Objective To analyze the status of the bacteria in the operative area of transnasal skull base surgery and its correlation with postoperative intracranial infection.Methods The procedure of transnasal skull base surgery was divided into three stages:nasal passage preparation(stage 1),tumor resection(stage 2),and skull base reconstruction(stage 3).Bacterial sampling was taken from the mucosa of the anterior wall of sphenoid sinus or clival recess of sellar floor at the beginning of each stage;and the positive rate of bacterial culture in different stages of operation and its correlation with postoperative intracranial infection were analyzed.Results A total of 105 patients were enrolled in this study,and 315 samples were taken.The average time point of sampling in the three stages was 20.3,45.1 and 131.3 min after the beginning of operation,respectively.The positive results were 9 cases(2.9％)in the stage 1,8 cases(2.5％)in the stage 2,and 23 cases(7.3％)in the stage 3,which were 24 cases of Staphylococcus epidermidis,7 cases of Staphylococcus aureus,3 cases of hemolytic streptococcus,2 cases of Klebsiella pneumonia,and 4 cases of Escherichia coli.There was no significant difference in the positive cases between stage 1 and stage 2(P=0.955),but there were significant differences between stage 1 or 2 and stage 3(P=0.013;P=0.007).There were 36(11.4％)patients with at least one positive result in the three stages,17(16.2％)with cerebrospinal fluid leakage,and 12(11.4％)with intracranial infection.The risk of intracranial infection was 3.1 times higher in patients with positive bacterial culture than patients with negative bacterial culture(OR=3.1,95％CI:0.9-10.6),which was not statistically significant;patients with CSF leakage were 61.4 times higher than those without CSF leakage(OR=61.4,95％CI:11.2-337.1),which was statistically significant(P＜0.001).The consistency rate of bacteria in nasal cavity and postoperative cerebrospinal fluid culture was 57.1％.Conclusion The positive rate of bacterial culture in the operative area of transnasal skull base surgery increases significantly with the extension of operation time,which is a potential risk index of postoperative intracranial infection.

[Objective] To predict potential target genes for the treatment of glioblastoma (GBM) with stigmasterol and construct a relevant prognostic model, in order to reveal its antiglioma mechanism and the role of these target genes in the prognosis of GBM patients. [Methods] Differential expression genes in GBM and stigmasterol target genes were obtained via online databases. Venn diagram was used to select potential target genes for stigmasterol treatment of GBM, and enrichment analysis was performed using R language. Univariate COX regression analysis and least absolute shrinkage and selection operator (LASSO) analysis were made to select stigmasterol target genes related to the prognosis of GBM patients and construct a relevant prognostic model. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting analyses were used to detect the effect of stigmasterol on the expressions of related target genes. [Results] In this study, a total of 31 potential target genes for the treatment of GBM with stigmasterol were identified. Enrichment analysis showed that these target genes were associated with the activation of the G protein coupled receptor (GPCR) signaling pathway and the regulation of lipid metabolism. Regression analysis identified two stigmasterol target genes, namely, fatty acid binding protein 5 (FABP5) and alpha 1B adrenergic receptor (ADRA1B), which are associated with the prognosis of GBM. A prognostic model constructed based on these two genes could accurately predict the prognosis of GBM patients. Finally, stigmasterol inhibited the expressions of these two genes in GBM cells (FABP5: t=9.909, P=0.001; ADRA1B: t=3.319, P=0.029). [Conclusion] Stigmasterol’s anti-tumor effect may be linked to its regulation of GPCR signaling pathways and lipid metabolism. By inhibiting the expressions of FABP5 and ADRA1B, stigmasterol could potentially enhance the prognosis for GBM patients. Additionally, a prognostic model based on the expression levels of FABP5 and ADRA1B can be valuable for predicting patient outcomes and monitoring therapeutic efficacy in GBM.

【Objective】 To evaluate the efficacy and weight of sellar floor repair techniques such as different dura suture, bone reconstruction, and pedicled nasoseptal flap (PNSF) on the skull base reconstruction of medium and high flow cerebrospinal fluid leakage during endonasal endoscopic pituitary adenoma surgery. 【Methods】 We collected the data of Grade 2-3 cerebrospinal fluid leakage (Kelly grade) during endonasal endoscopic pituitary adenoma resection in our hospital from January 2015 to April 2021. Multiple reconstruction techniques such as dura suture, bone reconstruction and PNSF, and related factors such as age, sex, body mass index (BMI), diabetes, tumor size and diameter of diaphragmatic defect were recorded and introduced to multivariate regression to analyze the effects of the above factors on the duration of postoperative cerebrospinal fluid rhinorrhea and bed rest time, with a special focus on the weight priority of dura suture, bone reconstruction, and PNSF. 【Results】 A total of 281 patients were included, with the average age of (47±12.6) years, males accounting for 52.6%. There were 93 cases of PNSF, 268 cases of bone reconstruction, 109 cases of dura anchor suture, 50 cases of patch suture, and 122 cases without suture. The results of multivariate analysis indicated that the application of PNSF, bone reconstruction, and dura suture significantly reduced postoperative rhinorrhea time [reduced by 18.524, 35.876, and 16.983/19.791 (anchor suture/patch suture) hours, respectively; all P<0.001] and bed time [reduced by 16.797, 58.233, and 18.063/21.604 (anchor suture/patch suture) hours, respectively; all P<0.001], and there was no significant difference between anchor suture and patch suture. The weight of the standardized coefficient in reducing postoperative rhinorrhea time was dura suture>PNSF>bone reconstruction [Standard β=0.211/0.207 (anchor suture/patch suture)>0.200>0.165]. The weight of reducing bed time was bone reconstruction >dura suture > PNSF [Standard β=0.239>0.206/0.210 (anchor suture/patch suture) >0.164]. After stabilizing the learning curve in 25-30 cases, the average time for bone reconstruction was (3.9±0.4) minutes. After stabilizing learning curve in 30-40 cases, the dura suture technique took an average of (3.7±0.3) minutes per stitch, (3.7±1.0) stitches per case, and (13.6±2.7) minutes of total time consumption per case. 【Conclusion】 Dural anchoring and patching suture can both effectively shorten the duration of cerebrospinal fluid rhinorrhea and bed rest time. Bone reconstruction significantly improves the stability of reconstruction, especially in prompting patients’ early disengagement of bed rest. Moreover, the learning curves of the above two methods are economical and reasonable, and their weight is close to or even exceeds that of PNSF. Therefore, they can be an effective supplement or even substitute for PNSF.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To explore the clinical evaluation and management of placenta previa with placental implantation, in order to improve the diagnosis and treatment level of placenta previa with placental implantation.Methods:A retrospective analysis was conducted on the case data of two patients with high-risk placenta previa and placental implantation confirmed at the Third Affiliated Hospital of Southern Medical University. Based on previous reports, experience and shortcomings were summarized.Results:Selective surgery can reduce bleeding in placenta previa with placental implantation patients and reduce the risk of bleeding; Multi disciplinary consultation and multiple methods of hemostasis are important treatment measures for placenta previa with placental implantation; Preventive intervention measures need to fully evaluate the condition, taking into account factors such as the patient′s economic burden and intervention related complications.Conclusions:Standardized pregnancy management, multidisciplinary diagnosis and treatment, and the application of various surgical hemostasis measures can improve the success rate of placenta previa with placental implantation treatment.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

【Objective】 To construct an adipose derived stem cell-based alphastatin peptide glioma targeting vector and detect its anti-angiogenesis effect in vitro. 【Methods】 The adipose derived stem cell-based alphastatin peptide glioma targeting vector (Al-ADSCs) was constructed by transfecting the alphastatin peptide lentivirus vector into adipose derived stem cells (ADSCs). The expressions of stem cell markers on the surface of targeted vector were detected by flow cytometry. The expression of alphastatin peptide in the targeted vector and in the cell culture supernatant of the targeted vector were detected by Western blotting and ELISA, respectively. Cell migration assay was used to detect the tendency of the targeted vector toward CD133+ glioma stem cells, and lumen formation assay was used to detect the effect of the targeted vector on endothelial cell angiogenesis in vitro. 【Results】 After transfection, the surface markers of stem cells expressed by targeted vector did not significantly change compared with ordinary adipose derived stem cells. Western blotting showed that the targeted vector could successfully express alphastatin peptide. ELISA showed that the alphastatin peptide was detected in the cell culture supernatant of targeted vector \mg/L]. Cell migration test showed no significant difference in the tendency of CD133+ glioma stem cells between the targeted vector and ordinary adipose derived stem cells \. Lumen formation experiment showed that the targeted vector could inhibit endothelial cell-mediated angiogenesis in vitro [Lumen count: Control group (13.33±0.76)/HPF, ADSCs group (19.40±1.71)/HPF, Al-ADSCs group (7.27±0.31)/HPF, P<0.01]. 【Conclusion】 In the process of constructing the adipose derived stem cell-based alphastatin peptide glioma targeting vector, the stem cell biological characteristics and tumor tendency of targeted vector have no significant changes. This targeted vector can stably express and secrete alphastatin peptide and inhibit endothelial cell-mediated angiogenesis in vitro.

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

Objective: To explore the effect and mechanism of breviscapine(Bre) on the formation of intracranial aneurysm(IA) and its influence on nuclear factor erythroid 2-related factor 2(Nrf2) pathway in a rat model. Methods: The rat model of IA was established by elastase injection. The rats were randomly divided into Sham group, Model group and Bre group with 15 rats in each group. The Bre group was intraperitoneally injected with 50 mg/kg Bre every day, the Sham group and Model group were intraperitoneally injected with the same volume of normal saline for 3 weeks. During this period, the incidence of IA, survival rate and systolic blood pressure were recorded, immunofluorescence staining and qRT-PCR were employed to assay the expression of α-smooth muscle actin(α-SMA) and smooth muscle 22α(SM22α). Hydrogen peroxide(H2O2, 0.5 mmol/L) was used to treat rat vascular smooth muscle cells(VSMC) to induce oxidative damage, and then co-incubated with Bre(100 μmol/L) or/and ML385(Nrf2 inhibitor), Western blot, qRT-PCR, ELISA, DCFH-DA fluorescence staining and flow cytometry were used to detect the expression of Nrf2, contractile phenotype-related protein and inflammatory cytokine, reactive oxygen species(ROS) production and cell apoptosis rate, respectively. Results: In IA rats, Bre treatment up-regulated the expression of nuclear Nrf2, improved the pathological changes of IA, reduced the incidence of IA, improved the survival rate, and lowered the systolic blood pressure. In VSMC treated with H2O2, Bre pretreatment increased the expression of Nrf2, antioxidant enzymes, α-SMA and SM22α, reduced the expression of matrix metalloproteinases(MMP)-2 and MMP-9, the production of ROS and cell apoptosis, and reduced inflammation in cerebral arteries cell infiltration and expression of pro-inflammatory cytokines. Inhibition of Nrf2 weakened the therapeutic effect of Bre pretreatment in H2O2treated VSMC. Conclusion Bre can effectively reduce the oxidative stress and inflammation in VSMC, thereby reducing the formation and rupture of IA in rat. The mechanism may be related to the activation of the Nrf2 pathway.