Hepatitis B virus （HBV） exclusively infects liver parenchymal cells and forms covalently closed circular DNA （cccDNA） within their nuclei. HBV cccDNA serves as the essential template for viral gene transcription， the sole source of progeny virus production， and the key driver of viral antigen expression， and it is the molecular basis for the persistence of HBV infection. Therefore， elimination and/or functional silencing of cccDNA is the key to eradicate chronic HBV infection. This article discusses the critical scientific issues that need to be solved during elimination of the harm of HBV infection from the perspectives of the synthesis， transcription， and clearance of cccDNA， as well as the impact of nonparenchymal cells on cccDNA， in order to provide a reference for eradicating HBV infection in the future.

Objective To investigate correlations of the ratio of specific brain region volume to total brain volume(ratio％),standard uptake value(SUV)of specific brain region based on 18F-FDG PET/MR examination in Alzheimer disease(AD)patients,as well as the relationship between changes of these two.Methods Fifty AD patients were retrospectively collected.Based on FDG PET/MR,the ratio％and the mean SUV(SUVmean)of 40 specific brain regions were obtained,and the correlation between ratio％and SUVmean for each region were evaluated.According to a database of normal brains,Z-scores for ratio％and SUVmean were calculated to represent structural and functional changes in AD patients,and the correlation between these 2 Z-scores was assessed.Results Correlations were found between ratio％and SUVmean,also between Z-scores of these two parameters in 29 brain regions(r=0.288 to 0.778,all P＜0.05).Among them 7 brain regions,i.e.bilateral middle temporal gyrus,right fusiform gyrus,right hippocampus,right precuneus,left lingual gyrus and right parahippocampal gyrus exhibited correlation coefficients greater than 0.6.Conclusion There were some relationships between brain structural and metabolic functions and their changes in AD patients showed on FDG PET/MR.

Objective:To observe the therapeutic effect of combining low-frequency pulsed electrical stimulation with Beckman oral muscle exercise training in relieving drooling among persons with Parkinson′s disease (PD).Methods:A random number table was used to divide 120 PD patients with drooling into a mouth muscle training group, an electrical stimulation group, and an observation group, with 40 patients in each group. In addition to routine medication, the oral muscle training group was given Beckman oral muscle exercise training, the electrical stimulation group underwent low-frequency pulsed electrical stimulation treatment, while the observation group was provided with both. Before and after 4 weeks of treatment, the severity of salivation, the frequency of repeated empty swallowing, oral motor function, saliva secretion, and life quality of the three groups were evaluated using the Saliva Rating Scale (DRS), the Repeated Saliva Swallowing Test (RSST), oral motor function grading, the Parkinson′s Disease Saliva Clinical Scale (SCS-PD), saliva weighing, and the PD Quality of Life Scale (PDQ-39).Results:After the treatment the average DRS, SCS-PD, saliva weighing and PDQ-39 results of the observation group were significantly better than those before treatment and better than the other 2 groups′ averages. That group′s average RSST and oral motor function scores had increased significantly compared to before treatment, and compared with the other 2 groups′ averages at the same time point.Conclusions:Combining low-frequency pulsed electrical stimulation with Beckman oral muscle exercise can improve oral motor function, swallowing, and the life quality of PD patients who drool. It is more effective than electrical stimulation or oral muscle exercise training alone. Such combination therapy is worthy of clinical promotion and application.

Objective:To observe the therapeutic effect of combining low-frequency pulsed electrical stimulation with Beckman oral muscle exercise training in relieving drooling among persons with Parkinson′s disease (PD).Methods:A random number table was used to divide 120 PD patients with drooling into a mouth muscle training group, an electrical stimulation group, and an observation group, with 40 patients in each group. In addition to routine medication, the oral muscle training group was given Beckman oral muscle exercise training, the electrical stimulation group underwent low-frequency pulsed electrical stimulation treatment, while the observation group was provided with both. Before and after 4 weeks of treatment, the severity of salivation, the frequency of repeated empty swallowing, oral motor function, saliva secretion, and life quality of the three groups were evaluated using the Saliva Rating Scale (DRS), the Repeated Saliva Swallowing Test (RSST), oral motor function grading, the Parkinson′s Disease Saliva Clinical Scale (SCS-PD), saliva weighing, and the PD Quality of Life Scale (PDQ-39).Results:After the treatment the average DRS, SCS-PD, saliva weighing and PDQ-39 results of the observation group were significantly better than those before treatment and better than the other 2 groups′ averages. That group′s average RSST and oral motor function scores had increased significantly compared to before treatment, and compared with the other 2 groups′ averages at the same time point.Conclusions:Combining low-frequency pulsed electrical stimulation with Beckman oral muscle exercise can improve oral motor function, swallowing, and the life quality of PD patients who drool. It is more effective than electrical stimulation or oral muscle exercise training alone. Such combination therapy is worthy of clinical promotion and application.

Objective:To analyze the prognostic influencing factors in patients with isocitrate dehydrogenase (IDH) wild-type glioma, and further evaluate the value of surgical resection in prognosis.Methods:The clinical data and molecular pathological information of 647 patients with IDH wild-type glioma were retrieved from the Chinese Glioma Genome Atlas (CGGA) database (from 2006 to 2019). The clinical characteristics were recorded, including gender, age, initial symptoms, preoperative Karnofsky performance status (KPS) score, tumor location, tumor laterality, extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and postoperative treatment. Kaplan-Meier survival curve was plotted to calculate overall survival (OS) and progression-free survival (PFS), and comparisons were performed using the log-rank test. Multivariate Cox regression analysis was used to identify the independent influencing factors of prognosis in patients with IDH wild-type glioma.Results:Among the 647 patients with IDH wild-type glioma, there were 120 cases of WHO grade Ⅱ, 115 cases of grade Ⅲ, and 412 cases of grade Ⅳ; the median OS was 20.3 months. There were statistical differences in age, initial symptoms, tumor location, preoperative KPS score, extent of resection, MGMT promoter methylation status and postoperative treatment among patients with different WHO grades (P<0.01), but there were no statistical difference in gender and tumor laterality (P>0.05). The median OS and PFS in patients with WHO grade Ⅱ were significantly longer than those in patients with WHO grade Ⅲ and WHO grade Ⅳ (169.9 months vs. 24.7 and 14.4 months, 138.8 months vs. 17.7 and 11.4 months), the indexes in patients with WHO grade Ⅲ were significantly longer than patients with WHO grade Ⅳ, and there were statistical differences (P<0.05). The median OS and PFS in patients with total resection were significantly longer than those in patients with subtotal resection and partial resection (37.2 months vs. 20.3 and 8.5 months, 29.5 months vs. 17.6 and 6.0 months), the indexes in patients with subtotal resection were significantly longer than patients with partial resection, and there were statistical differences (P<0.05). Among 153 patients with MGMT promoter methylation who received postoperative chemoradiotherapy, the median OS and PFS in patients with total resection (67 cases) were significantly longer than those in patients with subtotal resection (64 cases) and partial resection (22 cases): 28.8 months vs. 18.4 and 9.0 months, 25.6 months vs. 16.6 and 6.5 months), the indexes in patients with subtotal resection were significantly longer than patients with partial resection, and there were statistical differences (P<0.05). Among 202 patients with MGMT promoter non-methylation who received postoperative chemoradiotherapy, the median OS and PFS in patients with total resection (81 cases) were significantly longer than those in subtotal resection (81 cases) and partial resection (40 cases): 31.3 months vs. 21.9 and 14.0 months, 22.7 months vs. 16.8 and 9.7 months, and there were statistical differences (P<0.05), but there were no statistical difference in the indexes between patients with subtotal and patients with partial resection (P>0.05). Multivariate Cox regression analysis result showed that age, extent of resection, WHO grade (grade Ⅲ/grade Ⅳ) and postoperative treatment were independent OS and PFS influencing factors in patients with IDH wild-type glioma (OS: HR = 1.327, 3.295, 3.406/7.964 and 1.597; 95% CI 1.079 to 1.633, 2.627 to 4.132, 2.225 to 5.216/5.339 to 11.880 and 1.288 to 1.981; P<0.01. PFS: HR = 1.282, 2.655, 3.143/6.511 and 1.477; 95% CI 1.039 to 1.583, 2.123 to 3.322, 2.049 to 4.819/4.376 to 9.690 and 1.181 to 1.849; P<0.05 or <0.01).Conclusions:The age, extent of resection, WHO grade and postoperative treatment are independent prognosis influencing factors in patients with IDH wild-type glioma. Treatment strategies should fully consider the clinical and molecular pathological characteristics to achieve maximal safe tumor resection and optimal survival benefit.

Objective: To identify Mycobacterium and analyze the drug resistance of Mycobacterium tuberculosis by using nanopore targeted sequencing technology, so as to provide the methodological reference for the rapid diagnosis of tuberculosis. Methods: Samples from patients aged 18 to 80 years old who were highly suspected of Mycobacterium tuberculosis infection and diagnosed with Mycobacterium tuberculosis infection in designated tuberculosis hospitals from March to November 2022 were collected for nanopore targeted sequencing technology. The detection status of Mycobacterium, types of Mycobacterium tuberculosis drug resistance, and gene mutation sites were analyzed. Results: A total of 200 samples were collected, including 160 respiratory tract samples and 40 non-respiratory tract samples. Nanopore targeted sequencing technology detected 194 positive mycobacterial samples, with a detection sensitivity of 97.00% (95%CI: 93.28%-98.77%). There were 187 positive cases of Mycobacterium tuberculosis and 7 cases of nontuberculous mycobacteria, with detection rates of 93.50% and 3.50%, respectively. Nanopore targeted sequencing technology identified 11 mutations in the rifampicin resistance gene rpoB, 1 mutation in the isoniazid resistance gene katG, 2 mutations in the gene inhA, 3 mutations in the ethambutol resistance gene embB, 2 mutations in the streptomycin resistance gene rpsL, 1 mutation in the gene rrs, 11 mutations in the pyraz inamide resistance gene pncA, 6 mutations in the fluoroquinolone resistance gene gyrA, 2 mutations in the gene gyrB, and 3 mutations in the aminoglycoside resistance gene rrs. It took 5-6 hours to complete the detection of one sample using nanopore targeted sequencing technology. Conclusions The nanopore targeted sequencing technology has high sensitivity for detecting Mycobacterium tuberculosis and can identify 42 nucleic acid mutation sites in 9 drug resistance genes associated with 7 anti-tuberculosis drugs. It is time-efficient and has certain applicability in the rapid diagnosis of tuberculosis and the analysis of drug resistance genes.

Objective To investigate correlations of the ratio of specific brain region volume to total brain volume(ratio％),standard uptake value(SUV)of specific brain region based on 18F-FDG PET/MR examination in Alzheimer disease(AD)patients,as well as the relationship between changes of these two.Methods Fifty AD patients were retrospectively collected.Based on FDG PET/MR,the ratio％and the mean SUV(SUVmean)of 40 specific brain regions were obtained,and the correlation between ratio％and SUVmean for each region were evaluated.According to a database of normal brains,Z-scores for ratio％and SUVmean were calculated to represent structural and functional changes in AD patients,and the correlation between these 2 Z-scores was assessed.Results Correlations were found between ratio％and SUVmean,also between Z-scores of these two parameters in 29 brain regions(r=0.288 to 0.778,all P＜0.05).Among them 7 brain regions,i.e.bilateral middle temporal gyrus,right fusiform gyrus,right hippocampus,right precuneus,left lingual gyrus and right parahippocampal gyrus exhibited correlation coefficients greater than 0.6.Conclusion There were some relationships between brain structural and metabolic functions and their changes in AD patients showed on FDG PET/MR.

Objective:To analyze the prognostic influencing factors in patients with isocitrate dehydrogenase (IDH) wild-type glioma, and further evaluate the value of surgical resection in prognosis.Methods:The clinical data and molecular pathological information of 647 patients with IDH wild-type glioma were retrieved from the Chinese Glioma Genome Atlas (CGGA) database (from 2006 to 2019). The clinical characteristics were recorded, including gender, age, initial symptoms, preoperative Karnofsky performance status (KPS) score, tumor location, tumor laterality, extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and postoperative treatment. Kaplan-Meier survival curve was plotted to calculate overall survival (OS) and progression-free survival (PFS), and comparisons were performed using the log-rank test. Multivariate Cox regression analysis was used to identify the independent influencing factors of prognosis in patients with IDH wild-type glioma.Results:Among the 647 patients with IDH wild-type glioma, there were 120 cases of WHO grade Ⅱ, 115 cases of grade Ⅲ, and 412 cases of grade Ⅳ; the median OS was 20.3 months. There were statistical differences in age, initial symptoms, tumor location, preoperative KPS score, extent of resection, MGMT promoter methylation status and postoperative treatment among patients with different WHO grades (P<0.01), but there were no statistical difference in gender and tumor laterality (P>0.05). The median OS and PFS in patients with WHO grade Ⅱ were significantly longer than those in patients with WHO grade Ⅲ and WHO grade Ⅳ (169.9 months vs. 24.7 and 14.4 months, 138.8 months vs. 17.7 and 11.4 months), the indexes in patients with WHO grade Ⅲ were significantly longer than patients with WHO grade Ⅳ, and there were statistical differences (P<0.05). The median OS and PFS in patients with total resection were significantly longer than those in patients with subtotal resection and partial resection (37.2 months vs. 20.3 and 8.5 months, 29.5 months vs. 17.6 and 6.0 months), the indexes in patients with subtotal resection were significantly longer than patients with partial resection, and there were statistical differences (P<0.05). Among 153 patients with MGMT promoter methylation who received postoperative chemoradiotherapy, the median OS and PFS in patients with total resection (67 cases) were significantly longer than those in patients with subtotal resection (64 cases) and partial resection (22 cases): 28.8 months vs. 18.4 and 9.0 months, 25.6 months vs. 16.6 and 6.5 months), the indexes in patients with subtotal resection were significantly longer than patients with partial resection, and there were statistical differences (P<0.05). Among 202 patients with MGMT promoter non-methylation who received postoperative chemoradiotherapy, the median OS and PFS in patients with total resection (81 cases) were significantly longer than those in subtotal resection (81 cases) and partial resection (40 cases): 31.3 months vs. 21.9 and 14.0 months, 22.7 months vs. 16.8 and 9.7 months, and there were statistical differences (P<0.05), but there were no statistical difference in the indexes between patients with subtotal and patients with partial resection (P>0.05). Multivariate Cox regression analysis result showed that age, extent of resection, WHO grade (grade Ⅲ/grade Ⅳ) and postoperative treatment were independent OS and PFS influencing factors in patients with IDH wild-type glioma (OS: HR = 1.327, 3.295, 3.406/7.964 and 1.597; 95% CI 1.079 to 1.633, 2.627 to 4.132, 2.225 to 5.216/5.339 to 11.880 and 1.288 to 1.981; P<0.01. PFS: HR = 1.282, 2.655, 3.143/6.511 and 1.477; 95% CI 1.039 to 1.583, 2.123 to 3.322, 2.049 to 4.819/4.376 to 9.690 and 1.181 to 1.849; P<0.05 or <0.01).Conclusions:The age, extent of resection, WHO grade and postoperative treatment are independent prognosis influencing factors in patients with IDH wild-type glioma. Treatment strategies should fully consider the clinical and molecular pathological characteristics to achieve maximal safe tumor resection and optimal survival benefit.