ObjectiveTo establish a mouse model of particulate matter 2.5 （PM_2.5）-induced dry eye and investigate whether Chufeng Yisuntang can ameliorate the PM_2.5-induced ocular surface damage by regulating the reactive oxygen species （ROS）/p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodsSixty 8-week-old male C57BL/6J mice were used. Ten were randomly selected as the control group. The remaining 50 mice received topical instillation of 1 drop （0.1 mL） of 5 g·L^-1 PM_2.5 suspension in both eyes， four times daily. Successfully modeled mice were randomized into four groups （n=10）： Model， p38 MAPK inhibitor， Chufeng Yisuntang， and combination （Chufeng Yisuntang at 7.3 g·kg^-1 + p38 MAPK inhibitor SB203580 at 5 mg·kg^-1）. Chufeng Yisuntang was administered via gavage， and the inhibitor group via intraperitoneal injection. The control and model groups received equal volumes of distilled water by gavage. All treatments lasted for 4 weeks. General conditions were dynamically observed. Tear secretion， tear film break-up time， and corneal fluorescein staining were assessed. After intervention for 4 weeks， hematoxylin and eosin （HE） staining was used to examine the histopathological changes. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure serum levels of ROS， malondialdehyde （MDA）， superoxide dismutase （SOD） 1， and SOD2. Western blot and Real-time PCR were employed to determine the protein and gene levels， respectively， of p38 MAPK， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cysteinyl aspartate-specific proteinase-3 （Caspase-3） in the corneal tissue. ResultsCompared with the control group， the model group exhibited reduced tear secretion volume and tear film breakup time， along with increased corneal fluorescein staining scores （P<0.01）. Compared with the model group， the Chufeng Yisuntang group， p38 MAPK inhibitor group， and combination group demonstrated increased tear secretion volume and tear film breakup time， along with decreased corneal fluorescein staining scores （P<0.01）. HE staining revealed that compared with the control group， the model group exhibited marked increases in corneal epithelial cell layers and epithelial thickness， along with reduced meibomian gland acini and intensely stained， densely packed nuclei around the acini. Compared with the model group， the Chufeng Yisuntang group， p38 MAPK inhibitor group， and combination group showed intact corneal structure， improved cell morphology， and reduced damage severity. ELISA revealed elevated ROS and MDA levels （P<0.01） and decreased SOD1 and SOD2 levels （P<0.01） in the model group compared with the control group. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination lowered ROS and MDA levels （P<0.01）， while raising SOD1 and SOD2 levels （P<0.05， P<0.01）. Western blot revealed that compared with the control group， the model group exhibited increased protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01） and reduced protein level of Bcl-2 （P<0.01）. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination down-regulated the protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， while up-regulating the protein level of Bcl-2 （P<0.01）. Compared with the Chufeng Yisuntang group， the combination group exhibited decreased protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01） and increased protein level of Bcl-2 （P<0.01）. Real-time PCR revealed that compared with the control group， the model group exhibited upregulated mRNA levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， and downregulated mRNA level of Bcl-2 （P<0.01）. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination down-regulated the mRNA levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， while up-regulating the mRNA level of Bcl-2 （P<0.05， P<0.01）. Compared with the Chufeng Yisuntang group， the combination group exhibited decreased mRNA levels of p38 MAPK， Bax， and Caspase-3 expression （P<0.05， P<0.01） and increased mRNA level of Bcl-2 （P<0.01）. ConclusionChufeng Yisuntang may partially protect against PM_2.5-induced corneal injury by inhibiting the ROS/p38 MAPK pathway， enhancing antioxidant defense， and reducing epithelial apoptosis.

ObjectiveThis paper aims to investigate the effects and mechanism of Mimenghua prescription in modulating the mitogen-activated protein kinase kinase （MEK）/rat sarcoma viral oncogene homolog （Ras）/rapidly accelerated fibrosarcoma kinase （Raf）/extracellular signal-regulated kinase （ERK） signaling pathway to inhibit inflammatory responses in a dry eye animal model. MethodsA total of 60 C57BL/6J mice （eight weeks old， half male and half female） were used in the experiment. Ten mice were randomly selected as the blank control group， while the remaining 50 were exposed to a controlled dry system and received instillation of 0.2% benzalkonium chloride （BAC） into the eyes for four weeks to establish a dry eye mouse model. After successful modeling， the mice were randomly divided into five groups： Model group， sodium hyaluronate group， and Mimenghua prescription groups with low dose （4.83 g·kg^-1）， medium dose （9.67 g·kg^-1）， and high dose （19.34 g·kg^-1）. The mice in the model group received an equal volume of normal saline via gavage for four weeks. The mice in the sodium hyaluronate group received instillation of sodium hyaluronate eye drops twice daily for 14 consecutive days. The tear secretion volume， tear film break-up time （TBUT）， and corneal fluorescein staining were evaluated once every two weeks. After four weeks of administration， mice were euthanized， and their lacrimal gland tissues and corneas were harvested. Hematoxylin-eosin （HE） staining was used to assess histopathological morphology. Western blot was performed to detect the protein expression levels of MEK， Ras， Raf， and ERK. Enzyme-linked immunosorbent assay （ELISA） was used to measure the contents and expressions of MEK， Ras， Raf， ERK， and interleukin （IL）-1β in lacrimal gland and corneal tissues of the mice in each group. Quantitative real-time polymerase chain reaction （Real-time PCR） was employed to determine mRNA expression levels of MEK， Ras， Raf， and ERK. ResultsThe Mimenghua prescription groups and the sodium hyaluronate group exhibited significantly increased tear secretion volume （P<0.05） and prolonged TBUT （P<0.05） after treatment. Ocular surface damage of mice was visibly recovered. Western blot results indicated that protein expression levels of MEK， Ras， Raf， and ERK in the lacrimal gland and corneal tissues were significantly downregulated in the sodium hyaluronate group and Mimenghua prescription group with high dose （P<0.05）. ELISA results showed that IL-1β levels were highest in the model group but significantly reduced in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）. Both ELISA and Real-time PCR results demonstrated that the expression levels of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues were significantly elevated in the model group （P<0.05）， but markedly downregulated in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）， suggesting that Mimenghua prescription can decrease the expressions of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues. ConclusionMimenghua prescription can reduce inflammatory responses， increase tear secretion， prolong TBUT， and promote corneal recovery by inhibiting the MEK， Ras， Raf， and ERK signaling pathways in lacrimal gland and corneal tissues.

AIM:To investigate the roles of up-regulated inwardly rectifier potassium channel 2.1(Kir2.1)in macrophage activation and cardiac inflammatory injury,in order to clarify the mechanism of Kir2.1 regulation in inflam-matory injury and cardiac repair.METHODS:The RAW264.7 macrophages were activated by lipopolysacharide(LPS)and treated with Kir2.1 agonist zacopride or lentivirus-Kir2.1 overexpression(Kir2.1-OE).Macrophages were randomly divided into control,LPS,LPS+zacopride(or LPS+Kir2.1-OE),and LPS+zacopride+BaCl2 groups.The effects of Kir2.1-OE and AG490[Janus kinase 2(JAK2)inhibitor]on the JAK2/signal transducer and activator of transcription 3(STAT3)signaling pathway in macrophages were also investigated.The expression of CD86,interleukin-6(IL-6)and Kir2.1 in M1 macrophages was detected by RT-qPCR or immunofluorescence staining.The expression of JAK2/STAT3 molecules was detected by Western blot.The RAW264.7 macrophages were incubated with LPS,LPS+zacopride or LPS+zacopride+BaCl2 for 12 h,and then co-cultured with H9C2(2-1)cardiomyocytes for 48 h.The expression of Kir2.1,IL-4,IL-6,IL-1β,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),caspase-3,cleaved caspase-3,calcium/calmodulin-dependent protein kinase II(CaMKII)and p-CaMKII in cardiomyocytes was detected by Western blot.We fur-ther compared the effects of zacopride and KN-93,a known CaMKII inhibitor,on cardiac CaMKII.After being incubated with LPS for 12 h and changed the medium,RAW264.7 macrophages were co-cultured with H9C2(2-1)cardiomyocytes which was pretreated with KN-93.The cardiomyocytes were divided into control,LPS,and LPS+KN-93 groups.The ex-pression of CaMKII and p-CaMKII were detected by Western blot.RESULTS:Zacopride inhibited LPS-induced M1-type polarization of macrophages in a Kir2.1-dependent manner as showed by a significant decrease in CD86(M1-type marker)and IL-6(P<0.05).Zacopride or Kir2.1-OE inhibited LPS-induced activation of JAK2/STAT3 inflammatory signaling pathway in macrophages,with effects similar to the JAK2 inhibitor AG490.The H9C2(2-1)cardiomyocytes were co-cul-tured with M1-polarized macrophages(P<0.05).Zacopride inhibited M1 macrophage-induced inflammatory injury in car-diomyocytes,which was manifested as decreased expression of IL-1β and IL-6,increased expression of IL-4,and de-creased apoptosis.Zacopride also inhibited activation of CaMKII in a Kir2.1-dependent manner in H9C2(2-1)cells co-cultured with macrophages(P<0.05).CONCLUSION:Up-regulation of Kir2.1 may inhibit LPS-induced M1-type polar-ization of macrophages via inhibiting JAK2/STAT3 signaling pathway.Up-regulation of macrophage Kir2.1 may play a pro-tective role in cardiac repair after myocardial infarction by negative regulation of CaMKII signaling.

Objective To evaluate the advantages of a real-time computer endoscopy-assisted system(EndoAngel)for colorectal lesions detection in colonoscopy.Methods 2 000 patients who underwent EndoAngel assisted colonoscopy and conventional colonoscopy were selected for the study in a single-center,self-controlled study.According to different examination methods,the patients were divided into artificial intelligence(AI)group and traditional colonoscopy group,each with 1 000 cases.The results were statistically analyzed and compared with the polyp detection rate and adenoma detection rate of the two groups using pathological diagnosis as the gold standard.Further subgroup analysis will be conducted based on the seniority of the operating physicians.Results AI group's polyp detection rate was higher(39.3％)than conventional colonoscopy group polyp detection rate(29.0％),with statistically significant difference(x2=23.59,P=0.000).Of these,the detection rates of hyperplastic polyps and adenomatous polyps were 19.1％and 25.2％,which were significantly higher than those of 12.4％and 20.8％in the conventional colonoscopy group,and the differences were statistically significant(x2=16.92,P=0.000;x2=5.46,P=0.019).Further subgroup analysis of the two groups by physician seniority,the polyp detection rate of AI low seniority group(36.6％)was higher than that of conventional colonoscopy low seniority group(20.40％),with a statistically significant difference(x2=32.20,P=0.000).Among them,the detection rates of hyperplastic polyp(17.8％)and adenomatous polyp(23.6％)in AI low seniority group were higher than those in the conventional colonoscopy low seniority group(12.8％vs 13.6％),and the differences were significant(x2=4.82,P=0.028;x2=16.51,P=0.000).There were no significant differences in adenomatous polyp detection rates between the two groups of senior physicians.Conclusion EndoAngel assisted system can improve the polyp detection rate of colonoscopy,especially for the effect of low seniority physicians is more significant.

Objective This study aims to analyze the factors influencing per capita current health expenditure in Guizhou Province from 2016 to 2022 using the gray correlation analysis method.Methods Based on the"SHA2011"accounting results of current health expenditure in Guizhou Province,as well as data from the"Guizhou Statistical Yearbook"and"Guizhou Health Statistical Yearbook",the gray correlation analysis method was used to analyze the factors influencing per capita current health expenditure in Guizhou Province from 2016 to 2022.Results The factors with the highest correlation to per capita current health expenditure in Guizhou Province were health expenditure(0.829),followed by the number of health technical personnel per thousand people(0.715),the number of practicing(assistant)physicians per thousand people(0.705),and per capita GDP(0.704).The factor with the lowest correlation was the proportion of the tertiary industry to GDP(0.543).Conclusion Health expenditure investment has the strongest correlation with per capita current health expenditure in Guizhou Province.Health re-source investment and health service capacity are the main influencing factors of per capita current health expenditure in Guizhou Province.At the same time,the impact of economic and social factors on current health expenditure should be fully recognized.

Objective:To compare the accuracy of a Chinese large language model (LLM) and radiologists in Chinese middle level professional qualification examination of radiology, and evaluate the quality of answer reasoning provided by the Chinese LLM.Methods:In this study, 100 high-quality questions were selected using stratified random sampling to form a test set. We asked the ERNIE Bot by dialogues on the website to provide the correct answers and answer reasoning for these questions. These questions were also answered by 15 radiologists with different levels of experience. The accuracy of Chinese LLM and that of radiologists were compared. Two radiologists evaluated the quality of answer reasoning using a 5-point semi-quantitative scale.Results:The accuracy of ERNIE Bot was 60.00%, which was lower than the median (interquartile) accuracy of 67.00% (64.00%, 73.00%) for radiologists, and the difference was statistically significant ( W=2.47, P=0.013). The word count of the reasoning provided by Ernie Bot was (196.44±99.25) words, with no significant difference in word count between correct and incorrect answer reasoning, which were (211.03±107.53) words and (174.55±81.84) words, respectively ( t=1.82, P=0.072). Among the correct answers, the quality of reasoning was scored as follows: 1 point for 3 questions, 2 points for 9 questions, 3 points for 12 questions, and 4 points for 36 questions. No reasoning received a score of 5. Conclusions:Chinese LLM demonstrates a certain level of medical knowledge and clinical reasoning ability, which can assist clinical teachers in educational activities. However, it is not yet able to independently tutor residents and lacks the ability of invitational and heuristic teaching.

Objective:To investigate the current status of Chinese-foreign cooperative education programs for medical majors, and to discuss the potential problems and development trends of this field.Methods:Related data were collected from the information platform of Chinese-Foreign Cooperation in Running Schools by Ministry of Education of the People's Republic of China, and the characteristics of Chinese-foreign cooperative education programs for medical majors were extracted for analysis. Categorical data were expressed as frequency (percentage), and continuous data were expressed as mean±standard deviation.Results:A total of 83 Chinese-foreign cooperative education programs for medical majors were included in the study, accounting for only 3.45% (83/2 406) of all programs. Chinese partners in these cooperative programs were mainly from East China (41 programs, 49.40%), while foreign partners were mainly from Europe (39 programs, 46.99%). The mean duration of these programs was (3.61±0.88) years, with an enrollment of (87.08±35.52) students. Most of the students were included in National General Higher Education Enrollment Plan (79 programs, 95.18%), and the main majors included nursing (39 programs, 46.99%), medical technology (19 programs, 22.89%), and clinical medicine (11 programs, 13.25%), with the main enrollment level of junior college (45 programs, 54.22%). Chinese partners in the cooperative programs mainly issued academic certificate (45 programs, 54.22%) or academic certificate plus degree certificate (36 programs, 43.37%), while most foreign partners did not issue such certificates (44 programs, 53.01%).Conclusions:There are several problems in Chinese-foreign cooperative education programs for medical majors, such as a limited number of programs, a significant regional difference, an imbalanced distribution of specialties, a low level of education, and inconsistency in issuance of certificates, which still requires further improvement and standardization. However, there are also high-level and high-quality programs for reference.

AIM:To investigate the roles of up-regulated inwardly rectifier potassium channel 2.1(Kir2.1)in macrophage activation and cardiac inflammatory injury,in order to clarify the mechanism of Kir2.1 regulation in inflam-matory injury and cardiac repair.METHODS:The RAW264.7 macrophages were activated by lipopolysacharide(LPS)and treated with Kir2.1 agonist zacopride or lentivirus-Kir2.1 overexpression(Kir2.1-OE).Macrophages were randomly divided into control,LPS,LPS+zacopride(or LPS+Kir2.1-OE),and LPS+zacopride+BaCl2 groups.The effects of Kir2.1-OE and AG490[Janus kinase 2(JAK2)inhibitor]on the JAK2/signal transducer and activator of transcription 3(STAT3)signaling pathway in macrophages were also investigated.The expression of CD86,interleukin-6(IL-6)and Kir2.1 in M1 macrophages was detected by RT-qPCR or immunofluorescence staining.The expression of JAK2/STAT3 molecules was detected by Western blot.The RAW264.7 macrophages were incubated with LPS,LPS+zacopride or LPS+zacopride+BaCl2 for 12 h,and then co-cultured with H9C2(2-1)cardiomyocytes for 48 h.The expression of Kir2.1,IL-4,IL-6,IL-1β,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),caspase-3,cleaved caspase-3,calcium/calmodulin-dependent protein kinase II(CaMKII)and p-CaMKII in cardiomyocytes was detected by Western blot.We fur-ther compared the effects of zacopride and KN-93,a known CaMKII inhibitor,on cardiac CaMKII.After being incubated with LPS for 12 h and changed the medium,RAW264.7 macrophages were co-cultured with H9C2(2-1)cardiomyocytes which was pretreated with KN-93.The cardiomyocytes were divided into control,LPS,and LPS+KN-93 groups.The ex-pression of CaMKII and p-CaMKII were detected by Western blot.RESULTS:Zacopride inhibited LPS-induced M1-type polarization of macrophages in a Kir2.1-dependent manner as showed by a significant decrease in CD86(M1-type marker)and IL-6(P<0.05).Zacopride or Kir2.1-OE inhibited LPS-induced activation of JAK2/STAT3 inflammatory signaling pathway in macrophages,with effects similar to the JAK2 inhibitor AG490.The H9C2(2-1)cardiomyocytes were co-cul-tured with M1-polarized macrophages(P<0.05).Zacopride inhibited M1 macrophage-induced inflammatory injury in car-diomyocytes,which was manifested as decreased expression of IL-1β and IL-6,increased expression of IL-4,and de-creased apoptosis.Zacopride also inhibited activation of CaMKII in a Kir2.1-dependent manner in H9C2(2-1)cells co-cultured with macrophages(P<0.05).CONCLUSION:Up-regulation of Kir2.1 may inhibit LPS-induced M1-type polar-ization of macrophages via inhibiting JAK2/STAT3 signaling pathway.Up-regulation of macrophage Kir2.1 may play a pro-tective role in cardiac repair after myocardial infarction by negative regulation of CaMKII signaling.

Objective:This study aims to explore the independent and interactive effects of childhood trauma (CT) and major depressive disorder (MDD) on amygdala subregion volumes and to examine whether volumetric changes in these subregions mediate the relationship between CT and depressive severity.Methods:A total of 129 MDD patients and 127 age- and sex-matched healthy controls were recruited from Nanjing Brain Hospital between October 2022 and November 2024. All participants underwent 3D-T 1 weighted MRI scans,and amygdala subregions were segmented using the FreeSurfer software. Depressive and anxiety symptoms were assessed with the 17-item Hamilton Depression Rating Scale (HAMD 17) and the Hamilton Anxiety Scale (HAMA),respectively. Childhood trauma exposure was evaluated via the Childhood Trauma Questionnaire (CTQ). Generalized linear models (GLM) were applied to analyze the main and interactive effects of MDD diagnosis (depression/healthy controls) and CT (presence/absence),adjusting for age,estimated intracranial volume,sex,medication history,and education years. Partial correlation and mediation analyses were conducted to explore associations between amygdala subregion volumes and clinical measures in MDD patients. Results:MDD diagnosis was independently associated with increased volumes in the right central nucleus ( Wald χ2=9.09, P=0.026) and medial nucleus ( Wald χ2=10.08, P=0.026). CT exposure was independently associated with reduced volumes in the right central nucleus ( Wald χ2=7.99, P=0.047) and medial nucleus ( Wald χ2=9.20, P=0.047). No significant interaction effects between MDD and CT were observed in any amygdala subregion. Mediation analysis revealed that reduced right medial nucleus volume partially mediated the relationship between total CTQ scores and depressive severity (proportion mediated: 26.69%,95% CI=0.002-0.060) and mediated the association between emotional neglect and depressive severity (proportion mediated: 26.75%,95% CI=0.006-0.150). Such mediating effects were not found for the right central nucleus. Conclusion:CT and MDD exhibit divergent patterns of influence on amygdala subregions. CT is linked to volumetric reductions,whereas MDD is associated with volumetric enlargement. Reduced volume of the right medial nucleus mediates the relationship between CT and depression severity.

Chronic heart failure(CHF)is a common end-stage manifestation of cardiovascular disease,and the"spleen-small intestine-heart"axis is its important mechanism.Current studies have shown that the"spleen"in TCM and mitochondria function are similar,and the physiological dysfunction of the"small intestine"is also closely related to intestinal bacterial dysbiosis,and the pathology of the spleen and the small intestine will be transmitted to the heart to accelerate the occurrence and development of CHF.Based on the relevant theory of spleen-small intestine-heart,this article described the correlation between abnormal mitochondrial energy metabolism and imbalance of intestinal flora and CHF from the aspects of the spleen,small intestine and heart,and believed that the essence of CHF is a pathological condition formed by mitochondrial energy metabolism crisis and intestinal microecological disorders,which could provide theoretical references for the TCM prevention and treatment of CHF.