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.

OBJECTIVE To explore the functional substance basis of Jinhong Tablet in the treatment of chronic superficial gastri-tis(CSG).METHODS Three different models were constructed to investigate the anti-inflammatory and antioxidant effects,func-tional material basis of Jinhong Tablet:inflammatory model in human gastric epithelial cells(GES-1)induced by lipopolysaccharide(LPS),LPS-induced inflammatory model in mouse gastric organoids,and ethanol-induced oxidative damage model in GES-1 cells.MTS assay was performed to detect cell proliferation activity;qPCR was applied to measure the relative mRNA expression of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-8(IL-8)in cells and gastric organoids;and the levels of superoxide dismutase(SOD),malondialdehyde(MDA),and reactive oxygen species(ROS)in cells were detected.RESULTS Jinhong Tablet and 10 functional components significantly reduced the relative expression of inflammation-relat-ed genes TNF-α,IL-1β,IL-6,and IL-8 in LPS-induced GES-1 cells and gastric organoids,suggesting that these 10 components are the functional substance basis for the anti-inflammatory effects of Jin Hong Tablet.Jin Hong Tablet and 11 functional components markedly decreased the levels of MDA and ROS and increased the activity of SOD,indicating that these 11 components were the func-tional substance basis of the antioxidant effects of Jinhong Tablet.CONCLUSION Through in vitro cell and gastric organoid experi-ments,it has been preliminarily determined that allocryptopine,corydaline,dehydrocorydaline,palmatine hydrochloride,chlorogenic acid,costunolide,rutin,quercitrin,dehydrocostus lactone,tetrahydrocoptisine,isochlorogenic acid B,toosendanin,protopine,and quercetin are the functional material basis of Jinhong Tablet in treating CSG,accumulating scientific evidence for the enhancement of the quality standards of Jinhong Tablet.

OBJECTIVE To explore the functional substance basis of Jinhong Tablet in the treatment of chronic superficial gastri-tis(CSG).METHODS Three different models were constructed to investigate the anti-inflammatory and antioxidant effects,func-tional material basis of Jinhong Tablet:inflammatory model in human gastric epithelial cells(GES-1)induced by lipopolysaccharide(LPS),LPS-induced inflammatory model in mouse gastric organoids,and ethanol-induced oxidative damage model in GES-1 cells.MTS assay was performed to detect cell proliferation activity;qPCR was applied to measure the relative mRNA expression of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-8(IL-8)in cells and gastric organoids;and the levels of superoxide dismutase(SOD),malondialdehyde(MDA),and reactive oxygen species(ROS)in cells were detected.RESULTS Jinhong Tablet and 10 functional components significantly reduced the relative expression of inflammation-relat-ed genes TNF-α,IL-1β,IL-6,and IL-8 in LPS-induced GES-1 cells and gastric organoids,suggesting that these 10 components are the functional substance basis for the anti-inflammatory effects of Jin Hong Tablet.Jin Hong Tablet and 11 functional components markedly decreased the levels of MDA and ROS and increased the activity of SOD,indicating that these 11 components were the func-tional substance basis of the antioxidant effects of Jinhong Tablet.CONCLUSION Through in vitro cell and gastric organoid experi-ments,it has been preliminarily determined that allocryptopine,corydaline,dehydrocorydaline,palmatine hydrochloride,chlorogenic acid,costunolide,rutin,quercitrin,dehydrocostus lactone,tetrahydrocoptisine,isochlorogenic acid B,toosendanin,protopine,and quercetin are the functional material basis of Jinhong Tablet in treating CSG,accumulating scientific evidence for the enhancement of the quality standards of Jinhong Tablet.

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 evaluate and compare the clinical value of unadjusted fracture risk assessment tool(FRAX) and adjusted FRAX in predicting the risk of hip fracture in patients with type 2 diabetes(T2DM).Methods:In this 10-year retrospective cohort study, 1 730 patients with T2DM were collected from August 2009 to July 2013. The 10-year risk of hip fracture was calculated using the China FRAX model. Hip fracture events during the follow-up period were collected through electronic medical records and telephone interviews. The value of FRAX and adjusted FRAX in predicting the risk of hip fracture in T2DM patients was evaluated from two aspects of discrimination and calibration. Cox regression model was used to investigate the relationship between diabetes related factors and hip fracture.Results:A total of 39 participants(2.3%) experienced hip fracture during a median follow-up of 10 years. The area under the curve of unadjusted FRAX was 0.760, but the calibration ability was poor [calibration χ2: 75.78, P<0.001; calibration ratio(observation/prediction): 3.97(95% CI 2.76~5.17)]. There was no significant improvement in calibration ability of adjusted FRAX. After adjustment for unadjusted or adjusted hip fracture probability calculated by FRAX(FRAX-HF), duration, estimated glomerular filtration rate, insulin use, cerebrovascular diseases, and diabetic peripheral neuropathy were significantly associated with an increased risk of hip fracture( P<0.05). Conclusion:The FRAX tool significantly underestimated the risk of hip fracture in T2DM patients, and there was still significantly underestimation after adjustment due to the failure to eliminate the influence of diabetes-related factors such as disease duration and peripheral neuropathy.

Objective:To evaluate the protection performance of military transport aircraft oxygen system for aircrew and provide the physiological tests basis for product design finalization.Methods:Four dummies and 4 healthy volunteers who were equipped with individual protection equipment and military transport aircraft oxygen system completed 4 tests in altitude chamber including the oxygen supply performance physical test of oxygen system, the rapid decompression physical test of oxygen system, the physiological tests of oxygen continuously supplying for 6 h and oxygen supply performance test in rapid decompression at 12.0 km. Oxygen concentration, respiratory resistance, safety pressure, peak value, peak duration and steady pressure of mask under rapid decompression were tested. Electrocardiograph and oxygen saturation of volunteers were monitored.Results:The oxygen partial pressure provided by military transport aircraft oxygen system under 12.0 km was ≥19.1 kPa corresponding to the respiration ventilation volume of 20 L/min of dummy. The expiratory resistance was no higher than 441.3 Pa and the inspiration resistance was no higher than 490.3 Pa before the safety pressure connected. The peak pressure value in rapid decompression with 1.0 L lung volume of dummy was no higher than 5.8 kPa. The oxygen partial pressure provided by military transport aircraft oxygen system for volunteers was over 21.9 kPa in the 6 h cruising flight. All 4 volunteers successfully completed the rapid decompression physiological tests at 12.0 km with good subjective and objective responses.Conclusions:The protection performance of military transport aircraft oxygen system for aircrew can provide enough protection against the hypoxia up to 12.0 km

Objective:To evaluate the protection performance of military transport aircraft oxygen system for aircrew and provide the physiological tests basis for product design finalization.Methods:Four dummies and 4 healthy volunteers who were equipped with individual protection equipment and military transport aircraft oxygen system completed 4 tests in altitude chamber including the oxygen supply performance physical test of oxygen system, the rapid decompression physical test of oxygen system, the physiological tests of oxygen continuously supplying for 6 h and oxygen supply performance test in rapid decompression at 12.0 km. Oxygen concentration, respiratory resistance, safety pressure, peak value, peak duration and steady pressure of mask under rapid decompression were tested. Electrocardiograph and oxygen saturation of volunteers were monitored.Results:The oxygen partial pressure provided by military transport aircraft oxygen system under 12.0 km was ≥19.1 kPa corresponding to the respiration ventilation volume of 20 L/min of dummy. The expiratory resistance was no higher than 441.3 Pa and the inspiration resistance was no higher than 490.3 Pa before the safety pressure connected. The peak pressure value in rapid decompression with 1.0 L lung volume of dummy was no higher than 5.8 kPa. The oxygen partial pressure provided by military transport aircraft oxygen system for volunteers was over 21.9 kPa in the 6 h cruising flight. All 4 volunteers successfully completed the rapid decompression physiological tests at 12.0 km with good subjective and objective responses.Conclusions:The protection performance of military transport aircraft oxygen system for aircrew can provide enough protection against the hypoxia up to 12.0 km