ObjectiveTo analyze the incidence rate and mortality of acute myocardial infarction (AMI) and their changing trends among the registered residents in Xiaoshan District, Hangzhou City from 2017 to 2023, so as to provide references for formulating policies related to AMI prevention. MethodsThe morbidity and mortality data of AMI among the registered residents in Xiaoshan District from 2017 to 2023 were collected through the Hangzhou Chronic Disease and Death Cause Monitoring System. Software such as Excel 2019, SPSS 25.0 and Joinpoint 4.9.1.0 were used to calculate the incidence rate, mortality, and average annual percentage change (AAPC) of AMI. ResultsFrom 2017 to 2023, the average annual crude incidence rate, age-standardized incidence rate using China standard population (ASIRC), and the age-standardized incidence rate using World standard population (ASIRW) of AMI in Xiaoshan District were 48.25/100 000, 29.14/100 000, and 21.64/100 000, respectively, and, from which the AAPCs were 5.495%, 6.010%, and 6.533%, respectively, all showing an upward trend. The average annual crude mortality rate, the age-standardized mortality rate using China standard population (ASMRC), and the age-standardized mortality rate using World standard population (ASMRW) were 11.76/100 000, 6.52/100 000, and 4.71/100 000, respectively, from which the AAPCs were -9.669%, -10.433% and -9.615%, respectively, all showing a downward trend. The average annual crude incidence rate of AMI was higher in males (65.87/100 000) than that in females (31.31/100 000). Moreover, the average annual crude mortality rate of AMI was higher in males (14.08/100 000) than that in females (9.52/100 000), and the difference was statistically significant (all P<0.001) .After age grouping, the crude incidence rate of AMI among the residents aged 35-, 45-, 55-, and 65- years in Xiaoshan District from 2017 to 2023 showed an upward trend over time, with AAPCs of 16.993%, 17.149%, 8.523%, and 5.002%, respectively. While the crude mortality rate in residents aged 35-, 75-, and 85-102 years showed an decreasing trend over time, with AAPCs of -23.977%, -15.467%, and -17.415%, respectively, but there was no statistically significant difference in the trends in incidence rate and mortality of other age groups (all P>0.05). ConclusionThe situation of AMI prevention and control among the registered residents in Xiaoshan District is not optimistic, and targeted measures should be strengthened for the male residents aged ≥35 years old.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 （Th17）/regulatory T cell （Treg） and Notch1 signaling pathway in mice with autoimmune thyroiditis （AIT）. MethodA total of 60 8-week-old NOD.H-2^h4 mice were randomly divided into the normal group， model group， western medicine group （selenium yeast tablet， 32.5 mg·kg^-1）， and low-dose （4.78 g·kg^-1·d^-1）， middle-dose （9.56 g·kg^-1·d^-1）， and high-dose （19 g·kg^-1·d^-1） Buzhong Yiqitang groups， with 10 mice in each group. The normal group was fed with distilled water， and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously， the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies （TGAb）， thyroid-stimulating hormone （TSH）， free triiodothyronine （FT3）， and free thyroid hormone （FT4） were detected by enzyme-linked immunosorbent assay （ELISA）， and thyroid tissue changes were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt （RORγt）， interleukin （IL）-17， forkhead box P3 （FoxP3）， IL-10， Notch1， and hair division-related enhancer 1 （Hes1） in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the normal group， the thyroid structure of the model group was severely damaged， and lymphocytes were infiltrated obviously. The levels of serum TGAb， FT3， and FT4 contents were significantly increased， and TSH content was significantly decreased （P<0.01）. The mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were significantly increased， while those of FoxP3 and IL10 were significantly decreased in the model group （P<0.01）. Compared with the model group， thyroid structural damage and lymphocyte infiltration were improved in the treatment groups， and serum TGAb， FT3， and FT4 contents were significantly decreased. TSH content was increased， and mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees （P<0.05， P<0.01）， and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice， and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.

ObjectiveThis paper aims to analyze the clinical characteristics and medication rationality of liver injury related to Epimedii Folium preparation （EP） and explore the possible risk factors of liver injury， so as to provide a reference for the safe clinical application of Epimedii Folium （EF）. MethodA retrospective analysis was conducted on liver injury cases related to EP from 2012 to 2016. ResultThe number of reported liver injury cases and the proportion of severe cases related to the use of EP show an increasing trend， indicating the objective existence of liver injury caused by EP. There are more cases of liver injury related to EP in women than in men， with an onset age range of 15-91 years old and a median onset age of 60 years old （median onset ages for men and women are 59 and 60 years old， respectively）. The time span from taking EP alone to the occurrence of liver injury is 1-386 days， with a median of 38 days. The time span from taking both EP and Western medicine to the occurrence of liver injury is 1-794 days， with a median of 34 days. EF-related liver injury preparations are mostly composed of traditional Chinese medicines that promote immunity and tonify the liver and kidney， indicating that immune stress in the body may be the mechanism of liver injury caused by the use of EP alone or in combination. There is no increasing trend of toxicity with time or dose in the liver injury caused by EP. By further exploring its risk factors， it is found that patients have unreasonable medication methods such as excessive dosage， repeated use， and multi-drug combination， which may also be one of the important risk factors for EF-related liver injury. ConclusionEP has a certain risk of liver injury and should be emphasized in clinical diagnosis and treatment. Immune stress may be the mechanism of liver injury caused by EP， and in clinical use， it is necessary to be vigilant about the risk of liver injury caused by unreasonable use and combined use with Western medicine.

Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95％CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.

Objective To analyze the literature on artificial intelligence in forensic research from 2012 to 2022 in the Web of Science Core Collection Database,to explore research hotspots and developmen-tal trends.Methods A total of 736 articles on artificial intelligence in forensic medicine in the Web of Science Core Collection Database from 2012 to 2022 were visualized and analyzed through the litera-ture measuring tool CiteSpace.The authors,institution,country(region),title,journal,keywords,cited references and other information of relevant literatures were analyzed.Results A total of 736 articles published in 220 journals by 355 authors from 289 institutions in 69 countries(regions)were identi-fied,with the number of articles published showing an increasing trend year by year.Among them,the United States had the highest number of publications and China ranked the second.Academy of Forensic Science had the highest number of publications among the institutions.Forensic Science Inter-national,Journal of Forensic Sciences,International Journal of Legal Medicine ranked high in publica-tion and citation frequency.Through the analysis of keywords,it was found that the research hotspots of artificial intelligence in the forensic field mainly focused on the use of artificial intelligence technol-ogy for sex and age estimation,cause of death analysis,postmortem interval estimation,individual identification and so on.Conclusion It is necessary to pay attention to international and institutional cooperation and to strengthen the cross-disciplinary research.Exploring the combination of advanced ar-tificial intelligence technologies with forensic research will be a hotspot and direction for future re-search.

Professor Lau Wanyee, a member of the Chinese Academy of Sciences and a pro-fessor at the Chinese University of Hong Kong, actively advocates conducting clinical researches through "planting fruit trees" and "growing orchards", aiming to cultivate a team of dual-skilled talents in clinical practice and research, effectively improve the scientific and technological level of clinical medicine in China, make voice heard in the international medical science field, and better serve human health. He organized a clinical research training course in scholars′ forum for Hepatobiliary Young Expert Working Group of Chinese College of Surgeons. Throughout three sessions of the training course, a distinct theme was focused on how to enhance the level of clinical research in China and make voice heard by the international scholars. A group of multi-dimensional experts were gathered, including experts from surgery, methodology, and management, as well as both renowned experts and young talents. A lively teaching model was adopted, combining guided presentations with interactive discussion and debate sessions. A clean and upright academic spirit was strongly advocated, in which international rules were adopted to conduct in-depth analysis and sharp criticism of seven proposed clinical research projects and four published papers with high international influence to find quarrel in a straw. This clinical research training course provides a new model of guidance for young physicians in conducting clinical research. As a result, all attendees felt deeply educated and benefited greatly from the training session. This training activity not only laid a solid foundation for the development of scientization, standardization, and internationali-zation of clinical research in digestive surgery in China, but also demonstrated a correct path for cultivating a group of young and middle-aged clinical medical scientists with scientific spirit.

ObjectiveTo explore the mechanism of Buzhong Yiqitang in ameliorating inflammatory injury in autoimmune thyroiditis (AIT) mice based on the Toll-like receptor 4（TLR4）/nuclear transcription factor-kappa B（NF-κB）/absent in melanoma 2（AIM2）inflammasome signaling pathway. MethodThe 120 genetically susceptible 8-week-old NOD.H-2^h4 mice were selected and randomly divided into control group， model group， low， medium and high dose groups of Buzhong Yiqitang （4.78， 9.56， 19.12 g·kg^-1）， and western medicine group （selenium yeast tablets， 3.033×10^-5 g·kg^-1）. The AIT model mice in each group drank ad libitum 0.05% sodium iodide aqueous solution for 8 weeks to establish the AIT model， and the control group drank ad libitum distilled water. Eight weeks later， the mice in each dosing group were divided into groups and gavage. The swelling of thyroid tissue was observed with the naked eye， and the weight of spleen was weighed. The content of serum inflammatory factors interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， and Real-time PCR was used to detect the expression of HMGB1， TLR4， AIM2， NF-κB p65，apoptosis-associated speck-like protein（ASC），cysteinyl aspartate-specific protease-1（Caspase-1）， IL-1β mRNA. Western blot was used to detect the expression of high motility group protein 1 （HMGB1）， TLR4， AIM2， NF-κB p65， phosphorylation（p）-NF-κB p65， ASC， Caspase-1， and IL-1β proteins in thyroid tissue， and immunofluorescence staining was used to observe the protein expression of HMGB1， AIM2， and NF-κB p65 in thyroid tissue of mice. ResultCompared with the control group， the thyroid tissue of mice in the model group was significantly swollen， the spleen quality was significantly increased， and the expression of HMGB1， TLR4， NF-κB p65， AIM2， ASC， Caspase-1， IL-1β in thyroid tissue was significantly increased （P<0.01）. Compared with the model group， the swelling of thyroid tissue in mice in each dose group of Buzhong Yiqitang was improved， the quality of spleen was significantly reduced， and the expression of HMGB1， TLR4， AIM2， NF-κB p65， p-NF-κB p65， ASC， Caspase-1， IL-1β in thyroid tissue was significantly reduced （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT， and regulating the abnormal activation of the TLR4/NF-κB/AIM2 inflammasome signal pathway may be one of its intervention mechanisms.

ObjectiveTo investigate the mechanism of Buzhong Yiqitang in ameliorating ferroptosis in autoimmune thyroiditis （AIT） mice based on the nuclear factor erythroid 2-related factor 2 （Nrf2）/peroxisome proliferator-activated receptor γ （PPARγ）/glutathione peroxidase 4 （GPX4） pathway. Method120 SPF-grade 7-8-week-old NOD.H-2^h4 mice were randomly divided into control group， model group， low-， medium-， and high-dose Buzhong Yiqitang groups， and western medicine group， with 20 mice in each group. Except for the control group， all mice were fed with classic high-iodine water （0.05% NaI） to induce AIT models after 8 weeks. The low-， medium-， and high-dose Buzhong Yiqitang groups were administered 4.78， 9.56， 19.12 g·kg^-1 of Buzhong Yiqitang， respectively， via gavage. The western medicine group was given 3.033×10^-5 g·kg^-1 selenium yeast tablet suspension via gavage， while the control and model groups were given an equal volume of distilled water via gavage. After 8 weeks of continuous treatment， samples were collected. The pathological morphology of mouse thyroid tissue was observed through hematoxylin-eosin （HE） staining，the content of serumantithyroid peroxidase autoantibody（TPOAb）and anti-thyroglobulin antibodies（TGAb）was measured by enzyme-linked immunosorbent assay （ELISA），the kit was used to detect the levels of superoxide dismutase （SOD）， and malondialdehyde （MDA） in mouse serum. Immunofluorescence was used to detect the localized expression of GPX4 in thyroid tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression of Nrf2， PPARγ， solute carrier family 7 member 11 （SLC7A11）， solute carrier family 3 member 2 （SLC3A2）， lysolipid lecithin acyltransferase 3 （LPCAT3）， and GPX4 mRNA in thyroid tissue. Western blot was used to detect the expression of Nrf2， PPARγ， SLC7A11， SLC3A2， LPCAT3， and GPX4 proteins in thyroid tissue. ResultCompared with control group， model group under light microscopy showed significant lymphocyte infiltration in the thyroid tissue， significantly increased levels of TGAb and TPOAb in serum （P<0.01）， significantly increased MDA levels and decreased SOD levels in serum （P<0.01）， significantly decreased expression of Nrf2， PPARγ， SLC7A11， SLC3A2， and GPX4 （P<0.01） in thyroid tissue， while the expression of LPCAT3 was significantly increased （P<0.01）. Compared with model group， the Buzhong Yiqitang groups and the western medication group under light microscopy showed lymphocyte infiltration in the thyroid tissue of was decreased， significantly decreased levels of TPOAb and TGAb in serum （P<0.05，P<0.01）， decreased MDA levels and increased SOD levels in serum（P<0.05，P<0.01），significantly increased expression of Nrf2， PPARγ， SLC7A11， SLC3A2， and GPX4， while the expression of LPCAT3 was significantly decreased （P<0.05，P<0.01） in the thyroid tissue. Compared with western medication group， Buzhong Yiqitang groups showed significant overall trends in the expression of Nrf2， PPARγ， SLC7A11， SLC3A2， GPX4， and LPCAT3 （P<0.05，P<0.01）. ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT， and its mechanism of action may be related to the regulation of Nrf2/PPARγ/GPX4 to inhibit ferroptosis.

ObjectiveTo explore the mechanism of Buzhong Yiqitang in improving autoimmune thyroiditis （AIT） by regulating helper T cell 17（Th17） cells through microRNA-155 （miR-155）/Nedd4 family interaction protein 1 （Ndfip1）/phosphatase and tensin homology （Pten） axis. MethodThe 100 SPF grade 8 week-old NOD.H-2^h4 mice were fed with high iodine water （0.05% NaI） for 8 weeks， and AIT model was made. They were divided into model group， Buzhong Yiqitang low-，medium-，and high-dose groups （4.78，9.56，19.12 g·kg^-1·d^-1） and selenium yeast tablet group （3.033×10^-5 g·kg^-1） according to random number table method. There were 20 mice in each group and 20 mice in the control group. The control group and the model group were given the same amount of distilled water. After 8 weeks of continuous administration， Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression of miR-155-5p， Ndfip1， Pten， protein tyrosine kinase 1 （Jak1）， signaling and transcriptional activator 3 （Stat3） retinoic acid-associated orphan receptor γt （RORγt）， and interleukin-17 （IL-17） mRNA in mouse thyroid tissue. Western blot was used to detect the expression of Ndfip1， Pten， Jak1， Stat3， RORγt， and IL-17 proteins in mouse thyroid tissue， immunohistochemical method was used to detect the expression of Ndfip1 and Pten proteins in mouse thyroid tissue； flow cytometry was used to detect the proportion of Th17 cells in mouse spleen. ResultCompared with the control group， the proportion of Th17 cells was increased （P<0.01）. The expressions of miR-155-5p， Jak1， Stat3， RORγt and IL-17 were increased （P<0.01）， while the expressions of Ndfip1 and Pten were decreased （P<0.01）. Compared with model group， the proportion of Th17 cells was decreased （P<0.05，P<0.01）. The expressions of miR-155-5p， Jak1， Stat3， RORγt and IL-17 were decreased （P<0.05，P<0.01）， while the expressions of Ndfip1 and Pten were increased （P<0.05，P<0.01）. ConclusionThe application of Buzhong Yiqitang can improve the autoimmune disorder of AIT mice， the mechanism of which may be related to the regulation of Ndfip1/Pten axis by miR-155 and then the regulation of Th17 cell differentiation.