ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop （TTFL） of biorhythm in the rat model of non-alcoholic fatty liver disease （NAFLD） and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank （n=20）， model （n=15）， and low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg^-1·d^-1， respectively） modified Ditan tang （n=10） groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage， and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid （NEFA） assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining， and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 （BMAL1/ARNTL） in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1， circadian locomotor output cycles kaput （CLOCK）， period circadian clock 2 （PER2）， and cryptochrome1 （Cry1） in the hypothalamus and liver were determined by Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed elevated levels of TG， TC， LDL-C， AST， and ALT （P<0.01） and a lowered level of HDL-C （P<0.05） in the serum， elevated levels of TG and NEFA in the liver （P<0.01）， pyknosis and deep staining of hypothalamic neuron cells， and a large number of vacuoles in the brain area. In addition， the model group showed lipid deposition in the liver， up-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.01）， and down-regulated mRNA and protein levels of Cry1 and PER2 （P<0.01） in the hypothalamus and liver. Compared with the model group， all the three modified Ditan tang groups showed lowered levels of TG， TC， LDL-C， ALT， and AST （P<0.05， P<0.01） and an elevated level of HDL-C （P<0.05） in the serum， and lowered levels of TG and NEFA （P<0.05， P<0.01） in the liver. Furthermore， the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells， reduced lipid deposition in the liver， down-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.05， P<0.01）， and up-regulated mRNA and protein levels of Cry1 and PER2 （P<0.05， P<0.01） in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK， BMAL1， Cry1， and PER2 in the TTFL of NAFLD rats.

Voice biomarkers， as an emerging smart medical technology， are now being used in applications such as assisting in the diagnosis and treatment of diseases， facilitating accurate and personalized medical services for patients. However， it also raises many ethical issues， including informed consent， privacy protection， accuracy and reliability， data security， legal risks， and other issues. This paper systematically sorted out the ethical issues in the applications of voice biomarkers in the medical field， summarized these issues， such as informed consent， privacy protection， accuracy and reliability， data security， and legal risks， as well as explored the corresponding coping strategies. These countermeasures encompassed utilizing new media platforms to raise public awareness of voice biomarkers， strengthening supervision and management to promote the privacy protection of voice biomarkers， reducing algorithm biases to promote the general benefits of voice biomarkers to the public， establishing multidisciplinary teams to protect the data security of voice biomarkers， and encouraging medical professionals and researchers to participate in policy research， with a view to providing references for promoting and regulating the applications of voice biomarkers in the medical field.

The existing epilepsy seizure detection algorithms have problems such as overfitting and poor generalization ability due to high reliance on manual labeling of electroencephalogram's data and data imbalance between seizure and interictal periods. An unsupervised learning detection method for epileptic seizure that jointed graph attention network (GAT) and Transformer framework (GAT-T) was proposed. In this method, channel correlations were adaptively learned by GAT encoder. Temporal information was captured by one-dimensional convolution decoder. Combining outputs of the two mentioned above, predicted values for electroencephalogram were generated. The collective anomaly score was calculated and the detection threshold was determined. The results demonstrated that GAT-T achieved the average performance exceeding 90% (or 99%) with a 0.25 s (or 2 s) time segment length, which could effectively detect epileptic seizures. Moreover, the channel association probability matrix was expected to assist clinicians in the initial screening of the epileptogenic zone, and ablation experiments also reflected the significance of each module in GAT-T. This study may assist clinicians in making more accurate diagnostic and therapeutic decisions for epilepsy patients.
Humans ; Electroencephalography/methods* ; Epilepsy/physiopathology* ; Algorithms ; Seizures/physiopathology* ; Neural Networks, Computer ; Signal Processing, Computer-Assisted

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Objective Summarize the key difficult problems faced by national regional medical centers,create a checklist of crucial issues,and propose strategic recommendations to support future development.Methods It employed a combination of literature review,field research,and in-depth interviews to develop an initial draft of the checklist for key issues in national regional medical centers.Additionally,two rounds of Delphi method consultation were conducted with experts from local government,exporting and supporting hospitals.The data gathered from the questionnaires in both rounds were analyzed,and essential questions were identified.Results The questionnaires achieved response rates of 99%and 100%in the two rounds,and the expert authority coefficients were 0.83 and 0.90.The final checklist for key issues in national regional medical centers encompassed a total of 6 problems.These included 3 challenges related to establishing sound management systems and mechanisms,1 challenge concerning human resource management improvement,1 challenge focusing on elevating medical service levels,and 1 challenge pertaining to other aspects of progress.Conclusion Currently,the development of national regional medical centers encounters crucial challenges,including the enhancement of management mechanisms,overall human resource management,and medical capabilities.The government should reinforce leadership assurance,coordination,and supervisory responsibilities.Exporting hospitals should enhance management systems and operational mechanisms.Supporting hospitals should focus on effective party building guidance and cooperation while consistently promoting the uniform development of national regional medical centers.

Objective Summarize the key difficult problems faced by national regional medical centers,create a checklist of crucial issues,and propose strategic recommendations to support future development.Methods It employed a combination of literature review,field research,and in-depth interviews to develop an initial draft of the checklist for key issues in national regional medical centers.Additionally,two rounds of Delphi method consultation were conducted with experts from local government,exporting and supporting hospitals.The data gathered from the questionnaires in both rounds were analyzed,and essential questions were identified.Results The questionnaires achieved response rates of 99%and 100%in the two rounds,and the expert authority coefficients were 0.83 and 0.90.The final checklist for key issues in national regional medical centers encompassed a total of 6 problems.These included 3 challenges related to establishing sound management systems and mechanisms,1 challenge concerning human resource management improvement,1 challenge focusing on elevating medical service levels,and 1 challenge pertaining to other aspects of progress.Conclusion Currently,the development of national regional medical centers encounters crucial challenges,including the enhancement of management mechanisms,overall human resource management,and medical capabilities.The government should reinforce leadership assurance,coordination,and supervisory responsibilities.Exporting hospitals should enhance management systems and operational mechanisms.Supporting hospitals should focus on effective party building guidance and cooperation while consistently promoting the uniform development of national regional medical centers.

Background Maternal exposure to bisphenol A (BPA) during pregnancy is closely related to adverse growth and development conditions such as preterm birth and low birth weight, but the relevant mechanisms are still unclear. UDP-glucuronosyltransferases (UGTs) can regulate the excretion of BPA conjugating with glucuronic acid through urine, which is one of the important pathways for BPA elimination. Objective To explore the changes in the expression of UGTs in placenta and fetal liver of rats before birth induced by maternal exposure to BPA during pregnancy. Methods Thirty SPF-grade healthy SD pregnant rats were randomly divided into five groups: control group, 0.05, 0.5, 5, and 50 mg·kg⁻¹ BPA groups. The pregnant rats were exposed to BPA dissolved in corn oil via oral gavage daily from gestational day (GD) 5 to GD 19. After anesthesia, the pregnant rats were sacrificed on GD 20 and the placentas were collected. Body length, tail length, and weight of the fetal rats were measured. Fetal liver tissues were then separated, and organ weights were measured. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to determine the mRNA and protein levels of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in the placenta and fetal liver tissues in each group. Results There were no differences in body length and tail length of the pups after maternal exposure to BPA during pregnancy. The fetal body weight and placenta weight in the 5 and 50 mg·kg⁻¹ BPA groups and the liver weight in the 5 mg·kg⁻¹ BPA group reduced compared with the control group (P<0.05). The results of UGTs expressions in placenta showed that compared with the control group, the UGT1A1 mRNA levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) and the UGT1A1 protein level in placenta of the 50 mg·kg⁻¹ BPA group increased (P<0.05); the UGT1A6 mRNA and protein levels in placenta of each BPA group did not change (P>0.05); the UGT1A9 mRNA level in placenta of the 50 mg·kg⁻¹ BPA group and the UGT1A9 protein levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05); while the levels of UGT2B1 mRNA in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). The results of UGTs expressions in fetal liver showed that compared with the control group, the UGT1A1, UGT1A6, UGT1A9, and UGT2B1 mRNA levels of each BPA group increased (P<0.05); no obvious alternation was observed in UGT1A6 protein levels in each BPA group (P>0.05); the relative protein levels of UGT1A9 in fetal liver in the 50 mg·kg⁻¹ BPA group increased (P<0.05); conversely, the relative protein levels of UGT2B1 in fetal liver in the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). Conclusion Maternal exposure to BPA during pregnancy can elevate the UGT1A1 gene and protein expressions, inhibit the UGT1A9 gene and protein expressions and UGT2B1 gene expressions in placenta. Besides, maternal exposure to BPA during pregnancy can raise the gene expressions of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in fetal liver, as well as the protein expression of UGT1A9, but inhibit the protein expression of UGT2B1. These changes may contribute to fetal developmental abnormalities after maternal exposure to BPA during pregnancy.

Objective Summarize the key difficult problems faced by national regional medical centers,create a checklist of crucial issues,and propose strategic recommendations to support future development.Methods It employed a combination of literature review,field research,and in-depth interviews to develop an initial draft of the checklist for key issues in national regional medical centers.Additionally,two rounds of Delphi method consultation were conducted with experts from local government,exporting and supporting hospitals.The data gathered from the questionnaires in both rounds were analyzed,and essential questions were identified.Results The questionnaires achieved response rates of 99%and 100%in the two rounds,and the expert authority coefficients were 0.83 and 0.90.The final checklist for key issues in national regional medical centers encompassed a total of 6 problems.These included 3 challenges related to establishing sound management systems and mechanisms,1 challenge concerning human resource management improvement,1 challenge focusing on elevating medical service levels,and 1 challenge pertaining to other aspects of progress.Conclusion Currently,the development of national regional medical centers encounters crucial challenges,including the enhancement of management mechanisms,overall human resource management,and medical capabilities.The government should reinforce leadership assurance,coordination,and supervisory responsibilities.Exporting hospitals should enhance management systems and operational mechanisms.Supporting hospitals should focus on effective party building guidance and cooperation while consistently promoting the uniform development of national regional medical centers.

Objective Summarize the key difficult problems faced by national regional medical centers,create a checklist of crucial issues,and propose strategic recommendations to support future development.Methods It employed a combination of literature review,field research,and in-depth interviews to develop an initial draft of the checklist for key issues in national regional medical centers.Additionally,two rounds of Delphi method consultation were conducted with experts from local government,exporting and supporting hospitals.The data gathered from the questionnaires in both rounds were analyzed,and essential questions were identified.Results The questionnaires achieved response rates of 99%and 100%in the two rounds,and the expert authority coefficients were 0.83 and 0.90.The final checklist for key issues in national regional medical centers encompassed a total of 6 problems.These included 3 challenges related to establishing sound management systems and mechanisms,1 challenge concerning human resource management improvement,1 challenge focusing on elevating medical service levels,and 1 challenge pertaining to other aspects of progress.Conclusion Currently,the development of national regional medical centers encounters crucial challenges,including the enhancement of management mechanisms,overall human resource management,and medical capabilities.The government should reinforce leadership assurance,coordination,and supervisory responsibilities.Exporting hospitals should enhance management systems and operational mechanisms.Supporting hospitals should focus on effective party building guidance and cooperation while consistently promoting the uniform development of national regional medical centers.

Objective Summarize the key difficult problems faced by national regional medical centers,create a checklist of crucial issues,and propose strategic recommendations to support future development.Methods It employed a combination of literature review,field research,and in-depth interviews to develop an initial draft of the checklist for key issues in national regional medical centers.Additionally,two rounds of Delphi method consultation were conducted with experts from local government,exporting and supporting hospitals.The data gathered from the questionnaires in both rounds were analyzed,and essential questions were identified.Results The questionnaires achieved response rates of 99%and 100%in the two rounds,and the expert authority coefficients were 0.83 and 0.90.The final checklist for key issues in national regional medical centers encompassed a total of 6 problems.These included 3 challenges related to establishing sound management systems and mechanisms,1 challenge concerning human resource management improvement,1 challenge focusing on elevating medical service levels,and 1 challenge pertaining to other aspects of progress.Conclusion Currently,the development of national regional medical centers encounters crucial challenges,including the enhancement of management mechanisms,overall human resource management,and medical capabilities.The government should reinforce leadership assurance,coordination,and supervisory responsibilities.Exporting hospitals should enhance management systems and operational mechanisms.Supporting hospitals should focus on effective party building guidance and cooperation while consistently promoting the uniform development of national regional medical centers.