Publications by authors named "Junru Liu"

55 Publications

Mechanism of megaloblastic anemia combined with hemolysis.

Bioengineered 2021 12;12(1):6703-6712

Department of Hematology, The First Affliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.

Megaloblastic anemia (MA) patients often exhibit hemolysis, but it is not clear whether there are other hemolytic mechanisms in addition to intramedullary hemolysis. We retrospectively analyzed the clinical characteristics of 124 MA patients, measured erythrocyte physical parameters in two patients with hemolysis and one healthy volunteer by atomic force microscopy, and measured 18F-FDG uptake in one MA patient with hemolysis. In multivariate analysis, hemolysis was associated with mean corpuscular volume (MCV) and indirect bilirubin. A receiver operating characteristic curve analysis, with sensitivity of 83.1% and specificity of 68.7%, suggested that the MCV cutoff value that predicts hemolysis is 116.4 fL. Hb was negatively correlated with MCV in the hemolysis group (r = -0.317, P = 0.007) but not in the nonhemolysis group. The erythrocyte peak-valley value, average cell surface roughness and surface area in the MA patients with hemolysis were significantly lower than those in controls (P < 0.05). 18F-FDG uptake by the liver and spleen was diffuse and increased in MA patients undergoing hemolysis. MA combined with extramedullary hemolysis could be caused by macrophages removing mechanically damaged erythrocytes and the retention of erythrocytes with decreased deformability when blood circulates through narrow spaces in the liver and spleen.
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http://dx.doi.org/10.1080/21655979.2021.1952366DOI Listing
December 2021

Suppressing mosquito populations with precision guided sterile males.

Nat Commun 2021 Sep 10;12(1):5374. Epub 2021 Sep 10.

Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA.

The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and Zika virus, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular genetic control system termed precision-guided sterile insect technique (pgSIT) in Aedes aegypti. PgSIT uses a simple CRISPR-based approach to generate flightless females and sterile males that are deployable at any life stage. Supported by mathematical models, we empirically demonstrate that released pgSIT males can compete, suppress, and even eliminate mosquito populations. This platform technology could be used in the field, and adapted to many vectors, for controlling wild populations to curtail disease in a safe, confinable, and reversible manner.
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http://dx.doi.org/10.1038/s41467-021-25421-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433431PMC
September 2021

Effective Picosecond Nd:YAG laser on seborrheic dermatitis and its mechanism.

J Cosmet Dermatol 2021 Sep 8. Epub 2021 Sep 8.

Department of Dermatology, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China.

Background: The Picosecond Nd:YAG laser has advantages in skin rejuvenation, which has little damage to surrounding tissues due to the ultra-short pulse width. We perform clinical application of Picosecond Nd:YAG laser's tender skin mode, which could improve the seborrheic dermatitis.

Materials And Methods: Sixty-three subjects with facial seborrheic dermatitis are randomized to be control and observation groups. Records regarding skin subjective improvement, skin barrier function-related data, skin microbial status, and dermoscopy detection of the two patient groups before and after treatments are investigated.

Results: Improvements of erythema and scales in observation group are significant compared with controls (p < 0.05). In terms of skin barrier function, there are significant changes regarding transepidermal water loss and epidermal seborrhea content in observation group after the laser treatments. Skin microbial state, pityrosporum furfur, and Demodex significantly decrement in observation group. Microscopical findings of infiltration mode advise that scales and capillary congestion and dilatation are significantly improved in observation group. Compared with controls, epidermal gloss increases, pore fineness improves, and capillary density decreases in the observation group.

Conclusions: Picosecond Nd:YAG laser could efficiently decrease erythema area and seborrheic dermatitis scales and reduce pruritus incidence. The sebaceous gland secretion of seborrhea and multiplying of epidermal parasitic microbiological are inhibited after laser treatment. Less epidermal seborrhea content and inflammation are induced by parasitic microbiology, which is helpful for skin barrier function and microvascular remodeling.
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http://dx.doi.org/10.1111/jocd.14414DOI Listing
September 2021

Engineered reproductively isolated species drive reversible population replacement.

Nat Commun 2021 06 2;12(1):3281. Epub 2021 Jun 2.

Division of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, San Diego, CA, USA.

Engineered reproductive species barriers are useful for impeding gene flow and driving desirable genes into wild populations in a reversible threshold-dependent manner. However, methods to generate synthetic barriers are lacking in advanced eukaryotes. Here, to overcome this challenge, we engineer SPECIES (Synthetic Postzygotic barriers Exploiting CRISPR-based Incompatibilities for Engineering Species), an engineered genetic incompatibility approach, to generate postzygotic reproductive barriers. Using this approach, we create multiple reproductively isolated SPECIES and demonstrate their reproductive isolation and threshold-dependent gene drive capabilities in D. melanogaster. Given the near-universal functionality of CRISPR tools, this approach should be portable to many species, including insect disease vectors in which confinable gene drives could be of great practical utility.
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http://dx.doi.org/10.1038/s41467-021-23531-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173020PMC
June 2021

Clinical value of minimal residual disease assessed by multiparameter flow cytometry in amyloid light chain amyloidosis.

J Cancer Res Clin Oncol 2021 May 8. Epub 2021 May 8.

Department of Haematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Purpose: To assess the feasibility and prognostic value of minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in newly diagnosed amyloid light chain (AL) amyloidosis.

Methods: Clinical data from 25 consecutive newly diagnosed AL amyloidosis patients with MRD data tested at 3 months after first-line therapy completion were retrospectively analysed in a single centre from 2012 to 2019. First-line therapy included 8 courses of VD or 4 courses of VD plus sequential autologous stem cell transplantation (ASCT), both without maintenance therapy.

Results: Of 25 patients with very good partial response (VGPR) or better, 19 (76%) achieved MRD negativity. Baseline characteristics were not different between MRD-negative and MRD-positive patients. More ASCT patients than non-ASCT patients (90.0% vs 53.3%, p = 0.043) achieved MRD negativity. In the MRD-negative and MRD-positive groups, cardiac response was observed in 93% and 25% (p = 0.019) and any organ response in 94% and 50%, respectively (p = 0.023). At a median follow-up of 25.1 months, MRD-negative patients showed significantly longer progression-free survival (PFS) from diagnosis than MRD-positive patients (24.52 vs 76.39 months, p = 0.004).

Conclusions: MRD negativity measured by MFC at 3 months after first-line therapy completion in patients with AL amyloidosis is measurable and associated with improved organ response rates and PFS over a long follow-up.
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http://dx.doi.org/10.1007/s00432-021-03653-zDOI Listing
May 2021

Effect of External Surface Diffusion Barriers on Platinum/Beta-Catalyzed Isomerization of n-Pentane.

Angew Chem Int Ed Engl 2021 Jun 17;60(26):14394-14398. Epub 2021 May 17.

State Key Laboratory of Chemical Engineering, School of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China.

We have developed a generalizable strategy to quantify the effect of surface barriers on zeolite catalysis. Isomerization of n-pentane, catalyzed by Pt/Beta, is taken as a model reaction system. Firstly, the surface modification by chemical liquid deposition of SiO was carried out to control the surface barriers on zeolite Beta crystals. The deposition of SiO leads to a very slight change in the physical properties of Beta crystals, but an obvious reduction in Brønsted acid sites. Diffusion measurements by the zero-length column (ZLC) method show that the apparent diffusivity of n-pentane can be more than doubled after SiO deposition, indicating that the surface barriers have been weakened. Catalytic performance was tested in a fixed-bed reactor, showing that the apparent catalytic activity improved by 51-131 % after SiO deposition. These results provide direct proof that reducing surface barriers can be an effective route to improve zeolite catalyst performance deteriorated by transport limitations.
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http://dx.doi.org/10.1002/anie.202104859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252482PMC
June 2021

Fasudil protects retinal ganglion cells and promotes axonal regeneration.

Pak J Pharm Sci 2020 Sep;33(5(Special)):2431-2437

Department of Ophthalmology, Shijiazhuang Third Hospital, Shijiazhuang, Hebei, China.

This study was aimed to investigate whether fasudil can protect retinal ganglion cells and promote axonal regeneration by inhibiting RhoA/Rock pathway. Long Evans rats were used to establish an optic nerve injury model. Apoptosis was detected by TUNEL, and surviving RGCs was detected by Fluoro-Gold retrograde label and hematoxylin-eosin (HE) staining was used to evaluate pathological changes and western blot was used to measure the expression of protein. After 10 days of optic nerve injury rat model, increased cell apoptosis and decreased FG-positive RGCs in rat eye, but fasudil could reverse these changes. In vitro, fasudil could not only increase the number of RGCs with protuberances, but also increase the length of protuberances. Moreover, fasudil could not only reduce the expression of total-cohoin, Rock, total-cofilin and total-MLC protein induced by optic nerve injury, but also reduce the relative expression of GTP-RhoA, p-cofilin and p-MLC protein. Fasudil protects retinal ganglion cells and promotes axonal regeneration by inhibiting RhoA / Rock pathway.
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September 2020

Inverse association of plasma hydrogen sulfide levels with visceral fat area among Chinese young men: a cross-sectional study.

Arch Endocrinol Metab 2021 Mar 19. Epub 2021 Mar 19.

Department of Endocrinology, The First Hospital of Qinhuangdao, Qinhuangdao, China,

Objective: To investigate the association between plasma Hydrogen Sulfide (HS) levels and visceral fat area (VFA) among Chinese young men.

Methods: This cross-sectional study involved 156 Chinese male subjects, aged 18-45 years, who visited the First Hospital of Qinhuangdao (Hebei, China) in 2014 for annual health check-up. Participants were categorized into: low (VFA < 75.57 cm), medium (75.57 cm ≤ VFA<100.37 cm), and high (VFA ≥ 100.37 cm) (n = 52/group). We estimated VFA and plasma HS levels by using bioelectrical impedance analysis and a fluorescence probe-based approach, respectively. The associations of HS with VFA and obesity anthropometric measures were assessed.

Results: In the high VFA group, the body mass index (BMI, 30.4 ± 2.45 kg/m), total body fat (TBF, 27.9 ± 3.23 kg), plasma HS (3.5 µmol/L), free fatty acid (FFA, 0.6 ± 0.24 mmol/L), triglyceride (TG, 2.0 mmol/L), and total cholesterol (TC, 5.5 ± 1.02 mmol/L) levels were significantly higher than that of those of the low and medium VFA groups, respectively ( < 0.05). Plasma HS levels were found to be inversely correlated with VFA, TBF, waist circumference, BMI, FFA, LnFINS, LnHOMA-IR, LnTG, TC, and LDL-C ( < 0.05). Multiple backward stepwise regression analysis revealed an inverse correlation of plasma HS levels with FFA (β = -0.214, = 0.005) and VFA (β = -0.429, < 0.001), independent of adiposity measures and other confounding factors.

Conclusion: VFA was independently and inversely associated with plasma HS levels among Chinese young men. Therefore, determining plasma HS levels could aid in the assessment of abnormal VAT distribution.
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http://dx.doi.org/10.20945/2359-3997000000339DOI Listing
March 2021

A confinable home-and-rescue gene drive for population modification.

Elife 2021 Mar 5;10. Epub 2021 Mar 5.

Section of Cell and Developmental Biology, University of California, San Diego, San Diego, United States.

Homing-based gene drives, engineered using CRISPR/Cas9, have been proposed to spread desirable genes throughout populations. However, invasion of such drives can be hindered by the accumulation of resistant alleles. To limit this obstacle, we engineer a confinable population modification home-and-rescue (HomeR) drive in targeting an essential gene. In our experiments, resistant alleles that disrupt the target gene function were recessive lethal and therefore disadvantaged. We demonstrate that HomeR can achieve an increase in frequency in population cage experiments, but that fitness costs due to the Cas9 insertion limit drive efficacy. Finally, we conduct mathematical modeling comparing HomeR to contemporary gene drive architectures for population modification over wide ranges of fitness costs, transmission rates, and release regimens. HomeR could potentially be adapted to other species, as a means for safe, confinable, modification of wild populations.
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http://dx.doi.org/10.7554/eLife.65939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968924PMC
March 2021

Clinical observation and dermoscopy evaluation of fractional CO laser combined with topical tranexamic acid in melasma treatments.

J Cosmet Dermatol 2021 Apr 22;20(4):1110-1116. Epub 2021 Feb 22.

Department of Dermatology, Yantai Yuhuangding Hospital, The Affiliated Hospital of Qingdao University, Yantai, Shandong, China.

Background: Melasma is an acquired refractory pigmentary disorder, which is a skin disease that predominantly affects females. This investigation aims to assess the efficacy of a low-power fractional CO laser combined with tranexamic acid (TXA) for melasma topical treatment with MASI and dermoscopy.

Materials And Methods: A randomized comparative split-face study was performed. Each treatment interval was 3 weeks with four times in total. At the same time, we applied TXA solution twice a day. Assessments were made by the MASI score of the melasma area severity index, and the dermoscopy performance was collected and analyzed.

Results: After treatments, the patient MASI score decreased significantly. Compared with the baseline, the MASI score was significantly lower than that of control group (P < .05), and the decrease ratio was higher than that of controls. Dermoscopy examination results verified that all lesions performed reticuloglobular pattern, granular, or punctate, with no structural pigmentation and obvious capillary dilation. After comprehensive treatments, the pigmentation area displayed lighter chroma, the follicle pore uniformity was completely improved, and the capillary dilation was significantly reduced.

Conclusions: Low-power fractional CO laser combined with topical TXA solution is a comparatively effective and safe method for melasma treatment. TXA could reduce the dilation of blood vessels.
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http://dx.doi.org/10.1111/jocd.13992DOI Listing
April 2021

Comparison of efficacy, safety, patients' quality of life, and doctors' occupational stress between lenalidomide-based and bortezomib-based induction in patients with newly diagnosed multiple myeloma.

Cancer Med 2021 03 2;10(5):1656-1667. Epub 2021 Feb 2.

Department of Hematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: In the new therapeutic era, comparisons between regimens containing lenalidomide and bortezomib are needed.

Methods: In this single-center, prospective study, patients received four to six cycles of lenalidomide+liposomal doxorubicin+dexamethasone (RAD) or bortezomib+liposomal doxorubicin+dexamethasone (PAD) every 4 weeks, with subsequent autologous stem cell transplantation (ASCT) and maintenance therapy. We compared the efficacy, safety, patients' quality of life, and doctors' occupational stress between RAD and PAD induction in newly diagnosed MM patients.

Results: The complete response (CR) rate was comparable between the RAD and PAD groups after induction (30.8% vs. 32.0%, p = 0.92). Common adverse events, including infections, peripheral neuropathy, and gastrointestinal disturbances, were more frequent in the PAD group, while leukopenia and rashes were more common in the RAD group. Compared with PAD, RAD improved patients' quality of life more quickly and caused less occupational stress for doctors. However, only 31.6% of patients collected adequate CD34+ cells (≥2 × 10 /kg) in the RAD group, which was significantly lower than that in the PAD group (95.5%, p < 0.001). The number of CD34+ cells collected was significantly higher in patients within three courses of RAD than in patients with four or five to six courses (14.18 ± 13.57 vs. 2.07 ± 2.42 vs. 1.51 ± 1.81 × 10 /kg, p = 0.028). The median progression-free survival and overall survival of the two groups were not reached by the end of follow-up.

Conclusion: Compared to PAD, RAD induction had comparable efficacy and a significantly better safety profile, improved quality of life for patients, and reduced occupational stress for doctors. However, RAD induction may need to be limited to four cycles to avoid irreversible damage to hematopoietic stem cells.

Clinical Trial Registration: This study was registered at www.chictr.org.cn (ChiCTR1900021558).
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http://dx.doi.org/10.1002/cam4.3762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940229PMC
March 2021

Analytical method for the out-of-plane buckling of the telescopic boom with guy cables.

Sci Prog 2021 Jan-Mar;104(1):36850420984330

School of Mechanical Engineering, Shenyang Jianzhu University, Shenyang, China.

The guy cables can effectively improve the bearing capacity for the telescopic boom of the crane, while the introduction of tensioned cables makes the buckling analysis complicated. The primary objective of this study was to propose an analytical method for the out-of-plane buckling of the telescopic boom with the spatial symmetric guy cables. To analyze the influence of the guy cables on the out-of-plane buckling property of the telescopic boom, the deflection differential equation of the multi-stepped telescopic boom with guy cables was established based on the theory of elastic beam, then the buckling characteristic equation to determine the critical load of the telescopic boom was derived. Comparison of results with that given by the finite element method showed the high accuracy of the proposed method. In the end, with this equation, the influences of the structural geometric parameters on the critical load were investigated. The results indicated that, in the engineering application, the critical load of the telescopic boom can be increased by decreasing the length ratio or increasing the angle between the two cables. The influence of angle on the out-of-plane buckling analysis of the telescopic boom can be neglected. With the proposed method, the buckling behavior of the telescopic boom with guy cables can be solved accurately. The present work is significant to structural design and safety analysis of the telescopic boom, and it can be utilized to provide technical support for the structural design of telescopic boom.
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http://dx.doi.org/10.1177/0036850420984330DOI Listing
January 2021

What Multiple Myeloma With t(11;14) Should Be Classified Into in Novel Agent Era: Standard or Intermediate Risk?

Front Oncol 2020 26;10:538126. Epub 2020 Oct 26.

Department of Hematology, Myeloma Research Center of Beijing, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Objective: To investigate the prognostic value of t(11;14) for multiple myeloma (MM) patients in novel agent era.

Methods: A total of 455 patients with fluorescence hybridization (FISH), before treatments from three hospitals in China, were included in the study. All patients received autologous stem cell transplantation (ASCT) after induction therapy as consolidation. High risk (HR) cytogenetics were defined as t(4;14), t(14;16), and/or del 17p.

Results: A total of 152 patients were in the HR group. Of patients without HR cytogenetics, 55 were in the t(11;14) group, and 248 were in the standard risk (SR) group without t(11;14). Gain in 1q21 was observed in 38.9% patients with t(11;14). There were no differences in median progression free survival (PFS) and overall survival (OS), respectively, between patients in the t(11;14) group and those in the SR group. Patients in the t(11;14) group had the longer median PFS and OS, respectively, compared with those in the HR group. Regardless of coexisting with 1q21 gain or not, patients in the t(11;14) group still had similar median PFS and OS compared to those in the SR group. Finally, multivariate analysis indicated that including 1q21 gain and bone marrow plasma cell with CD20 expression, no variables were found to predict the outcome of the t(11;14) group in our cohort.

Conclusions: These results confirm that outcomes of t(11;14) MM are similar to standard risk patients when they receive novel agent induction therapy consolidated by ASCT. Gain of 1q21 coexists with t(11;14) frequently. In addition, both bone marrow plasma cell with CD20 expression and 1q21 gain have no impact on median PFS or OS for patients with t(11;14).
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http://dx.doi.org/10.3389/fonc.2020.538126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649769PMC
October 2020

Total Synthesis and Immunological Evaluation of the Tri-d--d--heptose Antigen of the Lipopolysaccharide as a Vaccine Candidate against .

Org Lett 2020 11 29;22(22):8780-8785. Epub 2020 Oct 29.

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.

, the most common cause of chronic gastritis, peptic ulcers, and gastric cancers, infects around half of the world's population. Although the drawbacks of antibiotic-based combination therapy are emerging, no effective vaccine is available to prevent infections. Here, we describe the total synthesis of the unique α-(1→3)-linked tri-d--d--heptose antigen from the lipopolysaccharide of serogroups O3 and O6 and strains MO19, D2, D4, and D5 based on synthesis of the differentially protected d--d--heptosyl building blocks. Immunization of mice with the semisynthetic glycoconjugate elicited a very robust T-cell-dependent antigen-specific immune response, resulting in very high titers of IgG1 and IgG2b protective antibody isotypes. The postimmune sera recognized NCTC 11637 and bound strongly to the surface of the intact bacteria.
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http://dx.doi.org/10.1021/acs.orglett.0c03105DOI Listing
November 2020

A Sensitive, Rapid, and Portable CasRx-based Diagnostic Assay for SARS-CoV-2.

medRxiv 2020 Oct 20. Epub 2020 Oct 20.

Since its first emergence from China in late 2019, the SARS-CoV-2 virus has spread globally despite unprecedented containment efforts, resulting in a catastrophic worldwide pandemic. Successful identification and isolation of infected individuals can drastically curtail virus spread and limit outbreaks. However, during the early stages of global transmission, point-of-care diagnostics were largely unavailable and continue to remain difficult to procure, greatly inhibiting public health efforts to mitigate spread. Furthermore, the most prevalent testing kits rely on reagent- and time-intensive protocols to detect viral RNA, preventing rapid and cost-effective diagnosis. Therefore the development of an extensive toolkit for point-of-care diagnostics that is expeditiously adaptable to new emerging pathogens is of critical public health importance. Recently, a number of novel CRISPR-based diagnostics have been developed to detect COVID-19. Herein, we outline the development of a CRISPR-based nucleic acid molecular diagnostic utilizing a Cas13d ribonuclease derived from (CasRx) to detect SARS-CoV-2, an approach we term SENSR (Sensitive Enzymatic Nucleic-acid Sequence Reporter). We demonstrate SENSR robustly detects SARS-CoV-2 sequences in both synthetic and patient-derived samples by lateral flow and fluorescence, thus expanding the available point-of-care diagnostics to combat current and future pandemics.
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http://dx.doi.org/10.1101/2020.10.14.20212795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587836PMC
October 2020

Cooperation of ESIPT and ICT Processes in the Designed 2-(2'-Hydroxyphenyl)benzothiazole Derivative: A Near-Infrared Two-Photon Fluorescent Probe with a Large Stokes Shift for the Detection of Cysteine and Its Application in Biological Environments.

Anal Chem 2020 10 8;92(20):14236-14243. Epub 2020 Oct 8.

State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu 730000, China.

A rationally designed near-infrared two-photon fluorescent probe () for selectively detecting cysteine (Cys) has been developed based on a newly designed conjugation-enhanced 2-(2'-hydroxyphenyl)benzothiazole derivative as the fluorophore, an acrylate moiety as the Cys reaction site, and an -methylpyridinium scaffold as both the unit of organelle targeting and improving water solubility. The probe alone essentially emitted no fluorescence, whereas it achieved a superb near-infrared fluorescence emission (713 nm) enhancement within 15 min with a significant Stokes shift (302 nm) in the presence of Cys. The photoluminescence mechanism of the probe toward Cys was modulated by excited-state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) processes. It exhibited high selectivity and sensitivity (LOD = 102 nM) for monitoring Cys over other analytes such as Hcy/GSH/HS owing to a specific conjugate addition-cyclization reaction between Cys and the acrylate moiety. More importantly, the released fluorophore exhibits elevated quantum yields (1.52-18.17%) in different solvents and strong two-photon excited fluorescence with a sizeable two-photon action cross-section (Φ) of 213.5 GM at 820 nm in acetonitrile-PBS medium, which is highly desirable for two-photon fluorescence imaging of the living samples. Therefore, was successfully applied to the imaging of Cys in live cells, zebrafish, mouse brain, and abdominal cavity down to a depth of more than 200 μm using a one/two-photon fluorescence microscope.
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http://dx.doi.org/10.1021/acs.analchem.0c03490DOI Listing
October 2020

Health-related quality of life of patients with multiple myeloma: A real-world study in China.

Cancer Med 2020 11 2;9(21):7896-7913. Epub 2020 Sep 2.

Department of Haematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Purpose: This study aimed to assess the health-related quality of life (HRQOL) of Chinese patients with different stages of multiple myeloma (MM) who received various treatments and identify the factors associated with a lower quality of life in China.

Methods: A cross-sectional, anonymous questionnaire was distributed to adults with MM. The measures of quality of life included the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30, QLQ-myeloma-specific module 20 (MY20), and EuroQoL EQ-5D. The data, including patient factors, difficulties experienced during the diagnosis and treatment processes, psychosocial factors and disease- or treatment-related effects, were collected.

Results: Four hundred and thirty patients with MM were recruited from all 27 provinces of China, and their average age was 55.7 years. Many variables were significantly associated with the HRQOL of the patients with MM. In the multivariate analyses, performance status, psychosocial factors, disease phase, and an early diagnosis were significantly associated with the HRQOL. In the subgroup analysis, the HRQOL of the patients who underwent autologous stem cell transplantation (ASCT) was significantly higher than that of the non-ASCT patients. Treatment-related toxicities had a significant impact on the quality of life of the patients with MM, and 91.5% of the patients intended to stop the maintenance treatment.

Conclusions: The quality of life of patients with MM in China is affected by patient factors, difficulties experienced during the diagnosis and treatment processes, psychosocial factors, and disease- or treatment-related effects. Efforts should be exerted to improve the overall quality of life of these patients in China.
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http://dx.doi.org/10.1002/cam4.3391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643654PMC
November 2020

Association of two novel adiposity indicators with visceral fat area in type 2 diabetic patients: Novel adiposity indexes for type 2 diabetes.

Medicine (Baltimore) 2020 May;99(19):e20046

Department of Endocrinology, The First Hospital of Qinhuangdao, Qinhuangdao, 066000, Hebei Province, China.

The present study evaluated the performance of 2 novel adiposity indicators, body shape index (ABSI), and body roundness index (BRI), to determine the accumulation of visceral fat in type 2 diabetic patients.A cross-sectional study was performed on 233 type 2 diabetic patients from Qinhuangdao, China. Visceral fat area (VFA) was measured using bioelectrical impedance. Accumulation of visceral fat was defined as VFA ≥ 100 cm.In diabetic males, the area under the curve (AUC) values were 0.904 for waist circumference (WC), 0.923 for BRI, and 0.788 for ABSI. In diabetic females, the AUC values were 0.894 for WC, 0.915 for BRI, and 0.668 for ABSI. The AUCs were similar between BRI and WC (P > .05). The AUC for ABSI was lower compared to WC and BRI (P < .05). The optimal cut-off for BRI was 4.25 for diabetic males (sensitivity = 87.8% and specificity = 81.1%) and 4.75 for diabetic females (sensitivity = 80.8% and specificity = 88.1%).BRI was an effective indicator for determining the accumulation of visceral fat in type 2 diabetic patients, however, it was not better compared to WC.
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http://dx.doi.org/10.1097/MD.0000000000020046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220767PMC
May 2020

A drug-inducible sex-separation technique for insects.

Nat Commun 2020 04 30;11(1):2106. Epub 2020 Apr 30.

Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, 92092, USA.

Here, we describe a drug-inducible genetic system for insect sex-separation that demonstrates proof-of-principle for positive sex selection in D. melanogaster. The system exploits the toxicity of commonly used broad-spectrum antibiotics geneticin and puromycin to kill the non-rescued sex. Sex-specific rescue is achieved by inserting sex-specific introns into the coding sequences of antibiotic-resistance genes. When raised on geneticin-supplemented food, the sex-sorter line establishes 100% positive selection for female progeny, while the food supplemented with puromycin positively selects 100% male progeny. Since the described system exploits conserved sex-specific splicing mechanisms and reagents, it has the potential to be adaptable to other insect species of medical and agricultural importance.
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http://dx.doi.org/10.1038/s41467-020-16020-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193620PMC
April 2020

Early monoclonal protein decline pattern is an independent prognostic factor in patients with multiple myeloma.

Ann Hematol 2020 Mar 21;99(3):581-589. Epub 2020 Jan 21.

Department of Hematology, The First Affiliated Hospital of SunYat-sen University, 58 Second Zhongshan Road, Guangzhou, 510080, China.

Patients always have different responses to the same treatment due to the heterogeneity of multiple myeloma (MM). However, the relationship between monoclonal protein (M-protein) reduction rates during treatment and survival prognosis in MM patients remains controversial. We retrospectively analyzed 198 newly diagnosed MM patients who received regular bortezomib-based chemotherapy for at least 2 cycles and subsequent autologous stem cell transplantation (ASCT) plus continuous maintenance. The relationship between the early M-protein reduction rates and survival prognosis was evaluated. This study is the first to divide patients into three patterns, namely, A, B, and C, according to the M-protein reduction rate during the first two therapy cycles. The results showed that pattern B patients with progressive reduction in M-protein had better progression-free survival (PFS) and overall survival (OS) than did pattern A or C patients with precipitating or slow M-protein reduction (75.33 ± 18.81 versus 41.23 ± 9.13 or 26.60 ± 6.67 months; P < 0.001; 117.33 ± 18.44 versus 71.00 ± 10.06 or 39.73 ± 24.10 months; P = 0.003, respectively). In addition, biological analysis showed that pattern A + C patients had higher international staging system (ISS) stage III proportions (P = 0.008) and lactate dehydrogenase (LDH) elevations (P = 0.044) than pattern B patients. Furthermore, pattern A + C was a significant independent adverse parameter for PFS and OS (HR = 2.62, P = 0.001; HR = 2.15, P = 0.022, respectively). Thus, our results demonstrate that pattern A + C indicates an inferior survival prognosis in MM.
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http://dx.doi.org/10.1007/s00277-020-03915-9DOI Listing
March 2020

Assessment of a Split Homing Based Gene Drive for Efficient Knockout of Multiple Genes.

G3 (Bethesda) 2020 02 6;10(2):827-837. Epub 2020 Feb 6.

Section of Cell and Developmental Biology and

Homing based gene drives (HGD) possess the potential to spread linked cargo genes into natural populations and are poised to revolutionize population control of animals. Given that host encoded genes have been identified that are important for pathogen transmission, targeting these genes using guide RNAs as cargo genes linked to drives may provide a robust method to prevent disease transmission. However, effectiveness of the inclusion of additional guide RNAs that target separate genes has not been thoroughly explored. To test this approach, we generated a split-HGD in that encoded a drive linked effector consisting of a second gRNA engineered to target a separate host-encoded gene, which we term a gRNA-mediated effector (GME). This design enabled us to assess homing and knockout efficiencies of two target genes simultaneously, and also explore the timing and tissue specificity of Cas9 expression on cleavage/homing rates. We demonstrate that inclusion of a GME can result in high efficiency of disruption of both genes during super-Mendelian propagation of split-HGD. Furthermore, both genes were knocked out one generation earlier than expected indicating the robust somatic expression of Cas9 driven by germline-limited promoters. We also assess the efficiency of 'shadow drive' generated by maternally deposited Cas9 protein and accumulation of drive-induced resistance alleles along multiple generations, and discuss design principles of HGD that could mitigate the accumulation of resistance alleles while incorporating a GME.
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http://dx.doi.org/10.1534/g3.119.400985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003086PMC
February 2020

Microbial antigens-loaded myeloma cells enhance Th2 cell proliferation and myeloma clonogenicity via Th2-myeloma cell interaction.

BMC Cancer 2019 Dec 23;19(1):1246. Epub 2019 Dec 23.

Department of Hematology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China.

Background: Myeloma cells retain B cell functions, considered to be potential antigen presenting cells, yet there is little information regarding promoting Th2 cell proliferation or the direct effects to myeloma on the Th2 cells stimulated by microbial antigens-loaded myeloma cells.

Methods: Mixed lymphocyte reaction was used colorimetric assays via CCK8-kit. Surface molecular expression was performed by flow cytometry, cells sorting using microbeads. The concentrations of cytokines in serum were assessed using an ELISA kit. Clonogenic assay were performed in a methylcellulose culture system. Statistical analysis was assessed using the Student's t-test or one-way analysis of variance for multiple comparisons test.

Results: The expression of HLA-DR, CD80 and CD40 on RPMI8266 cell membrane surface was upregulated by interaction with interferon-γ and/or Bacillus Calmette-Guerin Vaccine (BCGV). RPMI8266 cells were able to induce the mixed lymphocyte reaction in a dose-dependent fashion. The Th2 ratio induced by RPMI8266 treated by BCGV and interferon-γ (treated-RPMI8266) cells was only slightly greater than by untreated-tumor cells, but the serum IL-4 level secreted by Th2 cells was markedly higher in treated-RPMI8266 cells group. Th2 cells stimulated by treated-myeloma cells could directly promote treated-myeloma cell clonogenicity in a dose-dependent manner. Anti-HLADR IgG2b completely blocked increased of IL-4 secretion by Th2 cells stimulated by treated-myeloma cells, while also blocked enhancing the clonogenicity of treated tumor cells stimulated by MM-Th2 cells.

Conclusions: These results indicate that a novel mechanism of myeloma pathogenesis in myeloma cells could act as an APC to present microbial Ags to Th2 cells, promoting Th2 cell proliferation, consequently facilitating tumor development by close interaction between Th2 myeloma cells. Taken together, the microbial Ag presenting course of MM-Th2-MM interactions-restricted by MHC class-II-may result in tumor development such that all factors involved in the system could have a potential for myeloma therapeutic intervention.
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http://dx.doi.org/10.1186/s12885-019-6469-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929311PMC
December 2019

Fecal Microbiota Taxonomic Shifts in Chinese Multiple Myeloma Patients Analyzed by Quantitative Polimerase Chain Reaction (QPCR) and 16S rRNA High-Throughput Sequencing.

Med Sci Monit 2019 Nov 3;25:8269-8280. Epub 2019 Nov 3.

Department of Hematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).

BACKGROUND Increasing evidence has suggested that gut flora play an important role in tumor progression and prognosis. However, the relationship between fecal microbiota and hematologic malignancy requires further investigation. This study aimed to characterize the relationship of the fecal microbial community in multiple myeloma (MM) patients. MATERIAL AND METHODS A total of 40 MM patients and healthy controls (n=17) were retrospectively collected from the First Affiliated Hospital of Sun Yat-sen University between October 2018 and May 2019. The fecal samples were collected for 16S rRNA high-throughput sequencing for the fecal microbial community, as well as diversity and correlation analysis. Furthermore, 21 MM patients and their family members were selected for the matched pair analysis to confirm the fecal microbiota taxonomic changes by qRT-PCR assay. RESULTS Diversity analysis showed that diversity measured by Shannon index was lower in MM patients compared with healthy controls. At the phylum level, higher abundances of Proteobacteria but lower abundances of Actinobacteria were identified in the MM group in comparison with the healthy control group. At the genus level, the proportion of Bacteroides, Faecalibacterium, and Roseburia was significantly higher in the MM group. The matched pair analysis showed that Pseudomonas aeruginosa and Faecalibacterium were significantly more abundant in the MM group. Further analysis on prognostic risk factors revealed that the Faecalibacterium prausnitzii level was significantly correlated with ISS stage. CONCLUSIONS Our study highlights the imbalanced composition and diversity of the gastrointestinal microbiome in MM patients, which could be further used as a potential biomarker for MM risk screening, therapeutic strategies, and prognostic prediction.
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http://dx.doi.org/10.12659/MSM.919988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855177PMC
November 2019

Columbamine suppresses the proliferation and malignization of colon cancer cells via abolishing Wnt/β-catenin signaling pathway.

Cancer Manag Res 2019 23;11:8635-8645. Epub 2019 Sep 23.

Department of General Surgery, Fifth Hospital in Wuhan, Wuhan, Hubei 430050, People's Republic of China.

Background: Colon cancer is one of the most common malignancies worldwide. Because of the side effects and defects in tolerance of chemotherapy, it is necessary to discover new drugs for colon cancer treatment. Columbamine has been identified as an effective anti-osteosarcoma compound with only minor side effects. In this study, we analyzed the anticancer effect of columbamine on colon cancer.

Methods: Human colon cancer cell lines were treatment with columbamine. MTT assay, colony formation assay, apoptosis detection and tumorigenicity assay were performed to detect the protective effect of columbamine on colon cancer development. Western blot assay and luciferase reporter assay were conducted to investigate the potential mechanism of the columbamine treatment.

Results: Columbamine significantly inhibited the proliferation, migration, invasion process of colon cancer cells, and dramatically promoted the apoptosis rate of colon cancer cells to further suppress the development of colon cancer to tumor. Both the signaling transducing and key factors expression of Wnt/β-catenin signaling pathway were obviously repressed by columbamine treatment in a dose-dependent manner.

Conclusion: The present study indicated that columbamine exerts its anti-tumor effect in colon cancer cells through abolishing Wnt/β-catenin signaling pathway. Columbamine may be a new therapy compound for colon cancer.
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http://dx.doi.org/10.2147/CMAR.S209861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764743PMC
September 2019

Reply to 'Concerns about the feasibility of using "precision guided sterile males" to control insects'.

Nat Commun 2019 09 2;10(1):3955. Epub 2019 Sep 2.

Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, United States of America.

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http://dx.doi.org/10.1038/s41467-019-11617-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718384PMC
September 2019

1q21 Gain Combined with High-Risk Factors Is a Heterogeneous Prognostic Factor in Newly Diagnosed Multiple Myeloma: A Multicenter Study in China.

Oncologist 2019 11 27;24(11):e1132-e1140. Epub 2019 Aug 27.

Department of Hematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China

Background: The prognostic value of 1q21 gain in newly diagnosed multiple myeloma (NDMM) remains controversial. Our aim was to investigate the prognostic value of 1q21 gain in a Chinese population.

Materials And Methods: We retrospectively identified 565 patients with NDMM from multiple centers in China.

Results: We detected 1q21 gain in 222 (39.3%) patients, among whom 144 had three copies of 1q21, 57 had four copies of 1q21, and 21 had at least five copies of 1q21. Copy number variation did not show any effect on the disease outcome. Multivariate analysis indicated that 1q21 gain was an independent factor for poor prognosis, but we found that 1q21 gain was strongly associated with other high-risk factors, such as del(17p), t(4;14), t(14;16), lactate dehydrogenase (LDH) level >300 U/L and International Scoring System (ISS) stage II-III ( < .001). Further analysis revealed that in the absence of other high-risk factors, isolated 1q21 gain resulted in similar progression-free survival (PFS; 52.0 vs. 52.8 months, = .810) and overall survival (OS; not reached vs. not reached, = .833); additionally, when present with other high-risk cytogenetic abnormalities or increased LDH levels, 1q21 gain lost its prognostic power. However, the presence of 1q21 gain increased the adverse impact of ISS stage. Furthermore, 1q21 gain predicted poor PFS and OS in patients who received bortezomib-based regimens. Moreover, autologous stem cell transplantation reversed the poor prognosis in patients with 1q21 gain.

Conclusion: Our results show that heterogeneity exists among patients with 1q21 gain and suggest that we should assess the impact of 1q21 gain on prognosis according to different treatment regimens and accompanying high-risk factors.

Implications For Practice: 1q21 gain is one of the most common chromosomal aberrations in multiple myeloma (MM); however, the prognostic value of 1q21 gain remains controversial. This study investigated the prognostic value of 1q21 gain in a Chinese population with newly diagnosed MM. The results showed that heterogeneity exists among patients with 1q21 gain and suggested that the impact of 1q21 gain on prognosis should be assessed according to different treatment regimens and accompanying high-risk factors. These results could help stratify risk in patients with MM and guide treatment decisions.
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http://dx.doi.org/10.1634/theoncologist.2019-0132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853115PMC
November 2019

A favorable inductive remission rate for decitabine combined with chemotherapy as a first course in <60-year-old acute myeloid leukemia patients with myelodysplasia syndrome features.

Cancer Med 2019 Sep 19;8(11):5108-5115. Epub 2019 Jul 19.

Department of Hematology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

In acute myeloid leukemia (AML), myelodysplasia-related changes contribute to a poor prognosis. This retrospective, propensity score-matched study analyzed 108 newly diagnosed AML patients with features of myelodysplasia syndrome (MDS) (aged 14-60 years) from 2014 to 2018, who received either idarubicin and cytarabine (IA) or decitabine, idarubicin and cytarabine (DAC+IA), and compared efficacy and toxicity between the two regimens. After propensity score matching, there were 54 patients in each group. The rate of complete remission (CR) was higher in the DAC+IA group than in the IA group (85.2% vs 68.5%, P = .040) after the first course, and toxicities were comparable in both groups. Multivariate analysis indicated that the combination with DAC was independent factor for CR rate after the first induction therapy (OR = 2.978, 95% CI:1.090-8.137, P = .033). Subgroup analysis showed a CR advantage for DAC+IA (vs IA) for patients of intermediate-high risk status according to National Comprehensive Cancer Network prognostic stratification. In conclusion, DAC+IA is therefore offered as a new induction choice for newly diagnosed AML patients with features of MDS, aged <60 years old, especially in intermediate-high risk status.
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http://dx.doi.org/10.1002/cam4.2418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718585PMC
September 2019

Transforming insect population control with precision guided sterile males with demonstration in flies.

Nat Commun 2019 01 8;10(1):84. Epub 2019 Jan 8.

Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093, California, USA.

The sterile insect technique (SIT) is an environmentally safe and proven technology to suppress wild populations. To further advance its utility, a novel CRISPR-based technology termed precision guided SIT (pgSIT) is described. PgSIT mechanistically relies on a dominant genetic technology that enables simultaneous sexing and sterilization, facilitating the release of eggs into the environment ensuring only sterile adult males emerge. Importantly, for field applications, the release of eggs will eliminate burdens of manually sexing and sterilizing males, thereby reducing overall effort and increasing scalability. Here, to demonstrate efficacy, we systematically engineer multiple pgSIT systems in Drosophila which consistently give rise to 100% sterile males. Importantly, we demonstrate that pgSIT-generated sterile males are fit and competitive. Using mathematical models, we predict pgSIT will induce substantially greater population suppression than can be achieved by currently-available self-limiting suppression technologies. Taken together, pgSIT offers to potentially transform our ability to control insect agricultural pests and disease vectors.
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http://dx.doi.org/10.1038/s41467-018-07964-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325135PMC
January 2019

Influencing Factors of the Diabetes Distress among Chinese Patients with Type 2 Diabetes Mellitus.

Psychiatr Danub 2018 Dec;30(4):459-465

The Endocrinology Department of the People's Hospital of Jinhua, Jinhua, 321000, China,

Background: Patients with Diabetes Mellitus (DM) are required to have long-term treatment regimen and strict self-management, which thus might lead to the Diabetes Distress (DD). Patients' DD varies in different regions with different levels of medical conditions. For improving the treatment effect of the patients with the Type-2-Diabetes-Mellitus (T2DM), this study explores the influencing factors of the patients' DD in the regions where the medical treatment are at low level.

Subjects And Methods: In this study, 167 adult patients with T2DM were selected from the People's Hospital of Jinhua city, an A-grade hospital of a small-mid-sized city in Eastern China. Based on these samples, the Diabetes Distress Scale with 17 items (DDS17) was adopted to measure the degree of patients' DD, and then regression analyses were carried out to investigate the influencing factors for their DD.

Results: The T2DM patients with moderate and high levels of DD take up 54.5% of the samples investigated in this study. According to the Spearman correlation analysis, sleep time, physical exercise, diet control, treatment regimen, TG and HbA1c significantly affect the patients' DD. Through the multivariate linear regression analysis, this study shows that (1) sleep time significantly influences the T2DM patients' DD (β=-0.213, P=0.034); (2) sleep time also impacts emotional burden (β=-0.379, P=0.027); (3) physical exercise (β=-0.195, P=0.002), treatment regimen (β=0.158, P=0.026) and diet control (β=0.158, P=0.026) are the three major influencing factors for regimen-related distress.

Conclusion: In the small-mid-sized city where the treatment regimen is not highly advanced, to alleviate the T2DM patients' DD, the medical staff should suggest the patients to improve sleep quality and exercise more, help them positively understand the insulin infusion therapy and take proper diet control.
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http://dx.doi.org/10.24869/psyd.2018.459DOI Listing
December 2018

Longitudinal Flow Cytometry Identified "Minimal Residual Disease" (MRD) Evolution Patterns for Predicting the Prognosis of Patients with Transplant-Eligible Multiple Myeloma.

Biol Blood Marrow Transplant 2018 12 22;24(12):2568-2574. Epub 2018 Aug 22.

Department of Hematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address:

Many questions about minimal residual disease (MRD) still need to be answered for multiple myeloma (MM). Flow MRD was monitored in 104 consecutive patients with MM after induction and at the 3rd, 6th, 9th, 12th, 18th, and 24th months post-transplant. Four MRD evolution patterns were revealed: Pattern 1 patients had persistent MRD-negative status after post-induction with no progression; pattern 2 patients had MRD-positive status postinduction but became MRD negative within 24 months post-transplant; pattern 3 patients had MRD-negative status postinduction but became MRD positive within 24 months post-transplant; and pattern 4 patients had persistent MRD-positive status after postinduction. Patients with MRD evolution pattern 1 had a better time to progression than did patients with the other evolution patterns (not reached versus not reached, versus 15.4 ± 2.4 months, versus 16.9 ± 3.0 months; log-rank test, P = .003, P = .000, and P = .000, respectively). Patients with MRD pattern 1 had a significantly longer overall survival than did patients with pattern 3 (not reached versus 35.2 ± 18.6 months; log-rank test, P = .000) and pattern 4 (not reached versus 23.8 ± 15.0 months, log-rank test, P = .000) but had a similar overall survival as pattern 2 patients (not reached versus not reached; log-rank test, P = .229). For progressing patients with MRD evolution pattern 2 or 3, the median interval of a sustained MRD-negative status was only 17 months and the median time from MRD reappearance to disease progression was only 4.6 months. A more complete MRD evolution pattern was developed to predict the outcomes for patients with MM. The optimal time of MRD assessment should include postinduction and 3rd and 24th month post-transplant. Regular MRD assessments will help detect relapse early. A sustained negative MRD status should last for at least 24 months.
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http://dx.doi.org/10.1016/j.bbmt.2018.07.040DOI Listing
December 2018
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