The occurrence and development of human malignancies is often accompanied by epigenetic changes, and DNA methylation is one of the most common epigenetic modification. Methylation events are often discovered in the early stage of gynecologic neoplasia. The methylation detection protocol based on liquid biopsy technology has made important progress in the screening and prognosis assessment of gynecologic tumors. The reliability of methylation detection in micro-noninvasive samples from multiple sources is similar to or better than that of traditional protocols and strategies. This article reviews the progress of methylation detection in screening, diagnosis and monitoring of gynecologic tumors, and discusses its value in the present and future diagnosis and treatment of gynecologic tumors.

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.

Objective To investigate the effect of cornus officinalis glycosides on apoptosis and oxidative damage of human renal tubular epithelial cells line induced by high glucose by regulating E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)pathway.Methods Human renal tubule epithelial cell line HK-2 was divided into control group(control,5.5 mmol/L glucose),model group(HG,30 mmol/L glucose),and total cornus offici-nalis glycosides groups with low,medium and high dose(L-COG,M-COG,H-COG).After Nrf2 pathway inhibitors were added,HK-2 cells were divided into H-COG group and ML385 group.CCK8 method was used to detect cell activity.Apoptosis was detected by flow cytometry.The expressions of Bcl-2 associated X protein(Bax),B-cell lymphoma/leukemia 2(Bcl-2),activated caspase3(cleaved caspase3),Nrf2/HO-1 pathway protein were detected by Western blot.Reactive oxygen species(ROS)content was detected by DCFH-DA,glutathione peroxi-dase(GSH-Px)activity,superoxide dismutase(SOD)activity,interleukin-6(IL-6)content and tumor necrosis factor α(TNF-α)content were detected by ELISA.Results Compared with control group,the cell activity,Bcl-2 protein expression,GSH-Px and SOD activity in model group were significantly decreased,and the apoptosis rate,Bax,Nrf2,HO-1 and cleaved caspase3 protein expression,ROS,IL-6 and TNF-α content were significantly in-creased(P＜0.05).Compared with model group,the cell activity,Bcl-2 protein expression,GSH-Px and SOD ac-tivity of L-COG,M-COG,and H-COG were significantly increased.Apoptosis rate,Bax,Nrf2,HO-1,cleave-caspase3 protein expression,ROS,IL-6,TNF-α content were significantly decreased(P＜0.05).Compared with H-COG,the cell activity,Bcl-2 protein expression,GSH-Px and SOD activity in ML385 group were significantly increased.The apoptosis rate,Bax and cleaved caspase3 protein expression,ROS,IL-6,TNF-α content were sig-nificantly decreased(P＜0.05).Conclusions The total cornus officinis glucoside may reduce the oxidative stress and inflammatory response of renal tubular epithelial cells induced by high glucose through inhibiting Nrf2/HO-1 pathway and then reduce cell apoptosis.

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 explore the antitussive action site and potential mechanism of Shegan Zhike Capsule.Methods The mouse cough model induced by concentrated ammonia was used to observe the dose effect relationship of the antitussive effect of Shegan Zhike capsule.The central antitussive effect of Shegan Zhike capsule was observed by using the cough model induced by electrical stimulation of superior laryngeal nerve in guinea pigs.The peripheral antitussive effect of Shegan Zhike capsule was observed by using the cough model of capsaicin desensitized guinea pigs induced by mechanical stimulation.The model of chronic bronchitis in guinea pigs was established by smoking,and the effects of Shegan Zhike Capsule on vasoactive amines histamine(HA)and 5-hydroxytryptamine(5-HT)were observed.Results Shegan Zhike capsule could significantly reduce the number of coughs in mice at the doses of 43.00,86.00 and 172.00 mg extract·kg-1(P<0.05 or P<0.01).The low-dose group,the middle-dose group,and the high-dose group of Shegan Zhike Capsule did not significantly inhibit the cough inducing effect of electrical stimulation of guinea pig superior laryngeal nerve at 30 min and 60 min after administration.Shegan Zhike capsule could significantly inhibit the cough of capsaicin desensitized guinea pigs caused by mechanical stimulation in the low dose group at 60 min,the medium dose group at 30 min and the high dose group at 30 min and 60 min(P<0.05).Compared with the model control group,the content of HA in serum of guinea pigs in low,medium and high dose groups of Shegan Zhike capsule decreased significantly(P<0.05 or P<0.01).The content of serum 5-HT in the high dose group decreased significantly(P<0.05).Conclusion The antitussive effect of Shegan Zhike Capsule was not in the center,and its peripheral antitussive effect was related to the inhibition of RARs receptors,and vasoactive amines such as HA and 5-HT were also involved.

Objective:To explore the average age at onset of endometrial cancer (EC) and the differences between domestic and international factors.Methods:Pubmed, Wanfang Database, VIP Information Resource System, and China National Knowledge Infrastructure (CNKI) were selected to extract clinical research data related to EC. Through data mining methods such as frequency analysis and cluster analysis, we compared the differences in the average age of onset of EC between domestic and foreign countries.Results:A total of 280 articles that met the inclusion criteria were selected, and frequency analysis found that the average age of onset of EC in the Chinese population was mostly concentrated under 57 years old, while in European and American countries, it was mainly concentrated above 57 years old. Through cluster analysis, it was found that the average age of onset in China was clustered in one category with most Asian countries, while European and American countries and Australian countries were clustered in another category. Through analysis of domestic and foreign articles, it was found that the average age of onset of EC did not show a significant upward or downward trend with years.Conclusions:There are differences in the average onset age of EC among different countries and regions. The onset age of EC in Asian populations is significantly earlier than that in European and American populations. The average onset age of EC in Chinese populations is 54 years old, and there is no trend towards a younger onset of EC.

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.

OBJECTIVE: To explore the genetic basis for a case of Lamb-Shaffer syndrome. METHODS: Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing(WES). Suspected variant was verified by Sanger sequencing. RESULTS: The patients was found to harbor a heterozygous c.1495delA(p.Thr499Glnfs*5) frameshift variant of the SOX5 gene by WES. Sanger sequencing confirmed that the same variant was a de novo variant. Based on the American College of Medical Genetics and Genomics guidelines, c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION The c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene probably underlies the Lamb-Shaffer syndrome in this patient.
Animals ; Genomics ; Heterozygote ; Humans ; Mutation ; SOXD Transcription Factors/genetics* ; Sheep ; Whole Exome Sequencing

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 explore the risk factors of urinary incontinence (UI) in China by using random forest algorithm, and to evaluate the predictive effect of each risk factor on UI.Methods:A baseline survey with a multistage stratified cluster sampling design was conducted between February 2014 and January 2016, and followed up by telephone from June to December 2018. A total of 55 477 adult women from six provinces of China participated the survey. According to the ratio of 1:1, under sampling method was used to randomly select the same number of women as UI from the non UI women. The data were randomly divided into training set and verification set according to 7:3. The training set was used to establish the random forest model, which including the candidate variables with P<0.2 in univariate analysis, and the verification set was used to verify the predictive effects. Results:A total of 30 658 patients (55.26%, 30 658/55 477) completed the follow-up, the median follow-up time was 3.7 years. Among the 24 985 women without UI at baseline, 1 757 (7.03%, 1 757/24 985) had UI at followed up, including 1 117 (4.47%, 1 117/24 985) with stress UI, 243 (0.97%, 243/24 985) with urgency UI and 397 (1.59%, 397/24 985) with mixed UI. When fixed the number of features as 2 and the number of random trees as 300 in the random forest model, the out of bag error rate estimation was the lowest; with such parameter settings, the classification accuracy was 64.3%, the sensitivity was 64.2%, and the specificity was 64.4%. The top10 predictive UI factors that screening by the variable importance measure in random forest model were obtained as follows: age, parity, delivery pattern, body mass index (BMI), menopause, history of diabetes, education level, history of pelvic surgery, regions, and marital status.Conclusion:We identified the top10 predictive UI factors that screening by the variable importance in random forest model as follows: age, parity, delivery pattern, BMI, menopause, history of diabetes, education level, history of pelvic surgery, regions, and marital status.