Muscle-secreted granulocyte colony-stimulating factor functions as metabolic niche factor ameliorating loss of muscle stem cells in aged mice.

The function and number of muscle stem cells (satellite cells, SCs) decline with muscle aging. Although SCs are heterogeneous and different subpopulations have been identified, it remains unknown whether a specific subpopulation of muscle SCs selectively decreases during aging. Here, we find that the number of SCs expressing high level of transcription factor Pax7 (Pax7Hi ) is dramatically reduced in aged mice. Myofiber-secreted granulocyte colony-stimulating factor (G-CSF) regulates age-dependent loss of Pax7Hi cells, as the Pax7Hi SCs are replenished by exercise-induced G-CSF in aged mice. Mechanistically, we show that transcription of G-CSF (Csf3) gene in myofibers is regulated by MyoD in a metabolism-dependent manner. Furthermore, myofiber-secreted G-CSF acts as a metabolic niche factor required for establishing and maintaining the Pax7Hi SC subpopulation in adult and physiological aged mice by promoting the asymmetric division of Pax7Hi and Pax7Mi SCs. Together, our findings uncover that muscles provide a metabolic niche regulating Pax7 SC heterogeneity in mice.

A Telomerase-Assisted Strategy for Regeneration of DNA Nanomachines in Living Cells.

DNA nanomachines have been engineered into diverse personalized devices for diagnostic imaging of biomarkers; however, the regeneration of DNA nanomachines in living cells remains challenging. Here, we report an ingenious DNA nanomachine that can implement telomerase (TE)-activated regeneration in living cells. Upon apurinic/apyrimidinic endonuclease 1 (APE1)-responsive initiation of the nanomachine, the walker of the nanomachine moves along tracks regenerated by TE, generating multiply amplified signals through which APE1 can be imaged in situ. Additionally, augmentation of the signal due to the regeneration of the nanomachines could reveal differential expression of TE in different cell lines. To the best of our knowledge, this is the first proof-of-concept demonstration of the use of biomarkers to assist in the regeneration of nanomachines in living cells. This study offers a new paradigm for the development of more applicable and efficient DNA nanomachines.

Metabolite-based cell sorting workflow for identifying microbes producing carbonyls in tobacco leaves.

Carbonyl compounds represented by aldehydes and ketones make an important contribution to the flavor of tobacco. Since most carbonyl compounds are produced by microbes during tobacco fermentation, identifying their producers is important to improve the quality of tobacco. Here, we created an efficient workflow that combines metabolite labeling with fluorescence-activated cell sorting (ML-FACS), 16S rRNA gene sequencing, and microbial culture to identify the microbes that produce aldehydes or ketones in fermented cigar tobacco leaves (FCTL). Microbes were labeled with a specific fluorescent dye (cyanine5 hydrazide) and separated by flow cytometry. Subsequently, the sorted microbes were identified and cultured under laboratory conditions. Four genera, Acinetobacter, Sphingomonas, Solibacillus, and Lysinibacillus, were identified as the main carbonyl compound-producing microbes in FCTL. In addition, these microorganisms could produce flavor-related aldehydes and ketones in a simple synthetic medium, such as benzaldehyde, phenylacetaldehyde, 4-hydroxy-3-ethoxy-benzaldehyde, and 3,5,5-trimethyl-2-cyclohexene-1-one. On the whole, this research has developed a new method to quickly isolate and identify microorganisms that produce aldehydes or ketones from complex microbial communities. ML-FACS would also be used to identify other compound-producing microorganisms in other systems. KEY POINTS: • An approach was developed to identify target microbes in complex communities. • Microbes that produce aldehyde/ketone flavor compounds in fermented cigar tobacco leaves were identified. • Functional microbes that produce aldehyde/ketone flavor compounds from the native environment were captured in pure cultures.

Linc-RAM is a metabolic regulator maintaining whole-body energy homeostasis in mice.

Long noncoding RNAs (lncRNAs) are known to have profound functions in regulating cell fate specification, cell differentiation, organogenesis, and disease, but their physiological roles in controlling cellular metabolism and whole-body metabolic homeostasis are less well understood. We previously identified a skeletal muscle-specific long intergenic noncoding RNA (linc-RNA) activator of myogenesis, Linc-RAM, which enhances muscle cell differentiation during development and regeneration. Here, we report that Linc-RAM exerts a physiological function in regulating skeletal muscle metabolism and the basal metabolic rate to maintain whole-body metabolic homeostasis. We first demonstrate that Linc-RAM is preferentially expressed in type-II enriched glycolytic myofibers, in which its level is more than 60-fold higher compared to that in differentiated myotubes. Consistently, genetic deletion of the Linc-RAM gene in mice increases the expression levels of genes encoding oxidative fiber versions of myosin heavy chains and decreases those of genes encoding rate-limiting enzymes for glycolytic metabolism. Physiologically, Linc-RAM-knockout mice exhibit a higher basal metabolic rate, elevated insulin sensitivity and reduced fat deposition compared to their wild-type littermates. Together, our findings indicate that Linc-RAM is a metabolic regulator of skeletal muscle metabolism and may represent a potential pharmaceutical target for preventing and/or treating metabolic diseases, including obesity.

Normal Absolute Monocyte Count in Combination with Normal/High Absolute Lymphocyte Count at the Time of Relapse is Associated with Improved Survival in Patients with Early Relapsed Acute Myeloid Leukemia.

This study aimed to examine the prognostic significance of peripheral absolute monocyte count (AMC) in combination with absolute lymphocyte count (ALC) at the time of relapse in a cohort of 57 patients with early relapsed (first complete remission <12 months) acute myeloid leukemia (AML). Both univariate and multivariate Cox proportional hazard regression analyses revealed that normal AMC in combination with normal/high ALC (versus low/high AMC in combination with low ALC) was significantly associated with improved OS. We concluded that the combination of AMC and ALC could be used as a prognostic marker for survival outcomes in early relapsed AML.

Unfavorable hydroxychloroquine COVID-19 research associated with authors having a history of political party donations.

We explored the degree to which political bias in medicine and study authors could explain the stark variation in Hydroxychloroquine (HCQ)/Chloroquine (CQ) study favorability in the US compared to the rest of the world. COVID-19/SARS-CoV-2 preprint and published papers between January 1, 2020-July 26, 2020 with Hydroxychloroquine and/or Chloroquine; 267 met study criteria, 68 from the US. A control subset was selected. HCQ/CQ study result favorability (favorable, unfavorable, or neutral) was noted. First and last main authors of each US study were entered into FollowTheMoney.org Website, extracting any history of political party donation. Of all US studies (68 total), 39/68 (57.4%) were unfavorable, with only 7/68 (10.3%) of US studies yielding favorable results-compared to 199 non-US studies, 66/199 (33.2%) unfavorable, 69/199 (34.7%) favorable, and 64/199 (32.2%) neutral. Studies with at least one US main author were 20.4% (SE 0.053, P < 0.05) more likely to report unfavorable results than non-US studies. US Studies with at least one main author donating to any political party were 25.6% (SE 0.085, P < 0.01) more likely to have unfavorable results. US studies with at least one author donating to the Democratic party were 20.4% (SE 0.045, P < 0.05) more likely to have unfavorable results. US authors were more likely to publish studies with medically harmful conclusions than non-US authors. Cardiology-specific HCQ/CQ studies were 44.2% more likely to yield harmful conclusions (P < 0.01). Inaccurate propagation of HCQ/CQ cardiac adverse effects with individual scientific author political bias has contributed to unfavorable US HCQ/CQ publication patterns and political polarization of the medications.

Recurrent primary pyogenic ventriculitis in an adult woman: a case report.

BACKGROUND: Recurrent primary pyogenic ventriculitis has not been reported previously. We present a unique case of recurrent primary pyogenic ventriculitis in an adult. And we believe that our study makes a significant contribution to the literature. CASE PRESENTATION: An adult woman with uncontrolled diabetes experienced two episodes of pyogenic ventriculitis caused by Escherichia coli over 4 years. She had typical imaging features, and the source of infection was undetermined. After antibiotic treatment, she recovered fully. CONCLUSIONS: Early recognition and therapy will improve patient prognosis.

P-selectin blockade ameliorates lupus nephritis in MRL/lpr mice through improving renal hypoxia and evaluation using BOLD-MRI.

BACKGROUND: Lupus nephritis is one of the most common and severe complications of systemic lupus erythematosus, of which poor prognosis is indicated by aggravated renal hypoxia and tubulointerstitial fibrosis. Cell adhesion molecules play a key role in the progression of lupus nephritis tubulointerstitial lesion, including P-selectin, which mediates the rolling of leukocytes and subsequent adhesion and infiltration and then initiates the inflammatory immune response and ischemia and hypoxia injury. However, the effects and mechanisms of P-selectin in lupus nephritis remain to be investigated, and a noninvasive measurement of lupus nephritis tubulointerstitial hypoxia and fibrosis remains to be explored. METHODS: Thirty-four MRL/lpr mice were randomly divided into the following three groups: MRL/lpr, saline, and anti-P-selectin, which consisted of no treatment, treatment with normal saline, and treatment with anti-P-selectin monoclonal antibody (mAb) from 12 to 16 weeks of age, respectively. Ten male C57BL/6 mice of the same age served as normal controls. 24-h urinary protein, urinary albumin-creatinine ratio, and periodic acid-Schiff were used to assess kidney damage; Western blot or immunohistochemical staining of the hypoxia probe Hypoxyprobe™-1, hypoxia-inducible factor 1α (HIF-1α), and CD31 were used to evaluate hypoxia in renal tissue; and NADPH oxidase subunit gp91phox and p22phox were used to examine renal oxidative stress. The correlation between kidney injury and blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) was calculated to assess the clinical value of BOLD-MRI. RESULTS: P-selectin is upregulated in lupus nephritis. Blocking P-selectin with mAb alleviated renal tubulointerstitial fibrosis, renal hypoxia, and peritubular capillary loss, without alteration of the levels of lupus activity indicators, anti-dsDNA antibody, or complement C3. BOLD-MRI showed that the reduced R2* values in the renal cortex and medulla of lupus mice were increased when treated with anti-P-selectin mAb as compared with those treated with normal saline, which were negatively correlated with Hypoxyprobe™-1 hypoxia probe and the expression of HIF-1α. CONCLUSIONS: Early intervention of lupus nephritis with anti-P-selectin mAb can significantly improve the hypoxic state of the kidney and reduce the severity of tubulointerstitial lesions. BOLD-MRI techniques are noninvasive and can dynamically evaluate the changes in renal lesions and intrarenal oxygenation levels before and after treatment in lupus nephritis.

In-situ fabrication of zeolite imidazole framework@hydroxyapatite composite for dispersive solid-phase extraction of benzodiazepines and their determination with high-performance liquid chromatography-VWD detection.

A novel zeolite imidazole framework@hydroxyapatite composite (ZIF-8@HAP) was constructed via in-situ growth and developed for efficient dispersive solid-phase extraction (DSPE) of three benzodiazepines from urine samples. The prepared composite was characterized by scanning electron microscopy, energy-dispersive spectrometer, Fourier-transform infrared spectrometry, X-ray diffractometry, zeta potential analyzer, and nitrogen adsorption-desorption experiment. Characterization results showed typical dodecahedron ZIF-8 crystals that were uniformly located on the surface of rod-like HAP. The combination of ZIF-8 and HAP made the surface area significantly enhanced from 4.68 to 205.44 m2 g-1. Compared with a commercial C18 adsorbent, ZIF-8@HAP exhibited superior removal performance for interfering components from urine and offered better extraction properties for the analytes. The prepared ZIF-8@HAP was applied as an adsorbent in DSPE, and the main experimental parameters, including pH and ionic strength of solution, adsorbent amount, adsorption time, elution solvent, and volume, were investigated. Under optimal conditions, the adsorption for 250 ng mL-1 of each analyte in 4 mL of urine was accomplished within 2 min using 60 mg of adsorbent. The method of ZIF-8@HAP-based DSPE followed by high-performance liquid chromatography gave enhancement factors of 13.3-15.3, linear ranges of 2.5-500 ng mL-1, and limits of detection (S/N = 3) of 0.7-1.4 ng mL-1. The relative recoveries at three spiked levels ranged from 88.7 - 102% with intra-day and inter-day precisions from 3.0 - 10.3% and 2.3 - 12.3%, respectively. These results indicated that the proposed strategy had promising applicability for convenient, rapid, and efficient determination of benzodiazepines in urine samples.Graphical abstract In-situ fabrication of ZIF-8@HAP composite for dispersive solid-phase extraction of benzodiazepines in urine samples.

Hypercortisolism and primary aldosteronism caused by bilateral adrenocortical adenomas: a case report.

BACKGROUND: Co-existing Cushing's syndrome and primary aldosteronism caused by bilateral adrenocortical adenomas, secreting cortisol and aldosterone, respectively, have rarely been reported. Precise diagnosis and management of this disorder constitute a challenge to clinicians due to its atypical clinical manifestations and laboratory findings. CASE PRESENTATION: We here report a Chinese male patient with co-existing Cushing's syndrome and primary aldosteronism caused by bilateral adrenocortical adenomas, who complained of intermittent muscle weakness for over 3 years. Computed tomography scans revealed bilateral adrenal masses. Undetectable ACTH and unsuppressed cortisol levels by dexamethasone suggested ACTH-independent Cushing's syndrome. Elevated aldosterone to renin ratio and unsuppressed plasma aldosterone concentration after saline infusion test suggested primary aldosteronism. Adrenal venous sampling adjusted by plasma epinephrine revealed hypersecretion of cortisol from the left adrenal mass and of aldosterone from the right one. A sequential bilateral laparoscopic adrenalectomy was performed. The cortisol level was normalized after partial left adrenalectomy and the aldosterone level was normalized after subsequent partial right adrenalectomy. Histopathological evaluation of the resected surgical specimens, including immunohistochemical staining for steroidogenic enzymes, revealed a left cortisol-producing adenoma and a right aldosterone-producing adenoma. The patient's symptoms and laboratory findings resolved after sequential adrenalectomy without any pharmacological treatment. CONCLUSIONS: Adrenal venous sampling is essential in diagnosing bilateral functional adrenocortical adenomas prior to surgery. Proper interpretation of the laboratory findings is particularly important in these patients. Immunohistochemistry may be a valuable tool to identify aldosterone/cortisol-producing lesions and to validate the clinical diagnosis.

The clinical characteristics of Chinese patients with unilateral renal agenesis.

BACKGROUND: We aimed to investigate the clinical characteristics of Chinese patients with unilateral renal agenesis. METHODS: We enrolled patients with unilateral renal agenesis diagnosed radiologically at the Department of Nephrology from January 2008 to January 2016. Patients with a solitary kidney due to nephrectomy or renal atrophy due to secondary factors were excluded. Clinical data were recorded and analyzed. RESULTS: In this study, 118 Chinese patients with unilateral renal agenesis were recruited, and the gender ratio (male/female) was 1.11:1. A total of 14 (11.9%) patients had additional abnormalities, 15 (12.7%) had a family history, and 30 (25.4%) presented with renal insufficiency. Kidney length, serum creatinine level and estimated glomerular filtration rate were significantly different between patients with and without family history (P < 0.05, respectively). Gender showed a significant difference between patients with and without other abnormalities. Kidney length and the incidence of proteinuria, hematuria, hypertension, and hyperuricemia were significantly different between patients with and without renal insufficiency. Logistic regression analysis revealed that family history was associated with severe renal failure (OR = 7.11, 95% CI 1.52-33.25). CONCLUSION: Renal insufficiency is common in patients with unilateral renal agenesis. Patients with renal insufficiency have shorter kidney lengths and a higher incidence of proteinuria, hypertension, hematuria, and hyperuricemia. Family history is considered a risk factor for severe renal failure.

Encapsulation of Azithromycin Ion Pair in Liposome for Enhancing Ocular Delivery and Therapeutic Efficacy on Dry Eye.

The aim of this work was to design a novel ocular delivery carrier based on liposomes loaded with azithromycin (AZM) for the treatment of dry eye (DE) disease. To improve the drug loading efficiency, an AZM-cholesteryl hemisuccinate (CHEMS) ion pair (ACIP) was first prepared, and the successful formation of the ACIP was characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRD), which demonstrated a stable interaction between CHEMS and AZM. The ACIP-loaded liposome (ACIP-Lip) appeared as spherical particles under TEM, with a uniform particle size of 60 ± 2 nm and zeta potential of -20.3 ± 4.6 mV. The entrapment efficiency (EE) and drug loading (DL) of ACIP-Lip were greatly improved to 95.6 ± 2.0 and 9.2 ± 0.7%, respectively, which was attributed to the enhanced loading capacity of the liposomes through use of the ion pair and addition of MCT. ACIP-Lip also exhibited a high stability during a 3 month storage period at both 4 and 25 °C. In vitro release of AZM from ACIP-Lip was pH-dependent, with a more rapid release at pH 6.0 than at pH 7.4, which is beneficial for ocular therapy. Furthermore, the corneal permeation of AZM was enhanced by ACIP-Lip, demonstrating an apparent permeability coefficient ( Papp × 106) of 8.92 ± 0.56 cm/s, which was approximately 2-fold greater that of the AZM solution. Finally, an in vivo pharmacodynamical study showed that the essential symptoms of DE rats were significantly improved by ACIP-Lip, as it was highly efficient and superior compared to hyaluronic acid sodium eye drops available on the market. Hence, ACIP-Lip is a promising formulation for DE treatment.

ACTH-independent Cushing's syndrome with bilateral cortisol-secreting adrenal adenomas: a case report and review of literatures.

BACKGROUND: Adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome (CS) with bilateral cortisol-secreting adenomas has been rarely reported in the literatures. Precise recognition and management of this disorder constitute a challenge to clinicians due to the difficulty of exact location of the functional lesions. CASE PRESENTATION: We herein report a new case of a Chinese female patient with a complaint of exertional dyspnea for over 10 years. ACTH-independent CS was diagnosed based on undetectable ACTH and unsuppressed cortisol levels by dexamethasone. Computed tomography (CT) scan indicated bilateral adrenal masses, and adrenal venous sampling (AVS) adjusted by plasma aldosterone revealed hypersecretion of cortisol from both adrenal glands. Bilateral cortisol-secreting adrenal adenomas were suspected and confirmed by the postoperative pathology in subsequent two-step bilateral laparoscopic adrenalectomy. The symptoms and signs of CS relieved after surgery with continuous glucocorticoid replacement. CONCLUSIONS: AVS adjusted by plasma aldosterone could be a useful technique in diagnosing ACTH-independent CS with bilateral adrenal adenomas prior to surgery. And the aldosterone ratio could be used to confirm the success of adrenal vein cannulation in this situation.

Identification of 8 Novel Mutations in Nephrogenesis-Related Genes in Chinese Han Patients with Unilateral Renal Agenesis.

BACKGROUND: Few genetic studies have focused on unilateral renal agenesis (URA), which is a disorder with insidious clinical manifestations and a tendency to result in renal failure. We aimed to detect pathogenic mutations in nephrogenesis-related genes, which were identified by a literature review conducted among a large cohort of Chinese Han patients with URA. METHODS: Totally, 86 unrelated URA patients were included. All URA patients were diagnosed by employing radiological methods. Patients with a solitary kidney owing to nephrectomy or renal atrophy due to secondary factors were excluded. Nine (10.5%) patients had a family history of abnormal nephrogenesis. Fifteen (17.4%) had other malformations in the urogenital system. All coding exons and adjacent intron regions of 25 genes were analyzed using next-generation sequencing and validated by Sanger sequencing and 100 ethnically matched healthy controls. RESULTS: Ten conserved mutations (9 missense mutations and 1 deletion mutation) were identified in SALL1, EYA1, RET, HNF1B, DSTYK, WNT4, and SIX5. All mutations were novel or rare (frequency <0.1%) in the public databases and absent from the 100 healthy controls. Nine patients carried mutations in candidate genes. Most of the patients carried one single heterozygous mutation, except for 2, who respectively carried compound heterozygous mutations and 2 single heterozygous mutations. In addition, 2 patients shared the same mutation in DSTYK. CONCLUSION: A total of 10.5% of our URA cases could be explained by mutations in our candidate genes. The mutations in nephrogenesis-related genes in the Chinese Han patients with URA had a decentralized distribution without any hotspot mutations.

Cell-Derived Microparticles in Patients with Type 2 Diabetes Mellitus: a Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: The aim of this study was to assess the association between circulating cell-derived microparticles (MPs) and type 2 diabetes mellitus (T2DM). METHODS: A literature search was performed systematically in PubMed and Embase to identify available case-control or cross-sectional studies that compared different types of cell-derived MPs in patients with T2DM and non-diabetic controls. Pooled standardized mean differences (SMDs) of each MP type were pooled using meta-analysis. RESULTS: Forty-eight studies involving 2,460 patients with T2DM and 1,880 non-diabetic controls were included for systematic review and 34 of which were included for quantitative study by meta-analysis. In the overall analysis, the levels of circulating total MPs (TMPs), platelet-derived MPs (PMPs), monocyte-derived MPs (MMPs) and endothelium-derived MPs (EMPs) were significantly higher in T2DM patients than those in controls (TMPs: SMD, 0.64; 95%CI, 0.12∼1.15; P=0.02; PMPs: SMD, 1.19; 95%CI, 0.88∼1.50; P <0.00001; MMPs: SMD, 0.92; 95%CI, 0.66∼1.17; P <0.00001; EMPs: SMD, 0.73; 95%CI, 0.50∼0.96; P <0.00001). Meanwhile, no significant difference was shown in leukocyte-derived MPs (LMPs) level between diabetic and non-diabetic groups (SMD, 0.37; 95%CI, -0.15∼0.89; P=0.17). CONCLUSIONS: The counts of TMPs, PMPs, MMPs and EMPs elevated in patients with T2DM. And cell-derived MPs may play a role in the pathogenesis of T2DM.

Chemical profiling approach to evaluate the influence of traditional and simplified decoction methods on the holistic quality of Da-Huang-Xiao-Shi decoction using high-performance liquid chromatography coupled with diode-array detection and time-of-flight mass spectrometry.

Da-Huang-Xiao-Shi decoction, consisting of Rheum officinale Baill, Mirabilitum, Phellodendron amurense Rupr. and Gardenia jasminoides Ellis, is a traditional Chinese medicine used for the treatment of jaundice. As described in "Jin Kui Yao Lue", a traditional multistep decoction of Da-Huang-Xiao-Shi decoction was required while simplified one-step decoction was used in recent repsorts. To investigate the chemical difference between the decoctions obtained by the traditional and simplified preparations, a sensitive and reliable approach of high-performance liquid chromatography coupled with diode-array detection and electrospray ionization time-of-flight mass spectrometry was established. As a result, a total of 105 compounds were detected and identified. Analysis of the chromatogram profiles of the two decoctions showed that many compounds in the decoction of simplified preparation had changed obviously compared with those in traditional preparation. The changes of constituents would be bound to cause the differences in the therapeutic effects of the two decoctions. The present study demonstrated that certain preparation methods significantly affect the holistic quality of traditional Chinese medicines and the use of a suitable preparation method is crucial for these medicines to produce special clinical curative effect. This research results elucidated the scientific basis of traditional preparation methods in Chinese medicines.

Diffusion weighted imaging and blood oxygen level-dependent MR imaging of kidneys in patients with lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is one of most common secondary glomerulonephritis. There is no ideal method to simultaneously assess renal structure and function in patients with LN. The aim of this study is to investigate the utility of diffusion weighted imaging (DWI) and blood oxygen level-dependent (BOLD) MR imaging in the assessment of renal involvement and pathological changes in patients with LN. METHODS: Sixty-five patients with LN and 16 healthy volunteers underwent coronal echo-planar DWI and BOLD MR imaging of the kidneys. The apparent diffusion coefficient (ADC) and R2* values of the kidneys were calculated with b values of 0 and 500 s/mm(2). The relationship between the renal injury variables and the ADCs or R2* values were evaluated. And 16 of 65 patients with LN underwent a repeated evaluation after the induction treatment for 9 to 12 months. RESULTS: The mean ADC values of kidneys in patients with LN were 2.40 ± 0.25 × 10(-3) mm(2)/s, the mean R2* values of the renal cortex and medulla were 11.03 ± 1.60/sec and 14.05 ± 3.38/sec respectively, which were all significantly lower than that in volunteers. In patients with LN, the mean ADC values were correlated with eGFR (r = 0.510, p < 0.01). There was a negative correlation between the mean ADC values and renal pathology chronicity indexes (r = -0.249, p < 0.05), the R2* values of the renal medulla and proteinuria (r = -0.244, p < 0.05), and the degree of tubulointerstitial lesions (r = -0.242, p < 0.05). The ADC and R2* values of kidneys were significantly higher than those of pre-treatment in complete remission patients. CONCLUSIONS: DWI and BOLD MR imaging of kidneys may be used to noninvasively monitor the disease activity and evaluate therapeutic efficacy in lupus nephritis.

Artesunate promotes cervical cancer cell apoptosis by regulating Bcl2 family molecules and reducing the mitochondrial membrane potential.

Artesunate (ART), an antimalarial drug, has a broad spectrum of antitumour effects in cancer types such as esophageal and gastric cancer. However, evidence demonstrating the role of ART in cervical cancer cells is limited. In the present study, the inhibitory effect of ART on the growth of cervical cancer cells through the modulation of the cell cycle and apoptosis was investigated. The growth-inhibitory effect of ART on a cervical cancer cell line (SiHa) was detected using a Cell Counting Kit-8 assay after treatment with ART for 24 h, after which the half-maximal inhibitory concentration (IC50) was calculated. Using flow cytometry assays, apoptosis, the cell cycle, the levels of reactive oxygen species (ROS) and calcium (Ca2+) ions, as well as the mitochondrial membrane potential were evaluated in SiHa cells following treatment with ART for 24 and 48 h. The mRNA expression levels of Bcl2, Bcl-xl, (myeloid cell leukaemia 1) Mcl-1, Bcl2-like protein 11 (BIM), (Bcl2-related ovarian killer protein) Bok, Bax and (Bcl2 homologous antagonist/killer) Bak in SiHa cells were detected using reverse transcription-quantitative PCR. ART inhibited the growth of SiHa cells in a dose-dependent manner. The IC50 of ART in SiHa cells was 26.32 µg/ml. According to the IC50 value, 15, 30 and 100 µg/ml ART were selected for further experiments, and normal saline (0 µg/ml ART) was used as the control group. The results indicated that treatment with 15, 30 and 100 µg/ml ART for 24 and 48 h induced apoptosis, increased the levels of ROS, the levels of Ca2+ and the mRNA expression levels of BIM, Bok, Bax and Bak, but decreased the cell proliferation indices, the mitochondrial membrane potential and the mRNA expression levels of Bcl2, Bcl-xl and Mcl-1 in a dose- and time-dependent manner. In conclusion, ART inhibited the growth of SiHa cells and induced apoptosis via a mechanism associated with the regulation of Bcl2 family member expression, which was associated with the increase of the levels of ROS and Ca2+ and the reduction of the mitochondrial membrane potential.

Prognostic significance of ß2-microglobulin decline index in multiple myeloma.

Purpose: To assess the prognostic significance of ß2-microglobulin decline index (ß2M DI) in multiple myeloma (MM). Methods: 150 MM patients diagnosed with MM were enrolled in this study. Cox proportional hazards model was used to analyze the uni- and multivariate prognosis in training cohort (n=105). A new combined prognostic model containing ß2M DI was built up based on the data in training cohort. The validation group was used to verify the model. Results: ß2M DI showed significant correlation with prognosis in both uni- and multivariate analyses and had a good correlation with complete response (CR) rate and deep remission rate. The ROC and calibration curves in validation cohort (n=45) indicated a good predictive performance of the new model. Based on the median risk score of the training group, we classified patients into high- and low- risk groups. In both training and validation groups, patients in the low-risk group had longer overall survival (OS) time than that in the high-risk group (p<0.05). Conclusion: ß2M DI is a good predictive index for predicting treatment response and survival time in MM patients. The prognostic model added with ß2M DI showed a better correlation with OS.