OBJECTIVE To investigate the effect of succinate dehydrogenase complex subunit A (sdha)gene on cell proliferation,cell cycle and apoptosis of mouse hepatic cell line BNL CL.2 cells. METHODS The BNL CL.2 cells were transfected by two kinds of sdha-shRNA lentivirus to knockdown sdha gene. The infection efficiency of BNL CL.2 cells infected with lentiviral vectors was analyzed by flow cytometry. The expression of sdha gene and SDHA protein was detected by real-time PCR and Western blotting,respectively. The effect of sdha gene on cell proliferation of BNL CL.2 cells was examined by growth curve,while cell cycle and apoptosis were analyzed by flow cytometry. RESULTS The infection efficiency of BNL CL.2 cells in sh-control group and in sdha-shRNA group was above 80%. Compared with sh-control group,the expression of sdha gene in BNL CL.2 cells infected with sdha-shRNA lentivirus was decreased by about 20 times(P<0.01),the expression of SDHA protein was decreased by about 10 times(P<0.01),and the growth rate was about 70%that of sh-control group(P<0.05). The cells were arrested in S phase,and the percentage of cells in S phase was 0.74 times that of sh-control group(P<0.01). The percentage of cells in G0/GI phase was 1.17 times that of sh-control group(P<0.01). The percentage of cells in G2/M was 1.37 times that of sh-control group(P<0.01). But there was no obvious difference in the apoptosis rate. CONCLUSION The reduced expression of SDHA protein can inhibit the proliferation of mouse hepatic cells,and the inhibitory mechanism may be cell cycle arrest. There is possibly no relationship between inhibition and cell apoptosis.

Objective To evaluate effects of acitretin on HaCaT cells cultured in hypoxic condition,and to preliminarily explore the possible therapeutic mechanisms of acitretin in psoriasis.Methods HaCaT cells were divided into several groups to be cultured in hypoxic condition with the presence of acitretin at concentrations of 10-5,10-6,10-7 and 10 8 mol/L respectively,with cells treated with dimethyl sulfoxide (DMSO) as DMSO control group and those receiving no treatment as blank control group.Cellular proliferative activity was evaluated by CCK-8 assay after 12-,24-and 36-hour hypoxic culture in vitro.The mRNA and protein expressions of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were determined by reverse transcription (RT)-PCR and Western-blot analysis,respectively,after 24-hour hypoxic culture.Results After 24-hour hypoxic culture,the cellular proliferation rate was inhibited by 13.31％ ± 1.15％,21.86％ ± 5.31％,32.05％ ± 2.99％ and 37.28％ ± 3.21％ in the 10 8-,10-7-,10-6-and 10-5-mol/L acitretin groups respectively.With the increase of culture duration and acitretin concentrations,the degree of inhibition on cellular proliferation increased gradually.Compared with the blank control group,the 10-5-mol/L acitretin group showed significantly decreased protein expression of HIF-1α (0.319 ± 0.180 vs.1.196 ± 0.088,P ＜0.05),as well as decreased mRNA and protein expressions of VEGF (mRNA:0.442 ± 0.090 vs.1.108 ± 0.073;protein:0.216 ± 0.066 vs.1.174 ± 0.186;both P ＜ 0.05).However,no significant difference was found in the mRNA expression of HIF-lα between the 10-5-mol/L acitretin group and blank control group.Conclusion Acitretin can suppress the in vitro proliferation of HaCaT cells cultured in hypoxic condition,and down-regulate the expressions of HIF-1α and VEGF proteins as well as VEGF mRNA.

Objective To analyze the clinical characteristics of AIDS-related non-Hodgkin lymphoma(ARL)and review relative literature for the diagnosis and treatment of ARL.Method The clinical data of ARL patients admitted to Peking Union Medical College Hospital from April 2009 to April 2011 were retrospectively analyzed.Results Five male ARL patients aged 32 to 65 years old were included in this retrospective study.Among them,two patients were found to be HIV-positive for the first time,three were on regular highly active anti-retroviral therapy(HAART)for 7-8 months before the emergence of lymphoma-related symptoms.CD4+ T cell count was(69-232)× 106/L at presentation.Two patients firstly presented with sore throat and throat ulcer,one with cervical nodules,one with pelvic mass,one with fever and edema in right thigh.Through pathological analysis,four patients had B cell-originated lymphoma,with one Burkitt lymphoma and three diffuse large B cell lymphomas; one patient had T-cell lymphoma.Four patients were treated with chemotherapy,with one complete remission,one relapse,one non-response,and one death.One patient had radiotherapy only and had progressed disease.Bone marrow suppression and gastrointestinal disturbance were the main adverse effects of chemotherapy.Conclusions Lymphoma should be considered in any HIV-infected patients presented with unexplainable adenopathy,recurrent sore throat or throat ulcer,or fever of unknown origin.Biopsy should be rigorously carried out.Appropriate chemotherapy,together with HAART,may improve the prognosis greatly.

Objective To prepare ultrasound(US)responsive nanodroplets(NDs)simultaneously loaded with anticancer drug Sorafenib(SF)and Doxorubicin(DOX),and to characterize its ultrasound responsibility in vitro and in vivo.Methods The SF/DOX NDs were prepared using the thin-film hydration method.The particle diameter,Zeta potential and drug-encapsulation efficiency were characterized.The acoustic droplets vaporization activity was monitored by in vitro ultrasound imaging and light microscope. The cavitation effect was monitored by in vitro ultrasound imaging and transmission electron microscopy. Results SF/DOX NDs were round in shape,the mean diameter and Zeta potential of SF/DOX NDs was (498 ± 67.34)nm,-(38.87 ± 3.78)mV,respectively.The entrapment efficiency of SF and DOX was (58.14±2.93)%,(51.23±4.11)%,respectively.SF/DOX NDs underwent a phase transition into bubbles and could be continuously imaged for more than 25 min in vitro,and afterward therapeutic ultrasound pulse induced inertial cavitation and substantially enhanced treatment.Conclusions US-responsible SF/DOX NDs are prepared using thin-film hydration mehtod,it can enhance ultrasonic echo in vitro and release anticancer drug by the aid of US exposure,which possesses greater researching and applicating value.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

BACKGROUNDAn zidovudine (AZT)-substitution regimen containing 24-week stavudine (d4T) followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associated with d4T in resource-limited settings. However, evidence is scarce. This study aims to assess the efficacy and safety of AZT-substitution regimen, aiming to find a regimen with better efficacy, less adverse events, and more affordability in resource-limited settings.

METHODSThis prospective, multicenter study enrolled 499 (190 on d4T regimen, 172 on AZT regimen, and 137 on AZT-substitution regimen) HIV-1-infected subjects who initiated combined antiretroviral therapy and attended follow-up visits over 96 weeks from 2009 to 2011. Lamivudine (3TC) and either nevirapine (NVP) or efavirenz (EFV) were the other two drugs in the antiretroviral regimens. Virologic and immunologic responses and adverse events were monitored at baseline and at weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96.

RESULTSIn terms of hematological adverse effects, AZT-substitution group had similar safety profiles to d4T group and was superior to AZT group. In comparison with AZT-substitution group, AZT group was associated with higher risk of developing anemia (adjusted hazard ratio (aHR) for anemia ≥ grade II, 8.44, 95% CI 1.81-39.46) and neutropenia (aHR for neutropenia ≥ grade II, 1.86, 95% CI 1.19-2.93). The prevalence of lipodystrophy in d4T group was 19.5%, while that in AZT-substitution group was zero. As to antiretroviral efficacy, these three groups showed no differences.

CONCLUSIONAZT-substitution regimen provides a relatively safe and effective first-line antiretroviral strategy in resource-limited settings.

Adult ; Anti-HIV Agents ; administration & dosage ; adverse effects ; therapeutic use ; Female ; HIV Infections ; drug therapy ; Humans ; Male ; Middle Aged ; Prospective Studies ; Stavudine ; administration & dosage ; adverse effects ; therapeutic use ; Zidovudine ; administration & dosage ; adverse effects ; therapeutic use