Ulcerative colitis （UC） is a chronic， non-specific intestinal inflammatory disease. Its pathogenesis is complex， involving interactions among genetic， immune， and environmental factors， and remains incompletely elucidated. Mitochondrial damage can trigger the abnormal release of mitochondrial damage-associated molecular patterns （mtDAMPs）， activating inflammatory pathways and thereby exacerbating the inflammatory response in UC. Mitophagy， a core mitochondrial quality control mechanism， can clear damaged mitochondria and effectively reduce the abnormal release of mtDAMPs and the accumulation of harmful substances， thereby mitigating inflammatory damage resulting from mitochondrial dysfunction. Mitophagy plays a crucial role in maintaining the integrity of the intestinal epithelial barrier function and in the prevention and intervention of UC. Notably， the function of the spleen governing transportation and transformation in traditional Chinese medicine shares similarities with the role of mitochondria in energy transformation and substance metabolism. Furthermore， the pathological state of the spleen failing in transportation and transformation may be related to mitochondrial dysfunction， while the pathogenic characteristics of "endogenous turbid pathogen" align with the inflammatory cascade responses triggered by abnormal release of mtDAMPs. Based on this theoretical correlation， this paper aims to explore the correlation between the traditional Chinese medicine theory of "spleen dysfunction in essence distribution leading to endogenous turbid pathogens" and mitophagy. Using the correlation as an entry point， the potential role of mitophagy in the pathogenesis of UC was elucidated. Additionally， by considering the epidemiological characteristics of UC in the Southwest region of China， a new thinking for the treatment of UC from the perspective of turbid pathogens was proposed based on the "fortifying the spleen and resolving turbidity" method to provide theoretical support and research enlightenment for further exploring the prevention and treatment of UC with traditional Chinese medicine.

OBJECTIVE To explore the mechanism of Jiawei xiaochaihu decoction against hippocampal neuronal apoptosis in acute epileptic model mice. METHODS Thirty-six male KM mice were randomly divided into four groups with 9 mice in each group： normal control group （normal saline）， epilepsy model group （normal saline）， Jiawei xiaochaihu decoction group [7 g/（kg·d）] and carbamazepine group [positive control， 30 mg/（kg·d）]. Except for the normal control group， the acute epilepsy model was established in the other groups. After successful modeling， mice in each group were given corresponding drugs or normal saline by intragastric administration once a day for 2 consecutive weeks. After drug intervention， the ultrastructure and pathological morphology of hippocampal CA1 region were observed. The number of TUNEL-positive cells in hippocampus was detected， and the expression levels of protein kinase B （AKT）， Caspase-3， B-cell lymphoma-extra large （Bcl-xL）， Bcl-2-associated X protein （Bax）， as well as the ratio of phosphorylated AKT（p-AKT） to AKT were determined. RESULTS Compared with the normal control group， severe ultrastructural and pathological damages were observed in the hippocampal CA1 region of epilepsy model group； the number of TUNEL-positive cells was significantly increased （ P ＜0.05）. The expression levels of p-AKT and Bcl-xL were significantly down-regulated （ P ＜0.05）， while the Bax and Caspase-3 were significantly up-regulated （ P ＜0.05），accompanied by a remarkable decrease of p-AKT/AKT ratio （ P ＜0.05）. Compared with the epilepsy model group， hippocampal tissue ultrastructure， pathological damage， and the aforementioned indicators were significantly improved in Jiawei xiaochaihu decoction group （ P ＜0.05）. CONCLUSIONS Jiawei xiaochaihu decoction can inhibit hippocampal neuronal apoptosis in acute epileptic mice， and its mechanism may be related to activating AKT phosphorylation， increasing p-AKT/AKT ratio， up-regulating Bcl-xL expression and down-regulating the expression of Bax and Caspase-3.

OBJECTIVE To explore the mechanism of Jiawei xiaochaihu decoction against hippocampal neuronal apoptosis in acute epileptic model mice. METHODS Thirty-six male KM mice were randomly divided into four groups with 9 mice in each group： normal control group （normal saline）， epilepsy model group （normal saline）， Jiawei xiaochaihu decoction group [7 g/（kg·d）] and carbamazepine group [positive control， 30 mg/（kg·d）]. Except for the normal control group， the acute epilepsy model was established in the other groups. After successful modeling， mice in each group were given corresponding drugs or normal saline by intragastric administration once a day for 2 consecutive weeks. After drug intervention， the ultrastructure and pathological morphology of hippocampal CA1 region were observed. The number of TUNEL-positive cells in hippocampus was detected， and the expression levels of protein kinase B （AKT）， Caspase-3， B-cell lymphoma-extra large （Bcl-xL）， Bcl-2-associated X protein （Bax）， as well as the ratio of phosphorylated AKT（p-AKT） to AKT were determined. RESULTS Compared with the normal control group， severe ultrastructural and pathological damages were observed in the hippocampal CA1 region of epilepsy model group； the number of TUNEL-positive cells was significantly increased （ P ＜0.05）. The expression levels of p-AKT and Bcl-xL were significantly down-regulated （ P ＜0.05）， while the Bax and Caspase-3 were significantly up-regulated （ P ＜0.05），accompanied by a remarkable decrease of p-AKT/AKT ratio （ P ＜0.05）. Compared with the epilepsy model group， hippocampal tissue ultrastructure， pathological damage， and the aforementioned indicators were significantly improved in Jiawei xiaochaihu decoction group （ P ＜0.05）. CONCLUSIONS Jiawei xiaochaihu decoction can inhibit hippocampal neuronal apoptosis in acute epileptic mice， and its mechanism may be related to activating AKT phosphorylation， increasing p-AKT/AKT ratio， up-regulating Bcl-xL expression and down-regulating the expression of Bax and Caspase-3.

Objective:To investigate the relationship between oxygen consumption (VO 2), carbon dioxide production (VCO 2), and Oxygen Consumption/lactate (VO 2/Lac) with risk of death in patients with severe ARDS. Methods:A retrospective cohort study method was used, and the study subjects were hospitalized for >5 days adult patients with severe ARDS in the central intensive care unit of Henan Provincial People's Hospital from 1 March 2020 to 30 June 2023. The following patients were excluded: IC test was not completed on the 4th day of ICU admission, IC test results were unreliable, mechanical ventilation duration had exceeded 48 h at the time of ICU transfer or admission, palliative care patients and pregnant and parturient women. Using indirect calorimetry to determine VO 2 and VCO 2 values on the 4th day of admission, reviewing medical records to obtain general condition, disease information, blood gas analysis (including lactate value), diagnostic and therapeutic measures, and following up deaths by telephone and time of death. The primary outcome measure was death at 90 days, and the secondary outcome measure was death at 28 days, length of stay in ICU, total length of stay, and total hospitalization cost. Cox regression analysis and linear regression analysis were used to investigate the relationship between VO 2, VCO 2, VO 2/Lac and primary and secondary outcome indexes. Results:A total of 216 patients were enrolled, 78 patients (36.1%) died and 138 patients (63.9%) survived at 90 days. After correction for confounders, the results of multifactorial Cox regression analysis suggested that compared with the Q4 group, HR (95% CI) for 90-day risk of death in the VO 2 Q1 and Q2 groups was 3.21 (1.38, 7.49) and 3.24 (1.42, 7.38), and HR (95% CI) for 90-day risk of death in the VCO 2 Q1, Q2 and Q3 groups was 5.88 (2.33, 14.84), 4.26 (1. 60, 11.34) and 3.54 (1.34, 9.35), respectively, and the HR (95% CI) for 90-day risk of death in the VO 2/Lac Q1, Q2 and Q3 groups were 8.72 (3.01, 25.25), 8.43 (2.91, 24.47) and 4.04 (1.34, 12.17) respectively. P-trends were all <0.05, indicating that VO 2, VCO 2 and VO 2/Lac were linearly and negatively associated with the risk of 90-day mortality. In addition, VO 2, VCO 2, and VO 2/Lac were negatively associated with 28-day risk of death and higher VO 2/Lac was negatively associated with length of ICU stay. Conclusions:VO 2, VCO 2 and VO 2/Lac were negatively associated with 90-day mortality risk and 28-day mortality risk in patients with severe ARDS and may be independent risk factors predicting mortality risk of such patients.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Objective To investigate the neuroprotective effect of ligustilide(LIG)-mediated phosphatase and tensin homolog(PTEN)-induced putative kinase 1(PINK1)/Parkin pathway on mitophagy in rats with cerebral ischemia-reperfusion injury.Methods 161 male Sprague Dawley(SD)rats were randomly divided into sham operation(Sham)group,model group,LIG low-dose group,LIG high-dose group,mitophagy inhibitor(Mdivi-1)group,LIG high-dose+Mdivi-1 group,and the positive drug Nimodipine(NMDP)group,each with 23 rats.A modified middle cerebral artery wire thrombus method was used to construct a cerebral ischemia/reperfusion model in rats,and the neurobehavioral scores of rats in each group were compared by Longa's five-point scale;the volume of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TCC)staining,the histopathology and ultrastructure of the hippocampus were examined by hematoxylin-eosin(HE)staining and transmission electron microscope(TEM).And the Na+-K+-Adenosine Triphosphate was measured by enzyme-linked immunosorbent assay(ELISA);double immunofluorescence staining for translocase of the outer membrane of mitochondrion 20(TOMM20)and Microtubule-associated protein 1 light chain 3(LC3)co-localized area percentage.Flow cytometry assay(FCM)to test the level of reactive oxygen(ROS);real-time fluorescence quantitative PCR(qRT-PCR)was used to measure the relative content of mitochondria in hippocampal neurons;and Western blot was performed to test the level of autophagy and the PINK1/Parkin pathway related protein expression.Results Compared with the Sham group,the neurological function score and cerebral infarction volume of the model group were increased,the hippocampal neurons showed pathological damage such as disordered arrangement,nucleolus disappearance and partial shrinkage of the nucleus and plasma,nuclear membrane rupture,swelling,membrane rupture and crista reduction of some mitochondria,a large number of autophagosomes were observed,and the colocalization area percentage of TOMM20 and LC3 was increased.TOMM20 and cytochrome C oxidase subunit IV isoform 1(COX4I1)in hippocampus and selective autophagy adaptor protein 62(p62)protein expression,mitochondrial encoded ATP synthase 6(mt-ATP6)/Ribosomal protein L13(Rpl13)ratio and Na+-K+-ATPase content decreased,while PINK1 and Parkin protein expression,LC3-II/I ratio and ROS relative content increased,and the differences were statistically significant(t=4.602～52.012,all P<0.01).Compared with the model group,the neurological function score,cerebral infarction volume,pathological and ultrastructural damage of hippocampal neurons were significantly improved in the LIG low,high dose and NMDP groups,and the differences were statistically significant(t=4.851～12.525,all P<0.01).The colocalization of TOMM20 and LC3 and the content of Na+-K+-ATPase were increased,while the expression of TOMM20,COX4I1 and p62 proteins and the mt-ATP6/Rpl13 ratio were decreased in the high-dose LIG group.The protein expression of PINK1 and Parkin,LC3-II/I ratio and ROS relative content were increased,and the differences were statistically significant(t=4.087～33.211,all P<0.01).Compared with the LIG high-dose group,the Mdivi-1 and LIG+Mdivi-1 groups had significantly decreased colocalization of TOMM20 and LC3 and Na+-K+-ATPase content,and significantly increased expression of TOMM20,COX4I1 and p62 proteins and mt-ATP6/Rpl13 ratio.The protein expression of PINK1 and Parkin,LC3-II/I ratio and ROS relative content were decreased,and the differences were statistically significant(t=4.008～43.415,all P<0.01).However,the percentage of TOMM20 and LC3 co-localization area,PINK1 and Parkin protein expression,LC3-II/I ratio and Na+-K+-ATPase content in the hippocampus of the LIG+Mdivi-1 group were higher than those of the Mdivi-1 group.The protein expression of COX4I1 and p62,mt-ATP6/Rpl13 ratio and ROS level were lower than those in MDIV-1 group,and the differences were statistically significant(t=3.721～21.513,all P<0.01).Conclusion LIG may activate mitophagy by regulating PINK1/Parkin signaling pathway to protect neurons from cerebral ischemia-reperfusion injury in rats.

Objective:To explore the clinical efficacy of three different surgical timings of modified cervical cerclage in twin pregnant women with cervical insufficiency.Methods:The clinical data of 73 twin pregnant women who underwent modified cervical cerclage and had pregnancy outcomes in Qilu Hospital of Shandong University (Qingdao) from April 2014 to July 2023 were retrospectively analyzed. According to the different timings of surgery, they were divided into prophylactic cerclage group, ultrasound-indicated cerclage group (further divided into cervical length (CL)≤15 mm and 15 mm10 mg/L was a risk factor for preterm birth before 34 weeks of gestation ( OR=5.230, 95% CI: 1.616-16.929; P=0.006). Conclusions:In twin pregnant women with cervical insufficiency, prophylactic cerclage has the same surgical effect as ultrasound-indicated cerclage, while both prophylactic cerclage and ultrasound-indicated cerclage could significantly improve maternal and fetal outcomes compared with emergency cerclage. Twin pregnancies with CL≤15 mm might benefit from cervical cerclage. Postoperative CRP>10 mg/L is an independent risk factor for preterm birth before 34 weeks of gestation.

Retrieving keyframes most relevant to text from small intestine videos with given labels can efficiently and accurately locate pathological regions. However, training directly on raw video data is extremely slow, while learning visual representations from image-text datasets leads to computational inconsistency. To tackle this challenge, a small bowel video keyframe retrieval based on multi-modal contrastive learning (KRCL) is proposed. This framework fully utilizes textual information from video category labels to learn video features closely related to text, while modeling temporal information within a pretrained image-text model. It transfers knowledge learned from image-text multimodal models to the video domain, enabling interaction among medical videos, images, and text data. Experimental results on the hyper-spectral and Kvasir dataset for gastrointestinal disease detection (Hyper-Kvasir) and the Microsoft Research video-to-text (MSR-VTT) retrieval dataset demonstrate the effectiveness and robustness of KRCL, with the proposed method achieving state-of-the-art performance across nearly all evaluation metrics.
Humans ; Video Recording ; Intestine, Small/diagnostic imaging* ; Machine Learning ; Image Processing, Computer-Assisted/methods* ; Algorithms

Objective To investigate the neuroprotective effect of ligustilide(LIG)-mediated phosphatase and tensin homolog(PTEN)-induced putative kinase 1(PINK1)/Parkin pathway on mitophagy in rats with cerebral ischemia-reperfusion injury.Methods 161 male Sprague Dawley(SD)rats were randomly divided into sham operation(Sham)group,model group,LIG low-dose group,LIG high-dose group,mitophagy inhibitor(Mdivi-1)group,LIG high-dose+Mdivi-1 group,and the positive drug Nimodipine(NMDP)group,each with 23 rats.A modified middle cerebral artery wire thrombus method was used to construct a cerebral ischemia/reperfusion model in rats,and the neurobehavioral scores of rats in each group were compared by Longa's five-point scale;the volume of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TCC)staining,the histopathology and ultrastructure of the hippocampus were examined by hematoxylin-eosin(HE)staining and transmission electron microscope(TEM).And the Na+-K+-Adenosine Triphosphate was measured by enzyme-linked immunosorbent assay(ELISA);double immunofluorescence staining for translocase of the outer membrane of mitochondrion 20(TOMM20)and Microtubule-associated protein 1 light chain 3(LC3)co-localized area percentage.Flow cytometry assay(FCM)to test the level of reactive oxygen(ROS);real-time fluorescence quantitative PCR(qRT-PCR)was used to measure the relative content of mitochondria in hippocampal neurons;and Western blot was performed to test the level of autophagy and the PINK1/Parkin pathway related protein expression.Results Compared with the Sham group,the neurological function score and cerebral infarction volume of the model group were increased,the hippocampal neurons showed pathological damage such as disordered arrangement,nucleolus disappearance and partial shrinkage of the nucleus and plasma,nuclear membrane rupture,swelling,membrane rupture and crista reduction of some mitochondria,a large number of autophagosomes were observed,and the colocalization area percentage of TOMM20 and LC3 was increased.TOMM20 and cytochrome C oxidase subunit IV isoform 1(COX4I1)in hippocampus and selective autophagy adaptor protein 62(p62)protein expression,mitochondrial encoded ATP synthase 6(mt-ATP6)/Ribosomal protein L13(Rpl13)ratio and Na+-K+-ATPase content decreased,while PINK1 and Parkin protein expression,LC3-II/I ratio and ROS relative content increased,and the differences were statistically significant(t=4.602～52.012,all P<0.01).Compared with the model group,the neurological function score,cerebral infarction volume,pathological and ultrastructural damage of hippocampal neurons were significantly improved in the LIG low,high dose and NMDP groups,and the differences were statistically significant(t=4.851～12.525,all P<0.01).The colocalization of TOMM20 and LC3 and the content of Na+-K+-ATPase were increased,while the expression of TOMM20,COX4I1 and p62 proteins and the mt-ATP6/Rpl13 ratio were decreased in the high-dose LIG group.The protein expression of PINK1 and Parkin,LC3-II/I ratio and ROS relative content were increased,and the differences were statistically significant(t=4.087～33.211,all P<0.01).Compared with the LIG high-dose group,the Mdivi-1 and LIG+Mdivi-1 groups had significantly decreased colocalization of TOMM20 and LC3 and Na+-K+-ATPase content,and significantly increased expression of TOMM20,COX4I1 and p62 proteins and mt-ATP6/Rpl13 ratio.The protein expression of PINK1 and Parkin,LC3-II/I ratio and ROS relative content were decreased,and the differences were statistically significant(t=4.008～43.415,all P<0.01).However,the percentage of TOMM20 and LC3 co-localization area,PINK1 and Parkin protein expression,LC3-II/I ratio and Na+-K+-ATPase content in the hippocampus of the LIG+Mdivi-1 group were higher than those of the Mdivi-1 group.The protein expression of COX4I1 and p62,mt-ATP6/Rpl13 ratio and ROS level were lower than those in MDIV-1 group,and the differences were statistically significant(t=3.721～21.513,all P<0.01).Conclusion LIG may activate mitophagy by regulating PINK1/Parkin signaling pathway to protect neurons from cerebral ischemia-reperfusion injury in rats.

BACKGROUND:Apoptosis plays an important role in secondary brain injury.Therefore,to explore the pathophysiological mechanism of promoting nerve cell survival after traumatic brain injury provides a new direction and theoretical basis for the prevention and treatment of traumatic brain injury. OBJECTIVE:To explore the expression changes of Lnx1 molecule in mammalian cortical neurons after brain injury and the possible mechanism involved in secondary brain injury. METHODS:Eighty adult SD rats were divided into 20 male and 20 female mice in sham operation group and 20 male and 20 female mice in traumatic brain injury group.The traumatic brain injury rat model was established by heavy falling method.At 6,12,24,48,and 72 hours after brain injury,the expression of related molecules in damaged cortical neurons was analyzed by RT-qPCR,western blot assay,and immunofluorescence staining. RESULTS AND CONCLUSION:(1)The brain tissue of traumatic brain injury group was bleeding and obvious tissue injury could be observed.Water content of brain tissue increased after traumatic brain injury.(2)Compared with the sham operation group,the expression of Lnx1 in cortical neurons after traumatic brain injury increased significantly at 24 hours after injury.(3)After traumatic brain injury,the expression of PBK and BCR protein decreased,and the pro-survival factor ctgf increased.(4)These findings suggest that after traumatic brain injury,the expression of Lnx1 is up-regulated in neurons,which may be due to the decrease of the expression of its target molecules PBK and BCR,and further promote the expression of living factor ctgf,which has a protective effect on the damaged neurons.