2024 Vol. 37, No. 2

Cover
2024-2 Cover
2024, 37(2)
Contents
2024-2 Contents
2024, 37(2): 1-2.
Original Article
Metabolomic Analysis in Saliva and Different Brain Regions of Older Mice with Postoperative Delirium Behaviors
LIU Xiao, CAO Ying, LIN Xiao Wan, GAO Dan Yang, MIAO Hui Hui, LI Tian Zuo
2024, 37(2): 133-145. doi: 10.3967/bes2024.015
  Objective  Postoperative delirium (POD) has become a critical challenge with severe consequences and increased incidences as the global population ages. However, the underlying mechanism is yet unknown. Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers.  Methods  Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group. Behavioral tests were conducted 24 h before surgery and 6, 9, and 24 h after surgery. Complement C3 (C3) and S100 calcium-binding protein B protein (S100beta) levels were measured in the hippocampus, and a metabolomics analysis was performed on saliva, hippocampus, cortex, and amygdala samples.  Results  In total, 43, 33, 38, and 14 differential metabolites were detected in the saliva, hippocampus, cortex, and amygdala, respectively. “Pyruvate” “alpha-linolenic acid” and “2-oleoyl-1-palmitoy-sn-glycero-3-phosphocholine” are enriched in one common pathway and may be potential non-invasive biomarkers for POD. Common changes were observed in the three brain regions, with the upregulation of 1-methylhistidine and downregulation of D-glutamine.  Conclusion  Dysfunctions in energy metabolism, oxidative stress, and neurotransmitter dysregulation are implicated in the development of POD. The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.
Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence
LIAO Zhen Yu, YANG Shuo, HU Song, LIU Jia, MAO Yong Jun, SUN Shu Qin
2024, 37(2): 146-156. doi: 10.3967/bes2024.016
  Objective   This study aimed to explore the association of single nucleotide polymorphisms (SNP) in the matrix metalloproteinase 2 (MMP-2) signaling pathway and the risk of vascular senescence (VS).  Methods   In this cross-sectional study, between May and November 2022, peripheral venous blood of 151 VS patients (case group) and 233 volunteers (control group) were collected. Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway, assessed through carotid-femoral pulse wave velocity (cfPWV), and analyzed using multivariate logistic regression. The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction (MDR) and generalized multifactor dimensionality regression (GMDR) modeling.  Results   Within the multivariate logistic regression models, four SNPs were screened to have significant associations with VS: chemokine (C‐C motif) ligand 2 (CCL2) rs4586, MMP2 rs14070, MMP2 rs7201, and MMP2 rs1053605. Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype, and those of the T/T genotype had a 19.375-fold increased risk. CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.  Conclusion   CCL2 rs4586, MMP-2 rs14070, MMP-2 rs7201, and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.
Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China
FAN Yu Feng, LIU Dong Xin, CHEN Yi Wang, OU Xi Chao, MAO Qi Zhi, YANG Ting Ting, WANG Xi Jiang, HE Wen Cong, ZHAO Bing, LIU Zhen Jiang, ABULIMITI Maiweilanjiang, AIHEMUTI Maimaitiaili, GAO Qian, ZHAO Yan Lin
2024, 37(2): 157-169. doi: 10.3967/bes2023.116
  Objective   China is among the 30 countries with a high burden of tuberculosis (TB) worldwide, and TB remains a public health concern. Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China. However, molecular epidemiological studies of Kashgar are lacking.  Methods   A population-based retrospective study was conducted using whole-genome sequencing (WGS) to determine the characteristics of drug resistance and the transmission patterns.  Results   A total of 1,668 isolates collected in 2020 were classified into lineages 2 (46.0%), 3 (27.5%), and 4 (26.5%). The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid (7.4%, 124/1,668), streptomycin (6.0%, 100/1,668), and rifampicin (3.3%, 55/1,668). The rate of rifampicin resistance was 1.8% (23/1,290) in the new cases and 9.4% (32/340) in the previously treated cases. Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains, respectively: 18.6% vs. 8.7 or 9%, P < 0.001. The estimated proportion of recent transmissions was 25.9% (432/1,668). Multivariate logistic analyses indicated that sex, age, occupation, lineage, and drug resistance were the risk factors for recent transmission. Despite the low rate of drug resistance, drug-resistant strains had a higher risk of recent transmission than the susceptible strains (adjusted odds ratio, 1.414; 95% CI, 1.023–1.954; P = 0.036). Among all patients with drug-resistant tuberculosis (DR-TB), 78.4% (171/218) were attributed to the transmission of DR-TB strains.  Conclusion   Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.
Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis
GU Wen Fei, SHI Xia, MA Xin, YU Jun Lei, XU Jin Chuan, QIAN Cheng Cheng, HU Zhi Dong, ZHANG Hui
2024, 37(2): 170-177. doi: 10.3967/bes2024.017
  Objective  To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis (EPTB).  Methods  This study was conducted at the Shanghai Public Health Clinical Center. A total of 115 patients underwent ultrasound-guided puncture biopsy, followed by MGIT 960 culture (culture), smear, GeneXpert MTB/RIF (Xpert), and histopathological examination. These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria: liquid culture and composite reference standard (CRS).  Results  When CRS was used as the reference standard, the sensitivity and specificity of culture, smear, Xpert, and histopathological examination were (44.83%, 89.29%), (51.72%, 89.29%), (70.11%, 96.43%), and (85.06%, 82.14%), respectively. Based on liquid culture tests, the sensitivity and specificity of smear, Xpert, and pathological examination were (66.67%, 72.60%), (83.33%, 63.01%), and (92.86%, 45.21%), respectively. Histopathological examination showed the highest sensitivity but lowest specificity. Further, we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80% and a specificity of 89.29%.  Conclusion  Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB. Compared with culture, smear, and Xpert, histopathological examination showed higher sensitivity but lower specificity. The combination of histopathology with Xpert showed the best performance characteristics.
Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China
SONG Yun, HE Ying, LU Xue Xin, ZHANG Xiao Mei, JIANG XIAO Lin, SONG Qing, HUANG Xue Yong, MA Hong Xia, YU Peng Cheng, ZHU Wu Yang
2024, 37(2): 178-186. doi: 10.3967/bes2024.018
  Objective  This study aimed to compare the current Essen rabies post-exposure immunization schedule (0-3-7-14-28) in China and the simple 4-dose schedule (0-3-7-14) newly recommended by the World Health Organization in terms of their safety, efficacy, and protection.  Methods  Mice were vaccinated according to different immunization schedules, and blood was collected for detection of rabies virus neutralizing antibodies (RVNAs) on days 14, 21, 28, 35, and 120 after the first immunization. Additionally, different groups of mice were injected with lethal doses of the CVS-11 virus on day 0, subjected to different rabies immunization schedules, and assessed for morbidity and death status. In a clinical trial, 185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule, and blood was collected for RVNAs detection on days 28 and 42 after the first immunization.  Results  A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day (P < 0.05). The groups 0-3-7-14, 0-3-7-21, and 0-3-7-28 showed no statistically significant difference (P > 0.05) in RVNAs levels at any time point. The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%, whereas that in the immunization groups was 40%. In the clinical trial, the RVNAs positive conversion rates on days 28 (14 days after 4 doses) and 42 (14 days after 5 doses) were both 100%, and no significant difference in RVNAs levels was observed (P > 0.05).  Conclusion  The simple 4-dose schedule can produce sufficient RVNAs levels, with no significant effect of a delayed fourth vaccine dose (14–28 d) on the immunization potential.
Anti-OX40 Antibody Combined with HBc VLPs Delays Tumor Growth in a Mouse Colon Cancer Model
LIU Jia Jia, SU Qiu Dong, YI Yao, SHEN Li Ping, BI Sheng Li
2024, 37(2): 187-195. doi: 10.3967/bes2024.019
  Objective  Combination immunotherapy strategies targeting OX40, a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation, differentiation, and effector function of tumor-infiltrating T cells, have attracted much attention for their excellent therapeutic effects. In this study, we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core virus-like particles (HBc VLPs) therapy using a mouse colon cancer model.   Methods  Humanized B-hOX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-hOX40 antibody. Tumor growth was monitored. Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.   Results  The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth, suggesting that a potent antitumor immunity was induced by the combination therapy. Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells (Teffs) and a significant decrease in regulatory T cells (Tregs) in the tumor microenvironment (TME), which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.   Conclusion  Combination therapy of anti-hOX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice, which may represent a potential design strategy for cancer immunotherapy.
Relationship of Retinal Nerve Fiber Layer Thickness and Retinal Vessel Calibers with Cognitive Impairment in the Asymptomatic Polyvascular Abnormalities Population
WANG Dan Dan, WANG An Xin, ZHANG Xiao Li, WEI Wen Bin, WU Shou Ling, ZHAO Xing Quan
2024, 37(2): 196-203. doi: 10.3967/bes2024.020
  Objective  Cognitive impairment (CI) in older individuals has a high morbidity rate worldwide, with poor diagnostic methods and susceptible population identification. This study aimed to investigate the relationship between different retinal metrics and CI in a particular population, emphasizing polyvascular status.  Methods  We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers, retinal nerve fiber layer (RNFL) thickness, and cognitive function of 3,785 participants, aged 40 years or older. Logistic regression was used to analyze the relationship between retinal metrics and cognitive function. Subgroups stratified by different vascular statuses were also analyzed.  Results  RNFL thickness was significantly thinner in the CI group (odds ratio: 0.973, 95% confidence interval: 0.953–0.994). In the subgroup analysis, the difference still existed in the non-intracranial arterial stenosis, non-extracranial carotid arterial stenosis, and peripheral arterial disease subgroups (P < 0.05).  Conclusion  A thin RNFL is associated with CI, especially in people with non-large vessel stenosis. The underlying small vessel change in RNFL and CI should be investigated in the future.
Letter to the Editor
Reinfection and Risk Factors of SARS-CoV-2 during an Omicron Wave 2022 in Shanghai
WANG Pei Qin, WANG Xiao Hang, WANG Jian, SHI Zhi Wen, CHU Dong Mei, WANG Zhi Fei, ZHANG Mu Bai, LIU Wei, ZHOU Zi Jie, XIE Wei Fen
2024, 37(2): 204-209. doi: 10.3967/bes2024.021
Establishment of an Iron Deficiency Model by Iron Depletion in Pregnant Rats
CHEN Xi, HAN Chao, ZHAO Jin Peng, SHEN Shi, WANG Li Yuan, REN Shou, WANG Tong Lei, MA Yan, XU Ze Chao, HUO Jun Sheng
2024, 37(2): 210-215. doi: 10.3967/bes2024.022
Atmospheric Particulate Matter 2.5 (PM2.5) Induces Cell Damage and Pruritus in Human Skin
HE Qiao, XUE Wan Ting, LI Li, YI Fan, LING Xiao, GUO Miao Miao
2024, 37(2): 216-220. doi: 10.3967/bes2024.023
Malvidin Mitigates Sepsis-induced Cardiac Injury by Modulating the TLR4-iNOS-COX-2 Inflammatory Pathway and the Bax/Bcl-2/Cyto-C Mitochondrial Apoptosis Pathway in a p38 MAPK-dependent Manner
ZHANG Wei, YUAN Si Long, QIANG Jing Chao, HUANG He, LI Da, SUN Ying, ZHANG Hong Gang
2024, 37(2): 221-227. doi: 10.3967/bes2024.024
Sodium Sulfite as a Novel Hypoxia Revulsant Involved in Hypoxic Regulation in Escherichia coli
YE Qiao, HUO Jia Nan, LUO Yuan, MEI Zhu Song, FANG Long Mei, GUO Bing Qian, WANG Guang Yun
2024, 37(2): 228-232. doi: 10.3967/bes2024.025
As a reducing salt, sodium sulfite could deprive oxygen in solution, which could mimic hypoxic stress in Caenorhabditis elegans. In this study, the wild-type Escherichia coli strain MG1655 was used to examine the inhibition of sodium sulfite-induced hypoxia by observing the bacterial growth curves. We also analyzed the growth curves of mutant strains (for arcA/B, soxR/S, fnr, and oxyR) related to E. coli hypoxic pathways to reveal roles of the related genes during hypoxia. The ultrastructure of hypoxia-inhibited bacteria were also observed using transmission electron microscopy. Sodium sulfite could maintain hypoxic condition of bacterial culture for 8 h with concentrations over 40 mmol/L. Complete ultrastructure of the bacteria indicated sodium sulfite did inhibit bacterial growth and division. Among the hypoxia genes, fnr and arcB played key roles in sodium sulfite-induced hypoxia. This study showed that sodium sulfite could be used as a novel hypoxia revulsant for bacterial cultures.