Tenofovir disoproxil fumarate for multiple nucleos(t)ide analogues treatment failure hepatitis B: Is monotherapy enough?

BACKGROUND AND AIM: Tenofovir disoproxil fumarate (TDF) is a first-line treatment for chronic hepatitis B virus (HBV) infection for its high potency and a low rate of drug resistance. This study investigated the efficacy and safety of TDF in Chinese patients with chronic hepatitis B (CHB) infection after treatment failure with multiple nucleos(t)ide analogues (NAs). METHODS: Patients included were aged 18-65 years, with treatment failure with multiple NAs (serum HBV DNA > 200 IU/mL after more than two different NA treatments). The primary endpoint was proportion of patients with serum HBV DNA < 20 IU/mL at Week 144 of TDF monotherapy. Secondary endpoints and safety were also assessed. RESULTS: Overall, 213 patients were enrolled. At Week 144, mean HBV DNA decreased significantly from baseline (4.4 vs 1.4 log10 IU/mL), with 77.0% patients (95% confidence interval: 71.1, 82.9) achieving serum HBV DNA < 20 IU/mL. Three (1.4%) patients experienced virological breakthrough during TDF monotherapy, without hepatitis flare. At Week 144, 15.3% and 4.7% patients (hepatitis B e antigen [HBeAg]-positive at baseline) experienced HBeAg loss and HBeAg seroconversion, respectively; 68.3% patients achieved normalized alanine aminotransferase levels. Overall, 58.7% patients experienced more than one adverse event (AE). Most common AEs were upper respiratory tract infection and blood creatine phosphokinase increase; 8.5% patients experienced study drug-related AEs; 9.4% patients experienced serious AEs (none were TDF-related). Among renal safety parameters, overall trend of mean serum phosphorous level remained stable, while mean estimated glomerular filtration rate increased slightly. CONCLUSIONS: Tenofovir disoproxil fumarate monotherapy is efficacious in CHB patients with multiple NAs treatment failure with no new safety findings.

A novel chemotherapeutic sensitivity-testing system based on collagen gel droplet embedded 3D-culture methods for hepatocellular carcinoma.

BACKGROUND: Patients suffering from advanced stage hepatocellular carcinoma (HCC) often exhibit a poor prognosis or dismal clinical outcomes due to ineffective chemotherapy or a multi-drug resistance (MDR) process. Thus, it is urgent to develop a new chemotherapeutic sensitivity testing system for HCC treatment. The presence study investigated the potential application of a novel chemotherapeutic sensitivity-testing system based on a collagen gel droplet embedded 3D-culture system (CD-DST). METHODS: Primary cells were separating from surgical resection specimens and then tested by CD-DST. To identify whether HCC cell lines or cells separating from clinical specimens contain MDR features, the cells were treated with an IC 50 (half maximal inhibitory concentration) or IC max (maximal inhibitory concentration) concentration of antitumor agents, e.g., 5-furuolouracil (5-FU), paclitaxel (PAC), cisplatin (CDDP), epirubicin (EPI), or oxaliplatin (L-OHP), and the inhibitory rates (IRs) were calculated. RESULTS: HepG2 cells were sensitive to 5-FU, PAC, CDDP, EPI, or L-OHP; the IC 50 value is 0.83 ± 0.45 µg/ml, 0.03 ± 0.02 µg/ml, 1.15 ± 0.75 µg/ml, 0.09 ± 0.03 µg/ml, or 1.76 ± 0.44 µg/ml, respectively. Only eight (8/26), nine (9/26), or five (5/26) patients were sensitive to the IC max concentration of CDDP, EPI, or L-OHP; whereas only three (3/26), four (4/26), or two (2/26) patients were sensitive to the IC 50 concentration of CDDP, EPI, or L-OHP. No patients were sensitive to 5-FU or PAC. CONCLUSIONS: The in vitro drug sensitivity exanimation revealed the MDR features of HCC and examined the sensitivity of HCC cells from clinical specimens to anti-tumor agents. CD-DST may be a useful method to predict the potential clinical benefits of anticancer agents for HCC patients.

High Expression of Phosphorylated Extracellular Signal-Regulated Kinase (ERK1/2) is Associated with Poor Prognosis in Newly Diagnosed Patients with Multiple Myeloma.

BACKGROUND Previous research has demonstrated that the extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway is commonly activated in multiple myeloma (MM) patients. However, the prognostic value of activation of the MEK/ERK signaling pathway in newly diagnosed patients with MM has not been reported. MATERIAL AND METHODS Expression levels of p-ERK1/2 protein in bone marrow biopsy specimens obtained from 60 newly diagnosed patients with MM were analyzed using immunohistochemistry, and classified into 3 groups: high p-ERK1/2 expression, low p-ERK1/2 expression, and negative group. Correlations between clinicopathological characteristics, including expression levels of p-ERK1/2 protein, progression-free survival (PFS), and overall survival (OS), were analyzed using univariate and multivariate analysis. RESULTS Phosphorylated-ERK1/2 protein was positive in 47 bone marrow specimens, including 19 specimens with high p-ERK1/2 expression and 28 specimens with low p-ERK1/2 expression. Univariate Kaplan-Meier analysis showed that in newly diagnosed patients with MM, high p-ERK1/2 expression, high ISS staging, serum creatinine (Scr) ≥177 µmol/l, serum ß2-microglobulin (ß2-MG) ≥5.5 µmol/l, and serum calcium (Ca) ≥2.75 mmol/l were significantly associated with shorter OS and PFS. Additionally, high ECOG scores (score 2-4) were associated with shorter PFS in newly diagnosed patients with MM. Multivariate Cox regression analysis showed that in newly diagnosed patients with MM, high p-ERK1/2 expression was significantly associated with shorter OS and PFS. Additionally, in newly diagnosed patients with MM, serum Ca ≥2.75 mmol/l was significantly associated with shorter PFS, and serum ß2-MG ≥5.5 µmol/l was significantly associated with shorter OS. CONCLUSIONS High p-ERK1/2 expression is an independent factor for poor prognosis in newly diagnosed patients with MM.

Serum lipid levels and suicidality: a meta-analysis of 65 epidemiological studies.

BACKGROUND: We conducted a systematic review and meta-analysis to determine the association between serum lipid levels and suicidality, as evidence from previous studies has been inconsistent. METHODS: We identified relevant studies by searching Medline, Web of Science, EMBASE, and the Cochrane Database of Systematic Reviews (1980 to Dec. 5, 2014). Studies assessing the association between serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) levels and suicidality were included. We used a random-effects model to take into account heterogeneity among studies. RESULTS: We included 65 studies with a total of 510 392 participants in our analysis. Compared with the nonsuicidal patients, suicidal patients had significantly lower serum TC (weighted mean difference [WMD] -22.35, 95% confidence interval [CI] -27.95 to -16.75), LDL-C (WMD -19.56, 95% CI -26.13 to -12.99) and TG (WMD -23.40, 95% CI -32.38 to -14.42) levels, while compared with the healthy controls, suicidal patients had significantly lower TC (WMD -24.75, 95% CI -27.71 to -21.78), HDL-C (WMD -1.75, 95% CI -3.01 to -0.48) and LDL-C (WMD -3.85, 95% CI -7.45 to -0.26) levels. Furthermore, compared with the highest serum TC level category, a lower serum TC level was associated with a 112% (95% CI 40%-220%) higher risk of suicidality, including a 123% (95% CI 24%-302%) higher risk of suicide attempt and an 85% (95 CI 7%-221%) higher risk of suicide completion. The cut-off values for low and high serum TC level were in compliance with the categories reported in the original studies. LIMITATIONS: A major limitation of our study is the potential heterogeneity in most of the analyses. In addition, the suicidal behaviour was examined using different scales or methods across studies, which may further explain heterogeneity among the studies. CONCLUSION: We identified an inverse association between serum lipid levels and suicidality. More mechanistic studies are needed to further explain this association.

Abdominal obesity and its association with health-related quality of life in adults: a population-based study in five Chinese cities.

BACKGROUND: This study aimed to investigate the prevalence of abdominal obesity and its association with the health-related quality of life (HRQOL) in a randomly selected Chinese sample. METHODS: A population-based sample of 3,600 residents aged 18-80 years was selected randomly from 5 Chinese cities. Demographic information, and waist and hip circumference measurements were obtained. The Mandarin version of the Short Form 36 Health Survey questionnaire (SF-36) was used to assess the HRQOL. Waist circumference (WC) and waist-to-hip ratio (WHR) were used as measures of abdominal obesity, and the prevalence of abdominal obesity and its association with HRQOL were analysed. RESULTS: Among the 3,184 participants included in the analysis, the prevalence of abdominal obesity was about 45% in both women and men as evaluated by WC, and about 40% in women and 33% in men as evaluated by WHR. The prevalence varied by city, region, age, marital status, education level, family income, smoking, and the presence of chronic diseases. Both WC and WHR increased with age, and men had larger WC and WHR than women in most age groups. In women, abdominal obesity, as determined by both WC and WHR, was associated with meaningful impairments in 4 physical health scales and 2 mental health scales. In men, abdominal obesity, as determined by WC, was associated with 1 physical health scale and 1 mental health scale, and it was associated with 2 physical health scales based on WHR. CONCLUSIONS: Physical health, but not mental health, was more vulnerable to impairment with abdominal obesity, and the impairments varied between genders. Public health agencies should emphasize that abdominal obesity impairs physical health.

The safety, immunogenicity, and efficacy of heterologous boosting with a SARS-CoV-2 mRNA vaccine (SYS6006) in Chinese participants aged 18 years or more: a randomized, open-label, active-controlled phase 3 trial.

Continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enhanced transmissibility, significant immune escape, and waning immunity call for booster vaccination. We evaluated the safety, immunogenicity, and efficacy of heterologous booster with a SARS-CoV-2 mRNA vaccine SYS6006 versus an active control vaccine in a randomized, open-label, active-controlled phase 3 trial in healthy adults aged 18 years or more who had received two or three doses of SARS-CoV-2 inactivated vaccine in China. The trial started in December 2022 and lasted for 6 months. The participants were randomized (overall ratio: 3:1) to receive one dose of SYS6006 (N = 2999) or an ancestral receptor binding region-based, alum-adjuvanted recombinant protein SARS-CoV-2 vaccine (N = 1000), including 520 participants in an immunogenicity subgroup. SYS6006 boosting showed good safety profiles with most AEs being grade 1 or 2, and induced robust wild-type and Omicron BA.5 neutralizing antibody response on Days 14 and 28, demonstrating immunogenicity superiority versus the control vaccine and meeting the primary objective. The relative vaccine efficacy against COVID-19 of any severity was 51.6% (95% CI, 35.5-63.7) for any variant, 66.8% (48.6-78.5) for BA.5, and 37.7% (2.4-60.3) for XBB, from Day 7 through Month 6. In the vaccinated and infected hybrid immune participants, the relative vaccine efficacy was 68.4% (31.1-85.5) against COVID-19 of any severity caused by a second infection. All COVID-19 cases were mild. SYS6006 heterologous boosting demonstrated good safety, superior immunogenicity and high efficacy against BA.5-associated COVID-19, and protected against XBB-associated COVID-19, particularly in the hybrid immune population.Trial registration: Chinese Clinical Trial Registry: ChiCTR2200066941.

Pharmacological profiling of a berbamine derivative for lymphoma treatment.

ABSTRACT: Ca2+/calmodulin-dependent protein kinase II γ (CAMKIIγ) has been identified as a potential target for treating cancer. Based on our previous study of berbamine (BBM) as a CAMKIIγ inhibitor, we have synthesized a new BBM derivative termed PA4. Compared with BBM, PA4 showed improved potency and specificity and was more cytotoxic against lymphoma and leukemia than against other types of cancer. In addition to indirectly targeting c-Myc protein stability, we demonstrated that its cytotoxic effects were also mediated via increased reactive oxygen species production in lymphoma cells. PA4 significantly impeded tumor growth in vivo in a xenograft T-cell lymphoma mouse model. Pharmacokinetics studies demonstrated quick absorption into plasma after oral administration, with a maximum concentration of 1680 ± 479 ng/mL at 5.33 ± 2.31 hours. The calculated oral absolute bioavailability was 34.1%. Toxicity assessment of PA4 showed that the therapeutic window used in our experiments was safe for future development. Given its efficacy, safety, and favorable pharmacokinetic profile, PA4 is a potential lead candidate for treating lymphoma.

The relationship between self-rated health and objective health status: a population-based study.

BACKGROUND: Self-rated health (SRH), a subjective assessment of health status, is extensively used in the public health field. However, whether SRH can reflect the objective health status is still debatable. We aim to reveal the relationship between SRH and objective health status in the general population. METHODS: We assessed the relationship between SRH and objective health status by examining the prevalence of diseases, laboratory parameters, and some health-related factors in different SRH groups. Data were collected from 18,000 residents randomly sampled from the general population in five cities of China (3,600 in each city). SRH was assessed by a single-item health measure with five options: "very good," "good," "fair," "bad," and "very bad." The differences in prevalence of diseases, laboratory parameters, and health-related factors between the "healthy" (very good plus good), "relatively healthy" (fair), and "unhealthy" (bad plus very bad) groups were examined. The odds ratios (ORs) referenced by the healthy group were calculated using logistic regression analysis. RESULTS: The prevalence of all diseases was associated with poorer SRH. The tendency was more prominent in cardio-cerebral vascular diseases, visual impairment, and mental illnesses with larger ORs. Residents with abnormalities in laboratory parameters tended to have poorer SRH, with ORs ranging from 1.62 (for triglyceride) to 3.48 (for hemoglobin among men) in a comparison of the unhealthy and healthy groups. Most of the health-related factors regarded as risks were associated with poorer SRH. Among them, life and work pressure, poor spiritual status, and poor quality of interpersonal relationships were the most significant factors. CONCLUSIONS: SRH is consistent with objective health status and can serve as a global measure of health status in the general population.

MicroRNA-181a modulates gene expression of zinc finger family members by directly targeting their coding regions.

MicroRNAs (miRNAs) are small endogenous, non-coding RNAs that specifically bind to the 3' untranslated region (3'UTR) of target genes in animals. However, some recent studies have demonstrated that miRNAs also target the coding regions of mammalian genes. Here, we show that miRNA-181a downregulates the expression of a large number of zinc finger genes (ZNFs). Bioinformatics analysis revealed that these ZNFs contain many miR-181a seed-matched sites within their coding sequences (CDS). In particular, miR-181a 8-mer-matched sequences were mostly localized to the regions coding for the ZNF C2H2 domain. A series of reporter assays confirmed that miR-181a inhibits the expression of ZNFs by directly targeting their CDS. These inhibitory effects might be due to the multiple target sites located within the ZNF genes. In conclusion, our findings indicate that some miRNA species may regulate gene family by targeting their coding regions, thus providing an important and novel perspective for decoding the complex mechanism of miRNA/mRNA interplay.

Excessive daytime sleepiness assessed by the Epworth Sleepiness Scale and its association with health related quality of life: a population-based study in China.

BACKGROUND: Excessive daytime sleepiness (EDS) is a common condition worldwide that has many negative effects on people who were afflicted with it, especially on their health-related quality of life (HRQOL). The Epworth Sleepiness Scale (ESS) is a commonly used method for evaluating EDS in English-speaking countries. This paper reported the prevalence of subjective EDS in China as assessed by the Mandarin version of the ESS; tested the scale's response rate, reliability and validity; and investigated the relationship between ESS scores and HRQOL. METHODS: A population-based sample of 3600 residents was selected randomly in five cities in China. The demographic information was collected, subjective EDS was assessed by the Mandarin version of the ESS (ESS scores >10), and HRQOL was evaluated by the Mandarin version of the 36-item Short Form Health Survey (SF-36). RESULTS: The Mandarin version of ESS had very few missing responses, and the average response rate of its eight items was 97.92%. The split-half reliability coefficient and Cronbach's α coefficient were 0.81 and 0.80, respectively. One factor was identified by factor analysis with an eigenvalue of 2.78. The ESS scores showed positive skewness in the selected sample, with a median (Q1, Q3) of 6 (3, 0). 644 (22.16%) respondents reported subjective EDS, and all of the scores of the eight dimensions of the SF-36 were negatively correlated with ESS scores. CONCLUSIONS: The Mandarin version of ESS is an acceptable, reliable, and valid tool for measuring EDS. In addition, subjective EDS is common in China, based on the ESS results, and impairs HRQOL.

[Clinical Observation of Neutropenia Patients with Hematonosis Treated with Polymyxin B Sulfate].

OBJECTIVE: To observe the clinical efficacy and safety of polymyxin B sulfate in febrile neutropenia patients with hematonosis. METHODS: Clinical data of 50 patients in the department of hematology, Fujian Medical University Union Hospital from October 2019 to September 2020 were collected. All the patients developed febrile neutropenia after chemotherapy or hematopoietic stem cell transplantation. According to the results of drug susceptible test, polymyxin B sulfate was administrated mainly when the empirical antimicrobial treatments was poor and the pathogenic microbes test was positive. RESULTS: A total of 85 times of infection occurred in 50 patients. The infection sites were lung, blood flow, intestinal tract, oral cavity, perianal, soft tissue and nasal cavity. Gram negative bacteria was the main pathogenic microbe. After administration of polymyxin B sulfate when the etiology was confirmed, the total effective rate was 68%, especially the effective rate increased significantly after more than 7 days of polymyxin B sulfate treatment. Also, 24% and 8% of the patients were discharged automatically and died respectively. The effective rate of patients receiving carbapenem antibiotics changed to polymyxin B sulfate within 14 or 7 days was 80% and 70.6%, respectively, while the effective rate of patients who changed after 2 weeks was only 33.3%. The effective rate of patients receiving tigecycline changed to polymyxin B sulfate within 14 or 7 days was 80% and 66.7%, respectively. The incidence of adverse reactions of polymyxin B sulfate was low, most of which were mild, and only one patient occurred rhabdomyolysis. CONCLUSION: Polymyxin B sulfate has good clinical efficacy and safety in febrile neutropenia patients with hematonosis.

A miRNA-mediated attenuation of hepatocarcinogenesis in both hepatocytes and Kupffer cells.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate a variety of physiological and pathological functions. miR-26a is one of the many miRNAs that have been identified as regulators of cancer development and as potential anticancer drug targets. However, the specific cellular and molecular mechanisms by which miR-26a attenuates hepatocarcinogenesis are still elusive. Here, we interrogated mouse models with miR-26a cell-specific overexpression in either hepatocytes or myeloid cells to show that miR-26a strongly attenuated the chemical-induced hepatocellular carcinoma (HCC). miR-26a overexpression broadly inhibited the inflammatory response in both hepatocytes and macrophages by decreasing several key oncogenic signaling pathways in HCC promotion. These findings thus reveal new insights into a concerted role of miR-26a in both hepatocytes and Kupffer cells to suppress hepatocarcinogenesis, thereby highlighting the potential use of miR-26a mimetics as potential approaches for the prevention and treatment of HCC.

MicroRNA-423 promotes cell growth and regulates G(1)/S transition by targeting p21Cip1/Waf1 in hepatocellular carcinoma.

MicroRNAs (miRNAs) are small non-coding RNA molecules that are often located in genomic breakpoint regions and can act as oncogenes or tumor suppressor genes in human cancer. Our previous study showed that microRNA-423 (miR-423), which localized to the frequently amplified region of chromosome 17q11, was upregulated in hepatocellular carcinoma (HCC). However, the potential functions and exact mechanistic roles of miR-423 in hepatic carcinogenesis remain unknown. Here, we demonstrated that miR-423 significantly promotes cell growth and cell cycle progression at the G(1)/S transition in HCC cells. In particular, we found that miR-423-3p contributes to these effects, whereas miR-423-5p does not. Further studies revealed that p21Cip1/Waf1 is a downstream target of miR-423 in HCC cells, as miR-423 bound directly to its 3' untranslated region and reduced both the messenger RNA and protein levels of p21Cip1/Waf1. Moreover, enforced expression of p21Cip1/Waf1 abrogated miR-423-induced effects on HCC cell proliferation and cell cycle progression. These findings indicate that miR-423 exerts growth-promoting effects in hepatic carcinogenesis through the suppression of tumor suppressor p21Cip1/Waf1 expression. The results of this study define miR-423 as a new oncogenic miRNA in HCC.

Misuse of statistical methods in 10 leading Chinese medical journals in 1998 and 2008.

Statistical methods are vital to biomedical research. Our aim was to find out whether progress has been made in the last decade in the use of statistical methods in Chinese medical research. We reviewed 10 leading Chinese medical journals published in 1998 and in 2008. Regarding statistical methods, using a multiple t-test for multiple group comparison was the most common error in the t-test in both years, which significantly decreased in 2008. In contingency tables, no significant level adjustment for multiple comparison significantly decreased in 2008. In ANOVA, over a quarter of articles misused the method of multiple pair-wise comparison in both years, and no significant difference was seen between the two years. In the rank transformation nonparametric test, the error of using multiple pair-wise comparison for multiple group comparison became less common. Many mistakes were found in the randomised controlled trial (56.3% in 1998; 67.9% in 2008), non- randomised clinical trial (57.3%; 58.6%), basic science study (72.9%; 65.5%), case study or case series study (48.4%; 47.2%), and cross-sectional study (57.1%; 44.2%). Progress has been made in the use of statistical methods in Chinese medical journals, but much is yet to be done.

[Expression and Clinical Significance of Heat Shock Protein 90 in Multiple Myeloma Patients].

OBJECTIVE: To investigate the expression of HSP90 in bone marrow samples of multiple myeloma (MM) patients and explore its clinical significance. METHODS: Maxvision immunohistochemistry technique was used to detect the protein expression level of HSP90 76 MM patients and 29 normal healthy donors. The clinical characteristics of the patients were collected, and the correlation between the HSP90 expression and the clinical characteristics was analyzed. RESULTS: The count of MM patients with positive HSP90 protein was significantly higher than that of normal healthy donor, and there were no significant correlation between HSP90 expression and age, sex, hemoglobin (Hb), creatinine (CREA), blood calcium, lactate dehydrogenase (LDH), bone marrow plasma cell proportion and MM subtypes (P>0.05), but HSP90 expression was correlated with ß2-microglobulin (ß2-MG) and ISS stage (P<0.05). The survival time was lower in MM patients with high expression HSP90 as compared with low expression HSP90 MM patients. CONCLUSION: HSP90 protein was over-expressed in MM patients, and was correlated with ß2-microglobulin, ISS stage and OS of MM patients.

Pharmacokinetics and Safety of Intravenous and Subcutaneous Auto-injector Single-dose Belimumab in Healthy Chinese Volunteers: A phase 1, Randomized, Open-label Study.

INTRODUCTION: Belimumab is a recombinant human immunoglobulin G1λ monoclonal antibody indicated as an intravenous (IV) 10 mg/kg and subcutaneous (SC) 200-mg dose for the treatment of systemic lupus erythematosus (SLE). Belimumab 10 mg/kg IV has been approved for the treatment of patients with SLE in China. This phase 1 study investigated the pharmacokinetics (PK), safety, and tolerability of belimumab 200 mg SC and the approved IV formulation in a healthy Chinese population. METHODS: This was a 13-week open-label, randomized, parallel-group study in healthy Chinese volunteers. Eligible volunteers were randomized (1:2) to receive a single dose of IV or SC (via auto-injector) belimumab 200 mg. PK and safety endpoints were evaluated using descriptive statistics. RESULTS: Thirty-six healthy Chinese volunteers were enrolled and all completed the study. Concentration-time profiles were as expected for both formulations. Overall, 130 adverse events (AEs) were reported, with 28 AEs reported in 11 (91.7%) volunteers in the IV group and 102 AEs in 24 (100%) volunteers in the SC group. Of the 130 AEs, 104 (80.0%) were considered to be treatment-related (27 [20.8% of total AEs] treatment-related AEs in the IV group; 77 [59.2% of total AEs] in the SC group). Although the occurrence of AEs was higher in the SC group, most volunteers (91.7%) experienced AEs of mild intensity. The most frequently reported AEs included injection site pain (n = 19 [79.2%]) and oropharyngeal pain (n = 5 [20.8%]) in the SC group, and positive bacterial test, upper respiratory tract infection, blood uric acid increase, white blood cell count increase, asthenia, and diarrhea (n = 2 [16.7%], each) in the IV group. CONCLUSIONS: PK profiles of 200 mg SC and IV belimumab administrations were similar to previous studies, and safety profiles were acceptable, supporting the use of the SC dose in Chinese patients with SLE. TRIAL REGISTRATION: NCT04136145.

Systemic lupus erythematosus (SLE) is a long-term autoimmune disease that affects patients' quality of life. Belimumab is an antibody used in several countries in combination with standard therapy to treat patients with SLE. Belimumab can be given monthly either via a vein (intravenous, IV) or weekly under the skin (subcutaneous, SC). In China, only the IV belimumab has been approved for the treatment of patients with SLE. Therefore, we carried out a study in healthy Chinese volunteers to compare the concentration of a single dose of IV or SC belimumab in the body over time, and to investigate the safety of SC belimumab to assist its approval in China. In our study, the concentration and safety of both administration methods were similar; however, more volunteers from the SC treatment group had urinalysis-related side effects compared with the IV treatment group. All of these side effects were of mild intensity and did not require treatment. These results suggest that SC belimumab could be used for the treatment of Chinese patients with SLE.

Comparative analysis of effectiveness of asthma control test-guided treatment versus usual care in patients with asthma from China.

OBJECTIVE: The present study compared the effectiveness of asthma control test (ACT)-guided treatment vs. usual care (UC) in patients with asthma from China. METHODS: This prospective, phase IV, multicenter, cluster-randomized, open-label 24-week study was conducted in China; patients were randomized to either ACT-guided treatment or UC group. The patients recorded peak expiratory flow, symptoms, and medication in a diary card every day and completed ACT at every clinic visit. For the UC group, patients completed ACT after the physician's treatment decision. RESULTS: In total, 83.6% patients (n = 443/530; ACT: n = 209, UC: n = 234) completed the study. A significantly higher proportion of patients (adjusted OR [95% CI]: 7.87 (1.29, 48.11; p = 0.027) responded to the treatment and had ACT total score ≥20 or demonstrated an improvement of >3 points in ACT total score in ≥1 post-baseline assessment in the ACT-guided treatment vs. UC group. A higher proportion of patients had an ACT total score ≥20 and an improvement of >3 points in ACT total score at Week 24 in the ACT-guided treatment vs. the UC group (adjusted OR (95% CI):2.28 (1.07, 4.85; p = 0.036). A significant difference (p = 0.005) in change from baseline in ACT total score was observed in ACT-guided treatment vs. UC group at Week 24. The mean annual exacerbation rate was similar in both the groups. CONCLUSIONS: ACT-guided treatment was more effective in achieving ACT total score ≥20 or showing an improvement of >3 points in the ACT total score and well tolerated compared with UC treatment in the 24-week treatment period. TRIAL REGISTRATION: Clinical trials.gov Identifier: NCT02868281, https://clinicaltrials.gov/; GlaxoSmithKline study ID: 201097, https://www.gsk-studyregister.com/.

MicroRNA-1285 inhibits the expression of p53 by directly targeting its 3' untranslated region.

The well-known tumor suppressor p53 plays critical roles in the modulation of multiple cellular processes. The regulation of p53 is complicated and remains elusive. In this study, we used a high-throughput luciferase reporter screen to demonstrate that p53 can be regulated by microRNA-1285 (miR-1285). Notably, miR-612, which has the same seed sequence as miR-1285, cannot bind to the 3' untranslated region (3' UTR) of p53. Mutational analyses confirmed that the 3' UTR of p53 mRNA contains two miR-1285 target sites, which are nearly perfectly complementary to the mature miR-1285 sequence. Ectopic expression of miR-1285 inhibits expression of p53 mRNA and protein. In contrast, silencing of miR-1285 increases p53 expression. Furthermore, miR-1285 inhibits the transcription of p21, a master gene downstream of p53. In conclusion, our findings provide the first evidence that miR-1285 directly regulates the expression of p53 by directly targeting its 3' UTR.