1.Efficacy evaluation of extending or switching to tenofovir amibufenamide in patients with chronic hepatitis B: a phase Ⅲ randomized controlled study
Zhihong LIU ; Qinglong JIN ; Yuexin ZHANG ; Guozhong GONG ; Guicheng WU ; Lvfeng YAO ; Xiaofeng WEN ; Zhiliang GAO ; Yan HUANG ; Daokun YANG ; Enqiang CHEN ; Qing MAO ; Shide LIN ; Jia SHANG ; Huanyu GONG ; Lihua ZHONG ; Huafa YIN ; Fengmei WANG ; Peng HU ; Xiaoqing ZHANG ; Qunjie GAO ; Chaonan JIN ; Chuan LI ; Junqi NIU ; Jinlin HOU
Chinese Journal of Hepatology 2024;32(10):883-892
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).
2.Safety profile of tenofovir amibufenamide therapy extension or switching in patients with chronic hepatitis B: a phase Ⅲ multicenter, randomized controlled trial
Zhihong LIU ; Qinglong JIN ; Yuexin ZHANG ; Guozhong GONG ; Guicheng WU ; Lvfeng YAO ; Xiaofeng WEN ; Zhiliang GAO ; Yan HUANG ; Daokun YANG ; Enqiang CHEN ; Qing MAO ; Shide LIN ; Jia SHANG ; Huanyu GONG ; Lihua ZHONG ; Huafa YIN ; Fengmei WANG ; Peng HU ; Xiaoqing ZHANG ; Qunjie GAO ; Peng XIA ; Chuan LI ; Junqi NIU ; Jinlin HOU
Chinese Journal of Hepatology 2024;32(10):893-903
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).
3.Status risk factors and prevention and control strategies of familial aggregation of Helicobacter pylori infection
Lihua SONG ; Sijing HAN ; Shuqin REN ; Wen YANG ; Sihong DING ; Yixin ZHONG ; Yao QIN ; Huiyue ZHANG ; Yang ZHANG
Journal of Public Health and Preventive Medicine 2024;35(2):148-151
Objective To investigate the status of familial aggregation of Helicobacter pylori (Hp) infection in Jinniu District, Chengdu, and analyze its risk factors so as to provide a basis for developing prevention and control strategies of family aggregation of Hp infection. Methods A total of 172 subjects in the Second Affiliated Hospital of Chengdu Medical College · 416 Hospital of Nuclear Industry from January 2022 to January 2023 were selected as the research subjects. All subjects underwent 13C-urea breath test (13C-UBT) to diagnose whether there was Hp infection. Analyze the current situation of family aggregation of Hp infection in the region, collect general data of survey subjects, analyze the relevant factors affecting Hp family aggregation infection, and develop prevention and control strategies based on this. Results A total of 242 people from 97 households were surveyed, and the Hp family aggregation rate was 29.33%. Univariate analysis showed that there were statistically significant differences in family aggregation of Hp infection in terms of different age groups (χ2=9.719, P=0.008), marital status (χ2=8.496, P=0.014), occupations (χ2=19.462, P<0.001), frequencies of dining out (χ2=5.457, P=0.019), previous Hp test results (χ2 =4.131, P=0.042) and test results after treatment (χ2=12.000, P=0.001), with statistical significance (P<0.05). Multivariate logistic regression analysis showed that the frequency of dining out 2 days or more per week and a positive Hp test results in the past were risk factors for family aggregation of Hp infection, while the occupation of teachers/medical staff/management/technology personnel and a negative Hp results after treatment were protective factors (P<0.05). Conclusion Family aggregation of Hp infection is related to family members' occupation, frequency of dining out, previous Hp test results and Hp test results after eradication, which deserves attention in clinical practice.
4.Stratified Treatment in Pediatric Anaplastic Large Cell Lymphoma: Result of a Prospective Open-Label Multiple-Institution Study
Tingting CHEN ; Chenggong ZENG ; Juan WANG ; Feifei SUN ; Junting HUANG ; Jia ZHU ; Suying LU ; Ning LIAO ; Xiaohong ZHANG ; Zaisheng CHEN ; Xiuli YUAN ; Zhen YANG ; Haixia GUO ; Liangchun YANG ; Chuan WEN ; Wenlin ZHANG ; Yang LI ; Xuequn LUO ; Zelin WU ; Lihua YANG ; Riyang LIU ; Mincui ZHENG ; Xiangling HE ; Xiaofei SUN ; Zijun ZHEN
Cancer Research and Treatment 2024;56(4):1252-1261
Purpose:
The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored.
Materials and Methods:
On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL).
Results:
A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse.
Conclusion
This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).
5.Epidemiological characteristics of newly diagnosed occupational pneumoconiosis in Guangdong Province from 2011 to 2020
Ming LIU ; Xianzhong WEN ; Su WANG ; Shanyu ZHOU ; Xudong LI ; Lihua XIA ; Shijie HU
China Occupational Medicine 2023;50(4):472-475
Objective To analyze the epidemiological characteristics of newly diagnosed occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis") in Guangdong Province from 2011 to 2020. Methods Clinical data of newly diagnosed pneumoconiosis in Guangdong Province from 2011 to 2020 was collected from the “Health Hazards Monitoring Information System” under “China Disease Prevention and Control Information System”. The distribution of the cases was analyzed retrospectively. Results A total of 2 731 cases of newly diagnosed pneumoconiosis were reported from 2011 to 2020 in Guangdong Province, with cases at stages Ⅰ,Ⅱ, and Ⅲ accounting for 61.6%, 23.8%, and 14.6%, respectively. Except for talc pneumoconiosis, 12 other types of pneumoconiosis were reported. The top three incidence of diseases were silicosis, other pneumoconiosis, and welder's pneumoconiosis, accounting for 58.8%, 22.0% and 11.0%, respectively. Males accounted for 97.5%, and females 2.5%. The median age of onset was 47 years old. The median dust exposure duration was 9.8 years, with 19.4% of cases having a dust exposure duration less than 5.0 years. And 80.7% of the cases were distributed in the Pearl River Delta region. The industries with the new cases were mainly the manufacturing (accounting for 69.4%), and 34.8% of cases were found in private limited liability companies. Cases in medium- and small-sized enterprises accounted for 35.7% and 34.3% respectively. Conclusion Silicosis, other pneumoconiosis, and welder's pneumoconiosis are predominant in Guangdong Province. The prevention and control of pneumoconiosis should focus on small- and medium-sized private enterprises in the concentrated manufacturing industry in the Pearl River Delta region.
6.Determination and analysis of monitoring period and measuring duration of personal internal exposure dose
Zheng LU ; Fuping WEN ; Yuqin LI ; Lijiao WANG ; Wenhui XIAO ; Lihua HE ; Yihua XIA
Chinese Journal of Radiological Health 2023;32(3):316-321
Objective To develop a reasonable plan of monitoring personal internal exposure dose. Methods This paper introduced the methods of monitoring the individual dose and direct measurement of three representative radionuclides. Results The maximum monitoring periods were determined according to the radionuclide retention characteristics and the reporting standards and requirements, which were m(1)/m(T/2) ≤ 3 and m(T/2)/m(T) ≤ 3. The lower detection limit of the instrument was derived from the monitoring periods and the annual radionuclide intake limit, which should be lower than the derived method detection limit of the corresponding radionuclide. Then the measuring duration of the instrument that meets the corresponding conditions was derived from the derived method detection limit of the instrument and the maximum monitoring period. Conclusion Our results provide a reference for the formulation of a plan of monitoring personal internal exposure dose.
7.Bilateral basal ganglia hemorrhage due to tentorial dural arteriovenous fistula: a case report and systematic literature review
Bing WEN ; Jie SHEN ; Lihua MA ; Bin GUO ; Yiming LIU ; Guangrun XU ; Tan WANG ; Qinzhou WANG
Chinese Journal of Neurology 2022;55(2):109-116
Objective:To investigate the clinical characteristics of cerebral hemorrhage caused by tentorial dural arteriovenous fistula (TDAVF).Methods:An unusual TDAVF case admitted to the Department of Neurology, Qilu Hospital, Shandong University in March 2020, complicated with hypertension with successive bilateral basal ganglia hemorrhage in short term was reported. The characteristics of cerebral hemorrhage caused by TDAVF reported in the literature were summarized and analyzed.Results:Digital subtraction angiography (DSA) revealed that there was arteriovenous fistula in the tentorial foramen area of this patient (male, 33 years old), and the TDAVF was fed by the right meningohypophyseal trunk, bilateral middle meningeal artery and posterior cerebral artery. A shunted pouch was present in the tentorial foramen area, and retrograde reflux drainage was seen in the deep venous system, from the meningeal vein to superior sagittal sinus or sigmoid sinus. Transarterial embolization was performed and subsequently DSA showed obliteration of the fistula. This patient experienced no clinical decline or rehemorrhage during the 12 months follow-up period. Forty-one cases of TDAVF with hemorrhage of cerebral parenchyma which were reported before March 30, 2021 with detailed clinical and imaging data were summarized. The average age of onset of this group of patients was 57.2 years, and the ratio of male to female was about 3∶1. The hemorrhage was located in superior of the tentorium in 17 cases (41%), while in inferior of the tentorium in 24 cases (59%). Supratentorial intracerebral hemorrhage mainly occurred in occipital lobe and thalamus. DSA showed that the arteriovenous fistula was classified as Borden type Ⅲ or Cognard type Ⅳ in 36 cases (88%). Twenty-nine patients (71%) underwent a single surgical procedure, while 12 cases (29%) underwent combined surgical or other treatments. Overall, 37 patients (90%) achieved angiographically documented obliteration of the fistula and 39 patients (95%) experienced good or excellent outcomes.Conclusions:TDAVF often presents as cerebral parenchymal hemorrhage which is common in supratentorial region, but rare in basal ganglia region. The cause of cerebral hemorrhage in patients with hypertension may not be attributed to hypertension. Early diagnosis and intervention are of great significance to improve the prognosis of patients.
8.Clinical characteristics of adult Chinese patients with syncope: a multicenter clinical study
Fengjing YANG ; Xu LI ; Peng LIANG ; Zhongmei LIU ; Tong LIU ; Yun WU ; Shuanli XIN ; Gaoxing ZHANG ; Shilin YAN ; Lingping XU ; Lixin WANG ; Bo HU ; Wenwei YUE ; Jielin PU ; Zhichun HUANG ; Rui WANG ; Wen WEN ; Peihong LIN ; Li LI ; Zaixin YU ; Xiaodong WANG ; Xijiu LIU ; Jie ZHANG ; Xiufen QU ; Gary TSE ; Yikun PAN ; Kui HONG ; Jieming ZHU ; Lihua LI ; Wen PAN ; Yong WU ; Min WANG ; Changjun SONG ; Zengshuai WANG ; Jianting DONG ; Xinchun YANG ; Xitian HU ; Fujun WANG ; Wenling LIU
Chinese Journal of Cardiology 2022;50(10):1014-1020
Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.
9.Impact of age on the clinical outcome of sleeve gastrectomy
Peng ZHANG ; Wen WU ; Peirong TIAN ; Zhongtao ZHANG ; Tingfeng WANG ; Lihua CHEN
International Journal of Surgery 2021;48(5):316-323
Objective:To compare the effect of age on clinical outcome of laparoscopic sleeve gastrectomy (LSG) in the obese patients.Methods:A total of 113 patients who underwent LSG due to obesity and metabolic disorders between 2013 and 2018 at Fudan University Pudong Hospital, and completed the scheduled follow-up (1, 3, 6, and 12 months after surgery) were included for the retrospective analysis. The patients were divided into three groups based upon pre-operative age, including 15 to 30 year-old group ( n=58), 31 to 45 year-old group ( n=32), and 45 to 65 year-old group ( n=23). The body weight related parameters, glycemic and metabolic related parameters, lipid panel as well as arterial blood pressure were compared at pre-operative baseline, 1, 3, 6, and 12 months after surgery. The quantitative data were analyzed by repeated measurement ANOVA, and the P value was corrected by Bonferroni method. And the categorical variables were analyzed by chi square test. Results:The preoperative baseline data showed that with the increase of age, the preoperative body mass index gradually decreased, which were (40.1±5.9) kg/m 2, (37.1±6.6) kg/m 2 and (35.3±7.4) kg/m 2 in 16 to 30, 31 to 45 and 46 to 65 year-old groups, respectively. Otherwise, other metabolic related parameters were comparable. At 12 months after LSG, there was no significant difference in the amount of weight loss among the groups, but the percentage of total weight loss (% TWL) and the percentage of total BMI loss (%TBMIL) decreased significantly with age increasing. The %TBMIL in 16 to 30, 31 to 45 and 46 to 65 year-old groups were 32.3±7.5%, 28.4±8.4% ( P<005 compared with 16 to 30 year-old group) and 25.7±8.2% (compared with 16 to 30 year-old group P<0.001), respectively. In the patients with preoperative HbA1c>7%, HbA1c reduction in the three groups at 12 months after operation were 3.20% (compared with 46-65 year-old group P<0.001), 2.64% (compared with 46-65 year-old group P<0.05) and 1.34%, respectively. The proportions of patients with HbA1c < 6.5% were 95.8%, 88.9% and 50.0%, respectively. LDL, triglyceride and arterial blood pressure in all groups decreased and HDL increased rapidly within 3 months after operation, but there was no significant difference among the three groups. Conclusions:The improvement of blood glucose metabolism and the remission rate of type 2 diabetes mellitus (T2DM) in the patients with older age were worse than those in the younger patients, and the T2DM in the younger patients tends to obtain better clinical remission after LSG; in terms of weight loss, with the increase of age, %TWL and %TBMIL also showed a decreasing trend; however, the improvement of blood lipid and blood pressure after LSG was not affected by the factor of age. This study implies that patients who meet the indications of metabolic and bariatric surgery should be suggested to receive surgical treatment early in order to achieve better clinical outcomes.
10.DNA sequencing of H3F3A mutations in H3.3 immunohistochemistry-negative giant cell tumors of bone
Lihua GONG ; Wen ZHANG ; Xiaoqi SUN ; Ming ZHANG ; Yi DING
Chinese Journal of Pathology 2021;50(3):190-193
Objective:To investigate the subtypes of H3F3A DNA mutation in H3.3 immunohistochemistry (IHC) negative giant cell tumors of bone (GCTB).Methods:IHC expression of G34W mutated protein was evaluated in 181 cases GCTB. In H3.3 IHC negative cases, Sanger DNA sequencing analysis was used to detect the subtypes H3F3A mutations.Results:Overall, 164 (90.61%) cases of GCTB showed nuclear expression of H3.3, and 17 cases were negative. These 17 H3.3 negative cases were subjected to Sanger DNA sequencing analysis; results showed that eight presented rare mutation subtypes occurring at glycine 34 to leucine (G34L, 3/181, 1.66%), glycine 34 to valine (G34V, 3/181, 1.66%) and glycine 34 to arginine (G34R, 2/181, 1.10%), and the other nine cases were wild type (glycine 34, 9/181, 4.97%). Sanger DNA sequencing analysis confirmed the absence of G34W mutation in the H3.3 negative cases. Combining IHC and DNA sequencing analysis increased the detection rate of H3F3A mutation in the GCTB to 95.03%.Conclusions:H3.3 IHC could detect H3F3A G34W mutation in GCTB, but not for other rare mutation and wild types loci.


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