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.

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.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

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.

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.

The number of investigator-initiated trials(IIT)projects in medical institutions has increased rapidly,yet there are certain issues such as uneven quality and insufficient consideration of research design.The scientific review and ethical review of IIT complement each other.To improve the research quality and review efficiency of IIT and reduce review repeatability,this paper described the current situation of scientific review and ethical review of IIT in a tertiary A hospital.Combined with literature analysis,the common issues in scientific review and ethical review were summarized into four types:standardization,reliability,safety,and lag.Corresponding to these common issues,the reasons for their occurrence were analyzed as the lack of unified review points,the ambiguity of each review focus,the lack of review communication and exchange,and the lack of ability and awareness of relevant personnel.The explored solutions included establishing a collaborative review mechanism,by unifying the key points of collaborative review,clarifying the review responsibilities of each committee,building a review communication mechanism with the help of information technology,strengthening training and publicity,and other means.These solutions aimed to promote the organic combination of scientific review and ethical review,fully leverage the synergistic effect,improve the efficiency of review,and promote the high-quality and healthy development of IIT.

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.

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.