ObjectiveTo investigate the efficacy of sequential tenofovir alafenamide fumarate （TAF） therapy versus the regimen of entecavir （ETV） combined with TAF in chronic hepatitis B （CHB） patients experiencing low-level viremia （LLV） after ETV therapy， as well as their impact on virologic response， liver and renal function， and blood lipid levels. MethodsA total of 217 CHB patients with LLV after ETV treatment who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2020 to December 2023 were enrolled， and according to the treatment regimen， they were divided into TAF group （180 patients receiving sequential TAF therapy） and combined group （37 patients receiving ETV+TAF therapy）. The propensity score matching （PSM） method was used to match the patients at a ratio of 1∶1， and finally 37 patients were included in each group to balance the baseline confounding factors. The two groups were compared in terms of hepatitis B virus DNA （HBV DNA） clearance rate， hepatitis B envelope antigen （HBeAg） clearance rate， liver and renal function parameters （liver stiffness measurement ［LSM］， platelet count ［PLT］， aspartate aminotransferase ［AST］， alanine aminotransferase ［ALT］， and creatinine ［Cr］）， blood lipid levels （total cholesterol ［TC］， triglyceride ［TG］， high-density lipoprotein cholesterol ［HDL-C］， and low-density lipoprotein cholesterol ［LDL-C］）， and the incidence rate of adverse reactions. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the paired t-test was used for comparison within each group； the chi-square test was used for comparison of categorical data between groups. ResultsAfter 48 weeks of treatment， compared with the TAF group， the combined group had significantly higher HBV DNA clearance rate （86.49% vs 59.46%， χ²=6.852， P=0.009） and HBeAg clearance rate （59.46% vs 35.14%， χ²=4.391， P=0.036）. After treatment， compared with the TAF group， the combined group had significantly lower levels of LSM （7.01±1.50 kPa vs 7.90±1.68 kPa， t=2.404， P=0.019）， AST （18.02±2.28 U/L vs 21.12±2.85 U/L， t=5.166， P<0.001）， and ALT （19.85±3.86 U/L vs 22.00±3.90 U/L， t=2.383， P=0.020） and significantly higher levels of PLT ［（218.35±42.60）×10⁹/L vs （192.82±44.13）×10⁹/L， t=2.532， P=0.014］ and Cr （70.92±6.54 μmoL/L vs 67.60±6.13 μmoL/L， t=2.253， P=0.027）. After treatment， there was a slight increase in the level of TC in both the TAF group （5.60±0.89 mmol/L vs 5.18±0.85 mmol/L， t=2.076， P=0.041） and the combined group （5.45±0.80 mmol/L vs 5.02±0.83 mmol/L， t=2.269， P=0.026）. There was no significant difference in the incidence rate of adverse reactions between the TAF group and the combined group （21.62% vs 18.92%， χ²=0.084， P=0.772）. ConclusionFor ETV-treated CHB patients experiencing LLV， compared with sequential TAF therapy， the ETV+TAF combined therapy can effectively increase virologic response rate， alleviate liver fibrosis， and improve liver function， whereas sequential TAF therapy has less impact on renal function. Sequential or combined therapy with TAF may induce a slight increase in the level of TC， which should be taken seriously in clinical practice.

Objective:To explore the relationship between macrophage infiltration in the coronary plaque and downstream myocardial perfusion in mice.Methods:The experimental group consisted of 20 ApoE knockout mice models of the coronary plaque established by feeding with cholesterol-rich diets, and the control group consisted of 20 sex- and age-matched C57BL/6 mice with the same genetic background as ApoE mice.Adenosine stress myocardial contrast echocardiography was performed on all experimental animals to obtain the values of A, β and A×β of the left ventricular myocardium in anteroseptal and posterior walls both in the resting status and during adenosine stress. Concentrations of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were determined using mouse enzyme-linked immunosorbent assay kits according to the manufacturer′s instructions. The degree of macrophage infiltration in the coronary plaque was evaluated by pathological immunohistochemistry staining and the correlations with the above indicators were analyzed.Results:There were no statistically significant differences in heart rate and left ventricular structural parameters between two groups (all P>0.05). The experimental group had a lower left ventricular ejection fraction( P=0.021), and higher weight and serum levels of triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, IL-6, and TNF-α than the control group (all P<0.05). The values of A, β and A × β of the left ventricular myocardium in anteroseptal and posterior walls in the experimental group were significantly lower than those in the control group during adenosine stress (all P<0.05). In the experimental group, the value of the macrophage infiltration found in the plaque of the left main coronary artery correlated positively with the level of serum TNF-α ( r=0.63, P=0.003) and negatively correlated with the values of A×β of the left ventricular myocardium in anteroseptal and posterior walls during adenosine stress ( r=-0.74, P<0.001; r=-0.72, P<0.001; respectively). Conclusions:Myocardial perfusion in ApoE knockout mice models of the coronary atherosclerosis was related with degree of macrophage infiltration in the coronary plaque, and macrophages may play a role by releasing inflammatory mediator TNF-α.

OBJECTIVE To explore the influence of Zingiber officinale and processed Z. officinale on pharmacodynamic indexes and intestinal flora on gastric ulcer rats with spleen -stomach deficiency and cold type before and after processing with sand . METHODS The SD rats were randomly divided into normal group ，model group ，positive control group （Compound tianqi weitong capsule 0.45 g/kg），Z. officinale high-dose（15.0 g/kg）and low -dose（7.5 g/kg）groups，processed Z. officinale high- dose（15.0 g/kg）and low -dose（7.5 g/kg）groups，with 10 rats in each group . The rat model of gastric ulcer with spleen -stomach deficiency and cold type was established by intragastric administration of vinegar （day 1-10）and absolute ethanol （day 11）. Administration groups were given relevant liquid intragastrically ，and normal group and model group were given water intragastrically（day 5-10）. One hour after intragastric administration of absolute ethanol ，blood was taken from the femoral artery of rats ，the serum contents of motilin （MTL），gastrin（GAS），epidermal growth factor （EGF）as well as 4 items of blood coagulation [activated partial thromboplastin time （APTT），prothrombin time （PT），thrombin time （TT），fibrinogen（FIB）] were detect. The ulcer index and inhibition rate of ulcer in gastric tissue were calculated . The pathological changes of gastric tissue were observed，and the number and area of erosions were recorded . The diversity of gut microbiota in fecal samples of rats was detected . RESULTS Compared with model group ，the contents of MTL （except for processed Z. officinale low-dose group ），GAS（except for processed Z. officinale low-dose group ），EGF（except forofficinale groups） and FIB （except for Z. officinale groups），inhibitory rate of ulcer （only positive control group ）were all increased significantly （P＜0.05）. APTT（except for Z. officinale groups），PT（only processed Z. officinale high- dose group ），TT（except for Z. officinale groups），ulcer index （except for Z. officinale groups），the number （except for Z. officinale groups）and area of erosions （except for Z. officinale groups）were shortened and decreased significantly （P＜0.05）； improvement effects of processed Z. officinale were better than those of the same dose of Z. officinale on EGF ，4 items of blood coagulation（except for PT ，TT，FIB of processed Z. officinale low-dose group ），ulcer index （except for processed Z. officinale low-dose group ）and inhibitory rate of ulcer （P＜0.05）. Compared with model group ，α diversity indexes as ACE ，Shannon and Simpson of intestinal microorganisms in rats were increased significantly in processed Z. officinale group；the relative abundance of Proteobacteria was decreased significantly in processed Z. officinale group，while that of Bacteroidetes was increased significantly （P＜0.05）； the relative abundance of Limosilactobacillus was decreased significantly in Z. officinale group （P＜0.05）. CONCLUSIONS Z. officinale and processed Z. officinale can improve the symptoms of spleen -stomach deficiency and cold ，and enhance gastrointestinal function by increasing the content of GAS and MTL . Processed Z. officinale can significantly inhibit gastric ulcer of spleen -stomach deficiency and cold type ，which is related to the promotion of mucosal protection and repair ，improvement of coagulation functionand adjustment of gut microbiotadisorder .

Objective:To explore the clinicopathological characteristics and prognosis of patients with ovarian metastases from colorectal cancer.Methods:A total of 122 female patients with ovarian metastases from colorectal cancer underwent treatment in Cancer Hospital, Chinese Academy of Medical Sciences between 2010 and 2015 were recruited. The clinicopathological features, treatment details and survival data of these patients were retrospectively analyzed. Kaplan-Maier method was used for survival analysis, log rank test and Cox proportional hazards model were used for prognostic factor analysis.Results:The median overall survival (OS) was 19.7 months. The 1-year, 3-years and 5-years OS rates were 72.1%, 24.7% and 9.9%, respectively. A total of 99 (81.1%) patients underwent oophorectomy. The median OS of patients who underwent oophorectomy was 21.9 months, significantly longer than 10.3 months of patients without oophorectomy ( P<0.01). Ovary as the only site of metastasis, primary tumor resection, and oophorectomy were associated with improved survival (all P<0.01). Primary tumor resection and oophorectomy were independent prognostic factors for OS (both P<0.01). Conclusion:Patients with ovarian metastases from colorectal cancer might acquire a survival benefit from surgical resection of the primary tumor and ovaries.

Objective:To analyze the clinicopathological features and prognostic factors of patients with uterine clear cell carcinoma (UCCC).Methods:UCCC patients who underwent surgery and complete follow-up at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis.Results:The study included 34 patients. Only 18 patients (52.9%) were diagnosed with UCCC preoperatively and 8 patients (23.5%) underwent UCCC standard comprehensive staging surgery. Among the 34 patients, stage ⅠA was 17 cases (50.0%), stage ⅠB was 1 case (2.9%), stage Ⅱ was 4 cases (11.8%), stage ⅢA was 2 cases (5.9%), stage ⅢB was 1 case (2.9%), stage ⅢC1 was 5 cases (14.7%) and stage ⅣB was 4 cases (11.8%). The median follow-up period was 72 months, 5-years disease-free survival (DFS) rate and overall survival (OS) rates for all patients were 79.1% and 81.3%, respectively. Univariate analysis result showed that preoperative CA125 level, range of lymphadenectomy, tumor stage and peritoneal cytology were significantly associated with DFS ( P<0.05). Preoperative CA125 level, range of lymphadenectomy, tumor stage, peritoneal cytology and lymph vascular space invasion were significantly associated with OS ( P<0.05). Multivariate analysis result showed that peritoneal cytology was the only independent prognostic factor for DFS, the relapse risk of peritoneal cytology positive patients was 11.47 folds higher than that of the negative patients ( P=0.009). Tumor stage was the only independent prognostic factor for OS, the death risk of ⅣB stage patients was 25.29 folds higher than that of theⅠA stage ( P=0.009). Conclusions:The preoperative pathological diagnosis of UCCC is difficult, which results in incomplete surgical staging. Peritoneal cytology and tumor stage are independent prognostic factors for DFS and OS of UCCC patients, which deserve much more attention in clinical practice.

Objective:To analyze the clinicopathological features and prognostic factors of patients with uterine clear cell carcinoma (UCCC).Methods:UCCC patients who underwent surgery and complete follow-up at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis.Results:The study included 34 patients. Only 18 patients (52.9%) were diagnosed with UCCC preoperatively and 8 patients (23.5%) underwent UCCC standard comprehensive staging surgery. Among the 34 patients, stage ⅠA was 17 cases (50.0%), stage ⅠB was 1 case (2.9%), stage Ⅱ was 4 cases (11.8%), stage ⅢA was 2 cases (5.9%), stage ⅢB was 1 case (2.9%), stage ⅢC1 was 5 cases (14.7%) and stage ⅣB was 4 cases (11.8%). The median follow-up period was 72 months, 5-years disease-free survival (DFS) rate and overall survival (OS) rates for all patients were 79.1% and 81.3%, respectively. Univariate analysis result showed that preoperative CA125 level, range of lymphadenectomy, tumor stage and peritoneal cytology were significantly associated with DFS ( P<0.05). Preoperative CA125 level, range of lymphadenectomy, tumor stage, peritoneal cytology and lymph vascular space invasion were significantly associated with OS ( P<0.05). Multivariate analysis result showed that peritoneal cytology was the only independent prognostic factor for DFS, the relapse risk of peritoneal cytology positive patients was 11.47 folds higher than that of the negative patients ( P=0.009). Tumor stage was the only independent prognostic factor for OS, the death risk of ⅣB stage patients was 25.29 folds higher than that of theⅠA stage ( P=0.009). Conclusions:The preoperative pathological diagnosis of UCCC is difficult, which results in incomplete surgical staging. Peritoneal cytology and tumor stage are independent prognostic factors for DFS and OS of UCCC patients, which deserve much more attention in clinical practice.

Objective:To investigate the relationship between vulnerability of mouse coronary artery plaque and downstream myocardial perfusion and myocardial strain.Methods:Thirteen ApoE knockout mice with stable coronary plaques (stable plaque group)and 13 ApoE knockout mice with vulnerable coronary plaques(vulnerable plaque group) were selected as the experimental group, and 15 sex- and age-matched C57BL/6 mice with the same genetic background as ApoE mice were chosed as the control group. Myocardial contrast echocardiography (MCE) was carried out to quantify regional myocardial perfusion at rest and during adenosine stress using a Vevo 2100 system (Visual sonics). Replenishment curves of myocardial contrast were obtained, and rates of signal rise (β) and plateau intensity (A) were recorded. MBF was estimated by the product of A and β. Speckle tracking imaging combined with adenosine stress test was used to evaluate the longitudinal strain of left ventricular myocardium in mice. The vulnerability of the plaque was assessed by histopathology in serial tissue sections of proximal and middle left coronary artery according to the previously reported method.Results:There were no significant differences in body weight, heart rate, left ventricular end diastolic volume, left ventricular end systolic volume, left ventricular mass and ejection fraction among the three groups( P>0.05). The levels of serum triglyceride, total cholesterol, high density lipoprotein and low density lipoprotein in stable plaque group and vulnerable plaque group were significantly increased when compared with those in control group (all P<0.05). The pathological results showed that the coronary luminal stenosis rates in the stable plaque group and the vulnerable plaque group were (74.3±4.9)% and (75.5±7.1)% respectively, with no significant difference between the two groups( P>0.05). MBF of the middle anterior septum and left ventricular posterior wall in the experimental groups were significantly decreased when compared with that in the control group both in the resting status and during adenosine stress(all P<0.05). There were no significant differences in the MCE parameters between the stable plaque group and the vulnerable plaque group at rest( P>0.05). However, during adenosine stress, MBF of the vulnerable plaque group was decreased more significantly than that of the stable plaque group ( P<0.05). Compared with the control group, the values of longitudinal strain of the left ventricle in both experimental groups were decreased during resting status, without statistical significance (all P>0.05), but decreased significantly during adenosine stress and with more decrease in the vulnerable plaque group (all P<0.05). Conclusions:For the same degree of coronary artery stenosis in mice, the coronary artery vulnerable plaque group has less downstream myocardial perfusion and myocardial strain than the stable plaque group during adenosine stress. That is, the plaque vulnerability can affect the downstream myocardial perfusion and myocardial strain in the mouse model.

Objective:To explore the clinicopathological characteristics and prognosis of patients with ovarian metastases from colorectal cancer.Methods:A total of 122 female patients with ovarian metastases from colorectal cancer underwent treatment in Cancer Hospital, Chinese Academy of Medical Sciences between 2010 and 2015 were recruited. The clinicopathological features, treatment details and survival data of these patients were retrospectively analyzed. Kaplan-Maier method was used for survival analysis, log rank test and Cox proportional hazards model were used for prognostic factor analysis.Results:The median overall survival (OS) was 19.7 months. The 1-year, 3-years and 5-years OS rates were 72.1%, 24.7% and 9.9%, respectively. A total of 99 (81.1%) patients underwent oophorectomy. The median OS of patients who underwent oophorectomy was 21.9 months, significantly longer than 10.3 months of patients without oophorectomy ( P<0.01). Ovary as the only site of metastasis, primary tumor resection, and oophorectomy were associated with improved survival (all P<0.01). Primary tumor resection and oophorectomy were independent prognostic factors for OS (both P<0.01). Conclusion:Patients with ovarian metastases from colorectal cancer might acquire a survival benefit from surgical resection of the primary tumor and ovaries.

Objective To explore the effects of adenosine stress on myocardial perfusion in healthy mice by myocardial contrast echocardiography ( MCE) . Methods MCE was carried out to quantify regional myocardial perfusion at rest and during adenosine stress using a VEVO 2100 system in 26 C57BL/6 mice . Echocardiography images from standardized parasternal long axis and short axis at papillary muscle level were consecutively acquired in real‐time . All dynamic images were recorded for off‐line analysis . Left ventricular myocardial perfusion quantitative parameters were acquired both under resting status and during adenosine stress . Replenishment curves of myocardial contrast were obtained and myocardial blood flow ( MBF) was calculated . Results Twenty‐six experimental animals successfully underwent MCE before and during adenosine stress . T here was no significant difference in heart rate ,left ventricular structure and functional parameters before and during adenosine stress ( all P ＞0 .05) . Rates of signal rise β values which were used to estimate blood velocity of middle anterior septum and posterior wall in left ventricular long‐axis view and anterior wall ,lateral wall ,inferior wall and septal wall in short‐axis view at papillary muscle increased significantly during stress compared with those at rest ( all P ＜0 .05 ) . T here was no significant difference in the plateau intensity A values( all P ＞0 .05 ) . T he MBF in each segment of the myocardium increased significantly during stress compared with those in resting state ( all P ＜0 .05) . Conclusions T he physiological characteristics of myocardial perfusion in mice before and during adenosine stress were preliminarily obtained ,w hich provided a basis for the application of adenosine stress echocardiography in cardiovascular disease models such as coronary heart disease in mice .

Objective To investigate the prevalence of high-risk HPV subtypes in different pathological types of cervical cancer, and analyze the attribution of carcinogenic HPV subtypes in different pathological types. Methods A total of 1 541 patients with cervical cancer were treated between February 2009 and October 2016 in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. The median age at diagnosis was 49 years (ranged 20-82 years old). The numbers of patients with cervical cancer from North China, Northeast China, East China, Central China and other regions (including Northwest, Southwest and South China) were 961, 244, 175, 87 and 74 cases, respectively. Pathological types: 1 337 cases of squamous cell carcinoma (SCC), 87 usual adenocarcinoma (ADC), 23 adenosquamous carcinoma (ASC), 20 mucinous carcinoma (MC), 19 clear cell carcinoma (CCC), 12 endometrioid carcinoma (EC), 25 neuroendocrine carcinoma (NEC), 9 serous carcinoma (SC), 5 villous adenocarcinoma (VADC) and 4 minimal deviation adenocarcinoma (MDAC). The prevalence of high-risk HPV in different regions, age groups at diagnosis and pathological types in cervical cancer were analyzed. The attribution of 13 high-risk HPV subtypes in different pathological types of cervical cancer based on proportional attribution method, and the attribution of high-risk HPV subtypes prevented by 9-valent HPV vaccine in SCC and ADC were calculated. Results (1) The prevalence of high-risk HPV in 1 541 patients with cervical cancer was 86.6% (1 335/1 541). The multiple high-risk HPV infection rate in patients with SCC ≥60 years old (23.0%, 37/161) was significantly higher than those in patients aged 45-59 years old and≤44 years old [11.4% (85/747) vs 11.7% (50/429), P<0.01], and the high-risk HPV infection rates of patients with cervical cancer in North China, Northeast China, East China, Central China and other regions were respectively 86.8% (834/961), 87.7% (214/244), 83.4% (146/175), 83.9% (73/87) and 91.9% (68/74). SCC (86.8%, 1 337/1 541) and ADC (5.6%, 87/1 541) were the most common pathological types in cervical cancer. The high-risk HPV prevalence of SCC, ADC, ASC, MC, NEC and VADC were 90.1% (1 205/1 337), 74.7% (65/87), 87.0% (20/23), 65.0% (13/20), 72.0% (18/25) and 5/5 respectively. The high-risk HPV infection rates of SC, EC, CCC and MDAC were 4/9, 3/12, 2/19 and 0/4 respectively. (2) According to proportional attribution, HPV 16 (69.5%), HPV 18 (5.6%), HPV 58 (2.2%), HPV 31 (1.9%), HPV 52 (1.4%) and HPV 33 (1.3%) were the six common high-risk HPV subtypes in SCC. While, HPV 18 (44.1%), HPV 16 (20.5%), HPV 52 (2.3%), HPV 58 (1.2%) and HPV 51 (1.2%) were the main carcinogenic subtypes in ADC. The main carcinogenic high-risk HPV subtypes of ASC, NEC and MC were HPV 18 and HPV 16. The total attribution of HPV 16, 18, 31, 33, 45, 52 and 58 prevented by 9-valent HPV vaccine in SCC and ADC were 82.6% and 68.1% respectively; the attribution of HPV 45 in SCC and ADC were only 0.8% and 0. Conclusions SCC and ADC are the main pathological types in cervical cancer. SCC, ADC, ASC, MC, NEC and VADC are closely related to high-risk HPV infection. HPV 16 is the main carcinogenic genotypes of SCC. HPV 18 maybe play an important role in the pathogenesis of ADC.