Ethyl pyruvate attenuates cellular adhesion and proliferation of diffuse large B-cell lymphoma by targeting c-Jun.

Diffuse large B-cell lymphoma (DLBCL) stands out as the most common type of malignant cancer, representing the majority of cases of non-Hodgkin's lymphoma. Ethyl pyruvate (EP) is a derivative of pyruvic acid and found to have potent anti-tumor properties. Despite its potential benefits, the impact of EP on DLBCL remains ambiguous. Our objective is to elucidate the role of EP in modulating the development of DLBCL. Analysis of cholecystokinin-8 (CCK-8) revealed that treatment with EP significantly diminished the viability of DLBCL cells. Furthermore, EP administration suppressed colony formation and hindered cell adhesion and invasion in DLBCL cells. Examination of cell cycle progression showed that EP treatment induced arrest at the G1 phase and subsequently reduced the S phase population in DLBCL cells. EP treatment consistently exhibited apoptosis-inducing properties in Annexin-V assays, and notably downregulated the expression of Bcl-2 while increasing levels of proapoptotic cleaved caspase 3 and BAX in DLBCL cells. Additionally, EP treatment decreased the overexpression of c-Jun in c-Jun-transfected DLBCL cells. Further, EP demonstrated DNA-damaging effects in TUNEL assays. In vivo, xenograft animal models revealed that EP treatment significantly mitigated DLBCL tumor growth and suppressed DLBCL cell adhesion to bone marrow stromal cells. In summary, these findings suggest that EP mitigates DLBCL progression by inducing apoptosis, inducing cell cycle arrest, and promoting DNA damage.

Efficacy and safety of generic pomalidomide plus low-dose dexamethasone in relapsed or refractory multiple myeloma: a multicenter, open-label, single-arm trial.

This multicenter, open-label, single-arm trial (ClinicalTrials.gov, NCT05236621) was conducted to confirm the efficacy and safety of generic pomalidomide plus dexamethasone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Total 79 eligible RRMM patients were planned to be included. Patients were treated with generic pomalidomide (4 mg daily on days 1-21, orally) and low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally; 20 mg for patients aged > 75 years) in 28-day cycles until disease progression with a maximum treatment duration of 2 years. The primary endpoint is the overall response rate (ORR) assessed by the independent review committee per the 2016 International Myeloma Working Group guidelines. A total of 85 eligible patients were included in this study from 32 centers in China, with a median age of 62.0 (range, 39-76) years, a median prior line of therapy of 4 (range, 1-16), and 41.2% patients with high-risk cytogenetics. The ORR was 38.8% (95% confidence interval (CI), 28.44-50.01). The disease control rate was 67.1% (95% CI, 56.02-76.87), meanwhile, the median progression-free survival was 5.55 months (95% CI, 3.68-7.52). Among the treatment-related adverse events (TRAEs), infective pneumonia (17.6%) was the most frequent non-hematologic adverse event, while a decrease in neutrophil count (52.9%) was the most common grade ≥ 3 TRAE. The study results indicated that the generic pomalidomide demonstrated consistent efficacy and a safety profile similar to the branded pomalidomide when combined with low-dose dexamethasone in Chinese RRMM patients.Registration number ClinicalTrials.gov NCT05236621, retrospectively registered on February 11, 2022.

[Analysis and Prevention of Gene Mutation Types of Severe Thala- ssemia in Hakka People in Gannan of Jiangxi Province].

OBJECTIVE: To investigate the types and proportion of gene mutations of thalassemia in Hakka people in Gannan Area of Jiangxi, and to provide some references for prevention and treatment of thalassemia major, genetic counseling and epidemiological studies. METHODS: 81 cases Hakka patients with severe thalassemia admitted treated in First Affiliated Hospital of Gannan Medical College from January 2009 to June 2019 were enrolled. The deletion type of α-thalassemia was detected by Gap-PCR. The point mutations of α-thalassemia and ß-thalassemia were detected by PCR-RDB. The thalassemia gene was detected and analyzed in the patients with anemia, and the frequency of gene mutation was calculated. RESULTS: Among 81 Hakka patients with thalassemia major, 4 ß-thalassemia (homozygote) genotypes were detected out, including: CD41-42（TTCT）(19 cases), ß-IVS-II-654 (C→T) (9 cases), -28M (A→G) (1 case), CD17 (A→T) (1 case); 12 ß-thalassemithalassemia (heterozygote) genotypes were detected out, including: CD41-42(-TTCT)/ß-IVS-II-654(C→T) (15 cases, 29.41%), ß-IVS-II-654(C→T)/ß-28M(A→G) (13 cases，25.49%) ； CD41-42(-TTCT)/ß-28M(A→G) (9 cases，17.65%); ß-IVS-II-654(C→T) /CD27/28(+C) (3 cases， 5.88%) ； CD41-42(-TTCT)/CD27/28(+C)(3 case，5.88%)；ß-28M(A→G)/CD17(A→T) (2 cases，3.92%)；CD41-42(-TTCT)/CD17(A→T), CD41-42(-TTCT)/Βe, ß-IVS-II-654(C→T)/ß-29、ßCD17（A→T）/CD71-72(+a), ßCD71-72/ß-28M(A→G), ß-28M(A→G) /ß-IVS-II-654(C→T)(1 cases，1.96%). There were 3 cases of ß homozygous thalassemia with α-thalassemia gene and 5 cases of ß heterozygotes thalassemia with α-thalassemia gene. CONCLUSION: The incidence rate of thalassemia in Hakka people in Gannan Area of Jiangxi is relatively high. The distribution of gene mutation types is as follows: the genotype of CD41-42 (-TTCT) is the main genotype of ß-thalassemia (homozygous); the major genotypes of ß- thalassemia (heterozygotes) are CD41-42 (-TTCT)/ß-IVS-II-654 (C→T) and ß-IVS-II-654 (C→T) /ß-28M (A→G); CD41-42 (-TTCT) gene is dominant in ß-complex α-thalassemia.

Association between Psychological Factors and Condom Use with Regular and Nonregular Male Sexual Partners among Chinese MSM: A Quantitative Study Based on the Health Belief Model.

OBJECTIVE: The Chinese men who have sex with men (MSM) population is suffering from a high HIV infection rate owing to unprotected anal sex. The Health Belief Model (HBM) has been proven to be an effective frame associated with behavior maintenance. Based on HBM, we analyzed the beliefs associated with consistent condom use behavior with regular and nonregular partners among MSM to better provide targeted interventions and services. METHODS: A study was conducted in Sichuan Province, China, from November 2018 to April 2019, and 801 eligible participants were recruited by snowball sampling. Sociodemographic characteristics, AIDS-related characteristics, sexual behaviors, condom use behavior, and dimensions of HBM were investigated. Univariate, single multivariate, and summary multivariate models were employed to analyze the factors associated with consistent condom use. RESULTS: Of all participants, 39.1% and 53.6% had had anal sex with regular and nonregular partners in the last six months, respectively. Only 56.5% of them had used condoms consistently with regular partners, and only 60% of them had used condoms consistently with nonregular partners. When taking consistent condoms use with regular partners as the dependent variable, the dimensions of perceived threats (ORM = 1.28, 95% CI: 1.10, 1.49), perceived barriers (ORM = 0.70, 95% CI: 0.60, 0.82), self-efficacy (ORM = 1.23, 95% CI: 1.14, 1.32), and cues to action (ORM = 1.21, 95% CI: 1.02, 1.43) showed significant associations with the dependent variable. When taking consistent condoms use with nonregular partners as the dependent variable, the dimensions of perceived barriers (ORM = 0.77, 95% CI: 0.67, 0.89), self-efficacy (ORM = 1.22, 95% CI: 1.13, 1.32), and cues to action (ORM = 1.53, 95% CI: 1.30, 1.80) showed significant associations with the dependent variable. CONCLUSIONS: More attention should be focused on how to decrease the obstructive factors of condom use, how to improve the confidence of condom use, and how to layout more cues to action to promote consistent condom use behavior with regular and nonregular partners during anal sex among Chinese MSM.

The origin and spread of CRF85_BC, driven by heterosexual transmission among older people in Sichuan, China.

BACKGROUND: CRF_BC recombinants, including CRF07_BC and CRF08_BC, were considered the predominant subtypes in China. Since the discovery of HIV-1 circulating recombinant form CRF 85_BC in Southwest China in 2016, this BC recombinant forms had been reported in different regions of China. However, the history and magnitude of CRF85_BC transmission were still to be investigated. METHOD: We conducted the most recent molecular epidemiology of HIV-1 among newly reported HIV-1 infected patients in Sichuan in 2019 by sequencing and phylogenetic analysis of 1291 pol sequences. Then, we used maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of pol sequences to reconstruct the phylogeographic and demographic dynamics of the CRF85_BC. RESULTS: HIV-1 CRF85_BC (68/1291, 5.27%) became the fourth most prevalent strain revealing a significant increase in local population. CRF85_BC were only found in heterosexually infected individuals and the majority of CRF85_BC (95.45%) were circulating among the people living with HIV aged 50 years and over (PLHIV50+), suggesting a unique prevalent pattern. The founder lineages of CRF85_BC were likely to have first emerged in Yunnan, a province of Southwest China bordering Sichuan, in the early 2000s. It then spread exponentially to various places (including Guangxi, Sichuan, et al) and became endemic around 2008.6 (2006.7-2010.2) in Sichuan. CONCLUSION: Taken together, our findings on HIV-1 subtype CRF85_BC infections provided new insights into the spread of this virus and extended the understanding of the HIV epidemic in China.

[Effects of Different Routes in PMSC Transfusion on the Levels of Hematopoietic Regulatory Factors in Aplastic Anemia Rats].

OBJECTIVE: To investigate the effects of different routes in placental mesenchymal stem cells (PMSC) on serum expression levels of IL-4, IL-17, TNF-α and IFN-γ in aplastic anemia (AA) rats. METHODS: The rat model of aplastic anemia (AA rats) was established by 5-fluorouracil combined with busulfan. The rats was divided into four groups: control, experimental, PMSC-injected into the tail vein, and PMSC-injected into the medullary cavity. The general state of rats in each group was observed in detail before and after treatment. The serum levels of interleukin-4 (IL-4) , interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay (ELISA) at week 1, 3 and 5 after treatment. RESULTS: The serum levels of TNF-α, IFN-γ and IL-17 in the experimental group were significantly higher than those in the control group, while the level of IL-4 was significantly decreased (P＜0.05). The levels of TNF-α, IFN-γ and IL-17 gradually decreased after treatment while the level of IL-4 increased. By the fifth week, the above indexes were closed to the control group (P＞0.05), and the levels of TNF-α, IFN-γ and IL-17 in the group with PMSCs injected via the medullary cavity decrease more significantly than those group with PMSC injected via the tail vein, but level of IL-4 was not significantly different between two groups. CONCLUSION: The level of serum hematopoietic negative regulators increase significantly, and the level of hematopoietic promoting factors decreases significantly in aplastic anemia rats. PMSC can down-regulate the level of hematopoietic negative regulators and up-regulate the level of hematopoietic promoting factors in the rats with aplastic anemia, and the inhibition of hematopoietic negative regulators by intramedullary injection is more significant than that by caudal vein injection.

15-epi-lipoxin A4 inhibits TNF-α-induced tissue factor expression via the PI3K/AKT/ NF-κB axis in human umbilical vein endothelial cells.

Inflammation and coagulation are two important processes implicated in venous thromboembolism (VTE). 15-epi-lipoxin A4 (15-epi-LXA4) is the epimer of LXA4, a small lipid molecule, is known to play a key role in the resolution of inflammation. This study aimed to demonstrate whether 15-epi-LXA4 could suppress the inflammatory factor tumor necrosis factor-alpha (TNF-α)-induced upregulation of tissue factor (TF), an important regulator of the blood coagulation cascade, and evaluated the possible underlying mechanisms. We found that 15-epi-LXA4 not only reduced the up-regulation of mRNA and antigens, but also lowered the activity of TF (elevated by TNF-α) in primary culture of human umbilical vein endothelial cells (pc-HUVECs). In addition, 15-epi-LXA4 suppressed the activation of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, induced by TNF-α, in pc-HUVECs. 15-epi-LXA4 also inhibited the binding of NF-κB on the TF promoter, which is otherwise enhanced by TNF-α. The role of 15-epi-LXA4 in regulating TNF-α-induced effects was enhanced by the PI3K inhibitor and prevented by the PI3K activator. In conclusion, 15-epi-LXA4 lowered the TNF-α-induced high TF expression and activity by suppressing PI3K/AKT signaling activation, thereby reducing the binding capacity of NF-κB on the TF promoter in pc-HUVECs.

The impact of social factors on human immunodeficiency virus and hepatitis C virus co-infection in a minority region of Si-chuan, the People's Republic of China: a population-based survey and testing study.

BACKGROUND: While many human immunodeficiency virus (HIV) studies have been performed in Liangshan, most were focused only on HIV infection and based on a sampling survey. In order to fully understand HIV and hepatitis C virus (HCV) prevalence and related risk factors in this region, this study implemented in 2009, included a survey, physical examination, HIV and HCV test in two towns. METHODS: All residents in two towns of the Butuo county were provided a physical examination and blood tests for HIV and HCV, and then followed by an interview for questionnaire. RESULTS: In total, 10,104 residents (92.4%) were enrolled and 9,179 blood samples were collected for HIV and HCV testing, 6,072 were from individuals >14 years old. The rates of HIV, HCV, and HIV/HCV co-infection were 11.4%, 14.0%, and 7.7%, respectively for >14-year-old residents. The 25-34 yr age group had the highest prevalence of HIV, HCV, and HIV/HCV co-infections, reaching 24.4%, 26.2% and 16.0%, respectively. Overall, males had a much higher prevalence of all infections than females (HIV: 16.3% vs. 6.8%, HCV: 24.6% vs. 3.9%, HIV/HCV co-infected: 14.7% vs. 1.1%, respectively; P = 0.000). Approximately half of intravenous drug users tested positive for HIV (48.7%) and 68.4% tested positive for HCV. Logistic regression analysis showed that five factors were significantly associated with HIV and HCV infection: gender (odds ratio [OR]  = 5.8), education (OR = 2.29); occupation (student as reference; farmer: OR = 5.02, migrant worker: OR = 6.12); drug abuse (OR = 18.0); and multiple sexual partners (OR = 2.92). Knowledge of HIV was not associated with infection. CONCLUSION: HIV and HCV prevalence in the Liangshan region is very serious and drug use, multiple sexual partners, and low education levels were the three main risk factors. The government should focus on improving education and personal health awareness while enhancing drug control programs.

Risk factors for HIV/syphilis infection and male circumcision practices and preferences among men who have sex with men in China.

OBJECTIVE: To investigate factors associated with HIV infection and the frequency and willingness of male circumcision among men who have sex with men (MSM) in Chengdu city, China. METHODS: A cross-sectional survey provided information on participants' demographics, risk behaviors, circumcision, and uptake of HIV prevention services. RESULTS: Of 570 participants, 13.3% were infected with HIV and 15.9% with syphilis. An estimated 43.0% of respondents reported having unprotected receptive anal intercourse, and 58.9% reported having ≥2 male sexual partners in the past 6 months. Multivariable logistic regression revealed that syphilis, more male sex partners, predominantly receptive anal intercourse, and exclusively receptive male sex were associated with HIV infection. Higher level of education and peer education service were inversely associated with HIV infection. Nearly a fifth (18.0%) of participants were circumcised. More than half of uncircumcised participants expressed willingness to be circumcised. CONCLUSION: This study reveals a high prevalence of HIV and syphilis among MSM in Chengdu province of China. The frequency of unprotected receptive anal intercourse and multiple male sexual partnerships highlight the urgency for an effective comprehensive HIV prevention strategy. Although the willingness to accept male circumcision (MC) is high, further research is needed to assess the protective effective of MC among MSM.

Concurrent heroin use among methadone maintenance clients in China.

BACKGROUND: The study examined concurrent illicit heroin use among methadone maintenance clients in China and its association with clients' demographic characteristics, treatment experience, and personal social network. METHODS: Face-to-face surveys were conducted with 178 clients randomly recruited from six methadone maintenance treatment (MMT) clinics in Sichuan, China. Concurrent heroin use was measured based on self-report of heroin use during the past 30 days and a confirmatory urine morphine test. The participants' demographic characteristics and treatment factors were measured and examined. The drug use status of their family members and friends was also assessed. RESULTS: A total of 80 participants (44.9%) who either reported illicit heroin use in the past 30 days or had a positive urine test were defined as using heroin concurrently. Having drug-using friends was significantly associated with increased concurrent heroin use. Longer length of treatment (2 years or longer) was associated with increased concurrent heroin use. Among those who had both drug-using family members and friends, more women (71.4%) than men (50.0%) used heroin. For those who had no drug-using family members or friends, more men (34.8%) than women (20.8%) used heroin. DISCUSSION: Study findings indicate an urgent need to address concurrent illicit heroin use among MMT clients. Further examination of the influence of social networks on concurrent drug abuse behavior is encouraged. Results also highlight the importance of understanding gender differences in treatment seeking and behavioral changes, which is crucial to the development of gender-specific treatment strategies.

Motivational profiles of clients seeking methadone maintenance therapy in China.

OBJECTIVE: This study applied a stage-of-change model to examine the motivational profiles of clients seeking methadone maintenance therapy (MMT) in China. METHODS: Face-to-face interviews were conducted with a total of 179 clients from six MMT clinics. The University of Rhode Island Change Assessment (URICA) scale was used to measure the participants' motivation and readiness to change. Cluster analysis was performed to classify the sample into subgroups with respect to their change dimensions. RESULTS: The study sample was allocated into five distinct clusters: uninvolved, denial, pre-participation, ambivalent, and participation. Participants who were classified in the denial cluster were older than those in the pre-participation and participation clusters. A higher level of motivation to change was positively associated with continued heroin use and more severe drug problems. DISCUSSION: It would be beneficial to evaluate motivational profiles of individual clients in the treatment planning process and provide tailored interventions for sustained treatment retention and outcomes.

Prevalence and correlates of needle-sharing among new and long-term injection drug users in southwest China.

Three community-based surveys recruited 4,310 injection drug users (IDUs) in China from 2004 to 2006. Of the participants, 54.4% were ≤ 3-year new IDUs; 63.9% reported injecting more than two times daily; 31.5% shared needles in the last six months; 37.4% shared equipments in the last month; 30.2% reported their regular sex partners injected drugs; and 23.5% had commercial sex, with 52.2% reporting no condom use during last sex. The risky injection practices (sharing needles/equipments and high injection frequency) were less frequent among new IDUs, emphasizing that effective prevention needs to identify and intervene with IDUs early on. The study's limitations are noted.

[Sharing of needles and paraphernalia injection in new and long-term injection drug users in Sichuan, China].

OBJECTIVE: To examine the prevalence and correlates for needle-sharing among new and long-term injection drug users (IDUs) in Sichuan province, China. METHODS: Three consecutive cross-sectional surveys were conducted in 6 prefectures of Sichuan province, from 2003 to 2005. Questionnaire-based interviews provided information including socio-demographics, drug-use, sexual behaviors, and HIV-related services. Multivariable logistic regression methodology was used for data analysis. RESULTS: Of 3852 eligible participants, the rates of needle-sharing in the last 6 months for IDUs with a less than one year, one to three year, and more than three year injection history were 19.9%, 29.1%, and 36.3%, respectively. Needle-sharing for IDUs with a less than one-year injection history was independently associated with factors as: being female, having minority background, higher frequency of injection, sharing injecting equipments, ever having had a non-regular sex partner, or a regular sex partner who injected drugs, never had a test on HIV, being recruited in 2005, and from Zigong prefectures of Sichuan. Needle-sharing for IDUs with a 1-3 year injection history were independently associated with receiving less education, having higher frequency of injecting behavior, sharing injecting equipments, ever having had a non-regular sex partner/a regular sex partner who injected drugs, ever having had unprotected sex with a non-regular sex partner, ever having had unprotected sex with a commercial sex partner or client, never attended skill training for HIV/STD prevention, being recruited in 2005 and 2004, and being recruited from Deyang, Zigong, and Liangshan prefectures. Needle-sharing for IDUs with a more than three-year injection history was independently associated with factors as: less education, higher frequency of injecting, sharing injecting equipment, ever had a non-regular sex partner, ever had unprotected sex with a non-regular sex partner, ever had unprotected sex with a commercial sex partner or client, having had regular sex partners who inject drugs, never attended needle exchange programs, being recruited in 2005 and 2004, and being recruited from Deyang, Zigong, and Liangshan prefectures. CONCLUSION: The rates for both needle/paraphernalia sharing and unprotected sex behaviors were high in the IDUs in Sichuan province. These rates were higher among longer-term IDUs than in new IDUs. Our data underlined that better targeted, in-depth and sustained comprehensive intervention packages which including needle exchange, condom promotion along with distribution, and education, were urgently needed to reduce both IDU-related and sex-related risk behaviors among both new and longer term IDUs.