Ulcerative colitis （UC） is a chronic nonspecific inflammatory intestinal disease with a complex pathogenesis. Its recurrent attacks easily lead to persistent intestinal mucosal damage， resulting in a year-by-year increase in incidence and imposing a heavy burden on patients. Currently， the treatment of UC mainly relies on corticosteroids， immunosuppressants， and aminosalicylate preparations. However， these therapies are limited by significant side effects， strong drug resistance， and poor long-term prognosis. As one of the important inflammatory pathways， the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway can regulate the occurrence and development of UC through multiple pathways by modulating multiple downstream targets. Therefore， the JAK2/STAT3 signaling pathway offers a new research direction for the treatment of UC. Numerous studies have shown that the JAK2/STAT3 signaling pathway plays an important role in intestinal inflammatory responses， intestinal mucosal barrier damage， T helper cell 17 （Th17）/regulatory T cell （Treg） immune imbalance， intestinal epithelial cell apoptosis， and oxidative stress. Chinese medicine has attracted increasing attention because of its unique advantages， including fewer side effects， individualized diagnosis and treatment， and enhancement of efficacy with reduction of toxicity. In addition to traditional Chinese herbal formulas， more Chinese medicine monomers and extracts have played key roles because of their more precise therapeutic targets. In recent years， many studies have confirmed that Chinese medicine can exert therapeutic effects on UC by interfering with the JAK2/STAT3 signaling pathway， thereby alleviating intestinal inflammatory responses， repairing the intestinal mucosal barrier， regulating the balance of Th17/Treg immune cells， inhibiting intestinal epithelial cell apoptosis， and suppressing oxidative stress. This article summarizes and reviews recent research progress in this field from three aspects， including an overview of the JAK2/STAT3 signaling pathway， the relationship between the JAK2/STAT3 signaling pathway and UC， and the regulatory mechanisms of traditional Chinese medicine， with the aim of providing a theoretical basis for the future clinical treatment of UC and drug development.

Ulcerative colitis （UC） is a chronic nonspecific inflammatory intestinal disease with a complex pathogenesis. Its recurrent attacks easily lead to persistent intestinal mucosal damage， resulting in a year-by-year increase in incidence and imposing a heavy burden on patients. Currently， the treatment of UC mainly relies on corticosteroids， immunosuppressants， and aminosalicylate preparations. However， these therapies are limited by significant side effects， strong drug resistance， and poor long-term prognosis. As one of the important inflammatory pathways， the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway can regulate the occurrence and development of UC through multiple pathways by modulating multiple downstream targets. Therefore， the JAK2/STAT3 signaling pathway offers a new research direction for the treatment of UC. Numerous studies have shown that the JAK2/STAT3 signaling pathway plays an important role in intestinal inflammatory responses， intestinal mucosal barrier damage， T helper cell 17 （Th17）/regulatory T cell （Treg） immune imbalance， intestinal epithelial cell apoptosis， and oxidative stress. Chinese medicine has attracted increasing attention because of its unique advantages， including fewer side effects， individualized diagnosis and treatment， and enhancement of efficacy with reduction of toxicity. In addition to traditional Chinese herbal formulas， more Chinese medicine monomers and extracts have played key roles because of their more precise therapeutic targets. In recent years， many studies have confirmed that Chinese medicine can exert therapeutic effects on UC by interfering with the JAK2/STAT3 signaling pathway， thereby alleviating intestinal inflammatory responses， repairing the intestinal mucosal barrier， regulating the balance of Th17/Treg immune cells， inhibiting intestinal epithelial cell apoptosis， and suppressing oxidative stress. This article summarizes and reviews recent research progress in this field from three aspects， including an overview of the JAK2/STAT3 signaling pathway， the relationship between the JAK2/STAT3 signaling pathway and UC， and the regulatory mechanisms of traditional Chinese medicine， with the aim of providing a theoretical basis for the future clinical treatment of UC and drug development.

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis. Crosstalk between autophagy deficiency and inflammation response in foam cells (FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized low-density lipoprotein (ox-LDL) leads to abnormal crosstalk between autophagy and inflammation, thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4 (BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation (LLPS) on the regulatory regions of inflammatory genes. Curcumin (Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.

Objective:To evaluate the rationality of diving procedures and medical support through monitoring the stress, nutrition, and sleep quality of divers.Methods:The vital signs of divers were recorded by the monitor designed for high pressure condition. The bubble escape during decompression was evaluated by Doppler bubble monitor. The stress levels of divers were evaluated by the Stanford acute stress reaction questionnaire (SASRQ), and the sleep qualities of divers were evaluated by Pittsburgh sleep quality index (PSQI). The post-diving effects were evaluated by the tests of blood routine and blood biochemistry, and MRI examination of large joints (bilateral shoulders, hips, and knees).Results:The vital signs of the four divers were stable throughout the training, and there was no significant difference in the mean values of vital signs in each stage ( P>0.05). During the decompression, all Doppler bubble monitoring results were below level 2. The total scores of SASRQ before and after diving were both lower than 57 points, indicating a moderate and low stress level; the stress levels of divers decreased slightly after surfacing, but the differences were not statistically significant ( t=1.464, P=0.239). Before and after diving, the divers’ sleep quality was good, but it decreased after surfacing, and the differences were statistically significant ( t=-4.899, P=0.016). The results of blood routine test, biochemical test, and MRI of bilateral shoulders and hips of the four divers after diving were normal; the results of knee MRI showed that only one diver had a small amount of joint effusion. Conclusion:The physical and mental health of the divers in this training maintained good, indicating the procedures of and the medical support for the diving were safe and effective.

Objective:To monitor and analyze the divers’ body load during hyperbaric exposure in deep heliox saturation diving at sea, so as to provide reference for safeguarding the safety and health of divers.Methods:The heart rate and rating of perceived exertion (RPE) of the divers were taken to monitor their body loads and the results were analyzed.Results:The heart rates of the four divers were stable. At 6: 30 (63 m) on the third day of decompression, diver 1 had a very low heart rate of 43 beats/min and diver 3 had a heart rate of 53 beats/min. There was no statistically significant difference in the mean heart rates of divers during saturation exposure and each time point of decompression with those before entering the cabin. The overall RPE results of divers ranged from 6 to 16 points, and the overall trend of development was consistent with the pressure change; the highest load was shown in the stage from 100 m stable pressure to the end of excursion diving, while the loads in other stages were relatively small. The mean value of RPE before entering the cabin was slightly higher than that in the pressurized stage, and it reached the peak in the excursion diving stage and then remained stable in the decompression stage. The RPE results of divers in the second diving bell at the end of excursion diving stage were significantly higher than those before entering the cabin ( t=-4.700, P=0.018). Conclusion:It is of important value to guarantee the operation safety by monitoring the divers’ body loads under high pressure. The combination of monitoring heart rate and RPE results can accurately reflect the body load and is conducive to the safety of diving operation.

Objective:To evaluate the rationality of diving procedures and medical support through monitoring the stress, nutrition, and sleep quality of divers.Methods:The vital signs of divers were recorded by the monitor designed for high pressure condition. The bubble escape during decompression was evaluated by Doppler bubble monitor. The stress levels of divers were evaluated by the Stanford acute stress reaction questionnaire (SASRQ), and the sleep qualities of divers were evaluated by Pittsburgh sleep quality index (PSQI). The post-diving effects were evaluated by the tests of blood routine and blood biochemistry, and MRI examination of large joints (bilateral shoulders, hips, and knees).Results:The vital signs of the four divers were stable throughout the training, and there was no significant difference in the mean values of vital signs in each stage ( P>0.05). During the decompression, all Doppler bubble monitoring results were below level 2. The total scores of SASRQ before and after diving were both lower than 57 points, indicating a moderate and low stress level; the stress levels of divers decreased slightly after surfacing, but the differences were not statistically significant ( t=1.464, P=0.239). Before and after diving, the divers’ sleep quality was good, but it decreased after surfacing, and the differences were statistically significant ( t=-4.899, P=0.016). The results of blood routine test, biochemical test, and MRI of bilateral shoulders and hips of the four divers after diving were normal; the results of knee MRI showed that only one diver had a small amount of joint effusion. Conclusion:The physical and mental health of the divers in this training maintained good, indicating the procedures of and the medical support for the diving were safe and effective.

Objective:To monitor and analyze the divers’ body load during hyperbaric exposure in deep heliox saturation diving at sea, so as to provide reference for safeguarding the safety and health of divers.Methods:The heart rate and rating of perceived exertion (RPE) of the divers were taken to monitor their body loads and the results were analyzed.Results:The heart rates of the four divers were stable. At 6: 30 (63 m) on the third day of decompression, diver 1 had a very low heart rate of 43 beats/min and diver 3 had a heart rate of 53 beats/min. There was no statistically significant difference in the mean heart rates of divers during saturation exposure and each time point of decompression with those before entering the cabin. The overall RPE results of divers ranged from 6 to 16 points, and the overall trend of development was consistent with the pressure change; the highest load was shown in the stage from 100 m stable pressure to the end of excursion diving, while the loads in other stages were relatively small. The mean value of RPE before entering the cabin was slightly higher than that in the pressurized stage, and it reached the peak in the excursion diving stage and then remained stable in the decompression stage. The RPE results of divers in the second diving bell at the end of excursion diving stage were significantly higher than those before entering the cabin ( t=-4.700, P=0.018). Conclusion:It is of important value to guarantee the operation safety by monitoring the divers’ body loads under high pressure. The combination of monitoring heart rate and RPE results can accurately reflect the body load and is conducive to the safety of diving operation.

OBJECTIVE:To observe clinical efficacy and safety of mesalazine combined with Kangfuxin solution retention en-ema in the treatment of active ulcerative colitis(UC). METHODS:A total of 120 patients diagnosed as active UC selected from gastroenterology department of our hospital during Mar. 2012 to Aug. 2014 were divided into observation group and control group according to random number table,with 60 cases in each group. Both groups received conventional treatment of active UC. Control group was additionally given Mesalazine enteric coated tablets 1 g,tid,on the basis of routine treatment.Observation group was ad-ditionally given Kangfuxin solution 30 mL diluted with normal saline 150 mL for enema,qd,on the basis of control group. Both groups were treated for 30 d. The serum levels of TNF-α,IL-1,IL-8,IL-10,SOD,NO and LPO were observed in 2 groups be-fore and after treatment;clinical efficacies,recurrence rates,colonoscopy efficacies and the occurrence of ADR were compared be-tween 2 groups. RESULTS:Before treatment,there was no statistical significance in the serum levels of TNF-α,IL-1,IL-8, IL-10,SOD,NO or LPO between 2 groups(P>0.05).After treatment,the serum levels of TNF-α,IL-1,IL-8,NO and LPO in 2 groups were decreased significantly,while the serum levels of IL-10 and SOD were increased significantly;the serum levels of TNF-α,IL-1,IL-8,NO and LPO in observation group were significantly lower than control group,while the serum levels of IL-10 and SOD were significantly higher than control group,with statistical significance(P<0.05). Clinical response rate,recur-rence rate and colonoscopy response rate of observation group were 83.3%,11.7% and 88.3%,which were significantly better than 66.7%,30.0%,70.0%of control group,with statistical significance(P<0.05).There was no statistical significance in the in-cidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Mesalazine combined with Kangfuxin solution can effectively alle-viate inflammatory reaction in patients with active UC,and reduce oxygen free radical damage with good safety.

Adult ; Aged ; Altitude Sickness ; metabolism ; Bone Marrow ; metabolism ; Chronic Disease ; Humans ; Male ; Middle Aged ; Peptide Fragments ; metabolism