Objective:To investigate the feasibility of flight fatigue being detected via photoplethysmography (PPG) and regional cerebral oxygen saturation (rScO 2) in order to address the challenges posed by flight fatigue during prolonged or multiple consecutive flights. Methods:A total of 16 healthy male volunteers were enrolled. A wireless cerebral oximetry monitor headband was employed to collect PPG and rScO 2 data from the forehead while a multi-lead physiological data acquisition system was used concurrently to record three-lead electrocardiograms (ECGs). After 18 h of sleep deprivation, each volunteer performed a flight-simulating task, which was divided into 4 stages: the baseline period (T1), relaxation period (T2), early fatigue period (T3) and severe fatigue period (T4). Five-minute data was collected from each stage for analysis using AcqKnowledge 6.0. Heart rate (HR) and 3 HR variability (HRV) metrics, namely standard deviation of NN intervals (SDNN), root mean square of successive differences (RMSSD), and low frequency to high frequency power ratio (LF/HF), were computed independently from both ECG and PPG traces. The mean rScO 2 value for each stage was used to represent the cerebral oxygen saturation during that stage. The intra-class correlation coefficient (ICC) was employed to assess the consistency of the measurements, and the differences in HR and HRV indicators of the volunteers in the 4 stages of the experiment were analyzed. Results:The HR measured by ECG and PPG was highly consistent across the 4 stages among the 14 volunteers ( ICC=0.951, 0.963, 0.962, 0.963, P=0.013, 0.011, 0.021, 0.015), so were SDNN, RMSSD and LF/HF values ( ICC=0.935-0.983, all P<0.05). HR values calculated with either method showed significant differences across the 4 stages in the 14 volunteers ( F=21.63, 20.52, P=0.007, 0.008). HR gradually declined from T1 to T4, and was significantly lower at T4 than at T1 ( P=0.011, 0.009). There were significant differences in SDNN ( F=22.31, 24.26, P=0.006, 0.003), RMSSD ( F=22.30, 22.26, P=0.006, 0.006), and LF/HF ( F=20.37, 25.13, P=0.009, 0.002) across the 4 stages among the 14 volunteers. SDNN and RMSSD kept increasing as fatigue was intensified, while LF/HF decreased correspondingly. Statistically significant differences were found in SDNN, RMSSD and LF/HF values between T4 and T1 (all P<0.01). rScO 2 measured during the flight-simulating trial also differed significantly across the 4 stages ( F=21.39, P=0.007). rScO? at both T3 and T4 was significantly lower than at T1 ( P=0.009, 0.007). Conclusions:PPG can replace ECG for monitoring HR and HRV indicators under flight fatigue. Furthermore, the combination of PPG with rScO 2 monitoring allows for earlier detection of flight fatigue. This study is expected to offer a user-friendly and non-invasive approach to management of pilot fatigue.

Krüppel-like factor 5 (KLF5) has been confirmed as a key transcription factor in the occurrence and development of tumors, which is closely related to the malignant biological behaviors such as the proliferation and migration of tumor cells. This article summarizes the latest progress of KLF5 in tumor research, explores the mechanism and role of KLF5 in promoting tumor progression, aiming to further explore the potential of KLF5 as a therapeutic target and bring new thinking to the research in this field.

Objective To investigate the relationship between serum trimethylamine oxide(TMAO),neurofilament light chain protein(NfL),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)expression levels and short-term prognosis in aneurysmal subarachnoid hemorrhage(aSAH)patients.Method A total of 125 aSAH patients(aSAH group)and 125 healthy volunteers in the same period(control group)who were admitted in heji hospital affiliated to Changzhi Medical College from March 2020 to June 2023 were selected.The serum expression levels of TMAO,NfL and PGC-1α were compared between control group and aSAH group.The aSAH patients were followed up for 6 months after discharge.Their prognosis were evaluated using Glasgow Outcome Scale(GOS)and they were further divided into good prognosis and poor prognosis groups according to the GOS results.The serum expression levels of TMAO,NfL and PGC-1α were compared between the two groups.The poor prognosis influencing factors were analyzed by multivariate Logistic regression analysis,the serum TMAO,NfL and PGC-1α value in predicting poor prognosis were analyzed by receiver operating characteristic(ROC)curve.Result The expression levels of serum TMAO and PGC-1 α in the aSAH group were(2.63±0.36)μmol/L and(0.51±0.13)ng/mL,respectively,which were lower than those in the control group(3.18±0.57)μmol/L and(0.81±0.16)ng/mL(P<0.05).The expression level of serum NfL was significantly higher in the aSAH group(64.48±14.35 pg/mL)than in the control group(28.36±8.82 pg/mL)(P<0.05).Compared with the good prognosis group whose serum levels of TMAO and PGC-1 α were(2.80±0.80)μmol/L and(0.58±0.16)ng/mL,respectively,the poor prognosis group had significantly lower serum TMAO[(2.29±0.63)μmol/L]and PGC-1 α[(0.36±0.12)ng/mL](P<0.05).In contrast,poor prognosis group had a significantly higher level of NfL(76.70±15.61)pg/mL compared to good prognosis group(58.52±10.52)pg/mL(P<0.05).The proportion of patients with hypertension,patients with diabetes,patients with large or giant aneurysms,patients with Hunt Hess grade Ⅲ-Ⅳ,patients with onset to hospital time>12 h,and the level of C-reactive protein(CRP)were higher in the poor prognosis group than in the good prognosis group(P<0.05).Hunt Hess grade Ⅲ-Ⅳ,elevated serum CRP and NfL were independent risk factors for poor prognosis in aSAH patients(P<0.05),while elevated TMAO and PGC-1 α were protective factors(P<0.05).The area under the curve(AUC)of serum TMAO,NfL,PGC-1 α,and their combined prediction of poor prognosis in aSAH patients were 0.726,0.830,0.862,and 0.956,respectively.The AUC of the combined detection was greater than that of each indicator detected separately.Conclusion Serum TMAO and PGC-1α are lowly expressed in aSAH patients,and serum NfL is highly expressed,which are related to the occurrence of short-term poor prognosis,the combined detection of the three indicators has a high predictive value for short-term poor prognosis in aSAH patients.

Objective To investigate the relationship between serum trimethylamine oxide(TMAO),neurofilament light chain protein(NfL),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)expression levels and short-term prognosis in aneurysmal subarachnoid hemorrhage(aSAH)patients.Method A total of 125 aSAH patients(aSAH group)and 125 healthy volunteers in the same period(control group)who were admitted in heji hospital affiliated to Changzhi Medical College from March 2020 to June 2023 were selected.The serum expression levels of TMAO,NfL and PGC-1α were compared between control group and aSAH group.The aSAH patients were followed up for 6 months after discharge.Their prognosis were evaluated using Glasgow Outcome Scale(GOS)and they were further divided into good prognosis and poor prognosis groups according to the GOS results.The serum expression levels of TMAO,NfL and PGC-1α were compared between the two groups.The poor prognosis influencing factors were analyzed by multivariate Logistic regression analysis,the serum TMAO,NfL and PGC-1α value in predicting poor prognosis were analyzed by receiver operating characteristic(ROC)curve.Result The expression levels of serum TMAO and PGC-1 α in the aSAH group were(2.63±0.36)μmol/L and(0.51±0.13)ng/mL,respectively,which were lower than those in the control group(3.18±0.57)μmol/L and(0.81±0.16)ng/mL(P<0.05).The expression level of serum NfL was significantly higher in the aSAH group(64.48±14.35 pg/mL)than in the control group(28.36±8.82 pg/mL)(P<0.05).Compared with the good prognosis group whose serum levels of TMAO and PGC-1 α were(2.80±0.80)μmol/L and(0.58±0.16)ng/mL,respectively,the poor prognosis group had significantly lower serum TMAO[(2.29±0.63)μmol/L]and PGC-1 α[(0.36±0.12)ng/mL](P<0.05).In contrast,poor prognosis group had a significantly higher level of NfL(76.70±15.61)pg/mL compared to good prognosis group(58.52±10.52)pg/mL(P<0.05).The proportion of patients with hypertension,patients with diabetes,patients with large or giant aneurysms,patients with Hunt Hess grade Ⅲ-Ⅳ,patients with onset to hospital time>12 h,and the level of C-reactive protein(CRP)were higher in the poor prognosis group than in the good prognosis group(P<0.05).Hunt Hess grade Ⅲ-Ⅳ,elevated serum CRP and NfL were independent risk factors for poor prognosis in aSAH patients(P<0.05),while elevated TMAO and PGC-1 α were protective factors(P<0.05).The area under the curve(AUC)of serum TMAO,NfL,PGC-1 α,and their combined prediction of poor prognosis in aSAH patients were 0.726,0.830,0.862,and 0.956,respectively.The AUC of the combined detection was greater than that of each indicator detected separately.Conclusion Serum TMAO and PGC-1α are lowly expressed in aSAH patients,and serum NfL is highly expressed,which are related to the occurrence of short-term poor prognosis,the combined detection of the three indicators has a high predictive value for short-term poor prognosis in aSAH patients.

Krüppel-like factor 5 (KLF5) has been confirmed as a key transcription factor in the occurrence and development of tumors, which is closely related to the malignant biological behaviors such as the proliferation and migration of tumor cells. This article summarizes the latest progress of KLF5 in tumor research, explores the mechanism and role of KLF5 in promoting tumor progression, aiming to further explore the potential of KLF5 as a therapeutic target and bring new thinking to the research in this field.

Objective:To investigate the feasibility of flight fatigue being detected via photoplethysmography (PPG) and regional cerebral oxygen saturation (rScO 2) in order to address the challenges posed by flight fatigue during prolonged or multiple consecutive flights. Methods:A total of 16 healthy male volunteers were enrolled. A wireless cerebral oximetry monitor headband was employed to collect PPG and rScO 2 data from the forehead while a multi-lead physiological data acquisition system was used concurrently to record three-lead electrocardiograms (ECGs). After 18 h of sleep deprivation, each volunteer performed a flight-simulating task, which was divided into 4 stages: the baseline period (T1), relaxation period (T2), early fatigue period (T3) and severe fatigue period (T4). Five-minute data was collected from each stage for analysis using AcqKnowledge 6.0. Heart rate (HR) and 3 HR variability (HRV) metrics, namely standard deviation of NN intervals (SDNN), root mean square of successive differences (RMSSD), and low frequency to high frequency power ratio (LF/HF), were computed independently from both ECG and PPG traces. The mean rScO 2 value for each stage was used to represent the cerebral oxygen saturation during that stage. The intra-class correlation coefficient (ICC) was employed to assess the consistency of the measurements, and the differences in HR and HRV indicators of the volunteers in the 4 stages of the experiment were analyzed. Results:The HR measured by ECG and PPG was highly consistent across the 4 stages among the 14 volunteers ( ICC=0.951, 0.963, 0.962, 0.963, P=0.013, 0.011, 0.021, 0.015), so were SDNN, RMSSD and LF/HF values ( ICC=0.935-0.983, all P<0.05). HR values calculated with either method showed significant differences across the 4 stages in the 14 volunteers ( F=21.63, 20.52, P=0.007, 0.008). HR gradually declined from T1 to T4, and was significantly lower at T4 than at T1 ( P=0.011, 0.009). There were significant differences in SDNN ( F=22.31, 24.26, P=0.006, 0.003), RMSSD ( F=22.30, 22.26, P=0.006, 0.006), and LF/HF ( F=20.37, 25.13, P=0.009, 0.002) across the 4 stages among the 14 volunteers. SDNN and RMSSD kept increasing as fatigue was intensified, while LF/HF decreased correspondingly. Statistically significant differences were found in SDNN, RMSSD and LF/HF values between T4 and T1 (all P<0.01). rScO 2 measured during the flight-simulating trial also differed significantly across the 4 stages ( F=21.39, P=0.007). rScO? at both T3 and T4 was significantly lower than at T1 ( P=0.009, 0.007). Conclusions:PPG can replace ECG for monitoring HR and HRV indicators under flight fatigue. Furthermore, the combination of PPG with rScO 2 monitoring allows for earlier detection of flight fatigue. This study is expected to offer a user-friendly and non-invasive approach to management of pilot fatigue.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective:To investigate the effect and mechanism of non-selective histone deacetylase (HDAC) inhibitor sodium butyrate (NaB) on neuropathic pain and pain-induced memory impairment in mice.Methods:Forty clean grade male C57BL/6J mice were were divided into 4 groups by random number table method ( n=10 in each group): sham + saline, sham + NaB, chronic constriction injury (CCI)+ saline and CCI + NaB.The mouse CCI model was established by sciatic nerve ligation. Non-selective HDAC inhibitors NaB(300 mg/kg) was intraperitoneally injected into the mice in Sham+ NaB group and CCI+ NaB group once a day 15-28 days after modeling, while the mice in Sham+ saline group and CCI+ saline group were intraperitoneally injected with the same volume of saline. On the 14th and 28th day after operation, the athletic ability was measured by open field test (OFT), the pain behavior was measured by paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), and the memory function was measured by Y-maze. After the behavioral experiment, hippocampus and spinal dorsal horn tissues were taken for the activity of HDAC measurement, and hippocampus tissues were taken for the expression levels of BDNF and PSD95 measurement. SPSS 25.0 software was used for statistical analysis. The data were compared by repeated measurement ANOVA and one-way ANOVA. Results:After treatment with NaB, the interaction effects of the accuracy of spontaneous alternation of PWT, PWL and Y maze in mice were significant( F=21.07, 6.98, 7.79, all P<0.05). Compared with the Sham + saline group, the PWT((0.83±0.30)g, (0.25±0.22)g, (0.24±0.11)g; both P<0.05), the PWL((14.97±4.02)s, (5.99±1.51)s, (6.87±0.90)s; both P<0.05) and the spontaneous alternation in Y maze(71.57±2.80)%, (56.96±0.60)%, (62.86±4.94)%; both P<0.05) in CCI+ Saline group and CCI+ NaB group were lower. After treatment with NaB, compared with CCI + saline group, PWT((0.22±0.13)g, (0.62±0.23)g; P<0.05), PWL((5.62±2.00)s, (8.82±2.13)s; P<0.05)and the accuracy of spontaneous alternation of Y maze were significantly higher ((56.54±7.50)%, (66.35±8.20)%; P<0.05), the HDAC activity in hippocampus((173.40±7.38)%, (122.70±8.40)%; P<0.05)and in spinal cord ((153.40±10.58)%, (111.40±11.40)%; P<0.05)were significantly lower, and the expression of BDNF((0.65±0.06), (0.87±0.43); P<0.05)and PSD95((0.70±0.40), (0.87±0.04); P<0.05)were significantly higher in CCI + NaB group. Conclusion:NaB can improve neuropathic pain and pain-induced memory impairment.The mechanism may be related to the inhibition of HDAC activity and the up-regulation of BDNF and PSD95 expression in hippocampus.

Pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine (GEM) with the molecular-targeted drug erlotinib (Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuli-responsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment via simultaneous delivery of small interference RNA (siRNA) for synergistic pancreatic cancer treatment. This "all-in-one" delivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhibitory effects on the proliferation and migration of tumor cells in vitro. Excitingly, the systemic injection of such a biomimetic drug co-delivery system not only resulted in superior inhibitory effects against orthotopic pancreatic tumor and patient-derived tumor (PDX), but also greatly extended the survival rate of tumor-bearing mice. Our findings provide a promising therapeutic strategy against pancreatic cancer through the enhanced synergistic effect of target therapy, chemotherapy and anti-fibrotic therapy, which represents an appealing way for pancreatic cancer treatment.