Inflammatory mediators and immune function in different stages of systemic lupus erythematosus.

This study aimed to study the relationship between the expression levels of inflammatory mediators IL-36ß and IL-36R and disease symptoms, laboratory indices and somatic immune function in Systemic Lupus Erythematosus (SLE) of different stages. In this research 70 patients with SLE who were treated in public hospitals from February 2020 to December 2021 were randomly divided into the stable group (n=35) and active group (n=35), and serum IL-36 was measured in the two groups ß and IL-36R concentration with the standard curve of Enzyme-Linked Immunosorbent Assay (ELISA) to analyze IL-36ß and IL-36R concentrations. 36ß and IL-36R concentrations were analyzed in relation to the Disease activity score of systemic lupus erythematosus (SLEDAI), disease duration, typical symptoms of SLE and experimental characteristics. Results showed that the differences in IL-36ß and IL-36R concentrations between the stable and active groups overall and for each disease duration group were tiny. There was no significant correlation between serum IL-36ß and IL-36R concentrations and SLEDAI scores in stable and active patients, and a negative correlation between them and disease duration. Serum inflammatory mediator IL-36R concentrations were significantly higher in patients with mucosal ulcers and the difference was statistically significant. differences in IL-36ß concentrations were statistically significant only for indicators of decreased erythrocyte count and IL-36R concentrations were statistically significant for indicators of decreased erythrocyte count, decreased haemoglobin and decreased lymphocytes The differences were huge and tiny in C4 decline, anti-dsDNA, and urinary routine protein. There was a significant positive correlation between IL-36ß and IL-36R concentrations in patients with stable and active SLE, with correlation coefficients of 0.448 and 0.452 respectively. The differences in IL-36ß and IL-36R concentrations between the stable and active groups were tiny for patients in the stable and active groups as a whole and for all disease groups. The differences in the number of each inflammatory mediator positive cells in the epidermal stratum corneum and superficial dermis between patients in the stable and active groups were tiny. In conclusion, IL-36ß and IL-36R proteins in SLE patients are expressed in immune cells as well as epithelial cells of patients, indicating that these two inflammatory mediators may be one of the early signals that activate the immune system of SLE patients and trigger the immune response of patients; the onset of SLE may be associated with the inflammatory response induced by IL-36ß and IL-36R.

Genome-wide associated variants of subclinical atherosclerosis among young people with HIV and gene-environment interactions.

BACKGROUND: Genome-wide association studies (GWAS) have identified some variants associated with subclinical atherosclerosis (SCA) in general population but lacking sufficient validation. Besides traditional risk factors, whether and how would genetic variants associate with SCA among people with HIV (PWH) remains to be elucidated. METHOD: A large original GWAS and gene-environment interaction analysis of SCA were conducted among Chinese PWH (n = 2850) and age/sex-matched HIV-negative controls (n = 5410). Subgroup analyses by age and functional annotations of variants were also performed. RESULTS: Different from HIV-negative counterparts, host genome had a greater impact on young PWH rather than the elders: one genome-wide significant variant (rs77741796, P = 2.20 × 10-9) and eight suggestively significant variants (P < 1 × 10-6) were identified to be specifically associated with SCA among PWH younger than 45 years. Seven genomic loci and 15 genes were mapped to play a potential role on SCA among young PWH, which were enriched in the biological processes of atrial cardiac muscle cell membrane repolarization and molecular function of protein kinase A subunit binding. Furthermore, genome-wide interaction analyses revealed significant HIV-gene interactions overall as well as gene-environment interactions with alcohol consumption, tobacco use and obesity among PWH. The identified gene-environment interaction on SCA among PWH might be useful for discovering high-risk individuals for the prevention of SCA, particularly among those with tobacco use and alcohol consumption. CONCLUSION: The present study provides new clues for the genetic contribution of SCA among young PWH and is the starting point of precision intervention targeting HIV-related atherosclerosis.

Low body mass index and efavirenz use are independently associated with self-reported fatigue in HIV-infected patients.

This retrospective cohort study was conducted from January 2009 to July 2016 to explore the occurrence and risk factors of self-reported fatigue within the first 6 months after receiving antiretroviral treatment (ART) among patients living with HIV in Taizhou City of Zhejiang province, Eastern China. In total, 1163 HIV-infected patients with a median follow-up duration of 27.8 months were included in the analysis. Among them, 261 (22.4%) reported fatigue within the first 6 months after ART. In the multivariable logistic regression analysis, self-reported fatigue within the first 6 months after ART was negatively associated with junior middle-school education or above, baseline CD4 cell count of 200-349 and >350 cells/µL (vs < 200 cells/µL), overweight at baseline (vs normal weight) but positively associated with ≥50 years old at initiation of ART (vs <30 years old), underweight at baseline, use of efavirenz (EFV) in the first-line regimen. Our data suggest that earlier initiation of ART and higher body mass index are preferred to restore the energy of HIV-infected patients with the EFV use in the era of ART in China.

A Network Pharmacology Approach Used to Estimate the Active Ingredients of Moutan Cortex Charcoal and the Potential Targets in Hemorrhagic Diseases.

Moutan Cortex charcoal has been used to ameliorate blood heat symptoms and treat pathologic hemorrhage down the ages. Although well known as an agent with the effect of astringency and hemostasis, its active ingredients and action mechanism remain unclear. In the present study, molecular docking technology was employed to screen the potential hemostatic compounds in Moutan Cortex charcoal and their target proteins. Protein-protein-interaction (PPI) analysis was performed to explain the functions and enrichment pathways of the target proteins. The results showed that a total of 25 compounds were estimated as active constituents targeting multiple proteins related to hemostatic diseases, including 5 proteins (SERPINC1, FVIII, FX, FII and FXII) that were considered as the key targets. Then the drug-target (D-T) network was constructed to analyze the underlying hemostatic mechanism of Moutan Cortex charcoal, followed by a hierarchical cluster analysis (HCA) for compounds clustering, and a coagulation screening test for compound verification on their coagulation activities, with the results indicating that M15 (5-Tetradecenoic acid) and M31 (1-Monolinolein) might be the key compounds contributing to the hemostasis effect of Moutan Cortex charcoal by involving in the pathways related to complement, coagulation cascades and the platelet activation, particularly by activating FVIII, FX, FII and FXII and inhibiting SERPINC1. This study has demonstrated that Moutan Cortex charcoal may work as a hemostatic through the interaction between multiple-compounds and multiple-proteins, which provides the basis for further researches on the hemostasis mechanism of Moutan Cortex charcoal.

Seroprevalence of Kaposi's sarcoma-associated herpesvirus among HIV-infected Uygurs in Xinjiang, China.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), which primarily affects human immunodeficiency virus (HIV)-infected adults with advanced immunodeficiency. Xinjiang province in China is an endemic area for Kaposi's sarcoma (KS), however, currently, only limited data for KSHV infection among HIV-infected individuals living in this endemic area is available. A cross-sectional study of 86 HIV positive participants was conducted in Xinjiang, China from 2014 through 2015. Plasma samples were collected and screened for KSHV and HIV infection. HIV pol gene and KSHV ORF-K1 gene were amplified and sequenced, genotypes were determined by phylogenetic analysis. Over all, prevalence was 48.9% (42/86; 95%CI 38.4-59.3%) for KSHV. Only CRF07_BC subtype has been identified among all these HIV positive individuals, while the subtype A and C of KSHV were detected in the participants. Meanwhile, we found that those with high CD4 counts (>500) showed a lower anti-KSHV titer, compared with other groups. Our study indicated a high prevalence of KSHV among HIV positive individuals in Xinjiang, China. Thus, management of HIV/AIDS patients should include KSHV screen and should consider the risk of KSHV-associated malignancies.

Quality assessment of crude and processed Arecae semen based on colorimeter and HPLC combined with chemometrics methods.

Raw Arecae Semen, the seed of Areca catechu L., as well as Arecae Semen Tostum and Arecae semen carbonisata are traditionally processed by stir-baking for subsequent use in a variety of clinical applications. These three Arecae semen types, important Chinese herbal drugs, have been used in China and other Asian countries for thousands of years. In this study, the sensory technologies of a colorimeter and sensitive validated high-performance liquid chromatography with diode array detection were employed to discriminate raw Arecae semen and its processed drugs. The color parameters of the samples were determined by a colorimeter instrument CR-410. Moreover, the fingerprints of the four alkaloids of arecaidine, guvacine, arecoline and guvacoline were surveyed by high-performance liquid chromatography. Subsequently, Student's t test, the analysis of variance, fingerprint similarity analysis, hierarchical cluster analysis, principal component analysis, factor analysis and Pearson's correlation test were performed for final data analysis. The results obtained demonstrated a significant color change characteristic for components in raw Arecae semen and its processed drugs. Crude and processed Arecae semen could be determined based on colorimetry and high-performance liquid chromatography with a diode array detector coupled with chemometrics methods for a comprehensive quality evaluation.

[Multicomponent Content Difference Among Different Processing Degrees of Moutan Cortex Charcoal].

Objective: To establish a method of simultaneously determining gallic acid,5-HMF,catechin and paeonol in the different processing degrees of Moutan Cortex charcoal by HPLC,and to compare the difference. Methods: The HPLC separation was carried out on a UltimateTMXB-C18column( 250 mm × 4. 6 mm,5 µm) with a mobile phase of acetonitrile and water containing 0. 5% formic acid. The flow rate was 1. 0 m L / min at 30 ℃ column temperature,and the detection wavelength was 245 nm. Results: The contents of gallic acid and 5-HMF were increased with the extension of processing time,but declined when it reached to a certain extent. And the contents of catechin and paeonol were decreased in the heating process. Conclusion: The differences of compounds content in different processing degree of Moutan Cortex charcoal were greatly. It provides a scientific basis for quality standard of Moutan Cortex charcoal.

Case report: A germline CHEK1 c.613 + 2T>C leads to a splicing error in a family with multiple cancer patients.

Background: Genome instability plays a crucial role in promoting tumor development. Germline mutations in genes responsible for DNA repair are often associated with familial cancer syndromes. A noticeable exception is the CHEK1 gene. Despite its well-established role in homologous recombination, germline mutations in CHEK1 are rarely reported. Case presentation: In this report, we present a patient diagnosed with ovarian clear cell carcinoma who has a family history of cancer. Her relatives include a grandfather with esophageal cancer, a father with gastric cancer, and an uncle with a brain tumor. The patient carried a typical genomic profile of clear cell carcinoma including mutations in KRAS, PPP2R1A, and PIK3R1. Importantly, her paired peripheral blood cells harbored a germline CHEK1 mutation, CHEK1 exon 6 c.613 + 2T>C, which was also found in her father. Unfortunately, the CHEK1 status of her grandfather and uncle remains unknown due to the unavailability of their specimens. Further evaluation via RT-PCR confirmed a splicing error in the CHEK1 gene, resulting in truncation at the kinase domain region, indicative of a loss-of-function mutation. Conclusion: This case highlights a rare germline CHEK1 mutation within a family with a history of cancer. The confirmed splicing error at the mRNA level underscores the functional consequences of this mutation. Documenting such cases is vital for future evaluation of inheritance patterns, clinical penetrance of the mutation, and its association with specific cancer types.

Behavioral and molecular tracing of risky sexual contacts in a sample of Chinese HIV-infected men who have sex with men.

Contact tracing, coupled with molecular epidemiologic investigation, is especially useful for identifying an infection with few cases in the population, such as human immunodeficiency virus (HIV) infection in China. No such research is available on Chinese men who have sex with men (MSM). From 2008 to 2010 in Taizhou Prefecture in China, every newly diagnosed HIV-infected MSM was invited to participate as an "index case" in a contact tracing survey by providing contact information for up to 8 sexual contacts, who themselves were approached to receive voluntary HIV counseling and testing. Those who tested HIV-positive were then subjected to another contact tracing survey. This process was repeated until no more sexual contacts were reported or tested positive. A total of 100 HIV-infected MSM served as "index cases," including the initial 49 cases identified through routine surveillance programs and 51 cases from the present survey. Traced MSM exhibited little willingness to receive voluntary counseling and testing. CRF01_AE (HIV type 1) was the dominant subtype. Seven of 49 independent sexual networks were deemed HIV transmission clusters. Fear of stigma or discrimination may deter Chinese MSM from receiving voluntary counseling and testing. Nonetheless, the integration of behavioral network analysis and HIV phylogenetic analysis provides enhanced evidence for developing tailored prevention strategies for HIV-infected MSM.

[Ki-67 expression and significance of different molecular subtypes of breast invasive ductal carcinoma].

OBJECTIVE: To analyze Ki-67 expression and explore its significance in different molecular subtypes of breast invasive ductal carcinoma (IDC). METHODS: The expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) and Ki-67 were detected in 126 cases of IDC by immunohistochemical staining. Then the molecular subtype of each case of IDC was determined.Statistical analysis was performed to determine the relationship between Ki-67 expression and the molecular subtypes with clinicopathological features of IDC. RESULTS: There was no statistically significant difference of Ki-67 expression in age and tumor size (P > 0.05).However, significant difference existed in histological grading and lymph node metastasis (P < 0.05). The expression level of Ki-67 was negatively correlated with ER expression (r = -0.273, P = 0.002) and PR expression (r = -0.242, P = 0.007) and positively with HER-2 expression (r = 0.245, P = 0.006) . A low expression of Ki-67 was in LumianlA subtype (17/17) and high expression in other molecular subtypes. Moreover, the rate of high expression (Ki-67 LI>50%) in each subtype progressively increased with the degree of molecular typing and Ki-67 expression in different molecular subtypes showed significant difference (P < 0.05). CONCLUSIONS: The expression level of Ki-67 is correlated with histological grading and molecular type of IDC. High expression of Ki-67 carries poor prognosis. Thus it is necessary to perform a variety of routine clinicopathological examinations, such as Ki-67, ER, PR and HER-2.

Differential genome-wide associated variants and enriched pathways of ECG parameters among people with versus without HIV.

OBJECTIVES: People with HIV (PWH) are more likely to develop ECG abnormalities. Substantial evidence exists for genetic contribution to ECG parameters among general population. However, whether and how would host genome associate with ECG parameters among PWH is unclear. Our research aims to analyze and compare genetic variants, mapped genes, and enriched pathways of ECG parameters among PWH and HIV-negative controls. DESIGN: A cross-sectional study. METHOD: We performed a large original genome-wide association study (GWAS) of ECG parameters among PWH ( n  = 1730) and HIV-negative controls ( n =  3746). Genome-wide interaction analyses were also conducted. RESULTS: A total of 18 novel variants were detected among PWH, six for PR interval including rs76345397 at ATL2 , 11 for QRS duration including rs10483994 at KCNK10 and rs2478830 at JCAD , and one for QTc interval (rs9815364). Among HIV-negative controls, we identified variants located at previously reported ECG-related genes ( SCN5A , CNOT1 ). Genetic variants had a significant interaction with HIV infection ( P  < 5 × 10 -8 ), implying that HIV infection and host genome might jointly influence ECG parameters. Mapped genes for PR interval and QRS duration among PWH were enriched in the biological process of viral genome replication and host response to virus, respectively, whereas enriched pathways for PR interval among HIV-negative controls were in the cellular component of voltage-gated sodium channel complex. CONCLUSION: The present GWAS indicated a distinctive impact of host genome on quantitative ECG parameters among PWH. Different from HIV-negative controls, host genome might influence the cardiac electrical activity by interfering with HIV viral infection, production, and latency among PWH.

PBX1-promoted SFRP4 transcription inhibits cell proliferation and epithelial-mesenchymal transition in endometrial carcinoma.

OBJECTIVE: To explore the effects and mechanisms of action of the PBX1/secreted frizzled-related protein 4 (SFRP4) axis in endometrial carcinoma (EC). METHODS: The expression of PBX1 and SFRP4 was analyzed using bioinformatics prediction, followed by validation in EC cells using quantitative reverse transcription-polymerase chain reaction and western blotting. After transduction with overexpression vectors for PBX1 and SFRP4, migration, proliferation, and invasion of EC cells were measured, accompanied by the detection of E-cadherin, Snail, N-cadherin, Vimentin, ß-catenin, GSK-3ß, and C-myc expression. The association between PBX1 and SFRP4 was validated using dual luciferase reporter gene and chromatin immunoprecipitation assays. RESULTS: PBX1 and SFRP4 were downregulated in EC cells. Overexpression of PBX1 or SFRP4 resulted in weakened cell proliferation, migration, and invasion, as well as decreased expression of Snail, N-cadherin, Vimentin, ß-catenin, GSK-3ß, and C-myc and increased expression of E-cadherin. PBX1 bound to the SFRP4 promoter and promoted its transcription. Knockdown of SFRP4 reversed the repression of overexpressed PBX1 in the malignant phenotypes and EMT of EC cells, and PBX1 repressed Wnt/ß-catenin pathway activation by upregulating SFRP4 transcription. CONCLUSION: PBX1 inhibited activation of the Wnt/ß-catenin pathway by promoting SFRP4 transcription, thereby suppressing malignant phenotypes in EC cells and the EMT process.

Discrimination and chemical composition quantitative model of Raw Moutan Cortex and Moutan Cortex Carbon based on electronic nose and machine learning.

Raw Moutan Cortex (RMC) is a traditional medicinal material commonly used in China. Moutan Cortex Carbon (MCC) is a processed product of RMC by stir-frying. As raw and processed products of the same Chinese herb pieces, they have different effects. RMC has the effects of clearing heat and cooling blood, promoting blood circulation and removing blood stasis, but MCC has the contrary effect of cooling blood and hemostasis. Therefore, it is necessary to distinguish them effectively. The traditional quality evaluation method of RMC and MCC still adopts character identification, and mainly relies on the working experience and sensory judgment of employees with experience. This will lead to strong subjectivity and poor repeatability. And the final evaluation result may cause inevitable errors and the processed products with different processing degrees in actual production, which affects the clinical efficacy. In this study, the electronic nose technology was introduced to objectively digitize the odor of RMC and MCC. And the discrimination model of RMC and MCC was constructed in order to establish a rapid, objective and stable quality evaluation method of RMC and MCC. According to the correlation analysis, the experiment found the content of gallic acid, 5-hydroxymethylfurfural (5-HMF), paeoniflorin and paeonol determined by high performance liquid chromatography (HPLC) had a certain correlation with their odor characteristics. Thus, partial least squares regression (PLSR) and support vector machine regression (SVR) were compared and established the chemical composition quantitative model. Results showed that the quantitative data of RMC and MCC odor could be used to predict the contents of the chemical components. It can be used for quality control of RCM and MCC.

Gliosarcoma with osteosarcomatous component: A case report and short review illustration.

BACKGROUND: Gliosarcoma (GS) represents a rare variant of glioblastoma in the central nervous system, characterized by biphasic histopathological features of gliomatous and sarcomatous components. Here, we present an unusual case of GS, which also demonstrated osteosarcomatous differentiation. CASE PRESENTATION: A 65-year-old female patient underwent gross total resection (GTR) of the right temporal lobe lesion. Subsequently received 60 Gy external beam radiation therapy and chemotherapy. Postoperative histopathological analysis indicated that the sarcomatous portion of the typical fibrosarcoma pattern mingled with areas of osteoid structure. The molecular pathological analysis demonstrated IDH1/2 wild-type and MGMT promoter island methylated phenotype. Target Enrichment Sequencing (TES) was performed on the gliomatous and sarcomatous components of the tumor tissues. TERT promoter, RB1, NF1, TP53 mutations and copy number variations (CNVs) on chromosome 7, 10q, 11q, 12, 13, 17 and 22 were observed in gliomatous and fibro-sarcomatous mixed tumor tissue; While we found TERT promoter, RB1, TP53 mutations and CNVs on chromosome 2q, 3q, 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 19 and 22 in osteosarcomatous component. Noteworthy, EGFR amplification was not observed in both gliomatous/fibro-sarcomatous and osteosarcomatous components. CONCLUSIONS: Integrated with histopathology, molecular pathology, and genomic alteration analysis, we report a case of GS with an extremely rare histopathologic phenotype of osteosarcomatous differentiation, who also suffered lung multi-metastases. Additionally, synthesizing the literature review, our study of this unusual differentiation of GS into osteosarcoma may provide novel insight into the natural history of GS.

Case Report: A novel LHFPL3::NTRK2 fusion in dysembryoplastic neuroepithelial tumor.

Neurotrophic tyrosine receptor kinase (NTRK) rearrangements are oncogenic drivers of various types of adult and pediatric tumors, including gliomas. However, NTRK rearrangements are extremely rare in glioneuronal tumors. Here, we report a novel NTRK2 rearrangement in a 24-year-old female with dysembryoplastic neuroepithelial tumor (DNT), a circumscribed WHO grade I benign tumor associated with epilepsy. By utilizing targeted RNA next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), reverse transcriptase PCR (RT-PCR), and Sanger sequencing, we verified an in-frame fusion between NTRK2 and the lipoma HMGIC fusion partner-like 3 (LHFPL3). This oncogenic gene rearrangement involves 5' LHFPL3 and 3' NTRK2, retaining the entire tyrosine kinase domain of NTRK2 genes. Moreover, the targeted DNA NGS analysis revealed an IDH1 (p.R132H) mutation, a surprising finding in this type of tumor. The pathogenic mechanism of the LHFPL3::NTRK2 in this case likely involves aberrant dimerization and constitutive activation of RTK signaling pathways.

Rapid measurement of total polyphenol content in tea by kinetic matching approach on microfluidic paper-based analytical devices.

In this work, a facile kinetic matching approach for total polyphenol content (TPC) measurement was developed based on the adoption of microfluidic paper-based analytical devices with symmetric channel distribution. A set of Folin-Ciocalteu reactions performed on the same paper chip were activated all at the same time through synchronized filling of sodium carbonate solution among individual channels. Gallic acid was found valid as a standard compound for kinetic matching measurement of tea samples. TPC of tea infusions was successfully measured within ten minutes without any complexed time control procedure needed. Under the optimized conditions, the new developed method showed good linearity in the TPC range of 10-100 mg/L (r > 0.9955) and the inter-chip precision was 5.6% (n = 11). The results measured with the new developed approach were in good agreement with those with the conventional FC assay.

Baseline Characteristics of Mitochondrial DNA and Mutations Associated With Short-Term Posttreatment CD4+T-Cell Recovery in Chinese People With HIV.

Background: Mitochondrial DNA (mtDNA) profiles and contributions of mtDNA variants to CD4+T-cell recovery in Euramerican people living with HIV (PLWH) may not be transferred to East-Asian PLWH, highlighting the need to consider more regional studies. We aimed to identify mtDNA characteristics and mutations that explain the variability of short-term CD4+T-cell recovery in East-Asian PLWH. Method: Eight hundred fifty-six newly reported antiretroviral therapy (ART)-naïve Chinese PLWH from the Comparative HIV and Aging Research in Taizhou (CHART) cohort (Zhejiang Province, Eastern China) were enrolled. MtDNA was extracted from peripheral whole blood of those PLWH at HIV diagnosis, amplified, and sequenced using polymerase chain reaction and gene array. Characterization metrics such as mutational diversity and momentum were developed to delineate baseline mtDNA mutational patterns in ART-naïve PLWH. The associations between mtDNA genome-wide single nucleotide variants and CD4+T-cell recovery after short-term (within ~48 weeks) ART in 724 PLWH were examined using bootstrapping median regressions. Results: Of 856 participants, 74.18% and 25.82% were male and female, respectively. The median age was 37 years; 94.51% were of the major Han ethnicity, and 69.04% and 28.62% were of the heterosexual and homosexual transmission, respectively. We identified 2,352 types of mtDNA mutations and mtDNA regions D-loop, ND5, CYB, or RNR1 with highest mutational diversity or volume. Female PLWH rather than male PLWH at the baseline showed remarkable age-related uptrends of momentum and mutational diversity as well as correlations between CD4+T <200 (cells/µl) and age-related uptrends of mutational diversity in many mtDNA regions. After adjustments of important sociodemographic and clinical variables, m.1005T>C, m.1824T>C, m.3394T>C, m.4491G>A, m.7828A>G, m.9814T>C, m.10586G>A, m.12338T>C, m.13708G>A, and m.14308T>C (at the Bonferroni-corrected significance) were negatively associated with short-term CD4+T-cell recovery whereas m.93A>G, m.15218A>G, and m.16399A>G were positively associated with short-term CD4+T-cell recovery. Conclusion: Our baseline mtDNA characterization stresses the attention to East-Asian female PLWH at risk of CD4+T-cell loss-related aging and noncommunicable chronic diseases. Furthermore, mtDNA variants identified in regression analyses account for heterogeneity in short-term CD4+T-cell recovery of East-Asian PLWH. These results may help individualize the East-Asian immune recovery strategies under complicated HIV management caused by CD4+T-cell loss.

Pharmacokinetic-pharmacodynamic modeling for Moutan Cortex/Moutan Cortex charcoal and the contributions of the chemical component using support vector regression with particle swarm optimization.

Moutan Cortex (MC) and Moutan Cortex charcoal (MCC) are two kinds of Chinese medicinal materials widely used in traditional Chinese medicine (TCM) with opposite drug efficacy. And the contributions of the chemical component to the drug efficacy are still not clear. In our study, a support vector regression (SVR) model with particle swarm optimization (PSO) has been developed for simultaneously characterizing the pharmacokinetics (PK) and pharmacodynamics (PD) of MC/MCC. Then the contributions of the chemical component to the drug efficacy of MC/MCC are calculated by the weight analysis of SVR. The experimental results show that the effective substances found by the PSO-SVR model in MC and MCC are consistent with TCM theory. And the PSO-SVR model is a better model for PK-PD compared with the back-propagation neural network (BPNN). In conclusion, the PSO-SVR is a valuable tool that linked PK and PD profiles of MC/MCC with multiple components and identified the contributions of multiple therapeutic materials to the drug efficacy.

Correction: Pharmacokinetic-pharmacodynamic modeling for Moutan Cortex/Moutan Cortex charcoal and the contributions of the chemical component using support vector regression with particle swarm optimization.

[This corrects the article DOI: 10.1039/D0RA04111D.].

LncRNA MEG3 inhibits the development of nasopharyngeal carcinoma by sponging miR-543 targeting KLF4.

BACKGROUND: Emerging evidence shows that long non-coding RNAs (lncRNAs) play a crucial role in tumor development by regulating biological behavior in various cancer cells. Several lncRNAs act as miRNA sponges by binding miRNA sequences and thus regulating mRNA expression. The lncRNA maternally expressed gene 3 (MEG3) has decreased expression levels in many cancer cells and acts as a tumor suppressor in different cancers. MEG3 also showed decreased expression in nasopharyngeal carcinoma (NPC) and plays a role in tumor suppression; however, the detailed mechanism of tumor suppression in NPC cells has not been reported. This paper aimed to explore the function and molecular mechanisms of MEG3 in the development of NPC. METHODS: MEG3 and miR-543 levels in NPC cells were detected by quantitative real-time PCR (qRT-PCR). The regulatory role of MEG3 in NPC cells was examined using knockdown and overexpression of MEG3 in C666-1 cells. Cell proliferation was analyzed by the cell counting kit-8 (CCK-8) assay, cell migration and invasion capacities were evaluated using Transwell assay, and cell apoptosis was assessed using flow cytometry. The relationship between MEG3 and miR-543 was investigated by luciferase reporter assay. MEG3- and Krüppel like factor 4 (KLF4)-mediated changes in NPC cell proliferation and apoptosis were analyzed, and KLF4, Bcl-2 and Bax protein expression levels were measured by western blotting. RESULTS: The results showed that MEG3 was decreased and miR-543 was increased in NPC cell lines, and upregulated MEG3 inhibited cell proliferation, migration, and invasion and promoted apoptosis, suggesting that MEG3 acts as a tumor suppressor in NPC cells. Furthermore, a luciferase reporter assay and western blotting indicated that MEG3 regulated KLF4 expression by sponging miR-543. Functionally, overexpression of MEG3 suppressed cell proliferation, promoted cell apoptosis and affected Bcl-2 and Bax protein levels via regulation of KLF4 expression mediated by sponging miR-543. CONCLUSIONS: These findings show that lncRNA MEG3 inhibits the development of NPC by sponging miR-543 targeting KLF4 and that MEG3 can serve as a new novel target for NPC therapeutics.