Home Life Sciences A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
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A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS

  • Jiamei Jiang , Meng Lv , Kaichao Yang , Gang Zhao and Yimu Fu EMAIL logo
Published/Copyright: November 8, 2023

Abstract

Listeria monocytogenes (LM) infections of the central nervous system are deadly and have vague symptoms. Traditional cerebro spinal fluid culture has a low positive rate, and because antibiotic use is common following therapy, it is more challenging to assess the response from pathogen content. In this case, a 66-year-old man who had a fever, a headache, and vomit was admitted to the hospital. He had diabetes, decline in thyroid function, and a history of pituitary tumor removal surgery. His initial treatment with ribavirin, ceftriaxone antibiotic, and moxifloxacin did not go well. Using two etiological tests (culture and metagenomic next-generation sequencing [mNGS]), his cerebrospinal fluid tested positively for LM. Ampicillin-sulbactam and meropenem were used as treatments once LM meningitis was identified. After treatment, his cerebrospinal fluid was assessed once more. Culture: negative; targeted next-generation sequencing (tNGS): positive and shows changes in the copy number of the LM. After 44 days of treatment, the patient finally stopped taking antibiotics, and the prognosis was good. Our study showed that mNGS and tNGS, as novel approaches for pathogen detection, are capable of identifying pathogens quickly, sensitively, and accurately, especially when there are few infections present (such as after antibiotic treatment). The two methods can be a powerful assistance for helping clinicians to choose the best course of action.

1 Background

Listeria monocytogenes (LM) is a gram-positive, facultatively anaerobic, intracellular bacteria extensively present in the environment [1]. Since the 1980s, it has been responsible for foodborne illness outbreaks and is the cause of listeriosis. In Europe, the prevalence of LM is estimated to be around 0.48 cases per 100,000 individuals, and infections can manifest either sporadically or in an epidemic manner. According to the Centers for Disease Control and Prevention (CDC), the yearly occurrence of laboratory-confirmed listeriosis in the United States is approximately 0.24 cases per 100,000 individuals. Various species of wild and domestic animals, including mammals and birds, have the potential to acquire LM infection, thereby serving as potential zoonotic reservoirs for this pathogen [2]. Animals usually undergo the infection asymptomatically, and its result may be contamination of food of animal origin, mainly meat and milk. Consuming contaminated food is the most common way to make people sick. Large amounts of infected food taken by a healthy host are unlikely to induce anything more than self-limiting febrile gastroenteritis [3,4]. However, it is a serious bacterial infection for those with immunosuppression, children, the elderly, pregnant women, and others [5]. In these people, there is an increase in symptoms such as fever, chills, muscle pain, headache, nausea, and vomiting, and it is associated with invasive infection and high mortality. LM mainly causes central nervous system (CNS) infections (meningitis or meningoencephalitis) and systemic infections.

Metagenomic next-generation sequencingr (mNGS) has demonstrated considerable promise for identifying infections of the CNS [6,7]. Numerous case studies show how mNGS can be used as a novel method to simultaneously and reliably detect Listeria monocytogenes meningitis (LMM) [811]. Targeted next-generation sequencing (tNGS), another sequencing method used in clinical microbial identification in addition to mNGS, is mostly immune to interference from the human genome and colonizing bacteria [12]. It is effective for identifying infectious diseases with low copy numbers that are well-known and widespread [13]. In this case, tNGS was applied for monitoring patient outcomes following therapy, while mNGS was utilized for recognizing patients with LMM. Together, the two methods provided enough etiological evidence to justify the development of treatment regimens.

2 Case presentation

2.1 Investigations

A 66-year-old man with “3 days of fever accompanied by severe headache for 1 day, vomiting, and lethargy for 10 h” was admitted to our hospital’s internal medicine observation room in the afternoon of February 10, 2023. The patient had a history of diabetes for more than 10 years (Insulin Lispro injection, 24 u in the morning and 22 u in the evening) and hypothyroidism for 10 years (sodiumlevothyroxine, 1#qd). The patient had a pituitary tumor removed in 2013, and cortisone acetate (25 mg qd) was administered postoperatively for a very long time. The patient experienced various symptoms without obvious causes 2 days before admission (February 7), including fever (up to 38.8°C), cough, less sputum, and other symptoms. After taking paracetamol via self-administration, the body’s temperature dropped. The patient started experiencing severe headache and a lingering fever (body temperature of 38.2°C) on February 9. The patient’s headache slightly lessened following moxifloxacin (100 mg qd) and ibuprofen (0.6 g qd) treatment in our hospital’s fever clinic (Table 1).

Table 1

History of microbiological testing and treatment

Date Hospital stay (days) Microbiological testing Result Treatment
9 Feb 0 Moxifloxacin 100 mg qd
10 Feb 1 Ceftriaxone 2 g qd
11 Feb 2 Antibody testing Ribavirin 0.5 g q8h + Ceftriaxone 2 g qd
12 Feb 3 First CSF test: mNGS + culture HSV-1 IgG(+), IgM(+) Not adjusted
14 Feb 5 First CSF mNGS: (+) L. monocytogene (149 reads) Ampicillin sodium and sulbactam sodium 3 g q6h + meropenem 1 g q8h
15 Feb 6 First CSF culture: (+) L. monocytogene Not adjusted
19 Feb 10 Second CSF test: tNGS + culture Not adjusted
21 Feb 12 Second CSF tNGS: (+) L. monocytogene (3 copies/mL) Not adjusted
22 Feb 13 Second CSF culture (−) Not adjusted
28 Feb 19 Third CSF test: tNGS Not adjusted
1 Mar 20 Third CSF tNGS: (−) Not adjusted
6 Mar 23 Not adjusted

Notes: HSV-1: herpes simplex virus type 1; CSF: cerebrospinal fluid; mNGS: metagenomics next-generation sequencing; L. monocytogene: Listeria monocytogene; +: positive; −: negative.

On the morning of February 10, the patient redeveloped headache, apathy, and ejected vomiting (stomach contents), but without limb twitches and hemisensory disturbances. Blood tests: C-reactive protein (CRP) 8.91 mg/L, white blood cell count (WBC) 7.98 × 109/L, procalcitonin (PCT) 0.05 ng/mL, interleukin (IL)-6 451 (pg/mL), lymphocytes 24.1%, and neutrophils 67.8% (Figure 1). Chest computer tomography showed an infection site in the right lung. Ceftriaxone (2.0 g qd) was administered to the patient to begin anti-infective therapy (Table 1). However, the symptoms, which included chills, deteriorating consciousness, and shortness of breath, persisted, and the persistent temperature (38.6–39.6°C) did not go away.

Figure 1 
                  Dynamic changes in condition and blood tests after admission: (a) body temperature and partial pressure of oxygen (mmHg, PO2), (b) CRP and WBC (×109), (c) PCT (ng/mL) and IL-6 (pg/mL), and (d) percentage of lymphocytes and neutrophils.
Figure 1

Dynamic changes in condition and blood tests after admission: (a) body temperature and partial pressure of oxygen (mmHg, PO2), (b) CRP and WBC (×109), (c) PCT (ng/mL) and IL-6 (pg/mL), and (d) percentage of lymphocytes and neutrophils.

2.2 Diagnosis and treatment

The patient was transferred to our department (emergency intensive-care unit [EICU]) on the morning of February 12, and a lumbar puncture was carried out to obtain cerebrospinal fluid samples for the biochemical and microbiological testing (culture and mNGS, Table 1). The patient had a 38.6°C body temperature (Figure 1a), shortness of breath (40 breaths per min), restlessness, a glasgow coma scale score of 10, disorientation, and a double pupil of 2 mm at this time. As can be seen in Figure 1b–d, the blood test results were higher than the readings from February 10. The brain’s magnetic resonance imaging (MRI; Figure 2a) revealed a left temporal pole arachnoid cyst and mild bilateral frontoparietal lobe ischemia. Herpes simplex virus type I (HSV-1) IgG (+), IgM (+), peripheral blood antibody test, may be viral encephalitis. Thus ribavirin (0.5 g q8h) was added to the anti-infective therapy. However, the patient did not improve significantly. He experienced symptoms like breathlessness, unconsciousness, brief convulsions, and restlessness on February 13 and required invasive ventilator-assisted breathing therapy. On February 14, cerebro spinal fluid (CSF) biochemical and mNGS results were released. Cerebrospinal fluid biochemistry: protein 5.14 g/L, glucose 7 mmol/L, chloride 124 mmol/L; CSF PCR: Mycobacterium tuberculosis DNA (−). CSF mNGS results: L. monocytogene positive (149 reads). On February 14, after receiving his initial diagnosis of LMM, he stopped taking ceftriaxone right away and changed his anti-infection regimen to ampicillin-sulbactam (3 g q6h) + meropenem (1 g q8h) (Table 1). The CSF culture produced the same result as the mNGS (L. monocytogene positive) the following day (February 15). The mold was negative after 5 days of cultivation.

Figure 2 
                  MRI demonstrated: (a) the third day after admission (12 February) and (b) Day 11 after admission (20 February). The results showed that LM infection did not cause parenchymal changes in the patient. The red arrow refers to the patient’s old cyst lesion.
Figure 2

MRI demonstrated: (a) the third day after admission (12 February) and (b) Day 11 after admission (20 February). The results showed that LM infection did not cause parenchymal changes in the patient. The red arrow refers to the patient’s old cyst lesion.

The patient continued to experience sporadic seizures and intermittent fever between February 14 and February 19 (Figure 1). CSF was collected for the second biochemical and microbiological test on the tenth day of admission (February 19) (tNGS and culture, Table 1). tNGS results: L. monocytogene (3 copies/mL) positive; culture: negative; CSF: leukocytes 620 × 106/L, protein 4.14 g/L, glucose 9 mmol/L, chlorine 125 mmol/L. The patient’s condition had improved compared to when they first arrived in the EICU.

2.3 Outcome

The peak fever gradually decreased after February 19 and returned to normal on February 22 (Figure 1a). And the patient’s blood tests result gradually decreased (Figure 1b–d), consciousness gradually returned to normal, and the frequency of seizures decreased. On February 23, he was taken off the ventilator and put into an oxygen nasal cannula. However, the brain MRI on February 20 (Figure 2b) did not reveal any appreciable variations from February 12 (Figure 2a). We considered temporal lobe cysts on MRI as an ancient lesion in patient and did not believe it was connected to LMM. A third CSF NGS (second tNGS, February 28, Table 1) test was conducted before the patient was transferred and the result was negative. The final blood test (March 4, Figure 1b–d) results had obviously normalized before discharge.

On March 6, the patient was transferred to rehabilitation hospital to continue receiving anti-infective treatment (ampicillin sulbactam sodium, vancomycin, and ceftazidime; the dosage for each medicine is unknown). After 44 days of targeted antibiotic therapy (through March 30), the patient stopped taking antibiotics. In early May, the patient recovered and was discharged from hospital. Currently, the patient is resuming self-care.

  1. Informed consent: Informed consent has been obtained from all individuals included in this study.

  2. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.

3 Methods

3.1 mNGS

The general detection process was as follows: (a) DNA extraction: the nucleic acid for the cfDNA libraries was extracted from 200 L of CSF. (b) RT-PCR and the 2100 Bioanalyzer equipment (Agilent Technologies, Inc.) were used to validate the library. The Nextseq CN500 was used for sequencing. (c) Bioinformatics analysis: first, removed low-quality tails and reads by Trimmomatic v0.36. Second, host reads (the reads mapping to the human reference genome GRCh37) were excluded using the short-read alignment tool Bowtie v2.2.6. Next, the remaining reads were aligned to the reference database, composing multiple public sequence resources of bacteria, viruses, and fungi.

3.2 tNGS

Total genome DNA extraction used the same procedures as mNGS. (a) Library preparation and enrichment: using the panel of 205 pathogens, the DNA was employed as a template for multiplex PCR amplification. Second, sequencing linkers and barcode sequences for sample identification were added to create pathogen sequencing libraries. Library concentrations were quantified using a Qubit 4.0 (Invitrogen). (b) Sequencing: high-throughput sequencing was performed using the Illumina Nextseq CN500 sequencing platform. (c) Bioinformatics analysis: first, the raw data obtained were filtering the low-quality data. Following identifying high-quality data by primer sequences, reads with correct paired-end overlap were compared with pathogen sequences from NCBI databases. The pathogen species and content in the samples can finally be identified.

4 Discussion

LM was first identified as a foodborne pathogen in the 1980s. It is a typical cold-tolerant bacteria that can grow at 4°C and is extremely resilient to salt and high temperatures [14]. CNS infections of LM consist of meningitis, encephalitis, and brain abscess [15,16]. The overall mortality rate was 30% [17]. An effective preventative strategy for vulnerable people is to steer clear of items that are often tainted with LM, such as soft-ripened cheeses, pate, prepared chilled meats, unpasteurized milk, and ready-to-eat chicken that has not been thoroughly cooked. In recent years, foodborne problems caused by Listeria and other pathogens have been frequent. In addition to avoiding contaminated food, many studies have proposed improving food quality [18]. For example, using natural substances with antioxidant and bactericidal effects (chia seeds, lemongrass essential oil, etc.) can help extend the shelf life of fruits, meat, dairy products, and others [19].

When infected with LM, timely diagnosis and appropriate early antibiotic therapy can significantly improve the patient’s survival rate (greater than 70%) [20]. However, only 15% of meningitis due to LM presents with the classical triad of meningitis (fever, headache, and nuchal rigidity) [21]. Therefore, the diagnosis of CNS infection caused by LM relies primarily on pathogen examination [5]. Bacterial culture is the “gold standard” for recognizing LM infections. However, the result of CSF culture might be affected by the rate of bacterial growth (which takes time) and the use of antibiotics [22,23]. Antibiotic use reduces bacterial burden and gradually lowers the percentage of cultures that are positive [24].

NGS has developed into a crucial technique for LM detection in cerebrospinal fluid in recent years since Yao et al. originally reported three cases of acute or subacute meningitis with negative cerebrospinal fluid culture but confirmed as LMM using NGS in 2016 [25,26]. We looked through six articles published on Pubmed since 2016 using the keywords “Listeria monocytogenes meningitis” or “Listeria monocytogenes & next-generation sequencing.” Moreover, we reviewed and discussed them (Table 2) to expect these cases. A total of 19 patients were featured in the six articles, each with different clinical presentations, such as fever (19/19), headache (11/19), diarrhea, nausea, vomiting (13/19), meningeal signs (14/19), coma (or consciousness disturbance, 11/19), hyperspasmia (5/17), and others. Intracranial bleeding, limited abduction of both eyes, hiccups, poor mental health, dysarthria, diplopia, and other symptoms were experienced by individual patients. All patients had a positive result of CSF mNGS within 2–4 days. Eight of 19 patients had a negative result of CSF culture. These results are similar to our case.

Table 2

Reports of NGS in the diagnosis of LMM from 2016 to 2023

Reference Age Gender Clinical manifestations Duration of CSF culture and results Duration of CSF mNGS and results Number of LM sequences detected by CSF mNGS Antimicrobial therapy Days of targeted antibiotic therapy Total course of the disease (days) Outcome
Fever Headache Diarrhea, nausea, vomiting Meningeal signs Coma or consciousness disturbance Hyperspasmia Others
Li et al. 2019 [30] 1 Female + + Unknown Unknown 4 days, positive 2 days, positive 2,561 Meropenem + amoxicillin sulbactam Unknown 83 Recovered
2 Female + + Unknown + + Unknown 5 days, positive 3 days, positive 1,011 Meropenem + vancomycin Unknown 23 Recovered
9 Male + + + Unknown Unknown 7 days, positive 2 days, positive 8 Meropenem + metronidazole Unknown 28 Recovered
Li et al. 2022 [9] 32–83 Five males and 1 female 6/6 3/6 2/6 6/6 4/6 2/6 Unknown 91 h, positive 47 h, positive 404 Five patients: meropenem + penicillin G + sulfamethoxazole tablets (SMZ), and 1 patient: linezolid + etimicin + SMZ (because of penicillin allergy) Unknown Unknown Five completely recovered and 1 neurological sequelae
Yu et al. 2023 [8] 23–61 Three males and 2 females 5/5 5/5 5/5 4/5 4/5 2/5 Limited abduction of both eyes, hiccups, poor mental health Unknown, 4 negative + 1 positive 2–4 days, positive 118–1,997 Penicillins and/or meropenem 15–37 days Unknown Three significantly improved and 2 fewer improvements
Zhang et al. 2021 [11] 64 Male + Unknown Unknown + Unknown Unknown Intracranial hemorrhage Unknown, positive Unknown, positive 118 Piperacillin Unknown Unknown Recovered
Yao et al. 2016 [26] 40–66 Three males 3/3 1/3 2/3 2/3 1/3 Unknown Ataxia, dysarthria, diplopia, vertigo, hypoventilation Unknown, negative Unknown, positive 74, 665,486 Unknown Unknown Unknown Unknown
Lan et al. 2020 [31] 66 Female + + + + + Unknown Unknown Unknown, negative 3 days, positive 486 Ampicillin + trimethoprim-sulfamethoxazole Unknown Unknown Recovered

The guideline panel recommends 21 days of therapy or longer [27]. As a result, it is important to continuously review changes in the patient’s condition and associated laboratory examination data, integrate microbiological testing, quickly gauge the effectiveness of anti-infection medications, and modify anti-infection treatment plans as appropriate. Five patients got targeted antibiotic therapy for 15–37 days in the literature review, presumably as a result of more serious morbidities that prolonged antibiotic therapy. tNGS is a method of sequencing which can detect a group of organisms [28]. As a result, in our case, tNGS was utilized twice following treatment for pathogen detection, effectively evaluating the treatment’s impact on patients and providing support for extended antibiotic therapy.

In the reviewed literature, the majority of patients were given meropenem and other antibiotics. After treatment, most patients (13/19) recovered, while three (who had severe disease) had fewer improvements or neurological sequelae. In our case, the antibiotic protocol resulted from carefully considering the guideline, literature, and the patient’s condition. However, some studies had shown that LM strains isolated from food have developed antibiotic resistance [29]. Susceptibility testing is still required for patients with LM infection in the future.

5 Conclusion

LM can be detected more quickly and accurately using mNGS and tNGS, which are also useful for diagnosing and monitoring LMM. They can offer compelling justification for extending antibiotic treatment.

Acknowledgements

The authors thank the patient and family for permitting us to use the data.

  1. Funding information: This work was supported by the Shanghai Sixth People’s Hospital Hospital Project (ynhg202208) and Shanghai Hospital Development Center (SHDC2020CR6030).

  2. Author contributions: Jiamei Jiang and Kaichao Yang provided medical records. Jiamei Jiang and Meng Lv drafted the manuscript. Yimu Fu and Gang Zhao revised the manuscript. All authors read and approved the final manuscript.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2023-05-30
Revised: 2023-09-01
Accepted: 2023-09-04
Published Online: 2023-11-08

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  34. The role of IL-31 and IL-34 in the diagnosis and treatment of chronic periodontitis
  35. Triple-negative mouse breast cancer initiating cells show high expression of beta1 integrin and increased malignant features
  36. mNGS facilitates the accurate diagnosis and antibiotic treatment of suspicious critical CNS infection in real practice: A retrospective study
  37. The apatinib and pemetrexed combination has antitumor and antiangiogenic effects against NSCLC
  38. Radiotherapy for primary thyroid adenoid cystic carcinoma
  39. Design and functional preliminary investigation of recombinant antigen EgG1Y162–EgG1Y162 against Echinococcus granulosus
  40. Effects of losartan in patients with NAFLD: A meta-analysis of randomized controlled trial
  41. Bibliometric analysis of METTL3: Current perspectives, highlights, and trending topics
  42. Performance comparison of three scaling algorithms in NMR-based metabolomics analysis
  43. PI3K/AKT/mTOR pathway and its related molecules participate in PROK1 silence-induced anti-tumor effects on pancreatic cancer
  44. The altered expression of cytoskeletal and synaptic remodeling proteins during epilepsy
  45. Effects of pegylated recombinant human granulocyte colony-stimulating factor on lymphocytes and white blood cells of patients with malignant tumor
  46. Prostatitis as initial manifestation of Chlamydia psittaci pneumonia diagnosed by metagenome next-generation sequencing: A case report
  47. NUDT21 relieves sevoflurane-induced neurological damage in rats by down-regulating LIMK2
  48. Association of interleukin-10 rs1800896, rs1800872, and interleukin-6 rs1800795 polymorphisms with squamous cell carcinoma risk: A meta-analysis
  49. Exosomal HBV-DNA for diagnosis and treatment monitoring of chronic hepatitis B
  50. Shear stress leads to the dysfunction of endothelial cells through the Cav-1-mediated KLF2/eNOS/ERK signaling pathway under physiological conditions
  51. Interaction between the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count in rats with LPS-induced pulmonary infection
  52. Meta-analysis of the rs231775 locus polymorphism in the CTLA-4 gene and the susceptibility to Graves’ disease in children
  53. Cloning, subcellular localization and expression of phosphate transporter gene HvPT6 of hulless barley
  54. Coptisine mitigates diabetic nephropathy via repressing the NRLP3 inflammasome
  55. Significant elevated CXCL14 and decreased IL-39 levels in patients with tuberculosis
  56. Whole-exome sequencing applications in prenatal diagnosis of fetal bowel dilatation
  57. Gemella morbillorum infective endocarditis: A case report and literature review
  58. An unusual ectopic thymoma clonal evolution analysis: A case report
  59. Severe cumulative skin toxicity during toripalimab combined with vemurafenib following toripalimab alone
  60. Detection of V. vulnificus septic shock with ARDS using mNGS
  61. Novel rare genetic variants of familial and sporadic pulmonary atresia identified by whole-exome sequencing
  62. The influence and mechanistic action of sperm DNA fragmentation index on the outcomes of assisted reproduction technology
  63. Novel compound heterozygous mutations in TELO2 in an infant with You-Hoover-Fong syndrome: A case report and literature review
  64. ctDNA as a prognostic biomarker in resectable CLM: Systematic review and meta-analysis
  65. Diagnosis of primary amoebic meningoencephalitis by metagenomic next-generation sequencing: A case report
  66. Phylogenetic analysis of promoter regions of human Dolichol kinase (DOLK) and orthologous genes using bioinformatics tools
  67. Collagen changes in rabbit conjunctiva after conjunctival crosslinking
  68. Effects of NM23 transfection of human gastric carcinoma cells in mice
  69. Oral nifedipine and phytosterol, intravenous nicardipine, and oral nifedipine only: Three-arm, retrospective, cohort study for management of severe preeclampsia
  70. Case report of hepatic retiform hemangioendothelioma: A rare tumor treated with ultrasound-guided microwave ablation
  71. Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling
  72. Rare presentation of double-clonal Waldenström macroglobulinemia with pulmonary embolism: A case report
  73. Giant duplication of the transverse colon in an adult: A case report and literature review
  74. Ectopic thyroid tissue in the breast: A case report
  75. SDR16C5 promotes proliferation and migration and inhibits apoptosis in pancreatic cancer
  76. Vaginal metastasis from breast cancer: A case report
  77. Screening of the best time window for MSC transplantation to treat acute myocardial infarction with SDF-1α antibody-loaded targeted ultrasonic microbubbles: An in vivo study in miniswine
  78. Inhibition of TAZ impairs the migration ability of melanoma cells
  79. Molecular complexity analysis of the diagnosis of Gitelman syndrome in China
  80. Effects of maternal calcium and protein intake on the development and bone metabolism of offspring mice
  81. Identification of winter wheat pests and diseases based on improved convolutional neural network
  82. Ultra-multiplex PCR technique to guide treatment of Aspergillus-infected aortic valve prostheses
  83. Virtual high-throughput screening: Potential inhibitors targeting aminopeptidase N (CD13) and PIKfyve for SARS-CoV-2
  84. Immune checkpoint inhibitors in cancer patients with COVID-19
  85. Utility of methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses
  86. Integrated analysis of the microbiome and transcriptome in stomach adenocarcinoma
  87. Berberine suppressed sarcopenia insulin resistance through SIRT1-mediated mitophagy
  88. DUSP2 inhibits the progression of lupus nephritis in mice by regulating the STAT3 pathway
  89. Lung abscess by Fusobacterium nucleatum and Streptococcus spp. co-infection by mNGS: A case series
  90. Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis
  91. Granulomatous polyangiitis involving the fourth ventricle: Report of a rare case and a literature review
  92. Studying infant mortality: A demographic analysis based on data mining models
  93. Metaplastic breast carcinoma with osseous differentiation: A report of a rare case and literature review
  94. Protein Z modulates the metastasis of lung adenocarcinoma cells
  95. Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro
  96. TAK-242, a toll-like receptor 4 antagonist, against brain injury by alleviates autophagy and inflammation in rats
  97. Primary mediastinum Ewing’s sarcoma with pleural effusion: A case report and literature review
  98. Association of ADRB2 gene polymorphisms and intestinal microbiota in Chinese Han adolescents
  99. Tanshinone IIA alleviates chondrocyte apoptosis and extracellular matrix degeneration by inhibiting ferroptosis
  100. Study on the cytokines related to SARS-Cov-2 in testicular cells and the interaction network between cells based on scRNA-seq data
  101. Effect of periostin on bone metabolic and autophagy factors during tooth eruption in mice
  102. HP1 induces ferroptosis of renal tubular epithelial cells through NRF2 pathway in diabetic nephropathy
  103. Intravaginal estrogen management in postmenopausal patients with vaginal squamous intraepithelial lesions along with CO2 laser ablation: A retrospective study
  104. Hepatocellular carcinoma cell differentiation trajectory predicts immunotherapy, potential therapeutic drugs, and prognosis of patients
  105. Effects of physical exercise on biomarkers of oxidative stress in healthy subjects: A meta-analysis of randomized controlled trials
  106. Identification of lysosome-related genes in connection with prognosis and immune cell infiltration for drug candidates in head and neck cancer
  107. Development of an instrument-free and low-cost ELISA dot-blot test to detect antibodies against SARS-CoV-2
  108. Research progress on gas signal molecular therapy for Parkinson’s disease
  109. Adiponectin inhibits TGF-β1-induced skin fibroblast proliferation and phenotype transformation via the p38 MAPK signaling pathway
  110. The G protein-coupled receptor-related gene signatures for predicting prognosis and immunotherapy response in bladder urothelial carcinoma
  111. α-Fetoprotein contributes to the malignant biological properties of AFP-producing gastric cancer
  112. CXCL12/CXCR4/CXCR7 axis in placenta tissues of patients with placenta previa
  113. Association between thyroid stimulating hormone levels and papillary thyroid cancer risk: A meta-analysis
  114. Significance of sTREM-1 and sST2 combined diagnosis for sepsis detection and prognosis prediction
  115. Diagnostic value of serum neuroactive substances in the acute exacerbation of chronic obstructive pulmonary disease complicated with depression
  116. Research progress of AMP-activated protein kinase and cardiac aging
  117. TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5
  118. Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target
  119. Metastasis from small cell lung cancer to ovary: A case report
  120. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury
  121. The effect of NK cell therapy on sepsis secondary to lung cancer: A case report
  122. Erianin alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation
  123. Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features
  124. Signalling pathways in the osteogenic differentiation of periodontal ligament stem cells
  125. Crosstalk between lactic acid and immune regulation and its value in the diagnosis and treatment of liver failure
  126. Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma
  127. Traumatic brain injury and rTMS-ERPs: Case report and literature review
  128. Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling
  129. Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
  130. The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles
  131. Inflammation-related signaling pathways in tendinopathy
  132. CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review
  133. Clinical analysis of severe Chlamydia psittaci pneumonia: Case series study
  134. Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane
  135. Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility
  136. Catharanthus roseus (L.) G. Don counteracts the ampicillin resistance in multiple antibiotic-resistant Staphylococcus aureus by downregulation of PBP2a synthesis
  137. Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia
  138. Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
  139. TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data
  140. Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway
  141. Ferroptosis: A potential target of macrophages in plaque vulnerability
  142. Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches
  143. Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins
  144. HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway
  145. IL-17 in osteoarthritis: A narrative review
  146. Circadian cycle and neuroinflammation
  147. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
  148. Hemorrhagic meningioma with pulmonary metastasis: Case report and literature review
  149. SPOP regulates the expression profiles and alternative splicing events in human hepatocytes
  150. Knockdown of SETD5 inhibited glycolysis and tumor growth in gastric cancer cells by down-regulating Akt signaling pathway
  151. PTX3 promotes IVIG resistance-induced endothelial injury in Kawasaki disease by regulating the NF-κB pathway
  152. Pancreatic ectopic thyroid tissue: A case report and analysis of literature
  153. The prognostic impact of body mass index on female breast cancer patients in underdeveloped regions of northern China differs by menopause status and tumor molecular subtype
  154. Report on a case of liver-originating malignant melanoma of unknown primary
  155. Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer
  156. The fibroblast growth factor–Klotho axis at molecular level
  157. Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations
  158. A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
  159. Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft
  160. Small breast epithelial mucin as a useful prognostic marker for breast cancer patients
  161. Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage
  162. Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
  163. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report
  164. Case report of atypical undernutrition of hypoproteinemia type
  165. Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer
  166. Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis
  167. Research progress of serum eosinophil in chronic obstructive pulmonary disease and asthma
  168. Clinicopathological characteristics of co-existing or mixed colorectal cancer and neuroendocrine tumor: Report of five cases
  169. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis
  170. Precisional detection of lymph node metastasis using tFCM in colorectal cancer
  171. Advances in diagnosis and treatment of perimenopausal syndrome
  172. A study of forensic genetics: ITO index distribution and kinship judgment between two individuals
  173. Acute lupus pneumonitis resembling miliary tuberculosis: A case-based review
  174. Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm
  175. Fractalkine modulates pulmonary angiogenesis and tube formation by modulating CX3CR1 and growth factors in PVECs
  176. Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function
  177. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms
  178. Evaluation of effects of small-incision approach treatment on proximal tibia fracture by deep learning algorithm-based magnetic resonance imaging
  179. An online diagnosis method for cancer lesions based on intelligent imaging analysis
  180. Medical imaging in rheumatoid arthritis: A review on deep learning approach
  181. Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach
  182. Utility of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in predicting acute-on-chronic liver failure survival
  183. A biomedical decision support system for meta-analysis of bilateral upper-limb training in stroke patients with hemiplegia
  184. TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
  185. Stochastic gradient descent optimisation for convolutional neural network for medical image segmentation
  186. Comparison of the prognostic value of four different critical illness scores in patients with sepsis-induced coagulopathy
  187. Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development
  188. Hepatobiliary surgery based on intelligent image segmentation technology
  189. Value of brain injury-related indicators based on neural network in the diagnosis of neonatal hypoxic-ischemic encephalopathy
  190. Analysis of early diagnosis methods for asymmetric dementia in brain MR images based on genetic medical technology
  191. Early diagnosis for the onset of peri-implantitis based on artificial neural network
  192. Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy
  193. Forecast of pain degree of lumbar disc herniation based on back propagation neural network
  194. SPA-UNet: A liver tumor segmentation network based on fused multi-scale features
  195. Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image
  196. Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke
  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
  198. ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis
  199. Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model
  200. Lung nodule segmentation via semi-residual multi-resolution neural networks
  201. Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI
  202. A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis
  203. Markov model combined with MR diffusion tensor imaging for predicting the onset of Alzheimer’s disease
  204. Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method
  205. Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis
  206. Monitoring and evaluation of anesthesia depth status data based on neuroscience
  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
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