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.

Tryptophan is an essential amino acid in all animals. After being metabolized through three pathways in the body, it generates many bioactive metabolites, which affect the physiological processes of the body and provide a basis for potential therapeutic targets of diseases, especially the Kynurenine pathway. This article introduces the roles of the three metabolic pathways of tryptophan in the occurrence and development of ulcerative colitis and colitis-associated colon cancer, with particular attention to the role of the Kynurenine pathway in immune regulation and its potential contradictory effects on ulcerative colitis and colitis-associated colon cancer.

Tryptophan is an essential amino acid in all animals. After being metabolized through three pathways in the body, it generates many bioactive metabolites, which affect the physiological processes of the body and provide a basis for potential therapeutic targets of diseases, especially the Kynurenine pathway. This article introduces the roles of the three metabolic pathways of tryptophan in the occurrence and development of ulcerative colitis and colitis-associated colon cancer, with particular attention to the role of the Kynurenine pathway in immune regulation and its potential contradictory effects on ulcerative colitis and colitis-associated colon cancer.

Pemphigus vulgaris (PV) is a group of autoimmune bullous diseases characterized by life-threatening intradermal blisters. Hashimoto thyroiditis (HT) is a kind of autoimmune disease with abnormal increase of thyroid peroxidase autoantibody (TPOAb), which is the thyroid specific antibody, leading to hypothyroidism. In recent years, the probability of HT in patients with PV is increasing, and the co-disease may be related to the effect of TPOAb autoantibody on oral keratinocytes. This article reviews the epidemiological relationship between PV and HT and the mechanism of TPOAb in their co-disease, in order to provide ideas for the diagnosis and treatment of both.

Pemphigus vulgaris (PV) is a group of autoimmune bullous diseases characterized by life-threatening intradermal blisters. Hashimoto thyroiditis (HT) is a kind of autoimmune disease with abnormal increase of thyroid peroxidase autoantibody (TPOAb), which is the thyroid specific antibody, leading to hypothyroidism. In recent years, the probability of HT in patients with PV is increasing, and the co-disease may be related to the effect of TPOAb autoantibody on oral keratinocytes. This article reviews the epidemiological relationship between PV and HT and the mechanism of TPOAb in their co-disease, in order to provide ideas for the diagnosis and treatment of both.

Objective:To provide basis for preventing flight safety accidents caused by hypoxia by exploring the subjective and objective performance of pilots in hypobaric hypoxia environment.Methods:The relevant data of pilots′ high altitude physiological training were retrospectively analyzed and a symptom questionnaire upon the training were summarized. The pilots were divided into excellent group (time of useful consciousness >6 min), good group (3 min ≤time of useful consciousness <6 min) and qualified group (2 min ≤time of useful consciousness <3 min) according to the time of useful consciousness. The hypoxia symptoms and physiological parameters of pilots in each group were statistically analyzed.Results:A total of 919 pilots were included, in which 416 were in excellent group, 490 were in good group and 13 were in qualified group. Among the 25 hypoxia symptoms, there were significant differences in the components of numbness and difficulty in calculation among 3 groups ( χ2=6.04, 7.79, P=0.049, 0.020), but there were no significant differences in the components of the other 23 hypoxia symptoms (all P>0.05). The changes of blood oxygen saturation were significant in group main effect, time main effect and their interaction ( F=25.65, 1 039.77, 25.22, all P<0.001). The change of heart rate was statistically significant in the main effect of time ( F=66.41, P<0.001) but in time main effect and their interaction (both P>0.05). There was no significant difference in respiratory rate among group main effect, time main effect and their interaction (all P>0.05). The distribution and variation of blood oxygen saturation were statistically significant differences among the 3 groups in the ranges of 81%-90%, 71%-80% and 65%-70% ( H=125.93, 372.83, 13.10, all P≤0.001) unlike the range of 91%-100% ( H=2.48, P=0.289). Conclusions:The excellent group showed better blood oxygen saturation maintaining and useful consciousness time enduring capabilities, and those imply them in better performance and consciousness that enable the operation in hypoxic environment with more ease.

Objective:To provide scientific basis for pilots′ hypoxia training by comparing and analyzing the effects of hypoxia training under normobaric and hypobaric environments.Methods:Forty-two healthy subjects were selected. The pilot reduced oxygen breathing device and hypobaric chamber were used to simulate 7 500 m hypoxia training, and blood oxygen saturation, heart rate, respiratory rate and hypoxia endurance time were monitored and recorded. The hypoxia symptom questionnaire was filled out by the subjects after 2 training sessions. The hypoxia endurance time and hypoxia tolerance grade of normobaric and hypobaric hypoxia training were analyzed, and the differences of blood oxygen saturation and hypoxia symptoms were compared between 2 hypoxia trainings.Results:Forty-two subjects completed the normobaric and hypobaric hypoxia trainings. The survival curve analysis of hypoxia endurance time showed that the median hypoxia endurance time of normobaric and hypobaric hypoxia training was [3.17(2.70, 3.64)] min and [3.67(3.46, 3.88)] min respectively, with no significant difference ( P>0.05). There was no significant difference in the grade distribution of hypoxia tolerance between 2 hypoxia trainings ( P>0.05). The blood oxygen saturation curves of 2 hypoxia trainings were basically consistent. There was no significant difference between 2 hypoxia trainings on blood oxygen saturation, heart rate and respiratory rate (all P>0.05). There were significant differences in difficulty in calculation, difficulty in concentration and with palpitation ( χ2=4.81, 3.97, 3.98, P=0.028, 0.046, 0.046). Conclusions:The analysis showed that most physiological responses and subjective symptoms of pilots are quite similar in the normobaric and hypobaric hypoxia training at simulated 7 500 m. Both normobaric and hypobaric exposures show the similar hypoxia training effect.

Objective:To provide basis for preventing flight safety accidents caused by hypoxia by exploring the subjective and objective performance of pilots in hypobaric hypoxia environment.Methods:The relevant data of pilots′ high altitude physiological training were retrospectively analyzed and a symptom questionnaire upon the training were summarized. The pilots were divided into excellent group (time of useful consciousness >6 min), good group (3 min ≤time of useful consciousness <6 min) and qualified group (2 min ≤time of useful consciousness <3 min) according to the time of useful consciousness. The hypoxia symptoms and physiological parameters of pilots in each group were statistically analyzed.Results:A total of 919 pilots were included, in which 416 were in excellent group, 490 were in good group and 13 were in qualified group. Among the 25 hypoxia symptoms, there were significant differences in the components of numbness and difficulty in calculation among 3 groups ( χ2=6.04, 7.79, P=0.049, 0.020), but there were no significant differences in the components of the other 23 hypoxia symptoms (all P>0.05). The changes of blood oxygen saturation were significant in group main effect, time main effect and their interaction ( F=25.65, 1 039.77, 25.22, all P<0.001). The change of heart rate was statistically significant in the main effect of time ( F=66.41, P<0.001) but in time main effect and their interaction (both P>0.05). There was no significant difference in respiratory rate among group main effect, time main effect and their interaction (all P>0.05). The distribution and variation of blood oxygen saturation were statistically significant differences among the 3 groups in the ranges of 81%-90%, 71%-80% and 65%-70% ( H=125.93, 372.83, 13.10, all P≤0.001) unlike the range of 91%-100% ( H=2.48, P=0.289). Conclusions:The excellent group showed better blood oxygen saturation maintaining and useful consciousness time enduring capabilities, and those imply them in better performance and consciousness that enable the operation in hypoxic environment with more ease.

Objective:To provide scientific basis for pilots′ hypoxia training by comparing and analyzing the effects of hypoxia training under normobaric and hypobaric environments.Methods:Forty-two healthy subjects were selected. The pilot reduced oxygen breathing device and hypobaric chamber were used to simulate 7 500 m hypoxia training, and blood oxygen saturation, heart rate, respiratory rate and hypoxia endurance time were monitored and recorded. The hypoxia symptom questionnaire was filled out by the subjects after 2 training sessions. The hypoxia endurance time and hypoxia tolerance grade of normobaric and hypobaric hypoxia training were analyzed, and the differences of blood oxygen saturation and hypoxia symptoms were compared between 2 hypoxia trainings.Results:Forty-two subjects completed the normobaric and hypobaric hypoxia trainings. The survival curve analysis of hypoxia endurance time showed that the median hypoxia endurance time of normobaric and hypobaric hypoxia training was [3.17(2.70, 3.64)] min and [3.67(3.46, 3.88)] min respectively, with no significant difference ( P>0.05). There was no significant difference in the grade distribution of hypoxia tolerance between 2 hypoxia trainings ( P>0.05). The blood oxygen saturation curves of 2 hypoxia trainings were basically consistent. There was no significant difference between 2 hypoxia trainings on blood oxygen saturation, heart rate and respiratory rate (all P>0.05). There were significant differences in difficulty in calculation, difficulty in concentration and with palpitation ( χ2=4.81, 3.97, 3.98, P=0.028, 0.046, 0.046). Conclusions:The analysis showed that most physiological responses and subjective symptoms of pilots are quite similar in the normobaric and hypobaric hypoxia training at simulated 7 500 m. Both normobaric and hypobaric exposures show the similar hypoxia training effect.

Objective To investigate the effect and underlying mechanism of Qingguang’an Granules (青光安颗粒剂, QGAG) on mitochondrial autophagy (mitophagy) of retinal ganglion cells (RGCs) in rats with chronic ocular hypertension (COH). Methods Sixty Sprague Dawley (SD) rats, half males and half females, were randomly assigned to three groups: the control, model, and QGAG (2.5 g/kg) groups, with 20 rats in each group. Rats’ model of COH was established by cauterizing episcleral veins in the model group and QGAG group. Three weeks after successful modeling, rats in the QGAG group were intragastrically administered with QGAG, while rats in the control group and the model group received an equal dose of normal saline. After three months of intragastric administration, intraocular pressure (IOP) of all rats was measured. The mitophagy was monitored by the immunofluorescence method, the mitochondrial membrane potential was measured using the JC-1 method, and the morphological changes of mitophagy in RGCs were observed by transmission electron microscopy. Meanwhile, rat RGCs were labeled using the fluorescent gold method, and RGCs density in each group was calculated. Moreover, RGCs apoptosis was observed by TdT-mediated dUTP Nick-End Labeling (TUNEL) assay. Finally, the expression levels of Parkin, optineurin, microtubule-associated protein 1 light chain 3-II/microtubule-associated protein 1 light chain 3-I (LC3-II/LC3-I), recombinant lysosomal associated membrane protein 1 (LAMP1), and B-cell lymphoma-2 (Bcl-2) in RGCs were determined by Western blot assay. The corresponding mRNAs were detected through quantitative real-time polymerase chain reaction (qRT-PCR). Results The QGAG reduced IOP in COH rats, and inhibited mitophagy and apoptosis of RGCs (P < 0.05). Besides, the QGAG significantly increased the expression levels of Parkin and Bcl-2 (P < 0.05), and inhibited the expression levels of optineurin, LAMP1, and LC3-II/LC3-I (P < 0.05) in RGCs of COH rats. Conclusion The QGAG can inhibit mitophagy in RGCs of COH rats and show a protective effect against optic nerve damage caused by glaucoma, which may be mediated through the mitophagy ubiquitination via the Parkin/PINK1-related pathway.