Objective To elucidate the molecular mechanisms underlying the effects of Kanggan Mixture(KGM)on key targets in rats with acute lung injury,network pharmacology and in vivo micro-CT experiments were employed.Methods Network pharmacology was utilized to forecast the target genes and principal pathways involved in the intervention of KGM in acute lung injury(ALI).Lipopolysaccharide(LPS)-induced ALI rat models were utilized,and micro-computed tomography(micro-CT)was employed to evaluate the extent of lung injury in vivo.Experiments were conducted to verify the intervention mechanism of KGM on ALI rats.Results The findings revealed that 190 chemical constituents were identified from KGM,and 579 potential targets and 204 pathways associated with KGM's impact on ALI were predicted.The principal components of KGM,such as quercetin,luteolin,kaempferol,betulin,and lupenone,exhibit anti-viral,anti-inflammatory,and immunomodulatory properties by targeting TP53,AKT1,SRC,EP300,and STAT3,and modulating the FoxO signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,and MAPK signaling pathway,demonstrating an influence on acute lung injury.Micro-CT results suggest that KGM can improve lung texture enhancement and lung injury in ALI rats,with an increase in end-expiratory lung volume(inspiratory phase-expiratory phase).The HE and W/D ratio results indicate that KGM can improve lung tissue injury and reduce the lung tissue wet/dry weight ratio(P<0.01).Blood cell analysis results show that the anti-inflammatory agent can decrease the WBC(white blood cell count)and N%(neutrophil percentage)in ALI rats'blood(P<0.01),and increase lymphocytes(P<0.05).Real-time quantitative PCR,WES,and immunohistochemistry results suggest that KGM can decrease the mRNA expression,protein distribution,and protein expression levels of TP53,AKT1,SRC,EP300,and STAT3 in lung tissue of ALI rats(P<0.05).Conclusion KGM has a certain intervention effect on acute lung injury,mainly achieved through the core targets STAT3,EP300,SRC,AKT1,and TP53.

Objective To elucidate the molecular mechanisms underlying the effects of Kanggan Mixture(KGM)on key targets in rats with acute lung injury,network pharmacology and in vivo micro-CT experiments were employed.Methods Network pharmacology was utilized to forecast the target genes and principal pathways involved in the intervention of KGM in acute lung injury(ALI).Lipopolysaccharide(LPS)-induced ALI rat models were utilized,and micro-computed tomography(micro-CT)was employed to evaluate the extent of lung injury in vivo.Experiments were conducted to verify the intervention mechanism of KGM on ALI rats.Results The findings revealed that 190 chemical constituents were identified from KGM,and 579 potential targets and 204 pathways associated with KGM's impact on ALI were predicted.The principal components of KGM,such as quercetin,luteolin,kaempferol,betulin,and lupenone,exhibit anti-viral,anti-inflammatory,and immunomodulatory properties by targeting TP53,AKT1,SRC,EP300,and STAT3,and modulating the FoxO signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,and MAPK signaling pathway,demonstrating an influence on acute lung injury.Micro-CT results suggest that KGM can improve lung texture enhancement and lung injury in ALI rats,with an increase in end-expiratory lung volume(inspiratory phase-expiratory phase).The HE and W/D ratio results indicate that KGM can improve lung tissue injury and reduce the lung tissue wet/dry weight ratio(P<0.01).Blood cell analysis results show that the anti-inflammatory agent can decrease the WBC(white blood cell count)and N%(neutrophil percentage)in ALI rats'blood(P<0.01),and increase lymphocytes(P<0.05).Real-time quantitative PCR,WES,and immunohistochemistry results suggest that KGM can decrease the mRNA expression,protein distribution,and protein expression levels of TP53,AKT1,SRC,EP300,and STAT3 in lung tissue of ALI rats(P<0.05).Conclusion KGM has a certain intervention effect on acute lung injury,mainly achieved through the core targets STAT3,EP300,SRC,AKT1,and TP53.

Objective:To construct a prognostic predictive model for patients with moderate to severe traumatic brain injury (msTBI) based on regional cerebral oxygen saturation (rScO 2) and transcranial Doppler ultrasound (TCD) monitoring parameters and validate its effectiveness. Methods:A retrospective cohort study was conducted to analyze the clinical data of 161 patients with msTBI who were treated at Henan Provincial People′s Hospital from January 2021 to December 2022, including 104 males and 57 females, aged 19-76 years [(53.1±12.8)years]. Glasgow coma scale (GCS) score was 3-12 points [(7.0±1.9)points]. Both rScO 2 and TCD monitoring were performed. Based on the results of prognostic evaluation of patients with the modified Rankin scale (mRS) score at 90 days after discharge, the patients were divided into good prognosis group (mRS score≤3 points, n=88) and poor prognosis group (mRS score of 4-6 points, n=73). The following data of the two groups were collected: the general data, clinical data, rScO 2 monitoring parameters and TCD monitoring parameters. Univariate analysis was employed to compare the differences in the relevant prognostic indicators. Multivariate Logistic stepwise regression analysis was conducted to determine the predictors of poor prognostic outcomes in msTBI patients and regression equations were constructed. A nomogram predictive model based on regression equations was drawn with R language. The discriminability of the model was evaluated by drawing the receiver operating characteristic (ROC) curve, to calculate the area under the curve (AUC), sensitivity, specificity, and Jordan index of the model, and measuring the consistency index (C index). Hosmer-Lemeshow (H-L) goodness of fit test was conducted to evaluate the fit of the model, and the calibration curve was used to evaluate the calibration degree of the model. Decision curve analysis (DCA) was employed to evaluate the clinical benefit and applicability of the model. Results:There were significant differences between the two groups in the clinical data (cerebral hernia formation, GCS on admission, acute physiology and chronic health evaluation II (APACHE II) score on admission, Rotterdam CT score on admission, oxygenation index on admission, mean arterial pressure on admission), rScO 2 monitoring parameters (mean rScO 2, maximum rScO 2, rScO 2 variability), TCD monitoring parameters [peak systolic blood flow velocity (Vs), average blood flow velocity (Vm), pulse index (PI)] ( P<0.05 or 0.01). The results of multivariate Logistic stepwise regression analysis showed that cerebral hernia formation ( OR=9.28, 95% CI 3.40, 25.33, P<0.01), Rotterdam CT score on admission ( OR=1.92, 95% CI 1.32, 2.78, P<0.01), rScO 2 variability ( OR=4.66, 95% CI 1.74, 12.43, P<0.01), Vs ( OR=0.66, 95% CI 0.61, 0.75, P<0.01) and PI ( OR=20.07, 95% CI 4.17, 16.50, P<0.01) were predictive factors for poor prognosis in patients with msTBI. The regression equation was constructed with the forementioned 5 variables: Logit [ P/(1- P)]=2.23×"brain hernia formation"+0.65×"Rotterdam CT score on admission"+1.54×"rScO 2 variability"-0.42×"Vs"+3.00×"PI"-6.75. The AUC of prognostic predictive model of msTBI patients was 0.90 (95% CI 0.85, 0.95), with the sensitivity and specificity of 86.3% and 78.4%, Youden index of 0.65 and C index of 0.90. H-L goodness of fit test showed that the calibration degree of the predictive model was accurate ( χ2 =12.58, P>0.05). The average absolute error of the calibration curve was 0.025, showing that the calibration of the model was good. DCA results showed that this model had higher net return rate than the reference model within the probability range of risk threshold (20%-100%), with good clinical application value in evaluating the risk of poor prognosis of msTBI patients. Conclusion:The model constructed based on the combination of rScO 2 and TCD monitoring parameters (rScO 2 variability, Vs and PI) with multiple clinical indicators (cerebral hernia formation and Rotterdam CT score on admission) has good predictive performance for the prognosis of msTBI.

Spinal cord injury (SCI) is a serious nervous system disease that usually leads to the impairment of the motor, sensory, and autonomic nervous functions of the spinal cord, and it places a heavy burden on families and healthcare systems every year. Due to the complex pathophysiological mechanism of SCI and the poor ability of neurons to regenerate, the current treatment scheme has very limited effects on the recovery of spinal cord function. In addition, due to their unique advantages, exosomes can be used as carriers for cargo transport. In recent years, some studies have confirmed that treatment with mesenchymal stem cells (MSCs) can promote the recovery of SCI nerve function. The therapeutic effect of MSCs is mainly related to exosomes secreted by MSCs, and exosomes may have great potential in SCI therapy. In this review, we summarized the repair mechanism of mesenchymal stem cells-derived exosomes (MSCs-Exos) in SCI treatment and discussed the microRNAs related to SCI treatment based on MSCs-Exos and their mechanism of action, which is helpful to further understand the role of exosomes in SCI.

Objective:To observe the clinical value of intracranial pressure (ICP) monitoring combined with target temperature management (TTM) in patients with acute anterior circulation ischemic stroke after mechanical thrombectomy.Methods:A prospective analysis was performed. Ninety-two patients with acute anterior circulation ischemic stroke who received mechanical thrombectomy from March 2019 to June 2022 in Department of Neurosurgery, He'nan Provincial People's Hospital were enrolled. Within 1-5 d of mechanical thrombectomy, these patients were randomly divided into observation group ( n=46) and control group ( n=46). The patients in observation group received comprehensive management for neurological critical illness through multimodal monitoring such as ICP real-time monitoring combined with TTM (controlling the core temperature at 33℃-35℃), while patients in control group received simple ICP real-time monitoring. ICP monitoring for both groups lasted for 5-7 d, and routine symptomatic support treatment was given. Stepwise treatment was adopted based on real-time changes of ICP. The differences in clinical data, ICP at different times, incidence of adverse events, length of hospital stay, mortality rate, and prognoses were compared between the 2 groups. Results:On the 2 nd, 3 rd, 4 th, and 5 th d of monitoring, the observation group had significantly decreased ICP compared with the control group ( P<0.05). Both observation group and control group had significantly increased ICP on the 2 nd, 3 rd, 4 th, and 5 th d of monitoring compared with that on the 1 st d of monitoring ( P<0.05). Compared with the control group, the observation group had statistically higher incidences of shivers and electrolyte disorders, and statistically lower incidences of unstable blood pressure, cerebral heart syndrome, septic shock, and cerebral hernia during hospitalization ( P<0.05). Compared with the control group, the observation group had significantly shortened hospital stay, and statistically lower modified Rankin scale (mRS) scores, higher Glasgow outcome scale-extended (GOS-E) scores, higher good prognosis rate, and lower mortality rate 6 months after mechanical thrombectomy ( P<0.05). Compared with the control group, the observation group had statistically lower incidences of postoperative cerebral hemorrhage conversion and recurrent cerebral infarction ( P<0.05). Kaplan-Meier survival analysis showed that the survival rate in the observation group was significantly higher than that in the control group ( P<0.05). Conclusion:ICP monitoring combined with TTM can reduce early complications, shorten hospital stay, reduce mortality, and improve long-term prognosis in patients with acute anterior circulation ischemic stroke after mechanical thrombectomy.

Obvious epigenetic differentiation occurred on Lycium barbarum in different cultivation areas in China. To investigate the difference and change rule of DNA methylation level and pattern of L. barbarum from different cultivation areas in China, the present study employed fluorescence-assisted methylation-sensitive amplified polymorphism(MSAP) to analyze the methylation level and polymorphism of 53 genomic DNA samples from Yinchuan Plain in Ningxia, Bayannur city in Inner Mongolia, Jingyuan county and Yumen city in Gansu, Delingha city in Qinghai, and Jinghe county in Xinjiang. The MSAP technical system suitable for the methylation analysis of L. barbarum genomic DNA was established and ten pairs of selective primers were selected. Among amplified 5'-CCGG-3' methylated sites, there were 35.85% full-methylated sites and 39.88% hemi-methylated sites, showing a high degree of epigenetic differentiation. Stoichiometric analysis showed that the ecological environment was the main factor affecting the epigenetic characteristics of L. barbarum, followed by cultivated varieties. Precipitation, air temperature, and soil pH were the main ecological factors affecting DNA methylation in different areas. This study provided a theoretical basis for the analysis of the epigenetic mechanism of L. barbarum to adapt to the diffe-rent ecological environments and research ideas for the introduction, cultivation, and germplasm traceability of L. barbarum.
China ; DNA Methylation ; DNA Primers ; Epigenesis, Genetic ; Lycium/genetics*

Objective:To analyze the correlation between electromagnetic perturbation index and intracranial pressure (ICP) in patients with acute ischemic stroke (AIS) after mechanical thrombectomy, and to explore their values in early warning of decompressive craniectomy (DC).Methods:Forty-three patients with AIS after mechanical thrombectomy admitted to our hospital from January 1, 2018 to December 31, 2019 were enrolled in our prospective cohort study. Electromagnetic perturbation index and invasive ICP were continually monitored for 1-5 d in all patients 24 h after mechanical thrombectomy. According to the mean ICP on the first d, all patients were divided into normal ICP group (ICP<15 mmHg), mild increased ICP group (15≤ICP≤22 mmHg) and moderate to severe increased ICP group (ICP>22 mmHg). According to the implementation of DC, these patients were divided into decompressive craniectomy group and non-decompressive craniectomy group. The differences in clinical data of patients in different ICP groups were compared. The correlation between electromagnetic perturbation index and ICP was analyzed by Pearson correlation method. Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic value of electromagnetic perturbation index in increased ICP (ICP>22 mmHg). Multivariate Logistic regression analysis was used to determine the independent influencing factors for DC after mechanical thrombectomy in AIS patients. ROC curve was used to evaluate the diagnostic values of electromagnetic perturbation index and ICP in DC implementation after mechanical thrombectomy in AIS patients.Results:(1) In these 43 patients, 8 had normal ICP, 13 had mild increased ICP, and 22 had moderate to severe increased ICP. There were significant differences in baseline Glasgow Coma Scale (GCS) scores, baseline National Institutes of Health Stroke Scale (NIHSS) scores, baseline Alberta stroke program early CT scale (ASPECTS) scores, percentage of patients accepted DC, and electromagnetic perturbation index among the 3 groups ( P<0.05). Correlation analysis showed that electromagnetic perturbation index was negatively correlated with ICP ( r=-0.699, P=0.000). ROC curve showed that the area under curve (AUC) of electromagnetic perturbation index in diagnosing ICP>22 mmHg was 0.850 ( 95%CI: 0.690-1.000, P=0.000), enjoying the optimal cutoff value of 126. (2) Among the 43 patients, 27 were in the decompressive craniectomy group and 16 were in the non-decompressive craniectomy group. Multivariable Logistic regression analysis showed that baseline NIHSS scores, baseline ASPECTS scores, electromagnetic perturbation index, and ICP were independent risk factors for DC implementation after mechanical thrombectomy in AIS patients ( P<0.05). ROC curve showed that the AUC of ICP in predicting DC implementation after mechanical thrombectomy was 0.851 ( 95%CI: 0.728-0.973, P=0.000), enjoying the optimal cutoff value of 18.5 mmHg; the AUC of electromagnetic perturbation index in predicting DC implementation after mechanical thrombectomy was 0.764 ( 95%CI: 0.609-0.919, P=0.004), enjoying the optimal cutoff value of 137.5. Conclusion:There is a good correlation between electromagnetic perturbation index and ICP, which can be used as reference indexes for early warning of DC after mechanical thrombectomy in AIS patients.

Objective:To explore the effect of problem-originated clinical medical curriculum(PCMC) teaching method combined with PDCA(plan, do, check and action) circulation in the training of craniocerebral ultrasound for neurologically intensive refresher physicians.Methods:Thirty-two refresher physicians who entered the neurosurgery ICU of Henan Provincial People's Hospital from January 2018 to December 2019 were divided into test group ( n=18) and control group ( n=14) according to the time of admission. The test group accepted the teaching mode of PCMC teaching method combined with PDCA circulation, the control group accepted the traditional teaching methods of demonstration, student practice and teacher evaluation. One week before graduation, the differences between two groups in the theoretical assessment, operational skills and questionnaire were compared to evaluate the effectiveness of teaching mode. SPSS 23.0 was used for t-test and chi-square test. Results:Compared with the control group, the individual scores and total scores of the theoretical and operational assessments of craniocerebral ultrasound in the test group were significantly improved, and the questionnaire survey showed that the test group was superior to the control group in all the 7 items of teaching effect and satisfaction with the teaching method, with statistical significance ( P < 0.05). There was no significant difference between the two groups in increasing their interest in learning ( P > 0.05). Conclusion:PCMC teaching method combined with PDCA circulation can improve the training effect and satisfaction of clinical teaching of craniocerebral ultrasound.

Objective:To analyze the risk factors for hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) after mechanical thrombectomy, and explore the clinical value of bedside ultrasound measurement of optic nerve sheath diameter (ONSD) in predicting postoperative HT.Methods:Clinical data of 268 patients with AIS, accepted mechanical thrombectomy in our hospital from April 2017 to October 2019, were collected. Bedside ultrasound measurement of ONSD was performed in all patients. According to dynamic cerebral imaging 7 d after surgery, patients were divided into HT group ( n=57) and non-HT group ( n=211). Patients from HT group were classified according to the European Acute Stroke Collaborative Study (ECASS) classification. Clinical data of patients from the two groups were compared, and multivariate Logistic regression analysis was used to analyze the influencing factors for HT in patients with AIS after mechanical thrombectomy. The predictive value of ONSD in incidence of postoperative HT in AIS patients was analyzed by receiver operating characteristic (ROC) curve. The clinical data of HT patients with different classification subtypes were compared. Results:HT patients had significantly longer time from puncture to recanalization, significantly higher percentage of patients having more than three times of thrombectomy, significantly higher percentage of patients having baseline collateral circulation scale score of 0, statistically lower baseline Alberta stroke program early CT scale (ASPECTS), and significantly increased ONSD within 7 d of surgery as compared with the NHT patients ( P<0.05). Multivariate Logistic regression analysis indicated that time from puncture to recanalization (OR=1.012, 95%CI: 1.001-1.023, P=0.037), percentage of patients having more than three times of thrombectomy(OR=2.467, 95%CI:1.107-5.501, P=0.027), baseline collateral circulation scale scores (OR=0.578, 95%CI: 0.338-0.989, P=0.045), and ONSD within 7 d of surgery (OR=1.405, 95%CI: 1.008-1.082, P=0.019) were independent influencing factors for HT in patients with AIS after mechanical thrombectomy. The optimal cut-off value of ONSD for diagnosis of HT was 5.035 mm, area under curve (AUC) was 0.777 (95% confidence interval: 0.704-0.849). In HT patients, parenchyma hemorrhage (PH)-1 type patients had significantly higher ONSD and proportion of patients with ONSD≥5.035 mm within 7 d of surgery as compared with hemorrhagic infarction (HI)-2 type patients, and PH-2 type patients had significantly higher ONSD and proportion of patients with ONSD≥5.035 mm within 7 d of surgery as compared with PH-1 type patients ( P<0.05). Conclusions:ONSD within 7 d of mechanical thrombectomy is an independent risk factor for HT in AIS patients; when ONSD≥5.035 mm, patients are prone to have HT, which is related to the severity of HT. Bedside ultrasound measurement of ONSD is helpful for early evaluation of HT after mechanical thrombectomy in anterior circulation AIS patients.

Objective To evaluate the feasible cervical cancer screening strategies in rural China. Methods The study was based on the health industry scientific research project of National Health Commission in 2015, cervical cancer screening technology and demonstration research suitable for rural areas in China, we collected health economics and epidemiological parameters and established the unscreening model and screening model with Treeage Pro 2011 software. Combining with the data acquired from site investigation, including population screening, treatment-related clinical materials and cost data, we simulated the occurrence and the development of cervical cancer of rural women in China under different screening and intervention programs and predicted the screening effects [cumulative incidence, cumulative risk of disease, life years and quality adjusted life years (QALY), gains] and costs after 20 years, and using health economic evaluation analysis (cost-effectiveness analysis, cost-utility analysis, cost-benefit analysis). Screening programs included five screening strategies [visual inspection with acetic acid/lugol's iodine (VIA/VILI), careHPV, ThinPrep cytology test (TCT), careHPV+TCT, careHPV+VIA/VILI] and three screening intervals (1-year, 3-year, 5-year), a total of fifteen screening programs. Results Compared with no screening, fifteen screening programs reduced the cumulative incidence by 22.65%-51.76%. Compared with TCT or VIA/VILI, for the same screening interval, the reduced cumulative incidence, the amounts of life-year saved and QALY and benefits gained of careHPV were the highest. The cost-effectiveness ratios of these screening programs ranged (0.44-3.24)×104 Yuan per life-year saved, cost-utility ratios ranged (0.15-1.01)×104 Yuan per QALY, benefit-cost ratios ranged 7.73-59.10. The results of incremental cost-effectiveness ratios showed that VIA/VILI every five years, VIA/VILI every three years, careHPV every five years, careHPV every three years and careHPV every year were dominant programs. Conclusions VIA/VILI screening is cost-effective, careHPV is slightly more expensive but more effective. In rural China, careHPV screening every five years could be recommended. This study provides a basis for the determination of cervical cancer screening methods feasible for rural areas in China.