Background High-speed train engineers' lower extremities are constrained by compulsive vigilance pedal tasks and limited space beneath the control console during driving. Shifts in alertness triggered by running route observation may share the same mental resource required by moderate-to-low physical exertion. Current research on improving cab design and maintaining optimal on-duty attention allocation remains limited. Objective To examine variations in lower extremity muscle load, gaze-tracking behavior, and driving performance under various combinations of vigilance pedal positions and route scenarios during simulated high-speed train tasks. To identify optimal working condition combinations that promote level and variety of physical activity and facilitate rational attention allocation. Methods A 4×2 within-subjects design were employed (4 vigilance pedal position profiles: knee front, side, and any; 2 route scenarios: monotonous and complex). Nine male college volunteers were recruited as simulated drivers to perform designated interval driving tasks. Surface electromyography and eye tracking were used to assess leg muscle load and gaze behavior respectively. Task performance and subjective fatigue were recorded. Results In all simulation driving tasks, skeletal muscle loads were low with the percentage of maximum voluntary contraction (%MVC) at approximately 4%. No fatigue tendencies were observed within single trial blocks (7 min), and the subjective fatigue ratings remained relatively low. While the activation of the dominant-side tibialis anterior was higher for the knee pedal than for the front (%MVC: 3.7% ± 3.13% vs. 1.08% ± 0.72%) or the side pedals (%MVC: 3.7% ± 3.13% vs. 1.4% ± 0.77%). The activation level of the dominant-side gastrocnemius was higher for the knee pedal than for the other three pedal profiles. For the any pedal condition, the intercept of the instantaneous median frequency curve for the dominant-side rectus femoris was lower in the monotonous route than in the complex route [(111.18 ± 35.78) Hz vs. (153.33 ± 39.12) Hz]. Among eye-tracking metrics, total fixations were higher during knee-level pedaling than side pedaling, while more saccades were recorded in monotonous routes than in complex ones. Regarding task performance, the any pedal yielded fewer missed signals than the front pedal, with 2/3 and 1/3 of participants preferring the front and knee pedals, respectively. The activation levels of the dominant tibialis anterior and dominant gastrocnemius muscles during the knee pedal × complex route combination were higher than any combination involving the front pedal. No statistically significant effect of pedal position or route scenario was found on other indicators. Conclusion The combination of knee pedal and complex route provides an optimal working setting for maximizing leg muscle mobility without compromising attention allocation or driving performance. It is recommended that train engineers modulate attention during monotonous routes to avoid emotional tension and increased muscle strain caused by over-monitoring. Given the ergonomic characteristics of high cognitive load, low physical exertion levels, and highly restricted lower limb mobility among high-speed train engineers, future cab designs should consider incorporating knee-level vigilance pedal and adjust safety alertness rules to allow reset via either front or knee pedal.

Background High-speed train engineers' lower extremities are constrained by compulsive vigilance pedal tasks and limited space beneath the control console during driving. Shifts in alertness triggered by running route observation may share the same mental resource required by moderate-to-low physical exertion. Current research on improving cab design and maintaining optimal on-duty attention allocation remains limited. Objective To examine variations in lower extremity muscle load, gaze-tracking behavior, and driving performance under various combinations of vigilance pedal positions and route scenarios during simulated high-speed train tasks. To identify optimal working condition combinations that promote level and variety of physical activity and facilitate rational attention allocation. Methods A 4×2 within-subjects design were employed (4 vigilance pedal position profiles: knee front, side, and any; 2 route scenarios: monotonous and complex). Nine male college volunteers were recruited as simulated drivers to perform designated interval driving tasks. Surface electromyography and eye tracking were used to assess leg muscle load and gaze behavior respectively. Task performance and subjective fatigue were recorded. Results In all simulation driving tasks, skeletal muscle loads were low with the percentage of maximum voluntary contraction (%MVC) at approximately 4%. No fatigue tendencies were observed within single trial blocks (7 min), and the subjective fatigue ratings remained relatively low. While the activation of the dominant-side tibialis anterior was higher for the knee pedal than for the front (%MVC: 3.7% ± 3.13% vs. 1.08% ± 0.72%) or the side pedals (%MVC: 3.7% ± 3.13% vs. 1.4% ± 0.77%). The activation level of the dominant-side gastrocnemius was higher for the knee pedal than for the other three pedal profiles. For the any pedal condition, the intercept of the instantaneous median frequency curve for the dominant-side rectus femoris was lower in the monotonous route than in the complex route [(111.18 ± 35.78) Hz vs. (153.33 ± 39.12) Hz]. Among eye-tracking metrics, total fixations were higher during knee-level pedaling than side pedaling, while more saccades were recorded in monotonous routes than in complex ones. Regarding task performance, the any pedal yielded fewer missed signals than the front pedal, with 2/3 and 1/3 of participants preferring the front and knee pedals, respectively. The activation levels of the dominant tibialis anterior and dominant gastrocnemius muscles during the knee pedal × complex route combination were higher than any combination involving the front pedal. No statistically significant effect of pedal position or route scenario was found on other indicators. Conclusion The combination of knee pedal and complex route provides an optimal working setting for maximizing leg muscle mobility without compromising attention allocation or driving performance. It is recommended that train engineers modulate attention during monotonous routes to avoid emotional tension and increased muscle strain caused by over-monitoring. Given the ergonomic characteristics of high cognitive load, low physical exertion levels, and highly restricted lower limb mobility among high-speed train engineers, future cab designs should consider incorporating knee-level vigilance pedal and adjust safety alertness rules to allow reset via either front or knee pedal.

Objective:This study aimed to evaluate the prognostic factors of clinical and histopathological parameters,including age,gender,tumor stage,tumor grade,tumor differentiation,lymph node metastasis(LNM),tumor frequency,and tumor count,in patients undergoing radical cystectomy(RC)combined with Mainz Pouch Ⅱ bladder reconstruction.Methods:A total of 237 bladder cancer patients(198 male and 39 female)who underwent RC combined with Mainz Pouch Ⅱ bladder reconstruction without chemotherapy or radiotherapy,from January 2004 to January 2023,were included in this study.Kaplan-Meier and Cox regression analyses were performed to assess the impact of age,tumor grade,tumor stage,tumor differentiation,LNM,tumor frequency,and tumor count on 5-year overall survival(OS)and 5-year cancer-specific survival(CSS).Results:The mean age at diagnosis was 59.8 years,with 198 male and 39 female patients.The mean follow-up duration was 47.8 months.In univariate analysis,patients younger than 65 years had significantly higher 5-year OS and 5-year CSS compared to those aged≥65 years.Patients with urothelial carcinoma showed better 5-year OS than those with non-urothelial carcinoma.Additionally,tumor stage,tumor grade,and LNM were negatively associated with 5-year OS and 5-year CSS.On multivariate analysis,only tumor grade and LNM remained statistically significant(P<0.05).Conclusions:Tumor grade and LNM were identified as independent prognostic risk factors for 5-year OS and 5-year CSS following RC combined with Mainz PouchⅡ bladder reconstruction.Moreover,the application of RC combined with Mainz Pouch Ⅱ bladder reconstruction should consider the patient's preferences and physical condition.

Objective:This study aimed to evaluate the prognostic factors of clinical and histopathological parameters,including age,gender,tumor stage,tumor grade,tumor differentiation,lymph node metastasis(LNM),tumor frequency,and tumor count,in patients undergoing radical cystectomy(RC)combined with Mainz Pouch Ⅱ bladder reconstruction.Methods:A total of 237 bladder cancer patients(198 male and 39 female)who underwent RC combined with Mainz Pouch Ⅱ bladder reconstruction without chemotherapy or radiotherapy,from January 2004 to January 2023,were included in this study.Kaplan-Meier and Cox regression analyses were performed to assess the impact of age,tumor grade,tumor stage,tumor differentiation,LNM,tumor frequency,and tumor count on 5-year overall survival(OS)and 5-year cancer-specific survival(CSS).Results:The mean age at diagnosis was 59.8 years,with 198 male and 39 female patients.The mean follow-up duration was 47.8 months.In univariate analysis,patients younger than 65 years had significantly higher 5-year OS and 5-year CSS compared to those aged≥65 years.Patients with urothelial carcinoma showed better 5-year OS than those with non-urothelial carcinoma.Additionally,tumor stage,tumor grade,and LNM were negatively associated with 5-year OS and 5-year CSS.On multivariate analysis,only tumor grade and LNM remained statistically significant(P<0.05).Conclusions:Tumor grade and LNM were identified as independent prognostic risk factors for 5-year OS and 5-year CSS following RC combined with Mainz PouchⅡ bladder reconstruction.Moreover,the application of RC combined with Mainz Pouch Ⅱ bladder reconstruction should consider the patient's preferences and physical condition.

Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical practice. Unfortunately, current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse reactions. As G protein-coupled receptors (GPCRs) are widely distributed throughout the body, including the pain transmission pathway and descending inhibition pathway, the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining momentum. Extensive research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse effects. This review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain, and discuss the potential benefits and adverse factors of this treatment. We will also concentrate on the development of biased agonists of GPCRs, and based on important examples of biased agonist development in recent years, we will describe universal strategies for designing structure-based biased agonists. It is foreseeable that, with the continuous improvement of GPCRs allosteric modulation and biased agonist theory, effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.

Objective:To compare the clinical effects on new bone formation and foot-ankle function between proximal tibial bone transport and distal tibial bone transport in the treatment of massive bone defects after tibial osteomyelitis debridement.Methods:From July 2012 to July 2017, 42 patients with chronic tibial osteomyelitis received bone transport surgery at Department of Orthopaedics, Nanfang Hospital.According to the Cierny-Mader classification for chronic osteomyelitis, all of them belonged to diffusive tibial osteomyelitis (type IV).Of them, 32 were treated by proximal tibial bone transport after tibial osteomyelitis debridement.In the proximal group, there were 27 males and 5 females, aged from 17 to 65 years and involving 20 left and 12 right sides. The other 10 cases received distal tibial bone transport. In the distal group, all of them were male, aged from 25 to 63 years and involving 6 left and 4 right sides. The 2 groups were compared in terms of external fixation index (EFI) and American Orthopaedic Foot & Ankle Society(AOFAS) Ankle and Hindfoot Scale.Results:There were no significant differences between the 2 groups in the preoperative general data such as gender, age or osteomyelitis site, indicating the 2 groups were comparable ( P>0.05). Both groups obtained complete follow-up. The proximal group was followed up for 590.1 d ± 287.3 d and the distal group for 615.6 d ± 130.6 d, showing no significant difference between groups ( P>0.05). In the proximal group 2 cases developed talipes equinovalgus after bone transport while in the distal group 3 cases did, and surgical intervention was needed for them. Surgical intervention was also carried out for16 cases of non-union at the docking site in the proximal group and for 2 ones in the distal group. The EFI was 76.2 d/cm±50.0 d/cm for the proximal group and 84.3 d/cm ± 59.9 d/cm for the distal group, showing no significant difference between groups ( P>0.05). The AOFAS scores were 81.4±10.1 for the proximal group and 60.0±5.9 for the distal group, showing a significant difference ( P<0.05). Conclusion:In the treatment of massive bone defects after tibial osteomyelitis debridement, no significant difference has been observed in the effect on bone formation between proximal tibial bone transport and distal tibial bone transport, but the former transport may have a less adverse effect on foot-ankle function.

Objective To summarize clinicopathologic features of papillary thyroid carcinoma (PTC) coexistent with chronic lymphocytic thyroiditis (CLT) and investigate risk factors for lymph node metastasis.Methods The medical records of 4 264 consecutive papillary thyroid carcinoma patients who received surgical treatment from Oct 2013 to Oct 2015 in Peking Union Medical College Hospital were reviewed.The diagnoses was confirmed by histopathological tests.Univariate analysis was performed to identify specific clinicopathologic features of PTC with CLT.Univariate and multivariate analysis were performed to determine whether each clinicopathologic feature was an independent risk factor for lymph node metastasis.Results In all 4 265 cases,there were 3 059 papillary thyroid microcarcinoma (PTMC) (71.7％),1 010 PTC patients (23.7％) with CLT.909 female patients (90％),624 cases with multifocal lesions (61.8％),422 cases with extra-thyroid extension (41.8％),429 cases with lymph node metastasis (42.5％),and 133 cases with metastatic lymph nodes(LNs) ≥6 (13.2％).The median age was 43 years old and median tumor size was 0.8 cm.Patients with CLT were more females (90.0％ vs.70.2％;P ＜ 0.001),younger median age (43 vs.44 years;P =0.001),and lower incidence of lymph node metastasis (42.5％ vs.50.9％;P ＜0.001).CLT was not associated with tumor size,multifocal lesions,extra-thyroid extension and metastatic LNs≥6 (0.8 cm vs.0.7 cm,61.8％ vs.62.9％,41.8％ vs.42.1％ and 13.2％ vs.14.8％,respectively,all P ＞ 0.05).In multivariate analysis,CLT was an independent protective factor for lymph node metastasis (OR =0.713,95％ CI 0.609-0.835,P ＜0.001).In PTC patients with lymph node metastasis,CLT was not associated with lymph node metastasis number (3 vs.3,P =0.300).Conclusions Chronic lymphocytic thyroiditis was an independent protective factor for papillary thyroid carcinoma patients with lymph node metastasis.But in patients with lymph node metastasis,the metastatic number didn't decrease.

Diabetic foot ulcer is a major complication of diabetes which is the most expensive and the most difficult to deal with and leads to a high rate of non-traumatic amputation.Diabetic foot osteomyelitis results from aggravation of diabetic foot ulcer.Unfortunately,the current therapeutic outcomes of diabetic foot osteomyelitis are still unsatisfactory because of its difficult diagnosis and special treatment protocols which are entirely different from those for conventional soft tissue infections.This paper summarizes the latest advances achieved in diagnosis and treatment of diabetic foot osteomyelitis.

The development of neuroimaging has led to a high diagnostic rate of cerebral small vessel disease (CSVD).The hemorrhage transformation (HT) and clinical prognosis after intravenous thrombolysis in acute ischemic stroke (AIS) with CSVD have become hot topics in recent years.Relevant studies have shown that different subtypes of CSVD may have different influences in HT and clinical prognoses in AIS.In clinic,each subtype of CSVD may not exist alone in one patient,therefore,some scholars put forward the concept of total burden of CSVD to further quantitatively assess the severity of CSVD in the whole brain and their effects on HT and clinical prognosis after intravenous thrombolysis of AIS.This article reviews the researches on HT and clinical prognosis after intravenous thrombolysis in AIS with CSVD.

Objective To determine the steam distillation processing of Elsholtzia and to optimize different parts volatile oil of the anti-bacterial activity and anti-oxidation activityfrom Elsholtzia. Methods The volatile oil of different parts from Elsholtzia was extracted by steam distillation. The anti-oxidationactivity was texted by DPPH. The antibacterial activity was detected by disk diffusion test. Results Watering 14 times, soaking 6 hours, extracting 3 hours by steam distillation to extracte different parts of volatile oil. It is effective that volatile oil inhibit Escherichia coli, Staphylococcus aureus, Dysentery bacillus＇s blessing. The sequential of antibacterial activity was that Escherichia coli ＞ Dysentery bacillus＇s blessing ＞ Staphylococcus aureus ＞Pseudomonas aeruginosa. The anti-oxidation activity increased the concentration of volatile oil, and was konwn to be the best when the content of the volatile oil is 10%. The anti-oxidation activity of VC was stonger than volatile oil. Conclusions It is effective that volatile oil inhibit Escherichia coli, Staphylococcus aureus, Dysentery bacillus＇s blessing and the volatile oil from inflorescence have a stronger antibacterial activity than the volatile oil from leaf.