Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objectives:To explore the dynamic changes of right ventricular global longitudinal strain (RVGLS) on echocardiography during the process of right ventricular fibrosis with right ventricular pressure overload.Methods:Animal models with RV pressure overload (n=5) were established by main pulmonary artery (PA) banding in piglets.The ratio of RV pressure to left ventricular (LV) pressure was greater than 60％ as assessed by the pressure measuring needle during the operation.Pre-and post-operative echocardiography were performed.Histopathological examination of RV tissues was performed at the end of the experiment.Results:During the establishment of the animal models,2 piglets died due to hemorrhagic shock,while 3 piglets survived and were included in the analysis.Systolic RV pressure,systolic PA pressure and mean PA pressure(measured at the proximal end of the constriction) were significantly increased immediately after PA banding,mean RV pressure and mean PA pressure were significantly inreased at 14 weeks postopseratively (all P<0.05).Tricuspid annulus plane systolic excursion and peak early diastolic velocity of tricuspid annulus (TV e') decreased immediately after operation (all P<0.05).They returned to the pre-operative level in the following three weeks.The absolute values of RVGLS were reduced after PA banding (all P>0.05).The RVGLS of the inner membrane layer began to recover after 3 weeks,and the RVGLS of the middle and outer membrane layers began to recover after 7 weeks.However,the time to peak RVGLS was significantly prolonged and could not be restored even untill the end of the experiment (14 weeks after surgery)(all P<0.05).At the end of the experiment,pathological examination revealed fibrous tissue hyperplasia in both the myocardial interstitium and endocardium.Conclusions:The measurement of intracardiac pressure and pathological results confirmed the success of the establishment of the animal model of increased right ventricular afterload.Both stress and strain cannot truly represent the intrinsic characteristics of the myocardium under pressure overload.The prolonged time to peak of longitudinal strain might indirectly reflect the progression of myocardial injury more persistently during the process of increased right ventricular afterload and myocardial injury.

Objectives:To explore the dynamic changes of right ventricular global longitudinal strain (RVGLS) on echocardiography during the process of right ventricular fibrosis with right ventricular pressure overload.Methods:Animal models with RV pressure overload (n=5) were established by main pulmonary artery (PA) banding in piglets.The ratio of RV pressure to left ventricular (LV) pressure was greater than 60％ as assessed by the pressure measuring needle during the operation.Pre-and post-operative echocardiography were performed.Histopathological examination of RV tissues was performed at the end of the experiment.Results:During the establishment of the animal models,2 piglets died due to hemorrhagic shock,while 3 piglets survived and were included in the analysis.Systolic RV pressure,systolic PA pressure and mean PA pressure(measured at the proximal end of the constriction) were significantly increased immediately after PA banding,mean RV pressure and mean PA pressure were significantly inreased at 14 weeks postopseratively (all P<0.05).Tricuspid annulus plane systolic excursion and peak early diastolic velocity of tricuspid annulus (TV e') decreased immediately after operation (all P<0.05).They returned to the pre-operative level in the following three weeks.The absolute values of RVGLS were reduced after PA banding (all P>0.05).The RVGLS of the inner membrane layer began to recover after 3 weeks,and the RVGLS of the middle and outer membrane layers began to recover after 7 weeks.However,the time to peak RVGLS was significantly prolonged and could not be restored even untill the end of the experiment (14 weeks after surgery)(all P<0.05).At the end of the experiment,pathological examination revealed fibrous tissue hyperplasia in both the myocardial interstitium and endocardium.Conclusions:The measurement of intracardiac pressure and pathological results confirmed the success of the establishment of the animal model of increased right ventricular afterload.Both stress and strain cannot truly represent the intrinsic characteristics of the myocardium under pressure overload.The prolonged time to peak of longitudinal strain might indirectly reflect the progression of myocardial injury more persistently during the process of increased right ventricular afterload and myocardial injury.

The integrity of lysosomes is of vital importance to survival of tumor cells. We demonstrated that LW-218, a synthetic flavonoid, induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy. LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D, as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents, which can alter the activity of cathepsins. Lysophagy, was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB. LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator. Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy. LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1. Moreover, LW-218 inhibited the leukemia cell growth

Objective:To test the validity and reliability of the Perceived Stress Scale-14 items (PSS-14) applied in cancer survivors.Methods:Totally 652 cancer survivors (patients who had finished active treatments and were in convalescence) were selected and a field questionnaire survey was conducted among them.Exploratory factor analysis and confirmatory factor analysis were performed to test the construct validity of PSS-14.Correlation between the two dimensions (discriminant validity) and correlation between stress and quality of life were analyzed to further test its validity.The intemal consistency reliability,split-half reliability,retest reliability and sensitivity analysis were adopted to test the reliability of PSS-14.Results:Two common factors were extracted in the exploratory factor analysis.The cumulative percentage of variance explained was 60.8％.The index of confirmatory factor analysis were:TLI =0.92,CFI =0.93,SRMR =0.07,RMSEA =0.08.The correlation coefficient between the two dimensions of PSS-14 was-0.16 (P ＜0.001).The correlation coefficients between the score of PSS-14 and each dimension of EORTC QLQ-C30 were 0.24-0.55 (P ＜ 0.001).The Cronbach α coefficients of the whole scale and the two dimensions named "perceived coping ability" and "perceived distress" were 0.78,0.91 and 0.88 respectively.After the scale was split into two parts,the Cronbach α coefficients of each part were 0.66 and 0.60.The Spearman-Brown coefficient was 0.79.The Guttman split-half coefficient was 0.79.After one item was removed from the scale each time,the Cronbach a coefficients of the remaining items varied from 0.75 to 0.77.The retest reliability of the whole scale and the two dimensions were 0.89,0.86 and 0.85 respectively.Conclusion:PSS-14 shows favorable validity and reliability,suggesting the utility to assess stress of cancer survivors as a self-administered inventory.

Objective: To study the coping styles and its relationship with quality of life among part of the female breast cancer patients in Shanghai in 2014. Methods: In August of 2014, 1-3 block groups affiliated to Shanghai Cancer Rehabilitation Club were selected from each of the 17 districts of Shanghai by convenient sampling method. Respondents were recruited from these block groups via putting up posters in the community or top three hospitals nearby. The inclusion criteria were as follows: female, aged from 18 to 80 years old; the initial diagnosis or primary tumor was breast cancer, and active treatments including surgery, radiotherapy and chemotherapy were finished; capable of basic reading and comprehension, and there was no communication disorder; daily activities were not limited, and with no mental disorder or dysgnosia. Totally 2 205 respondents were included. Questionnaire survey was conducted to collect the information of demographic characteristics, disease characteristics, result of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and result of the Ways of Coping Inventory-Cancer Version (WOC-CA). 1 968 valid questionnaires were withdrawn. The results of respondent characteristics and WOC-CA were under descriptive analysis, and the differences of coping styles among groups of different demographic characteristics were compared using t test. In addition, we analyzed the correlation between respondents' coping styles and quality of life using partial correlation analysis. Results: The average age of the 1 968 respondents was (58.7±7.4) years old, and BMI was (24.4±5.4) kg/m². The score of positive coping styles was 2.04±0.41, and the score of negative coping styles was 1.79±0.33. The scores of Physical Functioning (PF), Role Functioning (RF), Cognitive Functioning (CF), Emotional Functioning (EF), Social Functioning (SF), and Global Health (GH) were 83.40±12.18, 90.80±15.92, 80.72±16.29, 84.67±15.19, 80.99±20.91, 65.27±21.21, respectively. Positive coping styles correlated with PF, EF, and GH positively, and the correlation coefficients were separately 0.581 (P=0.046), 0.593 (P=0.045), 0.770 (P<0.001). Negative coping styles correlated with RF, CF, EF, and SF negatively, and the correlation coefficients were separately-0.672 (P=0.021),-0.815 (P=0.005),-0.121 (P<0.001),-0.123 (P<0.001). Conclusion Part of the female breast cancer patients in Shanghai in 2014 mainly adopted positive coping styles, and in general the positive coping styles correlated with quality of life positively and negative coping styles correlated with quality of life negatively.

Objective To investigate the association between different number of inferomedial screws (0-3 screws) and their efficacy in locking plate of proximal humerus fractures.Methods Data of 90 patients who had undergone locking plate for proximal humerus fracture between January 2007 and December 2012 were retrospectively analyzed.They were divided into four groups according to the number of inferomedial screws.In the NS (no-screw support) group,36 patients did not have inferomedial screws for mechanical support of the inferomedial region of the proximal humerus; in the OS (one-screw support) group,23 patients had the reconstruction by insertion of only one inferomedial screw; there were 19 patients in the TS (two-screw support) group and 12 in the ThS (three-screw support) group.There were no significant differences among 4 groups in sex,fracture type and age.The Constant scores of the shoulder function,changes in humeral head height at the latest follow-up,incidence of complications and time for fracture healing among the 4 groups were collected.Results The follow-ups for the patients ranged from 12 to 56 months (mean,21.4 months).At the latest follow-up,the ThS,TS,OS and NS groups had a mean Constant score of 76.7 (SD,11.6),74.1 (SD,7.4),66.8 (SD,10.7),65.8 (SD,10.2),respectively; the mean change in humeral head height were 1.4 (SD,1.0) mm,2.9 (SD,1.2) mm,5.3(SD,3.2) mm and 6.7(SD,3.3) mm,respectively.There were no significant differences between the ThS and TS groups in Constant score,and Constant scores in ThS and TS groups were significantly higher than those in OS and NS groups.However,the loss in humeral head height in the ThS group was significantly less than those in the TS,OS and NS groups,and the loss in humeral head height in TS group was significantly less than those in the OS and NS groups.There were no significant differences among 4 groups in time for fracture healing and incidence of complications.Conclusion Locking plate in general do not appear to be a panacea for proximal humerus fractures especially in cases of medial comminution or bone defects because of the malreduction of the medial cortical bone.However,medial support with two or three inferomedial screws being meticulously placed in the inferomedial region may enhance the mechanical stability of medial column support and allow for better maintenance of reduction.

Helicobacter pylori (H.pylori) associated gastritis is one of the most common infectious diseases in China and worldwide.Gastric marginal zone lymphoma,or mucosa associated lymphoid tissue (MALT) lymphoma is a rare neoplasm associated with H.pylori infection and the first neoplastic disease curable by antibiotics therapy alone.The pathologic diagnosis of gastric MALT lymphoma can be reached by histologic examination,immunohistochemical staining,and B-cell clonality studies.Eradication against H.pylori is the choice of therapy for early stage gastric MALT lymphoma.Refractory,localized disease may be treated with low-dose irradiation therapy with high rates of responding and long-term survival.Systemic chemotherapy is recommended for advanced stage gastric MALT lymphoma or high-grade transformed large B-cell lymphoma.A recent case with recurrent chronic active gastritis and gastric MALT lymphoma after H.pylori eradication therapy was reported.Recent advances in the studies of pathologic diagnosis and therapy of the disease were reviewed.

ObjectiveTo investigate the relationship between the expression of ER,PR,HER-2,Ki-67 and the effective rate of neoadjuvant chemotherapy (NAC) and to study the influence of NAC on expression of ER,PR,HER-2 and Ki-67 in breast cancer.Methods41 patients of breast cancer were performed 2 to 6 cycles of CAF chemotherapy.The expression of ER,PR,HER-2 and Ki-67 was detected by SP immunohistochemical method before and after NAC.ResultsThe effective rate of NAC was 73.17％ (30/41).The positive and negative efficiency rate was 67.86％ (19/28) vs 84.62％ ( 11/13 ) for ER,64.29％ (9/14) vs 77.78％ (21/27 ) for HER-2,70.00％ (14/20) vs 76.19％ ( 16/21 ) for Ki-67.The difference had no statistical significance (P ＞0.05).The positive and negative efficiency rate was 66.67％ (16/24) vs 82.35％ (14/17) for PR.The difference had statistical significance (P ＜ 0.05 ).The expression of ER,PR,HER-2 and Ki-67 before and after NAC changed in 10,8,3 and 9 cases respectively.The difference had no statistical significance (P ＞ 0.05).ConclusionsNAC has no influence on the expression of ER,PR,HER-2 and Ki-67.Patients with PR negative are more sensitive to NAC.The expression state of PR can be used to predict the curative effect of NAC.The expression state of ER,HER-2 and Ki-67 has no significant correlation with NAC.