Detection of folate receptor-positive circulating tumor cells as a biomarker for diagnosis, prognostication, and therapeutic monitoring in breast cancer.

OBJECTIVES: This study is to explore the clinical significance of folate receptor-positive circulating tumor cells (FR+ CTC) in the early diagnosis and disease progress in patients with breast cancer. METHODS: Folate receptor-positive circulating tumor cells was enriched from peripheral blood of the patients with immunomagnetic separation method and quantitated by folate receptor on the CTC with the ligand-targeted PCR. RESULTS: The levels of FR+ CTC were significantly higher in breast cancer patients compared with healthy controls. Detective rate of FR+ CTC was decreased in 19 of 27 patients underwent the surgery in 2 weeks post-operation compared with pre-operation; statistical analysis showed the difference was significant. We also found that the combination of FR+ CTC, CEA, CA125, and CA153 can significantly improve the diagnostic efficiency for breast cancer. CONCLUSIONS: This study showed the detective rate of FR+ CTC is significantly increased in the patients with breast cancer, and the detective level is associated with disease progress.

Cell-free fetal DNA testing and its correlation with prenatal indications.

BACKGROUND: The prenatal test of cell-free fetal DNA (cffDNA) is also known as noninvasive prenatal testing (NIPT) with high sensitivity and specificity. This study is to evaluate the performance of NIPT and its clinical relevance with various clinical indications. METHODS: A retrospective analysis was conducted on 14,316 pregnant women with prenatal indications, including advanced maternal age (≥35 years), maternal serum screening abnormalities, the thickened nuchal translucency (≥2.5 mm) and other ultrasound abnormalities, twin pregnancy/IVF-ET pregnancy, etc. The whole-genome sequencing (WGS) of maternal plasma cffDNA was employed in this study. RESULTS: A total of 189 (1.32%) positive NIPT cases were identified, and 113/189 (59.79%)cases were confirmed by invasive prenatal testing. Abnormal serological screening (53.14%) was the most common indication, followed by elderly pregnancy (23.02%). The positive prediction value for T21, T18, T13, sex chromosome abnormalities, other autosomal aneuploidy abnormalities, and CNV abnormalities were 91.84, 68.75,37.50, 66.67, 14.29, and 6.45%, respectively. The positive rate and the true positive rate of nuchal translucency (NT) thickening were the highest (4.17 and 3.33%), followed by the voluntary requirement group (3.49 and 1.90%) in the various prenatal screening indications. The cffDNA concentration was linearly correlated with gestational age (≥10 weeks) and the positive NIPT group's Z-score values. CONCLUSIONS: whole-genome sequencing of cffDNA has extremely high sensitivity and specificity for T21, high sensitivity for T18, sex chromosome abnormalities, and T13. It also provides evidence for other abnormal chromosomal karyotypes (CNV and non-21/18/13 autosomal aneuploidy abnormalities). The cffDNA concentration is closely related to the gestational age and determines the specificity of NIPT. Our results highlight NIPT's clinical significance, which is an effective prenatal screening tool for high-quality care of pregnancy.

Chronological Changes of Viral Shedding in Adult Inpatients With COVID-19 in Wuhan, China.

BACKGROUND: In December 2019, the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan. Epidemiological and clinical characteristics of patients with COVID-19 have been reported, but the relationships between laboratory features and viral load has not been comprehensively described. METHODS: Adult inpatients (≥18 years old) with COVID-19 who underwent multiple (≥5 times) nucleic acid tests with nasal and pharyngeal swabs were recruited from Renmin Hospital of Wuhan University, including general patients (n = 70), severe patients (n = 195), and critical patients (n = 43). Laboratory data, demographic data, and clinical data were extracted from electronic medical records. The fitted polynomial curve was used to explore the association between serial viral loads and illness severity. RESULTS: Viral load of SARS-CoV-2 peaked within the first few days (2-4 days) after admission, then decreased rapidly along with virus rebound under treatment. Critical patients had the highest viral loads, in contrast to the general patients showing the lowest viral loads. The viral loads were higher in sputum compared with nasal and pharyngeal swab (P = .026). The positive rate of respiratory tract samples was significantly higher than that of gastrointestinal tract samples (P < .001). The SARS-CoV-2 viral load was negatively correlated with portion parameters of blood routine and lymphocyte subsets and was positively associated with laboratory features of cardiovascular system. CONCLUSIONS: The serial viral loads of patients revealed whole viral shedding during hospitalization and the resurgence of virus during the treatment, which could be used for early warning of illness severity, thus improve antiviral interventions.

Nanopore Targeted Sequencing for the Accurate and Comprehensive Detection of SARS-CoV-2 and Other Respiratory Viruses.

The ongoing global novel coronavirus pneumonia COVID-19 outbreak has engendered numerous cases of infection and death. COVID-19 diagnosis relies upon nucleic acid detection; however, currently recommended methods exhibit high false-negative rates and are unable to identify other respiratory virus infections, thereby resulting in patient misdiagnosis and impeding epidemic containment. Combining the advantages of targeted amplification and long-read, real-time nanopore sequencing, herein, nanopore targeted sequencing (NTS) is developed to detect SARS-CoV-2 and other respiratory viruses simultaneously within 6-10 h, with a limit of detection of ten standard plasmid copies per reaction. Compared with its specificity for five common respiratory viruses, the specificity of NTS for SARS-CoV-2 reaches 100%. Parallel testing with approved real-time reverse transcription-polymerase chain reaction kits for SARS-CoV-2 and NTS using 61 nucleic acid samples from suspected COVID-19 cases show that NTS identifies more infected patients (22/61) as positive, while also effectively monitoring for mutated nucleic acid sequences, categorizing types of SARS-CoV-2, and detecting other respiratory viruses in the test sample. NTS is thus suitable for COVID-19 diagnosis; moreover, this platform can be further extended for diagnosing other viruses and pathogens.

Necessity for detection of SARS-CoV-2 RNA in multiple types of specimens for the discharge of the patients with COVID-19.

BACKGROUND: The SARS-CoV-2 RNA was detected positive again after discharged from hospital in some COVID-19 patients, with or without clinical symptoms such as fever or dry cough. METHODS: 1008 severe COVID-19 patients, with SARS-CoV-2 RNA positive detected with the mixed specimen of nasopharyngeal swab and oropharyngeal swab by real-time fluorescence quantitative PCR (RT-qPCR), were selected to monitor SARS-CoV-2 RNA with the 12 types of specimens by RT-qPCR during hospitalization. All of 20 discharged cases with COVID-19 were selected to detect SARS-CoV-2 RNA in isolation period with 7 types of specimens by RT-qPCR before releasing the isolation period. RESULTS: Of the enrolled 1008 severe patients, the nasopharyngeal swab specimens showed the highest positive rate of SARS-CoV-2 RNA (71.06%), followed by alveolar lavage fluid (66.67%), oropharyngeal swab (30.77%), sputum (28.53%), urine (16.30%), blood (12.5%), stool (12.21%), anal swab (11.22%) and corneal secretion (2.99%), and SARS-CoV-2 RNA couldn't be detected in other types of specimen in this study. Of the 20 discharged cases during the isolation period, the positive rate of SARS-CoV-2 RNA was 30% (6/20): 2 cases were positive in sputum at the eighth and ninth day after discharge, respectively, 1 case was positive in nasopharynx swab at the sixth day after discharge, 1 case was positive in anal swab at the eighth day after discharge, and 1 case was positive in 3 specimens (nasopharynx swab, oropharynx swab and sputum) simultaneously at the fourth day after discharge, and no positive SARS-CoV-2 RNA was detected in other specimens including stool, urine and blood at the discharged patients. CONCLUSIONS: SARS-CoV-2 RNA should be detected in multiple specimens, such as nasopharynx swab, oropharynx swab, sputum, and if necessary, stool and anal swab specimens should be performed simultaneously at discharge when the patients were considered for clinical cure and before releasing the isolation period.

A novel G6PD deleterious variant identified in three families with severe glucose-6-phosphate dehydrogenase deficiency.

BACKGROUND: Glucose-6-phosphate dehydrogenase deficiency (D-G6PD) is an X-linked recessive disorder resulted from deleterious variants in the housekeeping gene Glucose-6-phosphate 1-dehydrogenase (G6PD), causing impaired response to oxidizing agents. Screening for new variations of the gene helps with early diagnosis of D-G6PD resulting in a reduction of disease related complications and ultimately increased life expectancy of the patients. METHODS: One thousand five hundred sixty-five infants with pathological jaundice were screened for G6PD variants by Sanger sequencing all of the 13 exons, and the junctions of exons and introns of the G6PD gene. RESULTS: We detected G6PD variants in 439 (28.1%) of the 1565 infants with pathological jaundice. In total, 9 types of G6PD variants were identified in our cohort; and a novel G6PD missense variant c.1118 T > C, p.Phe373Ser in exon 9 of the G6PD gene was detected in three families. Infants with this novel variant showed decreased activity of G6PD, severe anemia, and pathological jaundice, consistent with Class I G6PD deleterious variants. Analysis of the resulting protein's structure revealed this novel variant affects G6PD protein stability, which could be responsible for the pathogenesis of D-G6PD in these patients. CONCLUSIONS: High rates of G6PD variants were detected in infants with pathological jaundice, and a novel Class I G6PD deleterious variants was identified in our cohort. Our data reveal that variant analysis is helpful for the diagnosis of D-G6PD in patients, and also for the expansion of the spectrum of known G6PD variants used for carrier detection and prenatal diagnosis.

A Novel CNGA1 Gene Mutation (c.G622A) of Autosomal Recessive Retinitis Pigmentosa Leads to the CNGA1 Protein Reduction on Membrane.

CNGA1 encodes a membrane protein on rod photoreceptor related to phototransduction. The present study was to identify a novel mutation of CNGA1 associated with autosomal recessive retinitis pigmentosa by using next generation sequencing of a Chinese family. Next generation sequencing and Sanger sequencing has identified a compound heterozygous mutation in CNGA1 gene, c0.472 del C (reported) and c0.829G>A (novel mutation, same as c0.622G>A according to NM_000087.3) of the proband. SIFT and Polyphen-2 predicted the CNGA1 G622A site to be possibly deleterious. Evolutionary conservation analysis of amino acid residues showed this aspartic acid is highly conserved between species, and protein structure prediction by I-TASSER server indicated that the D208N mutation induced a large disappear of interactions between S2 and S4. Flag-tagged CNGA1 and mutant G622A cDNA were generated and inserted into pCIG-eGFP vectors. Transfection of human embryonic kidney 293T cells was performed with lipofectamine. Interestingly, western blot and immunofluorescence results indicated that the expression of mutant CNGA1 (D208N) decreased significantly, especially on the membrane of transfected HEK293T cells. The novel variant c0.622G>A (p. D208N) in this study enriched the CNGA1 mutation spectrum. Besides, this mutant was predicted "possibly damaging" due to bioinformatics analysis and validated by laboratorial experiments. Our study suggests that this mutation lead to the CNGA1 protein reduction from the cell membrane.

An improved PCR-CTPP assay for the detection of ADH1B Arg48His polymorphism.

BACKGROUND: ADH1B Arg48His polymorphism is associated with the development of alcohol-related diseases. In this study, we aimed to explore an improved polymerase chain reaction with confronting two-pair primers (PCR-CTPP) assay for the detection of ADH1B Arg48His polymorphism. METHODS: A mismatch was introduced at the 3' end of each of the two allele-specific to increase the specificity of the reaction. But beyond that, a new mismatch at-3 positions of outer primers was designed to decrease the efficiency of the aforementioned primers and depresses the amplification of an internal nonspecific DNA control. A total of 180 samples from healthy volunteers Han Chinese were tested to evaluate this new assay. RESULTS: The protocol of PCR-CTPP was successful for genotyping of ADH1B Arg48His. The results from the improved PCR-CTPP assay were confirmed by Sanger sequencing, and correct genotyping rates were 100%.The genotype frequencies were 49.44% (89 cases) for His/His, 46.67% (84 cases) for Arg/His, and 3.89% (seven cases) for Arg/Arg respectively. CONCLUSIONS: This improved PCR-CTPP assay is simple, rapid, cost-effective, and reliable, specific for the detection of ADH1B Arg48His polymorphism in most clinical diagnostic laboratories.

Effects of rhBMP-2/7 Heterodimer and RADA16 Hydrogel Scaffold on Bone Formation During Rabbit Mandibular Distraction.

PURPOSE: The effects of a recombinant human bone morphogenetic protein-2/7 (rhBMP-2/7) heterodimer and a RADA16 (Ac-RADARADARADARADA-CONH2) hydrogel scaffold on bone formation during distraction osteogenesis were evaluated. MATERIALS AND METHODS: Forty New Zealand white rabbits, which underwent mandibular lengthening, were randomly divided into 5 groups. One group served as the control group. The others received 2 µg of rhBMP-2 homodimer, 2 µg of rhBMP-2/7 heterodimer, 100 µL of RADA16, or 100 µL of RADA16 plus 2 µg of rhBMP-2/7 heterodimer in the mandibular distraction gap at the beginning of distraction. Fluorine-18-labeled fluoride positron emission tomography was used to assess osteogenesis both after distraction and at the end of consolidation. Dual-energy x-ray absorptiometry (DEXA) examination and bone histologic findings were also evaluated. RESULTS: At the end of distraction, the radioactivity concentration in the distracted area was significantly greater in the RADA16 plus rhBMP-2/7 heterodimer group than in the other groups (P < .01). The differences among the other 4 groups were also statistically significant in the following order: rhBMP-2/7 heterodimer group greater than the rhBMP-2 homodimer group, which was greater than the RADA16 group (or control group; P < .05). However, the radioactivity concentration of the RADA16 group was slightly greater than that of the control group with a nonsignificant difference (P > .05). By the end of consolidation, the activity in the control group, RADA16 group, rhBMP-2 homodimer group, and rhBMP-2/7 heterodimer group had significantly diminished (P < .05). However, the activity in the RADA16 plus rhBMP-2/7 heterodimer group remained at the same level (P > .05). The DEXA results and bone histologic findings indicated that more callus regeneration was noted in the RADA16 plus rhBMP-2/7 heterodimer group than in any other group. CONCLUSIONS: The use of rhBMP-2/7 heterodimer and RADA16 hydrogel scaffold significantly promoted mandibular distraction osteogenesis.

Targeting casein kinase II restores Ikaros tumor suppressor activity and demonstrates therapeutic efficacy in high-risk leukemia.

Ikaros (IKZF1) is a tumor suppressor that binds DNA and regulates expression of its target genes. The mechanism of Ikaros activity as a tumor suppressor and the regulation of Ikaros function in leukemia are unknown. Here, we demonstrate that Ikaros controls cellular proliferation by repressing expression of genes that promote cell cycle progression and the phosphatidylinositol-3 kinase (PI3K) pathway. We show that Ikaros function is impaired by the pro-oncogenic casein kinase II (CK2), and that CK2 is overexpressed in leukemia. CK2 inhibition restores Ikaros function as transcriptional repressor of cell cycle and PI3K pathway genes, resulting in an antileukemia effect. In high-risk leukemia where one IKZF1 allele has been deleted, CK2 inhibition restores the transcriptional repressor function of the remaining wild-type IKZF1 allele. CK2 inhibition demonstrated a potent therapeutic effect in a panel of patient-derived primary high-risk B-cell acute lymphoblastic leukemia xenografts as indicated by prolonged survival and a reduction of leukemia burden. We demonstrate the efficacy of a novel therapeutic approach for high-risk leukemia: restoration of Ikaros tumor suppressor activity via inhibition of CK2. These results provide a rationale for the use of CK2 inhibitors in clinical trials for high-risk leukemia, including cases with deletion of one IKZF1 allele.

MicroRNA-139-5p inhibits bladder cancer proliferation and self-renewal by targeting the Bmi1 oncogene.

MiR-139-5p has been reported to be overexpressed in many types of cancers, but its role in bladder cancer has not been elucidated yet. Here, we report that miR-139-5p functions as a tumor suppressor in bladder cancer and inhibits the cancer stem cell self-renewal by targeting Bmi1 directly. We found that miR-139-5p expression was significantly downregulated in the bladder cancer specimens compared with that in adjacent normal tissues. In vitro, restoration of miR-139-5p expression significantly inhibited the proliferation of bladder cancer cells. Mechanism analysis revealed that miR-139-5p could decrease Bmi1 protein levels by binding to the 3' untranslated region of Bmi1 messenger RNA. Stem cell-related proteins such as c-MYC, NANOG, OCT4, and KLF4 and signaling pathways such as Wnt signaling were suppressed by restoration of miR-139-5p in bladder cancer cells. In addition, miR-139-5p expression also blocked self-renewal of bladder cancer stem cells by inhibiting Bmi1. In summary, our study supports that miR-139-5p acts as a tumor suppressor in bladder cancer development and suppresses cancer stem cell property of bladder cancer. Our study also suggests that miR-139-5p has the potential to be used as a therapeutic molecule for bladder cancer treatment.

Detection of viruses and atypical bacteria associated with acute respiratory infection of children in Hubei, China.

BACKGROUND AND OBJECTIVE: Acute respiratory infection is the major cause of disease and death in children, particularly in developing countries. However, the spectrum of pathogenic viruses and atypical bacteria that exist in many of these countries remains incompletely characterized. The aim of this study was to examine the spectrum of pathogenic viruses and atypical bacteria associated with acute respiratory infection in children under the age of 16. METHODS: A total of 10 435 serum sera specimens were collected from hospitalized children presenting with acute respiratory infection symptoms. Indirect immunofluorescence assays were performed to detect immunoglobulin M antibodies against nine common pathogens: mycoplasma pneumonia, influenza virus B, respiratory syncytial virus, parainfluenza virus, adenovirus, influenza virus A, legionella pneumophila, coxiella burnetii and chamydophila pneumonia. RESULTS: Of the 10 435 specimens examined, 7046 tested positive for at least one pathogen. Among all of the tested pathogens, mycoplasma pneumonia had the highest detection rate (56.9%). Influenza virus A and influenza virus B epidemics occurred during both winter and summer. The detection rate of respiratory syncytial virus and adenovirus was higher in spring. Cases of mixed infection were more complex: 4136 specimens (39.6%) tested positive for ≥2 pathogens. There were statistically significant difference in detection rates of mycoplasma pneumonia, influenza virus B, respiratory syncytial virus, parainfluenza virus, adenovirus, influenza virus A, legionella pneumophila and chamydophila pneumonia among different age groups (P < 0.05). CONCLUSIONS: The most common pathogens causing acute respiratory infection among children in Hubei of China were mycoplasma pneumonia, influenza virus B and respiratory syncytial virus. The detection rates for each pathogen displayed specific seasonal and age group variations.

A novel universal multiplex PCR improves detection of AZFc Y-chromosome microdeletions.

PURPOSE: To determine the frequencies and the characteristics of Y chromosome microdeletions (pl) in infertile men from central China to perform appropriate therapeutic choices by updated multiplex-PCR. METHODS: In this study, we established a novel universal primer-multiplex-PCR (U-M-PCR) method to overcome the disadvantages of traditional multiplex PCR (M-PCR). We chose 15 sequence-tagged sites (STS) for detection of Y chromosome microdeletions. 540 infertile male patients and 100 healthy male controls were selected in the study. RESULTS: Of the 540 male infertility patients, 48 Y-chromosome microdeletions were detected, with a total deletion rate of 8.9 %. Of these deletions, the rate of AZFa deletions (sY84) was 0.5 % (3/540), the rate of AZFb deletions (sY143) was 0.7 % (4/540) and the rate of AZFc deletions (sY242, sY254 and sY255) was 7.6 % (41/540). Compared with AZF deletion rates by M-PCR, we found U-M-PCR could detect AZFc deletion more specifically (1.0 % & 7.6 %). No Y-chromosome microdeletions were detected in the 100 males with normal semen (the control group). CONCLUSIONS: U-M-PCR method was more specific to detect AZFc microdeletions. It is necessary to use the U-M-PCR method to offer genetic screening and counseling to infertile men prior to intracytoplasmic sperm injection (ICSI) or in-vitro fertilization (IVF).

Meta-analysis of the association of the rs2234693 and rs9340799 polymorphisms of estrogen receptor alpha gene with coronary heart disease risk in Chinese Han population.

OBJECTIVE: The association between a common variant of the ESR1 gene rs2234693 and rs9340799 polymorphisms with coronary heart disease (CHD) have been reported, but the available data on this relationship are inconsistent. A meta-analysis was performed to quantitative analysis the association of ESR1 gene polymorphisms and CHD risk using previous case-control studies in Chinese Han population. METHODS: Several electronic databases were searched for relevant articles up to August 2012. After data collection, a meta-analysis was performed to assess heterogeneity, combine results and evaluate variations. Different effect models were used according to the difference in heterogeneity. Sensitivity analysis was assessed by omitting one study at a time. Publication bias was examined using Begg's funnel plot and Egger's linear regression test. RESULTS: Ten studies covering 3400 subjects on rs2234693 and rs9340799 polymorphisms in the ESR1 gene with CHD risk was included in this meta-analysis. For rs2234693 polymorphism, ten studies were combined to the meta-analysis. A significantly increased CHD risk was found in a dominant model (OR=1.35, 955 CI=1.01-1.81, P=0.05), recessive model (OR=1.40, 95% CI=1.15-1.69, P=0.0007), and additive model (OR=1.67, 95% CI=1.19-2.34, P=0.003). Subgroup for male but not for female showed that the CC genotype could increase the risk of CHD compared with TT and TC genotype in Chinese Han population. Concerning rs9340799 polymorphism, eight studies were combined to the meta-analysis. And no evidence of significant association with CHD risk was found in all genetic models. CONCLUSION: Our meta-analysis of 10 studies involving Chinese Han population suggests that the CC genotype of the ESR1 rs2234693 polymorphism is significantly associated with an increased risk of CHD in males only. There was no evidence however, of a significant association between the ESR1 rs9340799 polymorphism and CHD risk.

Tumor-suppressive effects of 1, 25-dihydroxyvitamin D3 in gastric cancer cells.

BACKGROUNDS/AIMS: It has been previously demonstrated that vitamin D acts as a prognostic indicator of gastric cancer and may be correlated with the incidence risk of gastric cancer. However, the effect of 1,25-dihydroxyvitamin D3 on the apoptosis of human gastric cancer cells is unclear. The aim of this study was to determine whether 1,25-dihydroxyvitamin D3 induced the cellular apoptosis of BGC-823 gastric cancer cells and to determine the potential mechanism of action. METHODOLOGY: We demonstrate that 1,25-dihydroxyvitamin D3 induced the apoptosis of gastric cancer cells via the processing of PARP and cleavage of caspase 3. Additionally, an increase in BAX expression and a decrease in ERK1/2 and AKT phosphorylation were associated with 1,25-dihydroxyvitamin D3-induced apoptosis. The mRNA expression levels of VDR, CYP24A1, and p21 were increased significantly following 1,25-dihydroxyvitamin D3 treatment. CONCLUSIONS: These findings suggest that 1,25-dihydroxyvitamin D3 exerts tumor-suppressive effects on BGC-823 human gastric cancer cells.

Sodium butyrate (SB) ameliorated inflammation of COPD induced by cigarette smoke through activating the GPR43 to inhibit NF-κB/MAPKs signaling pathways.

Cigarette smoke is recognized as a major trigger for individuals with chronic obstructive pulmonary disease (COPD), leading to an amplified inflammatory response. The onset and progression of COPD are affected by multiple environmental and genetic risk factors, such as inflammatory mechanisms, oxidative stress, and an imbalance between proteinase and antiprotease. As a result, conventional drug therapies often have limited effectiveness. This study aimed to investigate the anti-inflammatory effect of sodium butyrate (SB) in COPD and explore its molecular mechanism, thereby deepening our understanding of the potential application of SB in the treatment of COPD. In our study, we observed an increase in the mRNA and protein expressions of inflammatory factors interleukin-1beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), Matrix metallopeptidase 9 (MMP9) and MMP12 in both NR8383 cell and rat models of COPD. However, these expressions were significantly reduced after SB treatment. Meanwhile, SB treatment effectively decreased the phosphorylation levels of nuclear transcription factor-kappa B (NF-κB) p65, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) and inhibited the nuclear translocation of these proteins in the COPD cells, leading to a reduction in the expression of various inflammatory cytokines. Additionally, SB also inhibited the expression level of the Nod-like receptor pyrin domain 3 (NLRP3) inflammasome, which consists of NLRP3, apoptosis-associated speck-like protein (ASC), and Caspase-1 in the cigeratte smoke extract (CSE)-stimulated cells. Our results showed that CSE down-regulated the mRNA levels of G-protein-coupled receptor 43 (GPR43) and GPR109A, while SB only up-regulated the expression of GPR43 and had no effect on GPR109A. Moreover, additional analysis demonstrated that the knockdown of GPR43 diminishes the anti-inflammatory effects of SB. It is evident that siRNA-mediated knockdown of GPR43 prevented the reduction in mRNA expression of IL-1ß, IL-6, TNF-α, MMP9, and MMP12, as well as the expression of phosphorylated proteins NF-κB p65, JNK, and p38 MAPKs with SB treatment. These findings revealed a SB/GPR43 mediated pathway essential for attenuating pulmonary inflammatory responses in COPD, which may offer potential new treatments for COPD.

Functional Materials for Subcellular Targeting Strategies in Cancer Therapy: Progress and Prospects.

Neoadjuvant and adjuvant therapies have made significant progress in cancer treatment. However, tumor adjuvant therapy still faces challenges due to the intrinsic heterogeneity of cancer, genomic instability, and the formation of an immunosuppressive tumor microenvironment. Functional materials possess unique biological properties such as long circulation times, tumor-specific targeting, and immunomodulation. The combination of functional materials with natural substances and nanotechnology has led to the development of smart biomaterials with multiple functions, high biocompatibilities, and negligible immunogenicities, which can be used for precise cancer treatment. Recently, subcellular structure-targeting functional materials have received particular attention in various biomedical applications including the diagnosis, sensing, and imaging of tumors and drug delivery. Subcellular organelle-targeting materials can precisely accumulate therapeutic agents in organelles, considerably reduce the threshold dosages of therapeutic agents, and minimize drug-related side effects. This review provides a systematic and comprehensive overview of the research progress in subcellular organelle-targeted cancer therapy based on functional nanomaterials. Moreover, it explains the challenges and prospects of subcellular organelle-targeting functional materials in precision oncology. The review will serve as an excellent cutting-edge guide for researchers in the field of subcellular organelle-targeted cancer therapy.

An Innovative Teaching Approach for Diabetes Mellitus in Laboratory Medicine Uses the Clinical Laboratory Diagnostic Pathway.

Objectives: The routine teaching mode of diabetes mellitus (DM) is divided into various sub-majors of medical laboratory, which is not conducive to clinical laboratory physicians quickly mastering relevant knowledge. A novel DM laboratory testing pathway is established to improve teaching efficiency and enhance the effects of talent cultivation in laboratory medicine. Methods: The guidelines and expert consensuses of DM were gathered from professional websites and databases. The clinical laboratory diagnostic pathway was formulated, and the questionnaire and mutual evaluation were used to evaluate the teaching effectiveness of 8-year undergraduate students enrolled in 2018 and enrolled in 2019, respectively. Results: Clinical laboratory physicians developed and approved the DM clinical laboratory diagnostic pathway, which included the entire process of DM diagnosis and differential diagnosis, drug selection, treatment impact monitoring, prognosis evaluation, etc. The results of the questionnaires showed that, in comparison to the teaching mode used with the students enrolled in 2018 and enrolled in 2019, the percentages of more improvement and significant improvement were significantly increased (P < 0.01) and the percentages of no improvement and slight improvement were significantly decreased (P < 0.01). Following the instruction of the DM clinical laboratory diagnostic route, the results were greatly improved, including points emphasized and the accuracy of responding to questions, among other things, according to the teachers' and students' mutual evaluation (P < 0.05). Conclusions: To enhance the teaching quality in laboratory medicine, it is required to build the disease clinical laboratory diagnostic pathway for a novel teaching method. This may boost teachers' and students' confidence and broaden their knowledge.