Objective To establish a recurrence risk prediction model for meningioma based on HOXA9 DNA methylation.Methods Meningioma-related datasets were downloaded from GEO database for screening homeobox genes(HOXs)with prognostic values using differential methylation and ROC curve analysis and Cox regression analysis.The differentially methylated CpG sites with high predictive efficacy were selected to establish the risk prediction model using Lasso-Cox regression analysis,based on which the patients were divided into high-and low-risk groups by the cutoff value.The methylation levels of CpG sites were verified at the cell and tissue levels using methylation-specific PCR(MS-PCR).Clinical meningioma tissue samples were used to validate the predictive efficacy of the model.Results HOXA9 methylation level was significantly up-regulated in meningiomas(P<0.001)and showed a high diagnostic efficiency(AUC=0.884)as an independent risk factor for overall survival(P<0.01)positively correlated with the degree of malignancy and poor prognosis of meningioma(P<0.05).Risk stratification by HOXA9 methylation was more accurate than WHO grading for predicting recurrence and patient survival time.The AUCs of the sites cg03217995 and cg21001184 were both above 0.8 for meningioma diagnosis and above 0.6 for predicting recurrence.The patients'clinical characteristics differed significantly between the high-and low-risk groups(P<0.001),and the prediction score of the model was an independent prognostic factor for meningioma(P<0.05).MS-PCR results showed that the methylation levels of the two sites increased significantly in meningioma cells.In clinical samples,the combined model showed a high prediction efficiency(AUC=0.857),and the predicted risk of progression was highly consistent with the patients'actual condition.Conclusion High HOXA9 methylation level is a predictor for poor prognosis of meningiomas,and the combined prediction model based on its CpG sites provides a new approach to early screening of meningioma patients at risk of progression.

Objective To establish a recurrence risk prediction model for meningioma based on HOXA9 DNA methylation.Methods Meningioma-related datasets were downloaded from GEO database for screening homeobox genes(HOXs)with prognostic values using differential methylation and ROC curve analysis and Cox regression analysis.The differentially methylated CpG sites with high predictive efficacy were selected to establish the risk prediction model using Lasso-Cox regression analysis,based on which the patients were divided into high-and low-risk groups by the cutoff value.The methylation levels of CpG sites were verified at the cell and tissue levels using methylation-specific PCR(MS-PCR).Clinical meningioma tissue samples were used to validate the predictive efficacy of the model.Results HOXA9 methylation level was significantly up-regulated in meningiomas(P<0.001)and showed a high diagnostic efficiency(AUC=0.884)as an independent risk factor for overall survival(P<0.01)positively correlated with the degree of malignancy and poor prognosis of meningioma(P<0.05).Risk stratification by HOXA9 methylation was more accurate than WHO grading for predicting recurrence and patient survival time.The AUCs of the sites cg03217995 and cg21001184 were both above 0.8 for meningioma diagnosis and above 0.6 for predicting recurrence.The patients'clinical characteristics differed significantly between the high-and low-risk groups(P<0.001),and the prediction score of the model was an independent prognostic factor for meningioma(P<0.05).MS-PCR results showed that the methylation levels of the two sites increased significantly in meningioma cells.In clinical samples,the combined model showed a high prediction efficiency(AUC=0.857),and the predicted risk of progression was highly consistent with the patients'actual condition.Conclusion High HOXA9 methylation level is a predictor for poor prognosis of meningiomas,and the combined prediction model based on its CpG sites provides a new approach to early screening of meningioma patients at risk of progression.

Zhishi Xiebai Guizhi Tang， derived from Synopsis of the Golden Chamber （《金匮要略》， Han dynasty， ZHANG Zhongjing）， is a famous classical prescription commonly used for chest impediment. By means of bibliometrics， the authors collected 63 ancient Chinese medical books related to Zhishi Xiebai Guizhi Tang and screened 36 effective books for statistical analysis of the historical origin， composition， main indications， dosage， processing， decocting method and other aspects of the prescription. The findings revealed that Zhishi Xiebai Guizhi Tang was composed of five medicinal herbs， namely， Aurantii Fructus Immaturus， Allii Macrostemonis Bulbus， Cinnamomi Ramulus， Magnoliae Officinalis Cortex， and Trichosanthis Fructus， with the function of activating Yang， dissipating mass， dispelling phlegm and lowering Qi. The prescription was mainly used to treat chest impediment， chest fullness， chest pain， wheezing， coughing and shortness of breath caused by suppressed Yang Qi， stagnant heart Qi， stagnant phlegm and stasis， and phlegm evil blocking heart， chest or lungs. Additionally， it was found that there were 70 modern literature recording the clinical applications of Zhishi Xiebai Guizhi Tang， and the main system diseases treated were circulatory system （51， 72.85%）， endocrine system （4， 5.7%）， respiratory system （9， 12.85%） and digestive system （6， 8.57%）， of which circulatory system is dominated by coronary heart disease （chest impediment in traditional Chinese medicine）. The involved medical syndrome types mainly included internal obstruction of phlegm heat and turbidity， obstruction of phlegm turbidity and stasis， congealing cold， phlegm， stasis and Qi stagnation， chest Yang depression and combined phlegm and stasis. Ancient medical records and modern clinical application are the keys to ensure the safety and effectiveness of famous classical prescriptions and compound preparations. Therefore， this paper sorted and mined ancient medical books of Zhishi Xiebai Guizhi Tang and statistically analyzed its modern clinical application， aiming to provide a literature reference for the research and development of new drugs and clinical application of the prescription.

Objective:To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis (LC) treated and fully managed with long-term nucleos(t)ide analogues (NAs).Methods:The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019. LC patients who met the inclusion criteria were enrolled. The life-table method was used to calculate the incidence of liver cancer. Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC. A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance. The 2 test was used for rate comparison. Results:The median follow-up time of 198 LC cases treated with NAs was 6.0 years (1.0-15.3 years). By the end of the visit: (1) 16.2% (32/198) of LC patients had developed liver cancer, and the cumulative incidence of liver cancer in 1, 3, 5, 7, and 9 years were 0, 8.9%, 14.3%, 18.6%, and 23.4%, respectively, with an average annual incidence of 3.1%. Among the 32 cases with liver cancer, 68.7% had developed small liver cancer (22/32). (2) Univariate Cox model analysis showed that the development of liver cancer was related to four factors, i.e., the presence or absence of LC nodules, whether the baseline was first-line medication, the family history of liver cancer, and patient compliance. The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer. (3) The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules (21.7% vs. 11.5%, P = 0.029). The 5-year cumulative incidence of liver cancer in patients with non-first-line drugs was significantly higher than that of patients with first-line drugs (22.0% vs.8.2%, P = 0.003). The 5-year cumulative incidence of liver cancer in patients with poor compliance was significantly higher than that of patients with good compliance (21.3% vs. 12.7%, P = 0.014). The 5-year cumulative incidence of liver cancer in patients with a family history of liver cancer was significantly higher than that of patients without a family history of liver cancer (22.3% vs. 8.1%, P = 0.006). (4) Compared with patients with poor compliance, patients with good compliance had higher HBV DNA negative serconversion rate (98.7% vs. 87.8%, P = 0.005), and a lower virological breakthrough rate (12.1% vs. 29.3%, P = 0.007). Conclusion:The long-term NAs antiviral therapy can reduce the risk of liver cancer, but it cannot completely prevent the development of liver cancer, especially in patients with a family history of liver cancer and baseline hardened nodules (high risk of liver cancer). Furthermore, the complete management can improve patient compliance, ensure the efficacy of antiviral therapy, and reduce the risk of liver cancer development, so to achieve secondary prevention of liver cancer, i.e., early detection, diagnosis and treatment.

Objective:To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients.Methods:A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient’s clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients.Results:Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% vs. 3.8%, P = 0.046). Conclusion:For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.

Objective To observe the incidence of spontaneous clearance of hepatitis B virus (HBV) DNA in chronic hepatitis B (CHB) patients ,and to investigate the related factors of the spontaneous clearance of HBV DNA and to determine the time to start antiviral therapy .Methods Patients who met the inclusion criteria were recruited from the follow-up cohort of chronic HBV infection from January 2008 to August 2017 for observation .The liver function including alanine aminotransferase (ALT) levels ,HBV DNA load and serum markers of HBV were measured at baseline ,month 1 ,month 3 and month 6 of follow-up . Evaluation index included cumulative HBV DNA negative conversion rate and cumulative HBeAg negative conversion rate .Multivariable analysis was used to analyze the factors associated with the spontaneous clearance of HBV DNA .Results A total of 116 patients were recruited in this study .All the patients showed ALT level elevation at baseline .Without antiviral treatment ,the cumulative HBV DNA negative conversion rate was 12 .9％ after 6-month observation .HBeAg negative conversion rate was 22 .5％ .Multivariable analysis showed that patients without a family history of HBV infection ,baseline ALT level >3 times the upper limit of normal (ULN) and HBV DNA level <6 lg copies/mL had higher cumulative HBV DNA spontaneous clearance rate .HBV DNA negative conversion rate in patients whomet all the above three conditions was up to 75％ .Conclusions In CHB patients and ALT level elevation for the first time , some patients could achieve spontaneous clearance of HBV DNA without antiviral therapy .Patients without a family history of HBV infection ,baseline ALT level >3 ULN and HBV DNA level <6 lg copies/mL have higher rate of cumulative HBV DNA spontaneous clearance .

Objective To investigate the clinical application effect of independently designed subcutaneous tunnel in endo‐scopic thyroid operation .Methods A total of 480 cases of endoscopic thyroid operation were completed in our department from February 2005 to December 2014 ,in which 315 cases adopted the independently designed subcutaneous tunnel for separating the subcutaneous tissues in anterior thoracic region and the other 165 cases used the puncture stick for separating and constructing the subcutaneous tunnel .Results Using independently designed subcutaneous tunnel for constructing the subcutaneous tunnel in the anterior thoracic region had statistical difference in the operative time and intraoperative bleeding amount compared with the punc‐ture stick(P<0 .05) ,and the difference of postoperative complications between the two groups was statistically signifficant (P<0 .05) .Conclusion Adopting the independently designed subcutaneous tunnel for constructing subcutaneous tunnel has the advan‐tages of short time consuming ,less bleeding and fewer complications .The level and size of the constructed subcutaneous tunnel are easy to grasp ,so which is more convenient for endoscopic thyroid operation .

Introduction:The rearrangement of the anaplastic lymphoma kinase (ALK) gene accounts for approximately 1%–6%of lung adenocarcinoma cases and deifnes a molecular subgroup of tumors characterized by clinical sensitivity toALK inhibitors such as crizotinib. This study aimed to identify the relationship betweenALK rearrangement and the clinico?pathologic characteristics of non?small cell lung cancer (NSCLC) and to analyze the therapeutic responses of crizotinib and conventional chemotherapy toALK rearrangement in NSCLC patients. Methods:A total of 487 lung cancer patients who underwent testing forALK rearrangement in our department were included in this study.ALK rearrangement was examined by using lfuorescence insitu hybridization (FISH) assay. Results:Among the 487 patients, 44 (9.0%) were diagnosed withALK rearrangement by using FISH assay. In 123 patients with adenocarcinoma who were non?smokers and of a young age (≤58years old), the frequency ofALK rearrangement was 20.3% (25/123). Short overall survival (OS) was associated with non?adenocarcinoma tumor type (P=0.006), poorly differentiated tumors (P=0.001), advanced?stage tumors (P<0.001), smoking history (P=0.008), and wild?type epidermal growth factor receptor (EGFR) (P=0.008). Moreover, patients with poorly differentiated and advanced?stage tumors had a shorter time to cancer progression compared with those with well differentiated (P=0.023) and early?stage tumors (P=0.001), respectively. Conclusions:ALK?rearranged NSCLC tends to occur in younger individuals who are either non?smokers or light smokers with adenocarcinoma. Patients withALK rearrangement might beneift fromALK inhibitor therapy.

Objective Kunming strain(KM) mice were used as animal models. Nontoxic dextran conjugated with tetramethylrhodamine(TMR)and fluorecein isothiocyante(FITC)was microinjected to two of the 2-cell blastomere as molecular probe to trace the development fate of the blastomere ,in order to figure out the mechanisms of the formation of Em-Ab axis. Methods FITC- dextran was injected to zygote in order to make sure if it is noxious. Two blastomeres of 2-cell embryo were injected FITC- dextran and TMR- dextran respectively. Results When labeled embryo develeped to blastocyst, distribution of progeny of 2-cell embryo blastomeres can be detected.Conclusion The cells of blastomere randomly distributed either embryonic parts or extraembryonic parts of blastocyst.

Objective To explore the application value of spiral CT angiography in etiological diagnosis of spontaneous intracranial hematoma before surgery. Methods 48 patients with spontaneous intracranial hematoma following surgical indication assessed by CT scan were ascertained etiological diagnosis performed by CT angiography before surgery.Results The causes of intracranial hematoma were cerebral aneurysm(2 patients), arteriocenous malformation (5 patients), hypertension(40 patients), and no image in one patient performed by CT angiography.Conclusion CT angiography has important value in etiological diagnosis of spontaneous intracranial hematoma before surgery.