2022 Vol. 35, No. 9

2022, 35(9)
2022, 35(9): 1-2.
Original Article
Key Social Determinants to Narrow the Gap between Health-adjusted Life Expectancy and Life Expectancy in Megacities
XI Jun Yan, CHEN Yuan Yuan, ZHANG Yu Qin, LUO Ao, DU Zhi Cheng, LIANG Bo Heng, DONG Hang, LIN Xiao, QIN Peng Zhe, HAO Yuan Tao
2022, 35(9): 773-781. doi: 10.3967/bes2022.102
  Objective  Improvement in the quality of life is reflected in the narrowing of the gap between health-adjusted life expectancy (HALE) and life expectancy (LE). The effect of megacity expansion on narrowing the gap is rarely reported. This study aimed to disclose this potential relationship.  Methods  Annual life tables were constructed from identified death records and population counts from multiple administrative sources in Guangzhou, China, from 2010 to 2020. Joinpoint regression was used to evaluate the temporal trend. Generalized principal component analysis and multilevel models were applied to examine the county-level association between the gap and social determinants.  Results  Although LE and HALE in megacities are increasing steadily, their gap is widening. Socio-economic and health services are guaranteed to narrow this gap. Increasing personal wealth, a growing number of newborns and healthy immigrants, high urbanization, and healthy aging have helped in narrowing this gap.  Conclusion  In megacities, parallel LE and HALE growth should be highly considered to narrow their gap. Multiple social determinants need to be integrated as a whole to formulate public health plans.
Rabies Virus Neutralizing Activity, Safety, and Immunogenicity of Recombinant Human Rabies Antibody Compared with Human Rabies Immunoglobulin in Healthy Adults
ZHANG Jun Nan, MENG Ya Juan, BAI Yun Hua, LI Yu Feng, YANG Li Qing, SHI Nian Min, HAN Hui Xia, GAO Jian, ZHU Li Juan, LI Shu Ping, ZHANG Jing, ZHAO Qin Hua, WANG Xiu Qin, WEI Jing Shuang, REN Le Min, CAO Chen Hua, CHEN Chen, ZHAO Wei, LI Li
2022, 35(9): 782-791. doi: 10.3967/bes2022.103
  Objective  Preliminary assessment of rabies virus neutralizing activity, safety and immunogenicity of a recombinant human rabies antibody (NM57) compared with human rabies immunoglobulin (HRIG) in Chinese healthy adults.  Methods  Subjects were randomly (1:1:1) allocated to Groups A (20 IU/kg NM57), B (40 IU/kg NM57), or C (20 IU/kg HRIG). One injection was given on the day of enrollment. Blood samples were collected on days −7 to 0 (pre-injection), 3, 7, 14, 28, and 42. Adverse events (AEs) and serious AEs (SAEs) were recorded over a period of 42 days after injection.  Results  All 60 subjects developed detectable rabies virus neutralizing antibodies (RVNAs) (> 0.05 IU/mL) on days 3, 7, 14, 28, and 42. The RVNA levels peaked on day 3 in all three groups, with a geometric mean concentration (GMC) of 0.2139 IU/mL in Group A, 0.3660 IU/mL in Group B, and 0.1994 IU/mL in Group C. At each follow-up point, the GMC in Group B was significantly higher than that in Groups A and C. The areas under the antibody concentration curve over 0–14 days and 0–42 days in Group B were significantly larger than those in Groups A and C. Fifteen AEs were reported. Except for one grade 2 myalgia in Group C, the other 14 were all grade 1. No SAEs were observed.  Conclusion  The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG, and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar. Safety was comparable between NM57 and HRIG.
Montanide ISA-720 and Naloxone in HBsAg Vaccine Formulation: Cytokine Profiling and Monitoring of Long-Lasting Humoral Immune Responses
Mina Mirzaee, Setareh Haghighat, Bahareh Golkaran, Fatemeh Asgarhalvaei, Rayhaneh Mirzaee, Morteza Taghizadeh, Mohammad Ali Savoji, Behzad Esfandiari, Mehdi Mahdavi
2022, 35(9): 792-803. doi: 10.3967/bes2022.104
  Objective  This study aimed to investigate the effects of Montanide ISA-720 and Naloxone (NLX) in Hepatitis B surface antigen (HBsAg) vaccine formulation on cytokine and long-lasting antibody responses.  Methods  First, the HBsAg was formulated in Montanide ISA-720 adjuvant and Naloxone at 5 and 10 mg/kg. The experimental mice were immunized three times at a 2-week interval, and then IL-4, IL-2, TNF-α, and IFN-γ cytokines; long-lasting IgG antibody responses 220 days after the last shot; and IgG1/IgG2a isotypes were assessed by ELISA.  Results  The HBsAg-Alum group exhibited the highest IL-4 cytokine response among the experimental groups, whereas NLX in HBsAg-MON720 vaccine formulation did not affect cytokine responses. In addition, NLX in Alum-based vaccine suppressed IL-4 cytokine response and increased the IL-2/IL-4 cytokine ratio. Moreover, HBsAg-MON720 was more potent than HBsAg-Alum in the induction of antibody responses, and NLX in Alum- and MON720-based vaccines induced long-lasting antibody responses.  Conclusion  NLX in Alum-based vaccine decreased IL-4 cytokine response, increased IL-2/IL-4 cytokine ratio, and improved long-lasting humoral immune responses in both vaccine formulations. Therefore, the adjuvant activity of NLX in the vaccine formulation depends on the type of adjuvant and the nature of the antigen in the vaccine formulation.
The Viral Load of Epstein-Barr Virus in Blood of Children after Hematopoietic Stem Cell Transplantation
WANG Wen Jun, FENG Shun Qiao, HE Feng, DU Hai Jun, FENG Miao, WANG Rui Fang, MEI Guo Yong, LIU Mi, LIU Rong, YAO Hai Lan, HAN Jun
2022, 35(9): 804-810. doi: 10.3967/bes2022.052
  Objective  To detect the Epstein-Barr virus (EBV) viral load of children after hematopoietic stem cell transplantation (HSCT) using chip digital PCR (cdPCR).   Methods  The sensitivity of cdPCR was determined using EBV plasmids and the EBV B95-8 strain. The specificity of EBV cdPCR was evaluated using the EBV B95-8 strain and other herpesviruses (herpes simplex virus 1, herpes simplex virus 2, varicella zoster virus, human cytomegalovirus, human herpesvirus 6, and human herpesvirus 7). From May 2019 to September 2020, 64 serum samples of children following HSCT were collected. EBV infection and the viral load of serum samples were detected by cdPCR. The epidemiological characteristics of EBV infections were analyzed in HSCT patients.   Results  The limit of detection of EBV cdPCR was 110 copies/mL, and the limit of detection of EBV quantitative PCR was 327 copies/mL for the pUC57-BALF5 plasmid. The result of EBV cdPCR was up to 121 copies/mL in the EBV B95-8 strain, and both were more sensitive than that of quantitative PCR. Using cdPCR, the incidence of EBV infection was 18.75% in 64 children after HSCT. The minimum EBV viral load was 140 copies/mL, and the maximum viral load was 3,209 copies/mL using cdPCR. The average hospital stay of children with EBV infection (184 ± 91 days) was longer than that of children without EBV infection (125 ± 79 days), P = 0.026.   Conclusion  EBV cdPCR had good sensitivity and specificity. The incidence of EBV infection was 18.75% in 64 children after HSCT from May 2019 to September 2020. EBV cdPCR could therefore be a novel method to detect EBV viral load in children after HSCT.
Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance the Osteoblastic Differentiation of Periodontal Ligament Stem Cells Under High Glucose Conditions Through the PI3K/AKT Signaling Pathway
YANG Shuo, ZHU Biao, TIAN Xiao Yu, YU Han Ying, QIAO Bo, ZHAO Li Sheng, ZHANG Bin
2022, 35(9): 811-820. doi: 10.3967/bes2022.105
  Objective  High glucose (HG) can influence the osteogenic differentiation ability of periodontal ligament stem cells (PDLSCs). Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-exo) have broad application prospects in tissue healing. The current study aimed to explore whether hUCMSC-exo could promote the osteogenic differentiation of hPDLSCs under HG conditions and the underlying mechanism.  Methods   We used a 30 mmol/L glucose concentration to simulate HG conditions. CCK-8 assay was performed to evaluate the effect of hUCMSC-exo on the proliferation of hPDLSCs. Alkaline phosphatase (ALP) staining, ALP activity, and qRT-PCR were performed to evaluate the pro-osteogenic effect of hUCMSC-exo on hPDLSCs. Western blot analysis was conducted to evaluate the underlying mechanism.  Results   The results of the CCK-8 assay, ALP staining, ALP activity, and qRT-PCR assay showed that hUCMSC-exo significantly promoted cell proliferation and osteogenic differentiation in a dose-dependent manner. The Western blot results revealed that hUCMSC-exo significantly increased the levels of p-PI3K and p-AKT in cells, and the effect was inhibited by LY294002 (PI3K inhibitor) or MK2206 (AKT inhibitor), respectively. Moreover, the increases in osteogenic indicators induced by hUCMSC-exo were significantly suppressed by LY294002 and MK2206.  Conclusion   hUCMSC-exo promote the osteogenic differentiation of hPDLSCs under HG conditions through the PI3K/AKT signaling pathway.
H-NS Represses Biofilm Formation and c-di-GMP Synthesis in Vibrio parahaemolyticus
XUE Xing Fan, ZHNAG Miao Miao, SUN Jun Fang, LI Xue, WU Qi Min, YIN Zhe, YANG Wen Hui, NI Bin, HU Ling Fei, ZHOU Dong Sheng, LU Ren Fei, ZHANG Yi Quan
2022, 35(9): 821-829. doi: 10.3967/bes2022.106
  Objective  This study aimed to investigate the regulation of histone-like nucleoid structuring protein (H-NS) on biofilm formation and cyclic diguanylate (c-di-GMP) synthesis in Vibrio parahaemolyticus RIMD2210633.  Methods  Regulatory mechanisms were analyzed by the combined utilization of crystal violet staining, quantification of c-di-GMP, quantitative real-time polymerase chain reaction, LacZ fusion, and electrophoretic-mobility shift assay.  Results  The deletion of hns enhanced the biofilm formation and intracellular c-di-GMP levels in V. parahaemolyticus RIMD2210633. H-NS can bind the upstream promoter–proximal DNA regions of scrA, scrG, VP0117, VPA0198, VPA1176, VP0699, and VP2979 to repress their transcription. These genes encode a group of proteins with GGDEF and/or EAL domains associated with c-di-GMP metabolism.  Conclusion  One of the mechanisms by which H-NS represses the biofilm formation by V. parahaemolyticus RIMD2210633 may be via repression of the production of intracellular c-di-GMP.
Effect of Maximal Oxygen Pulse on Patients with Chronic Obstructive Pulmonary Disease
LI Yun Xiao, WANG Jun, WU Bo, LIN Fang, TAN Chun Ting, YU Gang Gang, NIE Shan, ZHAO Ran Ran, XU Bo
2022, 35(9): 830-841. doi: 10.3967/bes2022.107
  Objective  This study evaluated the effect of maximal oxygen pulse (O2Pmax) on patients with chronic obstructive pulmonary disease (COPD) and confirmed the predictive effect on acute exacerbations of COPD (AECOPD).  Methods  This retrospective study included 91 participants who underwent cardiopulmonary exercise testing (CPET), lung function testing, a dyspnea scale assessment, and a 3-year follow-up. The participants were divided into two groups according to the O2Pmax value. Exercise capacity, ventilatory conditions, gas exchange efficiency, and dyspnea symptoms were compared, and the correlations between O2Pmax and these indices were evaluated. The ability of O2Pmax to predict AECOPD was examined.  Results  Exercise capacity, ventilatory conditions, and gas exchange efficiency were lower, and dyspnea symptom scores were higher in the impaired O2Pmax group (P < 0.05). O2Pmax was positively correlated with forced vital capacity (FVC)%, forced expiratory volume in 1 sec (FEV1)%, FEV1/FVC%, anaerobic threshold (AT), work rate (WR)%, aximal oxygen uptake (V̇O2max)%, V̇O2/kgmax, V̇O2/kgmax%, WRAT, WRmax, V̇O2AT, V̇O2max, and V̇Emax, and was negatively correlated with EqCO2AT, and EqCO2max (P < 0.05). Most importantly, O2Pmax could be used to predict AECOPD, and the best cut-off value was 89.5% (area under the curve, 0.739; 95% CI, 0.609–0.869).  Conclusion  O2Pmax reflected exercise capacity, ventilation capacity, gas exchange capacity, and dyspnea symptoms in patients with COPD and may be an independent predictor of AECOPD.
Genetic Diversity, Antibiotic Resistance, and Pathogenicity of Aeromonas Species from Food Products in Shanghai, China
QU Feng Tian, WANG Wen Qing, LIU Qian, ZHOU Hai Jian, HU Jin Rui, DU Xiao Li, WANG Yue, XUE Jia Qi, CUI Zhi Gang, XIE Gui Lin, MENG Shuang
2022, 35(9): 842-853. doi: 10.3967/bes2022.108
  Objective  Aeromonas has recently been recognized as an emerging human pathogen. Aeromonas-associated diarrhea is a phenomenon occurring worldwide. This study was designed to determine the prevalence, genetic diversity, antibiotic resistance, and pathogenicity of Aeromonas strains isolated from food products in Shanghai.  Methods  Aeromonas isolates (n = 79) collected from food samples were analyzed using concatenated gyrB-cpn60 sequencing. The antibiotic resistance of these isolates was determined using antimicrobial susceptibility testing. Pathogenicity was assessed using β-hemolytic, extracellular protease, virulence gene detection, C. elegans liquid toxicity (LT), and cytotoxicity assays.  Results  Eight different species were identified among the 79 isolates. The most prevalent Aeromonas species were A. veronii [62 (78.5%)], A. caviae [6 (7.6%)], A. dhakensis [3 (3.8%)], and A. salmonicida [3 (3.8%)]. The Aeromonas isolates were divided into 73 sequence types (STs), of which 65 were novel. The isolates were hemolytic (45.6%) and protease-positive (81.0%). The most prevalent virulence genes were act (73.4%), fla (69.6%), aexT (36.7%), and ascV (30.4%). The results of C. elegans LT and cytotoxicity assays revealed that A. dhakensis and A. hydrophila were more virulent than A. veronii, A. caviae, and A. bivalvium. Antibiotic resistance genes [tetE, blaTEM, tetA, qnrS, aac(6)-Ib, mcr-1, and mcr-3] were detected in the isolates. The multidrug-resistance rate of the Aeromonas isolates was 11.4%, and 93.7% of the Aeromonas isolates were resistant to cefazolin.  Conclusion  The taxonomy, antibiotic resistance, and pathogenicity of different Aeromonas species varied. The Aeromonas isolates A. dhakensis and A. hydrophila were highly pathogenic, indicating that food-derived Aeromonas isolates are potential risks for public health and food safety. The monitoring of food quality and safety will result in better prevention and treatment strategies to control diarrhea illnesses in China.
Letter to the Editor
Construction of MicroRNA-Target Interaction Networks Based on MicroRNA Expression Profiles of HRV16-infected H1-HeLa Cells
SONG Qin Qin, WANG Yan Hai, WANG Xin Ling, SHI Bing Tian, WANG Rui Fang, SONG Juan, WANG Wen Jun, XIA Dong, XIA Zhi Qiang, WEI Qiang, HAN Jun
2022, 35(9): 854-860. doi: 10.3967/bes2022.109
In the present study we investigated the changes in miRNA levels inhuman rhinovirus 16 (HRV16)-infected cells. A small RNA deep sequencing experiment was performed through next-generation sequencing. In total, 53 differentially expressed miRNAs were confirmed by RT-qPCR, including 37 known miRNAs and 16 novel miRNAs. Interaction networks between differentially expressed miRNAs and their targets were established by mirDIP and Navigator. The prediction results showed that QKI, NFAT5, BNC2, CELF2, LCOR, MBNL2, MTMR3, NFIB, PPARGC1A, RSBN1, TRPS1, WDR26, and ZNF148, which are associated with cellular differentiation and transcriptional regulation, were recognized by 12, 11, or 9 miRNAs. Many correlations were observed between transcriptional or post-transcriptional regulation of an miRNA and the expression levels of its target genes in HRV16-infected H1-HeLa cells.
Evaluating the Quality of Case-control Studies involving the Association between Tobacco Exposure and Diseases in a Chinese Population based on the Newcastle-Ottawa Scale and Post-hoc Power
SHI Yu Lin, ZHAO Jian, AI Fei Ling, WANG Yu Tong, HU Kui Ru, WANG Xue Wei, YANG Wen Yi, WANG Jing Xin, AI Li Mei, WAN Xia
2022, 35(9): 861-866. doi: 10.3967/bes2022.110
Soft Tissue Myoepithelioma in Children: A Rare Case Report of the Mediastinum and a Review of the Literature
DU Hong Mei, CAI Wei Song
2022, 35(9): 867-871. doi: 10.3967/bes2022.112
Exercise for Health Suzhou Initiative
2022, 35(9): 872-873. doi: 10.3967/bes2022.113