Objective:To compare the effectiveness and safety profile of tenofovir amibufenamide (TMF) and tenofovir alafenamide (TAF), especially the effects on lipid metabolism in the treatment of chronic hepatitis B.Methods:A retrospective study was conducted on the virological response rate, biochemical response rate, renal function indicators, and lipid metabolism status of 159 cases with chronic hepatitis B (72 cases with TMF and 87 cases with TAF) after 48 weeks of antiviral treatment. The effects of the two drugs on lipid metabolism were further explored through cell and animal experiments.Results:There were no statistically significant differences in baseline age, gender ratio, treatment-na?ve and treatment-experienced proportions, hepatitis B virus (HBV) DNA and aminotransferase levels, renal function indicators, and serum lipid levels between the two groups. The levels of HBV DNA and transaminase were significantly reduced after 48 weeks of treatment in both groups. However, there were no statistically significant differences in virological response (84.2% vs. 75.8%, χ2=0.733, P=0.392) and biochemical response rate (86.1% vs. 85.1%, χ2=0.035, P=0.851) between the two groups. There was no significant change in the renal function index levels before and after treatment between the two groups of patients. Triglyceride [TG, 1.30 (0.93, 1.81) mmol/L vs. 1.30 (0.82, 1.84) mmol/L, Z=-0.196, P=0.844], total cholesterol [TC, 4.53 (3.91, 5.15) mmol/L vs. 4.55 (3.88, 5.24) mmol/L, Z=-1.131, P=0.258], high-density lipoprotein [HDL-C, 1.04 (0.90, 1.3) mmol/L vs. 1.08 (0.94, 1.30) mmol/L, Z=-0.811, P=0.417], low-density lipoprotein [LDL-C, 2.68 (2.04, 3.29) mmol/L vs. 2.57 (1.99, 3.49) mmol/L, Z=-1.716, P=0.086] and the ratio of total cholesterol to high-density lipoprotein [TC/HDL-C, 4.52 (3.10, 5.23) vs. 4.30 (3.27, 5.01), Z=-0.410, P=0.682] had not statistically significant differences in the TMF group before and after treatment. TG [1.24(0.95, 1.98) mmol/L vs. 1.42(1.09, 2.21) mmol/L, Z=-2.895, P=0.004], TC [4.44(3.74, 5.26) mmol/L vs. 4.68(4.07), 5.46) mmol/L, Z=-2.825, P=0.005], low-density lipoprotein (LDL-C) [2.74 (2.05, 3.58) mmol/L vs. 2.87 (2.34, 3.50) mmol/L, Z=-2.419, P=0.016] , and TC/HDL-C [3.89(3.13, 4.82) vs. 4.39(3.70, 5.40), Z=-4.478, P<0.001] levels were increased after TAF treatment, while HDL-C levels were decreased [1.19 (0.98, 1.35) mmol/L vs. 1.04 (0.90, 1.33) mmol/L, Z=-3.070, P=0.002]. The absolute values comparison changes had no statistically significant differences in TG [-0.04(-0.37, 0.46) mmol/L and 0.18 (-0.14, 0.46) mmol/L, Z=-1.853, P=0.064], TC [0.06(-0.38, 0.63) mmol/L vs. 0.23(-0.21, 0.65) mmol/L, Z=-1.010, P=0.312] and LDL-C level [-0.19(-0.33, 0.18) mmol/L vs. 0.18 (-0.13, 0.58) mmol/L, Z=-0.523, P=0.601] before and after treatment between the two groups of patients. The TMF group had higher HDL-C [0.06 (-0.16, 1.84) mmol/L vs. -0.12 (-0.26,0.04) mmol/L, Z=-2.890, P=0.004], but lower TC/HDL-C [-0.04(-0.67, 0.44) vs. 0.40(-0.14, 1.33), Z=-3.959, P<0.001] than the TAF group. HepG2 cells were interfered with 10 μg/ml TMF and TAF for 72 hours, respectively. Microscopic examination revealed that in the TMF group [12 196 (10 740, 14 345) vs. 4 029 (3 086, 5 425) cells, Z=-4.815, P<0.001] and TAF group [12 484 (11 176, 15 824) vs. 4 029 (3 086, 5 425), Z=-4.815, P<0.001], the number of intracellular lipid droplets was higher than that in the control group after Oil Red O staining, but the difference between the two groups was not statistically significant. Ten-week-old C57/BL6J male mice were given 3.8 mg/kg TMF or TAF by continuous gavage for 12 weeks. The liver tissue was stained with Oil Red O. The number of lipid droplets was higher in the liver tissue of mice in the TAF group than that of the control group [30 647 (28 050, 34 821) and 27 614 (25 214, 29 176), Z=-2.529, P=0.011], while the difference between the TMF group and control group was not statistically significant. The serum TG levels were higher in the TAF group mice [1.17 (1.11, 1.19) μmol/L vs. 1.06 (1.04, 1.09) μmol/L, Z=-2.060, P=0.039], TC [2.58 (2.55, 2.80) μmol/L L vs. 2.33 (2.18, 2.54) μmol/L, Z=-2.084, P=0.037] than those of the control group after drug administration, while HDL-C levels were lower than those of the control group [1.14 (1.13, 1.16) μmol/L vs. 1.29 (1.28, 1.32) μmol/L, Z=-2.313, P=0.021] and TMF group [1.14 (1.13, 1.16) μmol/L vs. 1.30 (1.28, 1.38) μmol/L, Z=-2.795, P=0.005]. However, there was no statistically significant difference in TG, TC, and HDL-C levels between the TMF and the control group. Conclusion:Both TMF and TAF can effectively inhibit HBV replication and promote liver function recovery, with no significant impact on renal function. However, TAF may generate an adverse effect on lipid metabolism in the body, while TMF has no obvious effect.

Objective:To investigate the differences in clinical and electrocardiographic characteristics between carriers of SCN5A mutations and non-SCN5A mutations in fever-induced Brugada syndrome.Methods:This study is a retrospective cohort study. A total of 263 patients with fever-induced Brugada syndrome who were admitted to Renmin Hospital of Wuhan University from January 2000 to December 2023 were selected. Their clinical manifestations, electrocardiographic characteristics, and major adverse cardiovascular events (MACE) at the time of diagnosis and during the follow-up period were collected. Among them, 200 patients underwent next-generation sequencing. Based on the genetic variation results, after excluding other mutations, they were divided into SCN5A mutation group, non-SCN5A sodium-related mutation group, potassium/calcium mutation group, and no mutation group. Comparisons were made among these groups in terms of their clinical and electrocardiographic characteristics.Results:Among the 263 patients with fever-induced Brugada syndrome, the mean age was (41.9±17.6) years, with 80.6% (212/263) being male. The median follow-up duration was 53.0 months, and 13.7% (36/263) of the patients experienced MACE. The rate of SCN5A mutation was 34.5% (69/200), while the rates of non-SCN5A sodium-related mutations and potassium/calcium-related mutations were 4.5% (9/200) and 3.5% (7/200), respectively. The SCN5A mutation group was younger than the non-SCN5A sodium-related mutation group and the no mutation group (ages were (33.8±14.7), (49.8±11.6), (44.6±15.7) years, respectively, P<0.001). The SCN5A mutation group also had a longer PR interval than the no mutation group ((176.8±32.3) ms vs. (163.9±28.6) ms, P=0.034). The incidence of MACE was higher in the non-SCN5A sodium-related mutation group than that in the no mutation group (55.6% (5/9) vs. 9.1% (9/99), P=0.002). Conclusions:Fever-induced Brugada syndrome patients carrying non-SCN5A mutations exhibit distinct clinical and electrocardiographic characteristics compared to those with SCN5A mutations. These differences warrant attention in clinical practice.

Objective:To compare the effectiveness and safety profile of tenofovir amibufenamide (TMF) and tenofovir alafenamide (TAF), especially the effects on lipid metabolism in the treatment of chronic hepatitis B.Methods:A retrospective study was conducted on the virological response rate, biochemical response rate, renal function indicators, and lipid metabolism status of 159 cases with chronic hepatitis B (72 cases with TMF and 87 cases with TAF) after 48 weeks of antiviral treatment. The effects of the two drugs on lipid metabolism were further explored through cell and animal experiments.Results:There were no statistically significant differences in baseline age, gender ratio, treatment-na?ve and treatment-experienced proportions, hepatitis B virus (HBV) DNA and aminotransferase levels, renal function indicators, and serum lipid levels between the two groups. The levels of HBV DNA and transaminase were significantly reduced after 48 weeks of treatment in both groups. However, there were no statistically significant differences in virological response (84.2% vs. 75.8%, χ2=0.733, P=0.392) and biochemical response rate (86.1% vs. 85.1%, χ2=0.035, P=0.851) between the two groups. There was no significant change in the renal function index levels before and after treatment between the two groups of patients. Triglyceride [TG, 1.30 (0.93, 1.81) mmol/L vs. 1.30 (0.82, 1.84) mmol/L, Z=-0.196, P=0.844], total cholesterol [TC, 4.53 (3.91, 5.15) mmol/L vs. 4.55 (3.88, 5.24) mmol/L, Z=-1.131, P=0.258], high-density lipoprotein [HDL-C, 1.04 (0.90, 1.3) mmol/L vs. 1.08 (0.94, 1.30) mmol/L, Z=-0.811, P=0.417], low-density lipoprotein [LDL-C, 2.68 (2.04, 3.29) mmol/L vs. 2.57 (1.99, 3.49) mmol/L, Z=-1.716, P=0.086] and the ratio of total cholesterol to high-density lipoprotein [TC/HDL-C, 4.52 (3.10, 5.23) vs. 4.30 (3.27, 5.01), Z=-0.410, P=0.682] had not statistically significant differences in the TMF group before and after treatment. TG [1.24(0.95, 1.98) mmol/L vs. 1.42(1.09, 2.21) mmol/L, Z=-2.895, P=0.004], TC [4.44(3.74, 5.26) mmol/L vs. 4.68(4.07), 5.46) mmol/L, Z=-2.825, P=0.005], low-density lipoprotein (LDL-C) [2.74 (2.05, 3.58) mmol/L vs. 2.87 (2.34, 3.50) mmol/L, Z=-2.419, P=0.016] , and TC/HDL-C [3.89(3.13, 4.82) vs. 4.39(3.70, 5.40), Z=-4.478, P<0.001] levels were increased after TAF treatment, while HDL-C levels were decreased [1.19 (0.98, 1.35) mmol/L vs. 1.04 (0.90, 1.33) mmol/L, Z=-3.070, P=0.002]. The absolute values comparison changes had no statistically significant differences in TG [-0.04(-0.37, 0.46) mmol/L and 0.18 (-0.14, 0.46) mmol/L, Z=-1.853, P=0.064], TC [0.06(-0.38, 0.63) mmol/L vs. 0.23(-0.21, 0.65) mmol/L, Z=-1.010, P=0.312] and LDL-C level [-0.19(-0.33, 0.18) mmol/L vs. 0.18 (-0.13, 0.58) mmol/L, Z=-0.523, P=0.601] before and after treatment between the two groups of patients. The TMF group had higher HDL-C [0.06 (-0.16, 1.84) mmol/L vs. -0.12 (-0.26,0.04) mmol/L, Z=-2.890, P=0.004], but lower TC/HDL-C [-0.04(-0.67, 0.44) vs. 0.40(-0.14, 1.33), Z=-3.959, P<0.001] than the TAF group. HepG2 cells were interfered with 10 μg/ml TMF and TAF for 72 hours, respectively. Microscopic examination revealed that in the TMF group [12 196 (10 740, 14 345) vs. 4 029 (3 086, 5 425) cells, Z=-4.815, P<0.001] and TAF group [12 484 (11 176, 15 824) vs. 4 029 (3 086, 5 425), Z=-4.815, P<0.001], the number of intracellular lipid droplets was higher than that in the control group after Oil Red O staining, but the difference between the two groups was not statistically significant. Ten-week-old C57/BL6J male mice were given 3.8 mg/kg TMF or TAF by continuous gavage for 12 weeks. The liver tissue was stained with Oil Red O. The number of lipid droplets was higher in the liver tissue of mice in the TAF group than that of the control group [30 647 (28 050, 34 821) and 27 614 (25 214, 29 176), Z=-2.529, P=0.011], while the difference between the TMF group and control group was not statistically significant. The serum TG levels were higher in the TAF group mice [1.17 (1.11, 1.19) μmol/L vs. 1.06 (1.04, 1.09) μmol/L, Z=-2.060, P=0.039], TC [2.58 (2.55, 2.80) μmol/L L vs. 2.33 (2.18, 2.54) μmol/L, Z=-2.084, P=0.037] than those of the control group after drug administration, while HDL-C levels were lower than those of the control group [1.14 (1.13, 1.16) μmol/L vs. 1.29 (1.28, 1.32) μmol/L, Z=-2.313, P=0.021] and TMF group [1.14 (1.13, 1.16) μmol/L vs. 1.30 (1.28, 1.38) μmol/L, Z=-2.795, P=0.005]. However, there was no statistically significant difference in TG, TC, and HDL-C levels between the TMF and the control group. Conclusion:Both TMF and TAF can effectively inhibit HBV replication and promote liver function recovery, with no significant impact on renal function. However, TAF may generate an adverse effect on lipid metabolism in the body, while TMF has no obvious effect.

Objective:To automatically synthesize Al 18F-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04, perform PET/CT imaging in vivo, and evaluate its diagnostic efficacy on tumors. Methods:Al 18F-NOTA-FAPI-04 was produced in All-in-one automatic synthesis module and its quality control was conducted by high performance liquid chromatography (HPLC) equipped with a radioactive detector. Al 18F-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice ( n=3) and 4T1 breast cancer models ( n=3) to determine its biodistribution. Then Al 18F-NOTA-FAPI-04 and 18F-FDG PET/CT imaging were performed in a hepatocellular carcinoma patient (male, 51 years old). Results:The synthesis time of Al 18F-NOTA-FAPI-04 was about 35 min, and the radiochemical yield was (25.2±1.9)% (attenuation correction, n=3). The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (46.11±3.07) GBq/μmol (attenuation correction, n=3). The radiochemical purity was above 99.0% and was still above 98.0% at room temperature after 6 h. PET/CT imaging in mice showed that physiological uptake of Al 18F-NOTA-FAPI-04 was mainly in biliary system and bladder, and Al 18F-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that Al 18F-NOTA-FAPI-04 obtained high tumor background ratio (TBR) values of 4.1, 8.9, 5.4, 4.8, 2.2 in parasternal lymph nodes, anterior diaphragmatic lymph nodes, hilar lymph nodes, pancreaticoduodenal ligament lymph nodes, abdominal aortic lymph nodes, respectively, while TBR values were 1.0, 2.8, 5.0, 2.1, 1.1 by 18F-FDG. Conclusions:Al 18F-NOTA-FAPI-04 can be synthesized with short time, high radiochemical yield and good stability using All-in-one module. Al 18F-NOTA-FAPI-04 PET/CT imaging has high contrast and excellent diagnostic efficacy on tumors.

Objective: To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) . Methods: The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis. Results: The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK⁺ and 9 ones (27.3%) ALK^-. Of them, 25 patients (19 ALK⁺ and 6 ALK^-) underwent auto-HSCT and 8 cases (5 ALK⁺ and 3ALK^-) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively. Conclusion ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.

Objective: To evaluate clinical outcomes of autologous (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for angioimmunoblastic T-cell lymphoma (AITL) . Methods: From June 2007 to June 2017, clinical data of AITL patients who underwent HSCT in eight hospitals were assessed retrospectively. Results: Of 19 patients, 13 male and 6 female with a median age of 50 (32-60) years old, 12 auto-HSCT and 7 allo-HSCT recipients were enrolled in this study, all donors were HLA-identical siblings. Two of allo-HSCT recipients were relapsed auto-HSCT ones. There were 5 patients (5/12) in complete response (CR) status and 7 (7/12) in partial remission (PR) status before transplantation in auto-HSCT group, and 2 (2/7) in PR status and 3 (3/7) in progression disease (PD) status before transplantation in allo-HSCT group. The median follow-up for the surviving patients was 46.5 months (range, 1-100 months) for the whole series, two patients lost in auto-HSCT group. Three patients developed acute graft-versus-host disease (aGVHD) and 5 chronic graft-versus-host disease (cGVHD) after allo-HSCT. Three patients died of primary disease and 1bleeding in auto-HSCT group. One patient died of primary disease and 2 transplantation-related mortality in allo-HSCT group. The 3-year cumulative overall survival (OS) were 56% (95%CI 32%-100%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.979) . The 3-year cumulative progression-free survival (PFS) were 34% (95%CI 14%-85%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.451) . Conclusion Both auto-HSCT and allo-HSCT were optimal choices for AITL. In clinical practice, which HSCT was better for AITL patients should be based on comprehensive factors including sensitivity to chemotherapy, risk stratification and disease status at transplantation.

We investigated the molecular characteristics of the full-length genome of 14 dengue serotype 1 virus (DENV-1)strains isolated in Sino-Myanmar border region in Yunnan Province,China during 2013-2015.Isolation of dengue virus was using C6/36 cell culture method.Viral RNA was extracted from virus isolates,and then the full-length genome was amplified by RT-PCR.The homology and phylogenetic analysis was made on the nucleotide and deduced amino acid sequences by bioinformatics software including ClastalX1.83 and MEGA6 etc.Results showed that fourteen strains of DENV-1 isolated from dengue fever cases,of these,9 strains from Ruili City of Dehong Prefecture,3 from Lincang Prefecture,2 from Kunming City.RT-PCR and sequencing indicated that the full-length genes (10 735 nt) of 14 DENV-1 strains were obtained,and their open reading frame (95-10 271) were coded 3 392 amino acid residues.The genotypes of DENV-1 were revealed by homology and phylogenetic analysis based on structural and non-structural proteins.Thirteen were genotype Ⅰ (G-Ⅰ) (7 from indigenous cases in Ruili and Lincang and 6 from imported case from Myanmar to Ruili,Lincang and Kunming),and 1 G-Ⅲ from imported case from India to Kunming.The phylogenic analysis indicated that the 13 isolates from Yunnan divided into 2 phylogenic subgroups,and they had a closer genetic relationship with the strains isolated from Southeast Asia.The gene sequences of the 13 G-Ⅰ strains have been acquired,the rate of their nucleotide homology and amino acid homology were 97.02 ％-100 ％ and 98.78 ％100 ％ respectively.Compared with 6 strains from Southeast Asia,nucleotide homology and amino acid homology were 96.53％-99.53％ and 97.33％-100％ respectively.Compared with prototype strain (US_Hawaii) of DENV-1,nucleotide homology and amino acid homology were 93.76％-94.45 ％ and 95.86 ％-96.91％ respectively.Compared with US_Hawaii strain,there were 44 and 150 different sites in amino acid of structural and non-structural proteins,respectively.The G-1 of DENV-1 have been popular in Sino-Myanmar border region in Yunnan,2013-2015.They have genetic diversity but multiple transmission sources were from Myanmar,and should strengthen control cross-border spread of dengue fever in this region.It is necessary to further study that change of the amino acid sites of Yunnan strains of DENV-1 is related to its antigenicity and pathogenicity.

OBJECTIVE To investigate the effect of amifostine(Amf)on the differentiation of human megakaryocyte cell line-Dami. METHODS Dami cells were treated with Amf 0.01-5.0 mmol · L-1 for 12 d. Dami cells were counted every day for the growth curve:only cells with a diameter>20μm. The platelet demarcation membrane system was observed by transmission electron microscopy. The expression of CD33,CD34,CD41a and DNA ploidy was detected by flow cytometry. RESULTS Amf 0.1-1.0 mmol · L-1 promoted the differentiation of Dami cells ,but inhibited their proliferation at a concentration>1.0 mmol · L-1. When these cells were treated with Amf 1.0 mmol · L-1 for 12 d,the platelet demarcation membrane system was observed,the percentage of cells with a diameter >20 μm was increased by 24.6%(P<0.01),the expression of CD41a was increased by 11.9%,while the expression of CD33 was decreased by 13.6%(P<0.05). Polyploidy cells(16N)were observed,and 4N,8N and 16N cells were increased to 31.56%,8.83% and 3.43%,respectively(P<0.05). CONCLUSION Amf 0.1-1.0 mmol · L-1 can promote the differentiation of Dami cells,but inhibit their proliferation at a high concentration(>1.0 mmol·L-1).