion:Early puberty in children can be predicted by psychosocial factors, and there are gender-specific differences.