Home Diagnostic value of recombinant heparin-binding hemagglutinin adhesin protein in spinal tuberculosis
Article Open Access

Diagnostic value of recombinant heparin-binding hemagglutinin adhesin protein in spinal tuberculosis

  • Feifei Pu , Jing Feng , Fei Niu and Ping Xia EMAIL logo
Published/Copyright: February 28, 2020
Download Article (PDF)
Open Medicine
From the journal Open Medicine Volume 15 Issue 1

Abstract

Background and aim

To explore the diagnostic value of recombinant heparin-binding hemagglutinin adhesin (HBHA) protein antigen in spinal tuberculosis.

Materials and methods

Forty patients with spinal tuberculosis were included in the experimental group and 40 healthy people were included in the control group. Serum IgG antibody expression level was detected with recombinant HBHA protein as the antigen, using enzyme-linked immunosorbent assay (ELISA) detection.

Results

Patients with spinal tuberculosis and healthy volunteers were included in this study. A total of 40 eligible patients with spinal tuberculosis were included (24 males and 16 females, aged 18-72 years, with an average age of 41.24 ± 15.74 years). Forty healthy people were included (21 males and 19 females, aged 18-70 years, with an average age of 41.33 ± 12.36 years). On comparing the groups, no significant difference was found in the general data (P >0.05). IgG antibody level in the experimental group was higher than that in the control group, and the difference was significant (P < 0.00001).

Conclusions

Detection of serum HBHA protein antibody is of great value in the auxiliary diagnosis of spinal tuberculosis, and high HBHA expression can be used as an indicator for diagnosis of spinal tuberculosis.

Keywords: Heparin-binding hemagglutinin adhesin; HBHA; Spinal tuberculosis; Diagnosis

1 Introduction

According to the World Health Organization’s global tuberculosis control report of 2011, there were about 8.8 million new tuberculosis cases worldwide in 2010 [1]. Nearly 20 percent of these patients developed extrapulmonary tuberculosis, and 1% to 5% of these patients had spinal tuberculosis [2]. Spinal tuberculosis is a common form of joint tuberculosis and encompasses about 50% of cases of bone tuberculosis, and 1% to 3% of all cases of tuberculosis [3].

Spinal tuberculosis is an occult disease, with the symptoms not being obvious and early diagnosis being difficult. Spinal tuberculosis is more common in young and middle-aged patients, mostly secondary to tuberculosis. The lesions of spinal tuberculosis are mostly located in the lumbar vertebra, followed by the thoracolumbar vertebra, upper thoracic vertebra, cervical vertebra and lumbosacral vertebra. Spinal tuberculosis starts slowly and patients usually seek treatment only when they have severe pain, obvious deformities or neurological symptoms. However, irreversible neurological deficits often occur in the later stages of the disease, so early diagnosis is critical [4]. The detection rates of traditional tuberculosis detection methods (such as tuberculin test, smear staining microscopy, Mycobacterium tuberculosis culture, and molecular biology method) for spinal tuberculosis are significantly lower than those for detecting pulmonary tuberculosis [3]. Therefore, it is especially necessary to explore new auxiliary examination methods for spinal tuberculosis.

The heparin-binding hemagglutinin adhesin (HBHA) of Mycobacterium tuberculosis is a bacterial protein that is of great significance in the pathogenesis of extrapulmonary tuberculosis through adhesion to epithelial cells [5]. Serum antibody tests have shown a significant value in the diagnosis of tuberculosis [6,7]. In this study, HBHA protein was used to detect HBHA antibody expression levels and explore the diagnostic value of HBHA in spinal tuberculosis.

2 Materials and methods

2.1 Acquisition of human tissue samples

In the experimental group, specimens were continuously collected between December 2015 and December 2017. During this period, data of 40 patients with spinal tuberculosis were recorded in the Wuhan No.1 Hospital, Wuhan Integrated TCM & Western Medicine Hospital, Tongji Medical College, Huazhong University of Science and Technology. In the patients with spinal tuberculosis, the preoperative imaging examination and serological indexes showed signs of spinal tuberculosis. The preoperative pulmonary imaging showed no obvious signs of tuberculosis infection, and other types of extrapulmonary tuberculosis were excluded. The postoperative histopathological sections of the lesion suggested tuberculosis infection, and the etiological examination showed positive anti-acid staining of the abscess or positive isolation and culture of Mycobacterium tuberculosis. In the control group, a series of healthy people were included from December 2015 to December 2017 in the physical examination center of Wuhan No.1 Hospital, Wuhan Integrated TCM & Western Medicine Hospital, Tongji Medical College, Huazhong University of Science and Technology. Tuberculosis, spinal tuberculosis, and other extrapulmonary tuberculosis were excluded by imaging examination.

Patients of the experimental and control groups that had one of the following conditions were excluded from the study: patients with tuberculosis with drug-resistance; patients with diseases affecting immune status, such as infection, trauma, and tumor; patients with tuberculosis of the lungs or other organs that was associated with autoimmune diseases; patients with genetic diseases; individuals who had not received the Bacillus Calmette Guerin vaccine; anyone with a history of tuberculosis contacts.

A total of 40 eligible patients with spinal tuberculosis were included (24 males and 16 females, aged 18-72 years, with an average age of 41.24 ± 15.74 years). Forty healthy people were included (21 males and 19 females, aged 18-70 years, with an average age of 41.33 ± 12.36 years).

2.2 Ethical approval and consent to participate

This process was approved by the Ethics Committee of the Wuhan No.1 Hospital, Wuhan Integrated TCM & Western Medicine Hospital, Tongji Medical College, Huazhong University of Science and Technology and conforms to the provisions of the Declaration of Helsinki. Informed consent was obtained from all subjects, and all patients and legal guardians signed the informed consent forms regarding the acquisition of human tissues that were used in this study, in accordance with National Regulations on the Use of Clinical Samples in China. This study met the relevant requirements of the regulations on the administration of medical institutions promulgated by the state council of the People’s Republic of China.

2.3 Reagents

Ni Sepharose 6 Fast Flow (ff) His-Tag column and CL-6B column (GE, USA). Protein Maker (Huamei, China). 7h9,7H11 and ADC enrichment broth (Difco, China). HRP-labeled goat anti-mouse IgG (Proteintech, China). The ECL chemiluminescence kit (Biyuntian, China).

2.4 Specimen collection and extraction of DNA

Two milliliters of venous blood was extracted using anticoagulant tube extraction in the morning on an empty stomach (Dalian treasure biological engineering co., LTD, China). Leucocyte genome DNA was extracted using this kit. DNA concentration was determined using a UV spectrophotometer and diluted to 100 ng/L in double steaming water.

2.5 Preparation of recombinant HBHA protein

E. coli BL21 (DE3) competent bacteria were transformed with the recombinant plasmid pETHBHA and were inoculated into Luria Broth (LB) broth (containing kanamycin 50 μg/mL) and cultured at 37°C for 16 hours. The bacteria were expanded at a ratio of 1:20 and cultured at 37°C for two hours (shaking speed 200 r/min). The isopropyl-β-D-thiogalactoside (IPTP) was added to a final concentration of 1 mmol/L, and the culture was maintained at 37°C for 4 hours to induce target protein expression. The induced bacteria were harvested, and the bacterial supernatant was obtained by ultrasonic lysis. The bacterial supernatant was mainly present in a soluble form. The target protein was purified using the non-denaturing Ni Sepharose 6 fast flow (His-Tag) column and subjected to 15% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The relatively pure protein eluent was collected and dialyzed by gradually reducing the urea concentration in phosphate buffer saline (PBS). The final protein concentration was determined using the bicinchoninic acid (BCA) Protein Concentration Assay Kit and stored in a -80°C freezer.

M. smegmatis bacteria were transformed with the recombinant plasmid pMVHBHA, plated on 7H11 agar plates containing kanamycin, and cultured for 5 days. Single clones were picked and inoculated in 7H9 liquid medium containing kanamycin and cultured for 5 days. The bacteria were collected by centrifugation and washed twice in PBS. Bacteria were ultrasonically disrupted. The supernatant was isolated after centrifugation, and the purified protein was obtained by a gradient elution with 0-500 mmol/L sodium chloride in PBS, through a CL-6B column. The final protein concentration was determined using the BCA Protein Concentration Assay Kit, and the protein was aliquoted and stored at -80°C.

2.6 HBHA-specific antibody expression level detection

Recombinant HBHA was packaged with an enzyme immunoassay (EIA) enzyme label plate, that was closed after using 3% BSA/PBS. The serum was diluted at a ratio of 1:80, the goat antihuman IgG labeled with horseradish peroxidase was diluted 1:20,000; and then, substrate was added within 30 minutes, using an enzyme standard instrument to measure the optical density (OD) value of specimen. A standard curve was generated to calculate the specimen concentration.

2.7 Statistical analysis

In this study, the software SPSS 20.0 (IBM, Chicago, IL, USA) was used to directly compare the OD value of serum antibody titers between different groups. The data presented an approximate normal distribution. P< 0.05 was considered statistically significant.

3 Results

Patients with spinal tuberculosis and healthy volunteers were included in this study, and the comparative analysis showed no significant difference in the general data between the two groups (P >0.05) (Table 1). The mean and standard deviation of the serum sample absorbance values in both the groups are listed. In the experimental group, antibody absorbance was 0.65 ± 0.16, whereas in the control group 0.06 ± 0.02. The t test was used for statistical analysis, and the HBHA antibody absorbance between the experimental group and the control group was statistically significant (P < 0.00001). The absorbance of antibodies is represented by a scatter plot (Figure 1).

Figure 1 The absorbance of serum HBHA antibody in the spinal tuberculosis group and the healthy control group. The absorbance of antibodies was 0.65 ± 0.16 and 0.06 ± 0.02 in the experimental group and the control group, respectively. A t test was used for statistical analysis, which showed that the difference in HBHA antibody absorbance between the experimental group and the control group was statistically significant (P < 0.00001).
Figure 1

The absorbance of serum HBHA antibody in the spinal tuberculosis group and the healthy control group. The absorbance of antibodies was 0.65 ± 0.16 and 0.06 ± 0.02 in the experimental group and the control group, respectively. A t test was used for statistical analysis, which showed that the difference in HBHA antibody absorbance between the experimental group and the control group was statistically significant (P < 0.00001).

Table 1

Comparison of general data in two groups

ItemsExperimental groupControl groupp-value
Age (year)41.24±15.7441.33±12.360.98
Male/Female (n/n)24/1621/190.50
Height (cm)169.6±6.2170.4±6.10.56
Body mass (kg)63.6±9.563.4±8.10.92
Body mass index (kg/cm2)21.8±2.821.0±2.40.17

4 Discussion

Spinal tuberculosis is a type of extrapulmonary tuberculosis and is difficult to diagnose. In fact, the diagnosis of spinal tuberculosis is usually based on clinical manifestations, combined with laboratory tests, imaging examinations, and the exclusion of other causes. It has not been easy to find a positive serum Mycobacterium tuberculosis culture. Bacteriological examination is an important method for the diagnosis of spinal tuberculosis, but its culture technology is still lagging behind, the positive rate is low, the current laboratory pathogen detection and identification methods are far from meeting the needs of clinical diagnosis [8]. Lesion biopsy usually has a certain disadvantage and risk factor, and the positive rate is not satisfactory [3,8]. Therefore, the identification of a more reliable diagnostic method for spinal tuberculosis will achieve practical value.

HBHA is a glycoprotein that is expressed and secreted on the surface of Mycobacterium tuberculosis and can appear in both bacteria and culture media [9,10]. HBHA binds to receptors containing heparin sulfate on non-phagocytes (such as epithelial cells) through its lysine rich c-terminal; and through this mechanism mediates extrapulmonary tuberculosis [11,12]. Therefore, it is of great significance to explore the value of HBHA in the diagnosis of tuberculosis immunology, especially in the diagnosis of pulmonary tuberculosis.

HBHA is closely associated with the onset of extrapulmonary tuberculosis. The drops degree testing of HBHA-specific IgG antibody in the serum of affected individuals revealed high concentrations of tuberculosis HBHA antibody, while healthy controls typically have low levels (including negative controls and those with latent infections). Increased serum HBHA antibody levels will serve as a marker for diagnosing tuberculosis [9,13].

HBHA has good immunogenicity and can stimulate peripheral blood mononuclear cells with latent infection to produce high levels of IFN-γ. Higher levels of HBHA antibody were detected in the serum of patients with tuberculosis, which suggests that HBHA has higher antigenicity [10,13]. Studies on HBHA have shown that it is associated with the onset of extrapulmonary tuberculosis, but its antibody levels in spinal tuberculosis have not been studied.

This study showed that serum HBHA antibody titers of patients with spinal tuberculosis were higher than those of healthy individuals, and the difference between the two groups was statistically significant. These results suggest that HBHA antibody levels can be used for the auxiliary diagnosis of spinal tuberculosis.

The pathopoiesis of spinal tuberculosis involves the spread of mycobacterium tuberculosis via blood or lymphatic channels; and then, the secretion of bacterial protein results in allergic disease [3]. Tuberculosis antibody expression levels in serum correlate with the growth and metabolic activity of Mycobacterium tuberculosis in the body. The body produces a variety of proteins that stimulate the formation of antibodies, and the detection of antibodies can be indirectly reflected by the tuberculosis bacterium growth and metabolic state. These processes can facilitate the diagnosis of tuberculosis [14,15]. However, HBHA protein is related to the incidence of pulmonary tuberculosis, and its corresponding increase in antibody level indicates the release of the HBHA antigen, which indirectly reflects the growth of tuberculosis bacteria [16].

In conclusion, detection of serum HBHA protein antibody is of great value in the auxiliary diagnosis of spinal tuberculosis, and high HBHA expression can be used as an indicator for the diagnosis of spinal tuberculosis.

Tel: +86-27-85860666

#These authors have made equal contributions to the work.

  1. Role of the funding source: This work is supported by grants from the research project of the Hubei Province Health and Family Planning Commission (No.WJ2017Z022), the Natural Science Fund Project of the Hubei Science and Technology Department (No.2016CFB666), the clinical research special fund of the Wu Jieping Medical Foundation (No.320.6750.17566), and the Funded Research Project of Wuhan No.1 Hospital, Wuhan Integrated TCM & Western Medicine Hospital (No. 2017Y01).

  2. Conflict of interest

    Conflict of interests: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

References

[1] Ramsay A, Steingart KR, Cunningham J, Pai M. Translating tuberculosis research into global policies: the example of an international collaboration on diagnostics. Int J Tuberc Lung Dis. 2011; 15(10): 1283-129310.5588/ijtld.11.0297Search in Google Scholar PubMed

[2] Schirmer P, Renault CA, Holodniy M. Is spinal tuberculosis contagious? Int J Infect Dis. 2010; 14(8): e659-66610.1016/j.ijid.2009.11.009Search in Google Scholar PubMed

[3] Dunn RN, Ben Husien M. Spinal tuberculosis. Bone Joint J. 2018; 100-B(4): 425-43110.1302/0301-620X.100B4.BJJ-2017-1040.R1Search in Google Scholar PubMed

[4] Pu F, Feng J, Yang L, Zhang L, Xia P. Misdiagnosed and mismanaged atypical spinal tuberculosis: A case series report. Exp Ther Med. 2019;18(5):3723-372810.3892/etm.2019.8014Search in Google Scholar PubMed PubMed Central

[5] Delogu G, Fadda G, Brennan MJ. Impact of structural domains of the heparin binding hemagglutinin of Mycobacterium tuberculosis on function. Protein Pept Lett. 2012; 19(10): 1035-103910.2174/092986612802762697Search in Google Scholar PubMed

[6] Shin AR, Lee KS, Lee JS, Kim SY, Song CH, Jung SB, et al. Mycobacterium tuberculosis HBHA protein reacts strongly with the serum immunoglobulin M of tuberculosis patients. Clin Vaccine Immunol. 2006; 13(8): 869-87510.1128/CVI.00103-06Search in Google Scholar PubMed PubMed Central

[7] Teimourpour R, Sadeghian A, Meshkat Z, Esmaelizad M, Sankian M, Jabbari AR. Construction of a DNA Vaccine Encoding Mtb32C and HBHA Genes of Mycobacterium tuberculosis. Jundishapur J Microbiol. 2015; 8(8): e2155610.5812/jjm.21556Search in Google Scholar PubMed PubMed Central

[8] Dela Garza Ramos R, Goodwin CR, Abu-Bonsrah N, Bydon A, Witham TF, Wolinsky JP, et al. The epidemiology of spinal tuberculosis in the United States: an analysis of 2002-2011 data. J Neurosurg Spine. 2017; 26(4): 507-51210.3171/2016.9.SPINE16174Search in Google Scholar PubMed

[9] Abebe F, Belay M, Legesse M, KL MC F, Ottenhoff THM. IgA and IgG against Mycobacterium tuberculosis Rv2031 discriminate between pulmonary tuberculosis patients, Mycobacterium tuberculosis-infected and non-infected individuals. PLoS One. 2018; 13(1): e019098910.1371/journal.pone.0190989Search in Google Scholar PubMed PubMed Central

[10] Wen HL, Li CL, Li G, Lu YH, Li HC, Li T, et al. Involvement of methylated HBHA expressed from Mycobacterium smegmatis in an IFN-γ release assay to aid discrimination between latent infection and active tuberculosis in BCG-vaccinated populations. Eur J Clin Microbiol Infect Dis. 2017; 36(8): 1415–142310.1007/s10096-017-2948-1Search in Google Scholar PubMed

[11] Veyron-Churlet R, Dupres V, Saliou JM, Lafont F, Raze D, Locht C. Rv0613c/MSMEG_1285 Interacts with HBHA and Mediates Its Proper Cell-Surface Exposure in Mycobacteria. Int J Mol Sci. 2018; 19(6). pii: E167310.3390/ijms19061673Search in Google Scholar PubMed PubMed Central

[12] Pavlicek RL, Fine-Coulson K, Gupta T, Quinn FD, Posey JE, Willby M, et al. Rv3351c, a Mycobacterium tuberculosis gene that affects bacterial growth and alveolar epithelial cell viability. Can J Microbiol. 2015; 61(12): 938-94710.1139/cjm-2015-0528Search in Google Scholar PubMed

[13] Belay M, Legesse M, Mihret A, Ottenhoff TH, Franken KL, Bjune G, et al. IFN-γ and IgA against non-methylated heparinbinding hemagglutinin as markers of protective immunity and latent tuberculosis: Results of a longitudinal study from an endemic setting. J Infect. 2016; 72(2): 189-20010.1016/j.jinf.2015.09.040Search in Google Scholar PubMed

[14] Menon J, Hoeppner VH, Judd A, Power CA, Bretscher PA. A hypothesis for the existence of two types of tuberculosis, reflecting two distinct types of immune failure to control the pathogen, based upon prevalence of mycobacterium-specific IgG subclasses. Scand J Immunol. 2018; 87(6): e1266510.1111/sji.12665Search in Google Scholar PubMed

[15] Kwizera R, Parkes-Ratanshi R, Page ID, Sekaggya-Wiltshire C, Musaazi J, Fehr J, et al. Elevated Aspergillus-specific antibody levels among HIV infected Ugandans with pulmonary tuberculosis. BMC Pulm Med. 2017; 17(1): 14910.1186/s12890-017-0500-9Search in Google Scholar PubMed PubMed Central

[16] Squeglia F, Ruggiero A, De Simone A, Berisio R. A structural overview of mycobacterial adhesins: Key biomarkers for diagnostics and therapeutics. Protein Sci. 2018; 27(2): 369-38010.1002/pro.3346Search in Google Scholar PubMed PubMed Central

Received: 2018-12-23
Accepted: 2020-01-13
Published Online: 2020-02-28

© 2020 Feifei Pu et al., published by De Gruyter

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

Articles in the same Issue

  1. Research Article
  2. MicroRNA-451b participates in coronary heart disease by targeting VEGFA
  3. Case Report
  4. A combination therapy for Kawasaki disease with severe complications: a case report
  5. Vitamin E for prevention of biofilm-caused Healthcare-associated infections
  6. Research Article
  7. Differential diagnosis: retroperitoneal fibrosis and oncological diseases
  8. Optimization of the Convolutional Neural Networks for Automatic Detection of Skin Cancer
  9. NEAT1 promotes LPS-induced inflammatory injury in macrophages by regulating miR-17-5p/TLR4
  10. Plasma matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 as prognostic biomarkers in critically ill patients
  11. Effects of extracorporeal magnetic stimulation in fecal incontinence
  12. Case Report
  13. Mixed germ cell tumor of the endometrium: a case report and literature review
  14. Bowel perforation after ventriculoperitoneal-shunt placement: case report and review of the literature
  15. Research Article
  16. Prognostic value of lncRNA HOTAIR in colorectal cancer : a meta-analysis
  17. Case Report
  18. Treatment of insulinomas by laparoscopic radiofrequency ablation: case reports and literature review
  19. Research Article
  20. The characteristics and nomogram for primary lung papillary adenocarcinoma
  21. Undiagnosed pheochromocytoma presenting as a pancreatic tumor: A case report
  22. Bioinformatics Analysis of the Expression of ATP binding cassette subfamily C member 3 (ABCC3) in Human Glioma
  23. Diagnostic value of recombinant heparin-binding hemagglutinin adhesin protein in spinal tuberculosis
  24. Primary cutaneous DLBCL non-GCB type: challenges of a rare case
  25. LINC00152 knock-down suppresses esophageal cancer by EGFR signaling pathway
  26. Case Report
  27. Life-threatening anaemia in patient with hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber syndrome)
  28. Research Article
  29. QTc interval predicts disturbed circadian blood pressure variation
  30. Shoulder ultrasound in the diagnosis of the suprascapular neuropathy in athletes
  31. The number of negative lymph nodes is positively associated with survival in esophageal squamous cell carcinoma patients in China
  32. Differentiation of pontine infarction by size
  33. RAF1 expression is correlated with HAF, a parameter of liver computed tomographic perfusion, and may predict the early therapeutic response to sorafenib in advanced hepatocellular carcinoma patients
  34. LncRNA ZEB1-AS1 regulates colorectal cancer cells by miR-205/YAP1 axis
  35. Tissue coagulation in laser hemorrhoidoplasty – an experimental study
  36. Classification of pathological types of lung cancer from CT images by deep residual neural networks with transfer learning strategy
  37. Enhanced Recovery after Surgery for Lung Cancer Patients
  38. Case Report
  39. Streptococcus pneumoniae-associated thrombotic microangiopathy in an immunosuppressed adult
  40. Research Article
  41. The characterization of Enterococcus genus: resistance mechanisms and inflammatory bowel disease
  42. Case Report
  43. Inflammatory fibroid polyp: an unusual cause of abdominal pain in the upper gastrointestinal tract A case report
  44. Research Article
  45. microRNA-204-5p participates in atherosclerosis via targeting MMP-9
  46. LncRNA LINC00152 promotes laryngeal cancer progression by sponging miR-613
  47. Can keratin scaffolds be used for creating three-dimensional cell cultures?
  48. miRNA-186 improves sepsis induced renal injury via PTEN/PI3K/AKT/P53 pathway
  49. Case Report
  50. Delayed bowel perforation after routine distal loopogram prior to ileostomy closure
  51. Research Article
  52. Diagnostic accuracy of MALDI-TOF mass spectrometry for the direct identification of clinical pathogens from urine
  53. The R219K polymorphism of the ATP binding cassette subfamily A member 1 gene and susceptibility to ischemic stroke in Chinese population
  54. miR-92 regulates the proliferation, migration, invasion and apoptosis of glioma cells by targeting neogenin
  55. Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma
  56. NF2 inhibits proliferation and cancer stemness in breast cancer
  57. Body composition indices and cardiovascular risk in type 2 diabetes. CV biomarkers are not related to body composition
  58. S100A6 promotes proliferation and migration of HepG2 cells via increased ubiquitin-dependent degradation of p53
  59. Review Article
  60. Focus on localized laryngeal amyloidosis: management of five cases
  61. Research Article
  62. NEAT1 aggravates sepsis-induced acute kidney injury by sponging miR-22-3p
  63. Pericentric inversion in chromosome 1 and male infertility
  64. Increased atherogenic index in the general hearing loss population
  65. Prognostic role of SIRT6 in gastrointestinal cancers: a meta-analysis
  66. The complexity of molecular processes in osteoarthritis of the knee joint
  67. Interleukin-6 gene −572 G > C polymorphism and myocardial infarction risk
  68. Case Report
  69. Severe anaphylactic reaction to cisatracurium during anesthesia with cross-reactivity to atracurium
  70. Research Article
  71. Rehabilitation training improves nerve injuries by affecting Notch1 and SYN
  72. Case Report
  73. Myocardial amyloidosis following multiple myeloma in a 38-year-old female patient: A case report
  74. Research Article
  75. Identification of the hub genes RUNX2 and FN1 in gastric cancer
  76. miR-101-3p sensitizes non-small cell lung cancer cells to irradiation
  77. Distinct functions and prognostic values of RORs in gastric cancer
  78. Clinical impact of post-mortem genetic testing in cardiac death and cardiomyopathy
  79. Efficacy of pembrolizumab for advanced/metastatic melanoma: a meta-analysis
  80. Review Article
  81. The role of osteoprotegerin in the development, progression and management of abdominal aortic aneurysms
  82. Research Article
  83. Identification of key microRNAs of plasma extracellular vesicles and their diagnostic and prognostic significance in melanoma
  84. miR-30a-3p participates in the development of asthma by targeting CCR3
  85. microRNA-491-5p protects against atherosclerosis by targeting matrix metallopeptidase-9
  86. Bladder-embedded ectopic intrauterine device with calculus
  87. Case Report
  88. Mycobacterial identification on homogenised biopsy facilitates the early diagnosis and treatment of laryngeal tuberculosis
  89. Research Article
  90. The will of young minors in the terminal stage of sickness: A case report
  91. Extended perfusion protocol for MS lesion quantification
  92. Identification of four genes associated with cutaneous metastatic melanoma
  93. Case Report
  94. Thalidomide-induced serious RR interval prolongation (longest interval >5.0 s) in multiple myeloma patient with rectal cancer: A case report
  95. Research Article
  96. Voluntary exercise and cardiac remodeling in a myocardial infarction model
  97. Electromyography as an intraoperative test to assess the quality of nerve anastomosis – experimental study on rats
  98. Case Report
  99. CT findings of severe novel coronavirus disease (COVID-19): A case report of Heilongjiang Province, China
  100. Commentary
  101. Directed differentiation into insulin-producing cells using microRNA manipulation
  102. Research Article
  103. Culture-negative infective endocarditis (CNIE): impact on postoperative mortality
  104. Extracorporeal shock wave therapy for the treatment of chronic pelvic pain syndrome
  105. Plasma microRNAs in human left ventricular reverse remodelling
  106. Bevacizumab for non-small cell lung cancer patients with brain metastasis: A meta-analysis
  107. Risk factors for cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage
  108. Problems and solutions of personal protective equipment doffing in COVID-19
  109. Evaluation of COVID-19 based on ACE2 expression in normal and cancer patients
  110. Review Article
  111. Gastroenterological complications in kidney transplant patients
  112. Research Article
  113. CXCL13 concentration in latent syphilis patients with treatment failure
  114. A novel age-biomarker-clinical history prognostic index for heart failure with reduced left ventricular ejection fraction
  115. Case Report
  116. Clinicopathological analysis of composite lymphoma: A two-case report and literature review
  117. Trastuzumab-induced thrombocytopenia after eight cycles of trastuzumab treatment
  118. Research Article
  119. Inhibition of vitamin D analog eldecalcitol on hepatoma in vitro and in vivo
  120. CCTs as new biomarkers for the prognosis of head and neck squamous cancer
  121. Effect of glucagon-like peptide-1 receptor agonists on adipokine level of nonalcoholic fatty liver disease in rats fed high-fat diet
  122. 72 hour Holter monitoring, 7 day Holter monitoring, and 30 day intermittent patient-activated heart rhythm recording in detecting arrhythmias in cryptogenic stroke patients free from arrhythmia in a screening 24 h Holter
  123. FOXK2 downregulation suppresses EMT in hepatocellular carcinoma
  124. Case Report
  125. Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  126. Research Article
  127. Clinical prediction for outcomes of patients with acute-on-chronic liver failure associated with HBV infection: A new model establishment
  128. Case Report
  129. Combination of chest CT and clinical features for diagnosis of 2019 novel coronavirus pneumonia
  130. Research Article
  131. Clinical significance and potential mechanisms of miR-223-3p and miR-204-5p in squamous cell carcinoma of head and neck: a study based on TCGA and GEO
  132. Review Article
  133. Hemoperitoneum caused by spontaneous rupture of hepatocellular carcinoma in noncirrhotic liver. A case report and systematic review
  134. Research Article
  135. Voltage-dependent anion channels mediated apoptosis in refractory epilepsy
  136. Prognostic factors in stage I gastric cancer: A retrospective analysis
  137. Circulating irisin is linked to bone mineral density in geriatric Chinese men
  138. Case Report
  139. A family study of congenital dysfibrinogenemia caused by a novel mutation in the FGA gene: A case report
  140. Research Article
  141. CBCT for estimation of the cemento-enamel junction and crestal bone of anterior teeth
  142. Case Report
  143. Successful de-escalation antibiotic therapy using cephamycins for sepsis caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia: A sequential 25-case series
  144. Research Article
  145. Influence factors of extra-articular manifestations in rheumatoid arthritis
  146. Assessment of knowledge of use of electronic cigarette and its harmful effects among young adults
  147. Predictive factors of progression to severe COVID-19
  148. Procedural sedation and analgesia for percutaneous trans-hepatic biliary drainage: Randomized clinical trial for comparison of two different concepts
  149. Acute chemoradiotherapy toxicity in cervical cancer patients
  150. IGF-1 regulates the growth of fibroblasts and extracellular matrix deposition in pelvic organ prolapse
  151. NANOG regulates the proliferation of PCSCs via the TGF-β1/SMAD pathway
  152. An immune-relevant signature of nine genes as a prognostic biomarker in patients with gastric carcinoma
  153. Computer-aided diagnosis of skin cancer based on soft computing techniques
  154. MiR-1225-5p acts as tumor suppressor in glioblastoma via targeting FNDC3B
  155. miR-300/FA2H affects gastric cancer cell proliferation and apoptosis
  156. Hybrid treatment of fibroadipose vascular anomaly: A case report
  157. Surgical treatment for common hepatic aneurysm. Original one-step technique
  158. Neuropsychiatric symptoms, quality of life and caregivers’ burden in dementia
  159. Predictor of postoperative dyspnea for Pierre Robin Sequence infants
  160. Long non-coding RNA FOXD2-AS1 promotes cell proliferation, metastasis and EMT in glioma by sponging miR-506-5p
  161. Analysis of expression and prognosis of KLK7 in ovarian cancer
  162. Circular RNA circ_SETD2 represses breast cancer progression via modulating the miR-155-5p/SCUBE2 axis
  163. Glial cell induced neural differentiation of bone marrow stromal cells
  164. Case Report
  165. Moraxella lacunata infection accompanied by acute glomerulonephritis
  166. Research Article
  167. Diagnosis of complication in lung transplantation by TBLB + ROSE + mNGS
  168. Case Report
  169. Endometrial cancer in a renal transplant recipient: A case report
  170. Research Article
  171. Downregulation of lncRNA FGF12-AS2 suppresses the tumorigenesis of NSCLC via sponging miR-188-3p
  172. Case Report
  173. Splenic abscess caused by Streptococcus anginosus bacteremia secondary to urinary tract infection: a case report and literature review
  174. Research Article
  175. Advances in the role of miRNAs in the occurrence and development of osteosarcoma
  176. Rheumatoid arthritis increases the risk of pleural empyema
  177. Effect of miRNA-200b on the proliferation and apoptosis of cervical cancer cells by targeting RhoA
  178. LncRNA NEAT1 promotes gastric cancer progression via miR-1294/AKT1 axis
  179. Key pathways in prostate cancer with SPOP mutation identified by bioinformatic analysis
  180. Comparison of low-molecular-weight heparins in thromboprophylaxis of major orthopaedic surgery – randomized, prospective pilot study
  181. Case Report
  182. A case of SLE with COVID-19 and multiple infections
  183. Research Article
  184. Circular RNA hsa_circ_0007121 regulates proliferation, migration, invasion, and epithelial–mesenchymal transition of trophoblast cells by miR-182-5p/PGF axis in preeclampsia
  185. SRPX2 boosts pancreatic cancer chemoresistance by activating PI3K/AKT axis
  186. Case Report
  187. A case report of cervical pregnancy after in vitro fertilization complicated by tuberculosis and a literature review
  188. Review Article
  189. Serrated lesions of the colon and rectum: Emergent epidemiological data and molecular pathways
  190. Research Article
  191. Biological properties and therapeutic effects of plant-derived nanovesicles
  192. Case Report
  193. Clinical characterization of chromosome 5q21.1–21.3 microduplication: A case report
  194. Research Article
  195. Serum calcium levels correlates with coronary artery disease outcomes
  196. Rapunzel syndrome with cholangitis and pancreatitis – A rare case report
  197. Review Article
  198. A review of current progress in triple-negative breast cancer therapy
  199. Case Report
  200. Peritoneal-cutaneous fistula successfully treated at home: A case report and literature review
  201. Research Article
  202. Trim24 prompts tumor progression via inducing EMT in renal cell carcinoma
  203. Degradation of connexin 50 protein causes waterclefts in human lens
  204. GABRD promotes progression and predicts poor prognosis in colorectal cancer
  205. The lncRNA UBE2R2-AS1 suppresses cervical cancer cell growth in vitro
  206. LncRNA FOXD3-AS1/miR-135a-5p function in nasopharyngeal carcinoma cells
  207. MicroRNA-182-5p relieves murine allergic rhinitis via TLR4/NF-κB pathway
https://doi.org/10.1515/med-2020-0017
Keywords for this article
Heparin-binding hemagglutinin adhesin; HBHA; Spinal tuberculosis; Diagnosis
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Article
  2. MicroRNA-451b participates in coronary heart disease by targeting VEGFA
  3. Case Report
  4. A combination therapy for Kawasaki disease with severe complications: a case report
  5. Vitamin E for prevention of biofilm-caused Healthcare-associated infections
  6. Research Article
  7. Differential diagnosis: retroperitoneal fibrosis and oncological diseases
  8. Optimization of the Convolutional Neural Networks for Automatic Detection of Skin Cancer
  9. NEAT1 promotes LPS-induced inflammatory injury in macrophages by regulating miR-17-5p/TLR4
  10. Plasma matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 as prognostic biomarkers in critically ill patients
  11. Effects of extracorporeal magnetic stimulation in fecal incontinence
  12. Case Report
  13. Mixed germ cell tumor of the endometrium: a case report and literature review
  14. Bowel perforation after ventriculoperitoneal-shunt placement: case report and review of the literature
  15. Research Article
  16. Prognostic value of lncRNA HOTAIR in colorectal cancer : a meta-analysis
  17. Case Report
  18. Treatment of insulinomas by laparoscopic radiofrequency ablation: case reports and literature review
  19. Research Article
  20. The characteristics and nomogram for primary lung papillary adenocarcinoma
  21. Undiagnosed pheochromocytoma presenting as a pancreatic tumor: A case report
  22. Bioinformatics Analysis of the Expression of ATP binding cassette subfamily C member 3 (ABCC3) in Human Glioma
  23. Diagnostic value of recombinant heparin-binding hemagglutinin adhesin protein in spinal tuberculosis
  24. Primary cutaneous DLBCL non-GCB type: challenges of a rare case
  25. LINC00152 knock-down suppresses esophageal cancer by EGFR signaling pathway
  26. Case Report
  27. Life-threatening anaemia in patient with hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber syndrome)
  28. Research Article
  29. QTc interval predicts disturbed circadian blood pressure variation
  30. Shoulder ultrasound in the diagnosis of the suprascapular neuropathy in athletes
  31. The number of negative lymph nodes is positively associated with survival in esophageal squamous cell carcinoma patients in China
  32. Differentiation of pontine infarction by size
  33. RAF1 expression is correlated with HAF, a parameter of liver computed tomographic perfusion, and may predict the early therapeutic response to sorafenib in advanced hepatocellular carcinoma patients
  34. LncRNA ZEB1-AS1 regulates colorectal cancer cells by miR-205/YAP1 axis
  35. Tissue coagulation in laser hemorrhoidoplasty – an experimental study
  36. Classification of pathological types of lung cancer from CT images by deep residual neural networks with transfer learning strategy
  37. Enhanced Recovery after Surgery for Lung Cancer Patients
  38. Case Report
  39. Streptococcus pneumoniae-associated thrombotic microangiopathy in an immunosuppressed adult
  40. Research Article
  41. The characterization of Enterococcus genus: resistance mechanisms and inflammatory bowel disease
  42. Case Report
  43. Inflammatory fibroid polyp: an unusual cause of abdominal pain in the upper gastrointestinal tract A case report
  44. Research Article
  45. microRNA-204-5p participates in atherosclerosis via targeting MMP-9
  46. LncRNA LINC00152 promotes laryngeal cancer progression by sponging miR-613
  47. Can keratin scaffolds be used for creating three-dimensional cell cultures?
  48. miRNA-186 improves sepsis induced renal injury via PTEN/PI3K/AKT/P53 pathway
  49. Case Report
  50. Delayed bowel perforation after routine distal loopogram prior to ileostomy closure
  51. Research Article
  52. Diagnostic accuracy of MALDI-TOF mass spectrometry for the direct identification of clinical pathogens from urine
  53. The R219K polymorphism of the ATP binding cassette subfamily A member 1 gene and susceptibility to ischemic stroke in Chinese population
  54. miR-92 regulates the proliferation, migration, invasion and apoptosis of glioma cells by targeting neogenin
  55. Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma
  56. NF2 inhibits proliferation and cancer stemness in breast cancer
  57. Body composition indices and cardiovascular risk in type 2 diabetes. CV biomarkers are not related to body composition
  58. S100A6 promotes proliferation and migration of HepG2 cells via increased ubiquitin-dependent degradation of p53
  59. Review Article
  60. Focus on localized laryngeal amyloidosis: management of five cases
  61. Research Article
  62. NEAT1 aggravates sepsis-induced acute kidney injury by sponging miR-22-3p
  63. Pericentric inversion in chromosome 1 and male infertility
  64. Increased atherogenic index in the general hearing loss population
  65. Prognostic role of SIRT6 in gastrointestinal cancers: a meta-analysis
  66. The complexity of molecular processes in osteoarthritis of the knee joint
  67. Interleukin-6 gene −572 G > C polymorphism and myocardial infarction risk
  68. Case Report
  69. Severe anaphylactic reaction to cisatracurium during anesthesia with cross-reactivity to atracurium
  70. Research Article
  71. Rehabilitation training improves nerve injuries by affecting Notch1 and SYN
  72. Case Report
  73. Myocardial amyloidosis following multiple myeloma in a 38-year-old female patient: A case report
  74. Research Article
  75. Identification of the hub genes RUNX2 and FN1 in gastric cancer
  76. miR-101-3p sensitizes non-small cell lung cancer cells to irradiation
  77. Distinct functions and prognostic values of RORs in gastric cancer
  78. Clinical impact of post-mortem genetic testing in cardiac death and cardiomyopathy
  79. Efficacy of pembrolizumab for advanced/metastatic melanoma: a meta-analysis
  80. Review Article
  81. The role of osteoprotegerin in the development, progression and management of abdominal aortic aneurysms
  82. Research Article
  83. Identification of key microRNAs of plasma extracellular vesicles and their diagnostic and prognostic significance in melanoma
  84. miR-30a-3p participates in the development of asthma by targeting CCR3
  85. microRNA-491-5p protects against atherosclerosis by targeting matrix metallopeptidase-9
  86. Bladder-embedded ectopic intrauterine device with calculus
  87. Case Report
  88. Mycobacterial identification on homogenised biopsy facilitates the early diagnosis and treatment of laryngeal tuberculosis
  89. Research Article
  90. The will of young minors in the terminal stage of sickness: A case report
  91. Extended perfusion protocol for MS lesion quantification
  92. Identification of four genes associated with cutaneous metastatic melanoma
  93. Case Report
  94. Thalidomide-induced serious RR interval prolongation (longest interval >5.0 s) in multiple myeloma patient with rectal cancer: A case report
  95. Research Article
  96. Voluntary exercise and cardiac remodeling in a myocardial infarction model
  97. Electromyography as an intraoperative test to assess the quality of nerve anastomosis – experimental study on rats
  98. Case Report
  99. CT findings of severe novel coronavirus disease (COVID-19): A case report of Heilongjiang Province, China
  100. Commentary
  101. Directed differentiation into insulin-producing cells using microRNA manipulation
  102. Research Article
  103. Culture-negative infective endocarditis (CNIE): impact on postoperative mortality
  104. Extracorporeal shock wave therapy for the treatment of chronic pelvic pain syndrome
  105. Plasma microRNAs in human left ventricular reverse remodelling
  106. Bevacizumab for non-small cell lung cancer patients with brain metastasis: A meta-analysis
  107. Risk factors for cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage
  108. Problems and solutions of personal protective equipment doffing in COVID-19
  109. Evaluation of COVID-19 based on ACE2 expression in normal and cancer patients
  110. Review Article
  111. Gastroenterological complications in kidney transplant patients
  112. Research Article
  113. CXCL13 concentration in latent syphilis patients with treatment failure
  114. A novel age-biomarker-clinical history prognostic index for heart failure with reduced left ventricular ejection fraction
  115. Case Report
  116. Clinicopathological analysis of composite lymphoma: A two-case report and literature review
  117. Trastuzumab-induced thrombocytopenia after eight cycles of trastuzumab treatment
  118. Research Article
  119. Inhibition of vitamin D analog eldecalcitol on hepatoma in vitro and in vivo
  120. CCTs as new biomarkers for the prognosis of head and neck squamous cancer
  121. Effect of glucagon-like peptide-1 receptor agonists on adipokine level of nonalcoholic fatty liver disease in rats fed high-fat diet
  122. 72 hour Holter monitoring, 7 day Holter monitoring, and 30 day intermittent patient-activated heart rhythm recording in detecting arrhythmias in cryptogenic stroke patients free from arrhythmia in a screening 24 h Holter
  123. FOXK2 downregulation suppresses EMT in hepatocellular carcinoma
  124. Case Report
  125. Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  126. Research Article
  127. Clinical prediction for outcomes of patients with acute-on-chronic liver failure associated with HBV infection: A new model establishment
  128. Case Report
  129. Combination of chest CT and clinical features for diagnosis of 2019 novel coronavirus pneumonia
  130. Research Article
  131. Clinical significance and potential mechanisms of miR-223-3p and miR-204-5p in squamous cell carcinoma of head and neck: a study based on TCGA and GEO
  132. Review Article
  133. Hemoperitoneum caused by spontaneous rupture of hepatocellular carcinoma in noncirrhotic liver. A case report and systematic review
  134. Research Article
  135. Voltage-dependent anion channels mediated apoptosis in refractory epilepsy
  136. Prognostic factors in stage I gastric cancer: A retrospective analysis
  137. Circulating irisin is linked to bone mineral density in geriatric Chinese men
  138. Case Report
  139. A family study of congenital dysfibrinogenemia caused by a novel mutation in the FGA gene: A case report
  140. Research Article
  141. CBCT for estimation of the cemento-enamel junction and crestal bone of anterior teeth
  142. Case Report
  143. Successful de-escalation antibiotic therapy using cephamycins for sepsis caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia: A sequential 25-case series
  144. Research Article
  145. Influence factors of extra-articular manifestations in rheumatoid arthritis
  146. Assessment of knowledge of use of electronic cigarette and its harmful effects among young adults
  147. Predictive factors of progression to severe COVID-19
  148. Procedural sedation and analgesia for percutaneous trans-hepatic biliary drainage: Randomized clinical trial for comparison of two different concepts
  149. Acute chemoradiotherapy toxicity in cervical cancer patients
  150. IGF-1 regulates the growth of fibroblasts and extracellular matrix deposition in pelvic organ prolapse
  151. NANOG regulates the proliferation of PCSCs via the TGF-β1/SMAD pathway
  152. An immune-relevant signature of nine genes as a prognostic biomarker in patients with gastric carcinoma
  153. Computer-aided diagnosis of skin cancer based on soft computing techniques
  154. MiR-1225-5p acts as tumor suppressor in glioblastoma via targeting FNDC3B
  155. miR-300/FA2H affects gastric cancer cell proliferation and apoptosis
  156. Hybrid treatment of fibroadipose vascular anomaly: A case report
  157. Surgical treatment for common hepatic aneurysm. Original one-step technique
  158. Neuropsychiatric symptoms, quality of life and caregivers’ burden in dementia
  159. Predictor of postoperative dyspnea for Pierre Robin Sequence infants
  160. Long non-coding RNA FOXD2-AS1 promotes cell proliferation, metastasis and EMT in glioma by sponging miR-506-5p
  161. Analysis of expression and prognosis of KLK7 in ovarian cancer
  162. Circular RNA circ_SETD2 represses breast cancer progression via modulating the miR-155-5p/SCUBE2 axis
  163. Glial cell induced neural differentiation of bone marrow stromal cells
  164. Case Report
  165. Moraxella lacunata infection accompanied by acute glomerulonephritis
  166. Research Article
  167. Diagnosis of complication in lung transplantation by TBLB + ROSE + mNGS
  168. Case Report
  169. Endometrial cancer in a renal transplant recipient: A case report
  170. Research Article
  171. Downregulation of lncRNA FGF12-AS2 suppresses the tumorigenesis of NSCLC via sponging miR-188-3p
  172. Case Report
  173. Splenic abscess caused by Streptococcus anginosus bacteremia secondary to urinary tract infection: a case report and literature review
  174. Research Article
  175. Advances in the role of miRNAs in the occurrence and development of osteosarcoma
  176. Rheumatoid arthritis increases the risk of pleural empyema
  177. Effect of miRNA-200b on the proliferation and apoptosis of cervical cancer cells by targeting RhoA
  178. LncRNA NEAT1 promotes gastric cancer progression via miR-1294/AKT1 axis
  179. Key pathways in prostate cancer with SPOP mutation identified by bioinformatic analysis
  180. Comparison of low-molecular-weight heparins in thromboprophylaxis of major orthopaedic surgery – randomized, prospective pilot study
  181. Case Report
  182. A case of SLE with COVID-19 and multiple infections
  183. Research Article
  184. Circular RNA hsa_circ_0007121 regulates proliferation, migration, invasion, and epithelial–mesenchymal transition of trophoblast cells by miR-182-5p/PGF axis in preeclampsia
  185. SRPX2 boosts pancreatic cancer chemoresistance by activating PI3K/AKT axis
  186. Case Report
  187. A case report of cervical pregnancy after in vitro fertilization complicated by tuberculosis and a literature review
  188. Review Article
  189. Serrated lesions of the colon and rectum: Emergent epidemiological data and molecular pathways
  190. Research Article
  191. Biological properties and therapeutic effects of plant-derived nanovesicles
  192. Case Report
  193. Clinical characterization of chromosome 5q21.1–21.3 microduplication: A case report
  194. Research Article
  195. Serum calcium levels correlates with coronary artery disease outcomes
  196. Rapunzel syndrome with cholangitis and pancreatitis – A rare case report
  197. Review Article
  198. A review of current progress in triple-negative breast cancer therapy
  199. Case Report
  200. Peritoneal-cutaneous fistula successfully treated at home: A case report and literature review
  201. Research Article
  202. Trim24 prompts tumor progression via inducing EMT in renal cell carcinoma
  203. Degradation of connexin 50 protein causes waterclefts in human lens
  204. GABRD promotes progression and predicts poor prognosis in colorectal cancer
  205. The lncRNA UBE2R2-AS1 suppresses cervical cancer cell growth in vitro
  206. LncRNA FOXD3-AS1/miR-135a-5p function in nasopharyngeal carcinoma cells
  207. MicroRNA-182-5p relieves murine allergic rhinitis via TLR4/NF-κB pathway
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 4.11.2025 from https://www.degruyterbrill.com/document/doi/10.1515/med-2020-0017/html
Scroll to top button