Epigenetic changes are important etiological factors of human tumor. The integrity of the genome is frequently challenged by the damage of DNA. However, the highly condensed structure of chromatin imposes significant obstacles on the repair processes. Eukaryotes have developed intricate mechanisms to overcome this repressive barrier imposed by chromatin. Covalent histone modifications and ATP-dependent chromatin remodeling play important roles in the process of DNA repair. Recent advances of the epigenetic regulations in the repair process were summarized. New findings in the cellular responses to DNA double strand breaks and how histone modifications and chromatin remodeling contributes to DNA double strand break repair were introduced. Future challenges in this field are also discussed.

Objective To explore the role of microRNA-206 (miR-206) in peripheral blood mononuclear cells (PBMCs) in infantile bronchiolitis caused by respiratory syncytial virus (RSV).Methods Thirty-five cases of infantile bronchiolitis and 25 cases of healthy controls were enrolled into the current study.PBMCs were isolated from the peripheral blood of both healthy subjects and those with infantile bronchiolitis in the acute and the convalescent stages.Total RNAs were extracted from PBMCs which were stimulated by phorbol-12-myristate-13-acetate (PMA) and Ionomycin, and then the RNA was transcribed reversely into cDNA.The expressions of miR-206 and Kruppel-like transcription factor 4 (KLF4) were detected by real-time quantitative polymerase chain reaction (qRT-PCR) method.Plasma interleukin-17 (IL-17) was determined by enzyme linked immunosorbent assay (ELISA).Results There was a significant difference in miR-206 levels of children with RSV bronchiolitis in the acute stage(0.055 ±0.018) and the convalescent stage(0.187 ±0.069) as well as the healthy controls(0.204 ± 0.075).Through pairwise comparison, the miR-206 levels in the children in the acute stage were significantly lower than those in the convalescent stage and healthy control group (P ＜ 0.01), but no statistical significance was found between the convalescent stage group and healthy control group(P ＞ 0.05).The levels of KLF4 mRNA of children in the acute stage,convalescent stage as well as the healthy subjects were 0.588 ± 0.161,0.086±0.024,0.075 ±0.019, respectively,which was significantly difference (P ＜ 0.01).The levels of IL-17 were (58.26 ±25.88) ng/L, (9.87 ± 3.01) ng/L, (7.65 ± 2.16) ng/L, respectively (P ＜ 0.01).Compared to the convalescent and the normal control group,both the KLF4 mRNA and IL-17 levels were markedly higher in the acute stage (P ＜ 0.01), but there were no significant differences between children with RSV bronchiolitis in convalescent stage and in the healthy controls (P ＞ 0.05).Furthermore, the result of this study showed a negative correlation between the expression of miR-206 and KLF4(r =-0.624 ,P ＜0.01)and IL-17 (r =-0.609 ,P ＜0.01) in children in the acute stage and a positive correlation between KLF4 mRNA and IL-17 in children in the acute stage (r =0.662, P ＜ 0.01).Conclusion The levels of miR-206 may play a role in the onset of RSV associated post-bronchiolitis (PB) and the low expression of miR-206 in children infected with RSV may increase the susceptibility to PB.

Indole alkaloid family has been the biggest so far among the various alkaloids,which contains pharmaceutical and effective constituents of various plants featuring diverse biological activities.Thanks to the development of metabonomics,to reveal the biosynthetic pathway of active components for the molecular mechanism of indole alkaloids and the regulation research of plant metabolism present a growing importance and significantly direct the researches of improving biological production.This paper reviewed the biosynthetic pathways of some indole alkaloids in accordance with the structure classification of indole alkaloids to lay a foundation for the further studies on the biosynthetic pathways of indole alkaloids and provide a reference for the biosynthetic pathways of other indole alkaloids.

Objective:To compare the real-world efficacy and safety profile of tenofovir amibufenamid (TMF) and tenofovir alafenamide (TAF) tablets in the treatment of patients with chronic hepatitis B (CHB).Methods:This retrospective study included patients with chronic hepatitis B who received TMF and TAF antiviral treatment at the Infectious Disease Outpatient Department of the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2023. The primary and secondary outcome was to study the patient HBV DNA conversion rate (<20 IU/ml), alanine aminotransferase (ALT) normalization rate, renal function, and lipid levels of patients at 48 weeks of treatment. The comparison of data between measurement data groups was differentiated using a t-test and Mann-Whitney U test. The inter-group comparison rate in count data was performed using the χ2 test or Fisher's exact probability. Results:A total of 440 cases were enrolled, including 220 in the TMF group (63 treatment-na?ve and 157 treatment-experienced) and 220 cases in the TAF group (61 treatment-na?ve and 159 treatment-experienced). In terms of efficacy, the HBV DNA seroconversion rates in the TMF group and TAF group were 90.5% and 85.2% ( P=0.372), respectively, while the ALT normalization rates were 92.1% and 88.5% ( P=0.505), respectively, at 48 weeks of treatment. The HBV DNA-negative conversion rate for the newly treated patients was 99.4% and 98.7%, respectively ( P=1.000), while the rates of ALT normalization were 94.9% and 92.3%, respectively ( P=0.863). In terms of safety profile, the serum creatinine level was lower in the TMF group than that in the TAF group at 48 weeks of treatment [TMF group 66.5 (56.3, 78.3) μmol/L, TAF group 70.6 (60.7, 77.8) μmol/L, Z=-2.282, P=0.022]. However, there was no statistically significant difference in other renal function and tubular function related indicators between the two groups of patients ( P>0.05). The serum high-density lipoprotein levels were higher in the TMF group than those in the TAF group [TMF 1.4 (1.1, 1.6) mmol/L vs. TAF group 1.3 (1.1, 1.6) mmol/L, Z=-2.204, P=0.027] at 48 weeks of treatment. However, there was no statistically significant difference in other blood lipid indicators between the two groups of patients ( P>0.05). Conclusion:There is no statistically significant difference in efficacy and safety profiles between TMF and TAF at 48 weeks in the treatment of patients with chronic hepatitis B, and the overall safety profile is favorable.

Objective:To study the diagnostic value of the artificial intelligence (AI) diagnostic system, ACR TI-RADS classification and AI+ ACR TI-RADS combined diagnostic performance in benign and malignant thyroid nodules and its guiding significance for surgical treatment.Methods:From Nov. 1, 2021, to Feb. 26, 2022, 349 patients with 605 thyroid nodules who received surgical treatment in Department of Thyroid (Hernia) Surgery, Department of General Surgery, the First Medical Center of the PLA General Hospital, were selected. There were 95 males and 254 females, male: female=1:2.67, aged 16-78 years, and the nodule diameter was 0.2-5.6 cm. SPSS 26.0 and R studio software were used for data processing. AI diagnostic system, ACR TI-RADS grading and AI+ ACR TI-RADS combined diagnostic efficacy were statistically analyzed, respectively. ROC curve analysis was performed in parallel.Results:The AUC value of AI+ ACR TI-RADS combined diagnosis was 0.900, greater than 0.857 of AI diagnostic system and 0.788 of ACR TI-RADS, and the difference was statistically significant ( Z= 7.631, both P<0.001) . The sensitivity of the combined diagnosis was 95.32%, the specificity was 84.61%, the accuracy was 92.56%, the positive predictive value was 94.69%, the negative predictive value was 86.27%, the missed diagnosis rate was 4.68%, and the misdiagnosis rate was 15.38%, which were better than the other two diagnostic methods. With an excellent coincidence rate with postoperative pathological results ( Kappa=0.804, P<0.001) . The accuracy of combined diagnosis in identifying the maximum diameter of different tumors was 89.58% for d≤0.5 cm, 96.09% for 0.54.0 cm, better than the other two diagnostic methods. Conclusions:The combined application of AI+ACR TI-RADS has a certain primary screening value in evaluating thyroid nodule properties. The combined diagnosis of the two can more effectively determine the benign and malignant thyroid nodules.

Objective:To investigate the application value of Overlap guiding tube (OGT) in Overlap esophagojejunostomy of laparoscopic total gastrectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 5 patients with gastric cancer who were admitted to Nanfang Hospital of Southern Medical University from June to July in 2021 were collected. There were 3 males and 2 females, aged from 48 to 61 years, with a median age of 54 years. Patients underwent laparoscopic total gastrectomy combined with OGT-assisted Overlap esophagojejunostomy. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination and telephone interview to detect postoperative anastomotic stenosis and esophageal reflux up to September 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR) or M(range). Count data were represented as absolute numbers. Results:(1) Surgical situations: 5 patients underwent laparoscopic total gastrectomy combined with OGT-assisted Overlap esophagojejunostomy and D 2 lymph node dissection success-fully, achieving R 0 resection. There was no combined organ resection, intraoperative conversion to laparotomy or combined thoracotomy. There was no intraoperative conversion to other esophagoje-junostomy method either. The tumor diameter, length of surgical incision, the number of lymph nodes dissected, time of esophagojejunal anastomosis, time of digestive reconstruction, operation time, volume of intraoperative blood loss of 5 patients were 3.0(2.8)cm, 5.0(2.0)cm, 47.0(21.0), 21.0(5.0)minutes, 62.0(23.0)minutes, 295.0(75.0)minutes, and 50.0(60.0)mL, respectively. The anvil fork of linear stapler was successfully inserted into esophageal lumen by once operation in 4 cases of 5 patients and by twice operation in 1 case to complete the esophagojejunostomy. (2) Post-operative situations: the time to first out-of-bed activities, time to postoperative first anal flatus, time to postoperative initial liquid diet intake, time to postoperative initial semi-liquid diet intake, time to abdominal drainage tube removal, duration of postoperative hospital stay of 5 patients were 2.0(1.0)days, 3.0(2.0)days, 4.0(3.0)days, 6.0(3.0)days, 7.0(4.0)days, and 9.0(6.0)days, respectively. Results of postoperative pathological examination of 5 patients showed gastric adenocar-cinoma in all the 5 patients, with the TNM staging as stage pT2-4aN0M0. The esophageal surgical margin was negative in all cases, and the length of proximal margin from esophagus was 5.0(4.0)cm. None of the 5 patients developed anastomotic leakage, anastomotic bleeding or anastomotic stenosis. Two cases with mild pneumonia (Clavien-Dindo grade Ⅱ) were cured by conservative treatment such as anti-infection and expectoration promotion. There was no unplanned secondary surgery or perioperative death occurred to the 5 patients. (3) Follow-up: 5 patients were followed up for 3 months. None of the 5 patients developed anastomotic stenosis or esophageal reflux during the follow-up. Conclusion:OGT-assisted Overlap esophagojejunostomy of laparoscopic total gas-trectomy is safe and feasible, with good short-term effects.

Objective:To investigate the hepatitis B surface antigen (HBsAg) clearance condition and its predictive factors after treatment with nucleos(t)ide analogues to pegylated interferon-α add-on therapy in patients with chronic hepatitis B.Methods:Patients with chronic hepatitis B who visited the First Affiliated Hospital of Zhengzhou University from 2018~2019 were prospectively enrolled. HBsAg≤ 1500 IU/mL, hepatitis B e antigen-negative, HBV DNA undetectable, received antiviral treatment with nucleos(t)ide analogues for at least one year, and pegylated interferon-α add-on therapy for 48 weeks were included. The primary endpoint of study was to determine the proportion of HBsAg clearance at 72 weeks. Concurrently, the predictive factors for HBsAg clearance were analyzed. Quantitative and qualitative data were analyzed using a t-test or non-parametric test and a Fisher's exact test.Results:A total of 38 cases were included in this study, of which 13 cases obtained HBsAg clearance at 48 weeks of therapy and another six cases obtained HBsAg clearance throughout the extended treatment period of 72 weeks, accounting for 50.00% of all enrolled patients. There was a significant difference in HBsAg dynamics between the HBsAg clearance group and the non-clearance group (P < 0.05). Univariate logistic regression analysis showed that patients' age, baseline, 12-and 24-week HBsAg levels, and early HBsAg reduction were predictive factors for HBsAg clearance at 72 weeks of treatment. Multivariate logistic regression analysis showed that age (OR = 1.311; P = 0.016; 95% confidence interval: 1.051~1.635) and HBsAg levels at 24 weeks of treatment (OR = 4.481; P = 0.004; 95% confidence interval: 1.634~12.290) were independent predictors for HBsAg clearance.Conclusion:Hepatitis B e antigen-negative, nucleos(t)ide analogue treated, HBsAg ≤ 1500 IU/mL, and HBV DNA undetectable, peg-IFNα add-on treatment for 48 weeks could promote HBsAg clearance in patients with chronic hepatitis B. Six of the sixteen cases (37.50%) who did not obtain HBsAg clearance at week 48 did so with the course of therapy extended to week 72. Hence, the optimal individualized treatment strategy should be customized according to the predictors rather than the fixed 48-week course. Age (≤ 38), baseline HBsAg level (≤2.86 log 10IU/ml), HBsAg level at 24 weeks (≤ 0.92 log 10IU/ml), and 12-week HBsAg decrease from baseline (≥ 0.67 log 10IU/ml) indicate that patients are highly likely to obtain HBsAg clearance at the 72 weeks of combination therapy, in which the combined indicator based on HBsAg level ≤0.92 log 10IU/ml at 24 weeks will identify 85.0% to 100.0% of patients with HBsAg clearance.