Objective:This study aimed to explore the serum levels of soluble programmed cell death protein 1 (sPD-1) and soluble programmed cell death-ligand 1 (sPD-L1) in patients with spontaneous intracerebral hemorrhage (ICH) and their clinical value in the prognostic analysis.Methods:This prospective cohort study included patients aged ≥18 years admitted to the department of critical care medicine at the Affiliated Hospital of Zunyi Medical University between January 2022 and October 2024 with a first episode of ICH presenting within 24 hours of onset. Patients with hemorrhage caused by other causes (e.g., tumor, medication and trauma) or incomplete data were excluded. Based on 28-day all-cause mortality, patients were divided into survival group and non-survival group. According to the 60-day neurological outcome, patients were divided into good neurological outcome group and poor neurological outcome group. Clinical and imaging data were collected, along with venous blood samples obtained within 24 hours of admission to measure serum levels of sPD-1 and sPD-L1. Predictive indicators were identified using LASSO-Logistic regression analysis was used to identify predictive indicators, and a nomogram was constructed to visualize the prediction model. Model performances were evaluated using receiver operating characteristic curves, decision curve analysis, calibration curves, and the Hosmer-Lemeshow test.Results:A total of 155 patients were included: 101 in the survival group and 54 in the death group; 56 in the favorable neurological outcome group and 99 in the poor neurological outcome group. Serum sPD-1 concentrations were significantly lower in the death group and poor neurological outcome group compared to the survival group and favorable neurological outcome group, respectively. Conversely, serum sPD-L1 concentrations were significantly higher in the death group and poor neurological outcome group compared to the survival group and favorable neurological outcome group (all P < 0.05). Serum sPD-1 and sPD-L1 were identified as predictors of 28-day mortality risk. A nomogram incorporating seven indicators—brainstem hemorrhage, hemorrhage volume, obstructive hydrocephalus, surgical intervention, admission NIHSS score, and admission serum sPD-1 and sPD-L1 levels—demonstrated superior predictive performance [AUC=0.984 (95% CI: 0.968-1.000)] compared to sPD-1 alone (AUC=0.712) or sPD-L1 alone (AUC=0.753). Serum sPD-1 was a predictor of poor 60-day neurological outcome. A nomogram incorporating obstructive hydrocephalus, admission NIHSS score, and admission serum sPD-1 level [AUC=0.818 (95% CI: 0.754-0.882)] outperformed sPD-1 alone (AUC=0.637) or sPD-L1 alone (AUC=0.602). Conclusions:Serum levels of sPD-1 were significantly lower in the non-survivors and the patients with poor neurological outcomes compared to the survivors and the patients with good neurological outcomes. However, serum levels of sPD-L1 were significantly higher in the non-survivors and the patients with poor neurological outcome. Serum sPD-1 was an independent predictor of 28-day mortality risk and 60-day poor neurological outcome; serum sPD-L1 was an independent predictor of 28-day mortality risk. A nomogram prediction model incorporating sPD-1 and sPD-L1 demonstrated good predictive performance for mortality risk and poor neurological outcome.

Objective To explore the the detection of MMP-2,-7,-9,and-12 enzymatic activity using the CEACAM1-derived fluorescent peptide substrate Site 84,investigating the application of substrate Site 84 to distinguishing between MMP-2 and MMP-9 in the gelatinase spectrum of MMPs.Methods The fluorescent enzymatic method was employed to observe the detection of MMP-2,-7,-9,and-12 enzymatic activity using substrate Site 84;further observations were made on the sensitivity and specificity of substrate Site 84 to enzymatic activity of MMP-2 and MMP-9 within the gelatinase spectrum;the kinetic parameters(Km and Kcat)of the enzymatic reaction between substrate Site 84 and MMP-2 were obtained.Results Using Site 84 as a substrate,enzymic kinetics curves for MMP-12,-7,-2 were obtained,but no enzymatic activity curve for MMP-9 was observed.Furthermore,Site 84 specifically detected the enzymatic activity of MMP-2 within the gelatinase spectrum,capable of detecting low concentration(0.6 μM)of MMP-2 enzymatic activity,but no obvious enzymatic reaction was observed for high concentration(6 μM)of MMP-9;the kinetics parameters for the enzymatic reaction between Site 84 and MMP-2 were Km=315 μM,Kcat/Km=2 565/MS.Conclusion The CEACAM1-derived substrate Site 84 serves as a novel fluorescent peptide substrate,enabling the acquisition of enzymatic activity curves for MMP-12,-7 and-2,and specifically detecting the enzymatic activity of MMP-2 within the MMP gelatinase spectrum.

Objective:To investigate the clinical and electrophysiological characteristics of patients with amyotrophic lateral sclerosis (ALS) with positive repetitive nerve stimulation (RNS) test results on the accessory nerve and negative needle electromyography (EMG) test results on the sternocleidomastoid with the goal to enrich the knowledge of disease progression in patients with ALS.Methods:The clinical data of 612 patients diagnosed with ALS at the Neurology Department of the First Medical Center, Chinese PLA General Hospital from June 2016 to August 2022 were collected. In total, 267 cases had undergone EMG tests on the sternocleidomastoid following a positive 3 Hz RNS test result on the accessory nerve, who were selected as the study subjects. The differences in clinical indicators were compared between RNS (+)/EMG (-) group and RNS (+)/EMG (+) group. A binomial distribution model with multiple variables was built to quantitatively analyze the major factors and their effects.Results:At the initial visit, 15.8% of patients with ALS were 3 Hz RNS (+) on the accessory nerve and EMG (-) on the ipsilateral sternocleidomastoid, accounting for 36.3% of RNS (+) patients. The decremental range of the 3 Hz RNS test delivered to the accessory nerve in these patients [-14% (-19%, -12%)] was lower than that in patients with RNS (+)/EMG (+) [-17% (-23%, -13%)] ( P<0.05), while the ratio of upper limb onset (64.9%) and non-definite diagnosis (28.9%) were higher [54.7% and 13.5% for patients with RNS (+)/EMG (+), P<0.05]. Furthermore, the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score [40 (37, 42)], body mass index (BMI) [23.8 (22.0, 25.4) kg/m 2] and forced vital capacity (FVC) [92.8% (76.6%, 103.8%)] were higher in patients with RNS(+)/EMG(+) ( P<0.05). The multivariate model suggested that, in patients with RNS (+)/EMG (-), the ratio of upper limb onset to lower limb onset was 1.04, while that of upper limb onset to bulbar onset was 2.02, and that of lower limb onset to bulbar onset was 1.94. The ratio of non-definite ALS to definite ALS was 1.13. The ALSFRS-R score, BMI, and FVC had a protective contribution to the electrophysiological function of the motor neurons. The ratio of the effect size of the ALSFRS-R or BMI to that of FVC was 3.37 and 1.14, respectively. Conclusions:Patients with ALS that were 3 Hz RNS (+) on the accessory nerve and EMG (-) on the ipsilateral sternocleidomastoid had a smaller decremental range of the compound muscle action potential amplitude, and a higher proportion of upper limb onset and non-definite ALS. A higher ALSFRS-R score, BMI, and FVC have a protective effect to the electrophysiological function of motor neurons. The effect size of the ALSFRS-R score is the largest, followed by BMI and FVC.

Objective:To investigate the incidence and mortality of breast cancer in tumor registration areas of Shanxi Province in 2019.Methods:A cross-sectional study was conducted. The tumor registration data reported by 13 tumor registration areas in Shanxi Province in 2019 were collected, and the overall incidence and mortality of breast cancer were analyzed. The stratified analysis was conducted by gender and region, and the incidence, mortality, accumulation rate (0-74 years old), age-specific incidence rate, age-specific mortality rate, Chinese population standardized rate and world population standardized rate were calculated. The standard population was based on the 2000 China population census standard population composition and Segi world standard population composition.Results:In 2019, there were 871 new cases of breast cancer in the tumor registration areas of Shanxi Province, with an incidence rate of 17.83/100 000, and 202 deaths, with a mortality rate of 4.13/100 000. The age-specific incidence of breast cancer was at a low level in 0-25 years old, it increased rapidly after 30 years old, and reached a peak in people aged 60 years old. The age-specific mortality showed a slow rising trend with the increase of age, and increased rapidly in people over 75 years old. The age-specific incidence and mortality of breast cancer in female were higher than those in male. Although the general trend of change concerning urban and rural age-specific incidence was similar, the trend of change concerning urban and rural age-specific mortality had their own characteristics. In 4 urban tumor registration areas, the highest male and female Chinese population standardized incidence rates were found in Yuci District of Jinzhong City (0.62/100 000) and Yangquan City (41.86/100 000). Male Chinese population standardized mortality rate was 0/100 000, and the highest female Chinese population standardized mortality rate was found in Yangquan City (12.62/100 000). In 9 rural tumor registration areas, the highest male and female Chinese population standardized incidence rates were found in Jishan County (2.59/100 000) and Pingding County (36.42/100 000). The highest Chinese population standardized mortality rates were found in Yuanqu County (0.89/100 000) and Jishan County (4.82/100 000).Conclusions:Women, urban area people and middle-aged and elderly people are the foci of breast cancer prevention and control in Shanxi Province.

Objective To clarify the clinical application effect of electronic medical record linkage time node reminder system(hereinafter referred to as reminder system)in trauma center.Methods A total of 90 patients with severe trauma admitted to the Trauma Center of Huzhou First People's Hospital from June 2022 to March 2023 were selected,and 45 patients admitted from June to October 2022 were included in control group for routine pre-hospital in-hospital treatment.Forty-five patients with severe trauma admitted from November 2022 to March 2023 were included in experimental group,and reminder system was implemented to guide the treatment process.The indexes of medical quality control,emergency black hole procedure time and patient outcome were compared between two groups.Results Bedside FAST ultrasound examination time,CT scan completion time,emergency room stay time,nursing waiting time,make diagnosis and treatment plan and surgical talk time,and travel transport time of patients in experimental group were significantly shorter than those in control group(P<0.05).There were no significant differences in the first tranexamic acid administration time,completion time of damage control treatment,length of stay in intensive care unit,duration of invasive mechanical ventilation and success rate of treatment between two groups(P>0.05).Conclusion The application of reminder system is helpful to strengthen the cooperation of medical care,shorten the unnecessary waiting time for treatment,and accelerate the time node transformation in the process of severe trauma treatment.

Objective:To investigate the association between split foot and electrophysiology in patients with amyotrophic lateral sclerosis (ALS).Methods:The clinically definite or clinically probable ALS patients hospitalized in the Department of Neurology, the First Medical Center of Chinese People′s Liberation Army General Hospital from April 2021 to December 2022 were prospectively collected. From April 2021 to December 2022, patients who visited the Chinese People′s Liberation Army General Hospital for other reasons without abnormal electrophysiological examination were collected as the control group. The incidence of split leg [the limb whose modified Medical Research Council Muscle Strength Scale (mMRC) score of ankle dorsiflexors was lower than that of ankle plantarflexors] in ALS patients was calculated, and the incidence of split foot (the limb whose mMRC score of hallux dorsiflexors was lower than that of hallux plantarflexors) in ALS patients was calculated. The amplitude of compound muscle action potential (CMAP) of common peroneal nerve and tibial nerve was detected to observe the involvement of motor neurons innervating ankle dorsiflexors and ankle plantarflexors. The characteristics of split leg and split foot in ALS patients were analyzed from the perspective of muscle strength, and the characteristics of split foot in ALS patients were analyzed from the perspective of electrophysiology. Receiver operating characteristic (ROC) curve was used to analyze the sensitivity and specificity of peroneal nerve/tibial nerve CMAP amplitude ratio in distinguishing ALS patients from controls.Results:A total of 101 ALS patients with lower limb involvement and 110 controls with normal lower limb muscle strength were collected. Among the 101 ALS patients with lower limb involvement, strength of ankle plantarflexors was greater than that of ankle dorsiflexors in 35.64% (36/101) patients, strength of ankle dorsiflexors was greater than that of ankle plantarflexors in 5.94% (6/101) patients, and strength of ankle plantarflexors and ankle dorsiflexors was equal in 58.42% (59/101) patients. Strength of hallux dorsiflexors was lower than that of hallux plantarflexors in 53.47% (54/101) patients, strength of hallux dorsiflexors was greater than that of hallux plantarflexors in 1.98% (2/101) patients, and the strength of hallux dorsiflexors and hallux plantarflexors was equal in 44.55% (45/101) patients. The incidence of split leg was negatively correlated with age ( OR=0.25, 95% CI 0.16-0.40, P<0.05), course of disease ( OR=0.52, 95% CI 0.38-0.80 P<0.05) and ALS functional revised scores ( OR=0.29, 95% CI 0.12-0.67, P<0.05). The incidence of split foot was negatively correlated with the onset time of lower limb symptoms ( OR=0.96, 95% CI 0.93-0.99, P<0.05). Compared with the control group, the differences of the decrease of CMAP amplitude in the common peroneal nerve and tibial nerve [the common peroneal nerve (6.45±2.56) mV vs (3.63±1.83) mV, tibial nerve (12.87±4.72) mV vs (9.18±6.22) mV] were statistically significant ( t=-4.65, t=-3.44, both P<0.001) and the differences of the peroneal nerve/tibial nerve CMAP amplitude ratio (0.54±0.24 vs 0.36±0.18) decrease was statistically significant ( t=-4.31, P<0.001) in patients with split foot. ROC curve analysis showed that the area under the ROC curve of CMAP amplitude ratio of common peroneal nerve/tibial nerve in ALS patients with split foot was 0.70, indicating that the accuracy of CMAP amplitude of common peroneal nerve/tibial nerve in distinguishing ALS patients from controls was low. Conclusions:In ALS patients with lower limb involvement, strength of ankle dorsiflexors is weaker than that of ankle plantarflexors, and strength of hallux dorsiflexors is weaker than that of hallux plantarflexors. At the diagnostic level, the CMAP amplitude ratio of common peroneal nerve/tibial nerve in ALS patients with split foot has a lower accuracy in the diagnosis of ALS.

Objective:To investigate the incidence and mortality of lung cancer in the cancer registration areas of Shanxi Province in 2017.Methods:The cancer registration data reported by 12 tumor registration areas of Shanxi in 2017 were sorted out and stratified by urban and rural areas and gender. The number of incidence and death ,the crude incidence and mortality, the cumulative rate (0-74 years), age-specific incidence and mortality, Chinese population standardized rate and world population standardized rate were calculated. The incidence and mortality were standardized by the 2000 China census standard population composition and Segi's world standard population composition.Results:In 2017, there were 2 275 new cases and 1 736 deaths of lung cancer in the tumor registration area of Shanxi Province. The crude incidence rate of lung cancer was 46.72/100 000 (male 63.99/100 000, female 28.80/100 000, urban area 58.05/100 000, rural area 39.09/100 000), Chinese population standardized rate was 31.67/100 000, the world population standardized rate was 32.10/100 000, and the cumulative rate (0-74 years) was 3.87/100 000. The crude mortality rate was 35.65/100,000 (male 49.84/100,000, female 20.93/100,000, urban area 44.53/100,000, rural area 29.67/100 000), Chinese population standardized rate was 23.82/100 000, the world population standardized rate was 24.14/100 000, and the cumulative rate (0-74 years) was 2.69/100,000. Overall, the age-specific incidence and mortality of lung cancer in 2017 were at a low level in 0-44 years age group, and increased rapidly after 45 years age group, and reached a peak in 85 years age group. The incidence and mortality of lung cancer in males were higher than that in females. Although there were some differences in the incidence and mortality of patients with different ago range in urban and rural areas, the overall trend was similar.Conclusions:Lung cancer is the most common malignant tumor threatening the health of residents in Shanxi Province. Male, urban areas and middle-aged and elderly population are the focus of cancer prevention and control in Shanxi Province. Lung cancer prevention and control should be targeted carried out according to the differences between urban and rural areas and gender.

Objective:To realize the understanding level of cancer awareness of residents in Shanxi Province, and to provide a scientific basis for cancer prevention and treatment.Methods:In April 2020, 1 897 local residents in Shanxi Province were recruited to fill in the core knowledge questionnaire of cancer prevention and treatment. The basic demographic information and the core knowledge of cancer prevention and control were collected, and the influencing factors for the understanding of the core knowledge of cancer prevention and treatment were analyzed by using multivariate logistic regression model.Results:In the survey on the awareness rate of core knowledge of cancer prevention and control among residents in Shanxi Province, 37 940 items were answered, among which 29 396 items were known, and the awareness rate of the population was 77.48% (29 396/37 940). The single-factor results showed that there were statistically significant differences in awareness rates of core knowledge of cancer prevention and treatment among the population with different gender, household registration, ethnic groups, education degree, occupation and different frequency of the health examination were statistically significant (all P < 0.05); there were no statistically significant differences in awareness rates of core knowledge among the population with different age, and smokers or non-smokers (all P >0.05).Multivariate logistic regression analysis showed that education degree of junior middle school or above ( OR = 3.412-16.767, 95% CI 1.755-32.476) and receiving physical examination once a year ( OR = 2.291, 95% CI 1.154-4.549) were the favorable factors for knowing the core knowledge of cancer prevention and treatment. Household location in rural area ( OR = 0.522, 95% CI 0.378-0.722) and non-Han nationality ( OR = 0.369, 95% CI 0.151-0.904) were the unfavorable factors for knowing the core knowledge of cancer prevention and treatment. Conclusions:The awareness of core knowledge of cancer prevention and treatment among residents in Shanxi Province is good, so it is necessary to continue to strengthen the publicity of cancer prevention and control and improve the awareness of cancer prevention and control in the future.

Nuclear receptor subfamily 2, group F, member 6 (NR2F6) is a member of orphan nuclear receptors, which is expressed in major tissues and organs of the human body, and plays an important role in the regulation of various biological functions and gene expressions. Recent studies have shown that the expression of NR2F6 was up-regulated in a variety of malignant tumors and showed significant correlations with cancer progression. These findings triggered the widespread interest in understanding the relationship between NR2F6 and cancer development and progression. In addition, the latest studies have underscored that NR2F6 was involved in enhancing antitumor immune responses that could serve as a potential target for immune regulation. This review summarizes the biological functions of NR2F6 and its role in tumors, with the aim to provide new insights into effective cancer therapies.
Gene Expression Regulation ; Humans ; Neoplasms/genetics* ; Receptors, Cytoplasmic and Nuclear/genetics* ; Repressor Proteins/genetics* ; Transcription Factors/genetics*

The intention to treat (ITT) principle is widely applied in the randomized controlled trials (RCTs), which is based on the intention to treat a subject (i.e. the planned treatment regimen) rather than the actual treatment given. With the development and progress of clinical trials, ITT principle needs to be reinterpreted. In the standard definition of ITT principle, the intentional grouping of subjects does not specifically refer to randomization, but rather to planned treatment regimen. In non-randomized clinical trials, that subjects agree to be included in a certain treatment regimen is also a type of intention. ITT principles can be applied to evaluate the effectiveness of treatment regimens under patient/doctor determined intentionality in single-arm clinical trials and non-randomized RWS (real world study, RWS). In the practical application, the grouping strategy based on ITT principle should be considered comprehensively according to the research purpose.