Pharmacophore an International Research Journal
Pharmacophore
Submit Manuscript
Open Access | Published: 2024 - Issue 4

Morphological Features of Osteoarthritis in Knee Arthroplasty. A Clinical Study Download PDF


, , , , , , ,
  1. Department of Therapy, Institute of Medicine, Chechen State University, Grozny, Russia.

  2. Department of Dentistry, Faculty of Medicine, Astrakhan State Medical University, Astrakhan, Russia.

  3. Department of Pediatrics, Faculty of Medicine, North-Ossetian State Medical Academy, Vladikavkaz, Russia.

  4. Department of Therapy, F.F. Erisman Faculty of the Institute of Public Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.

  5. Department of Therapy, Faculty of Medicine, Saratov State Medical University named after V.I.Razumovsky, Saratov, Russia.

Abstract

The regional clinic performed 187 knee replacement procedures on osteoarthritis (OA) patients. Materials were randomly selected for morphological analysis from 30 patients, 11 of whom were men and 19 of whom were women, ages 40 to 76. Of the thirty individuals that underwent morphological investigations, three (10%) had stage I OA; eight (26.7%) had stage II OA identified, and nineteen (63.3%) had stage III OA. Just one in four patients (48 individuals, or 25.7%) who received endoprosthetics had at least one round of inpatient conservative or minimally invasive surgical therapy for OA. The morphological research revealed that 11 (36.7%) of the patients who received arthroplasty had validated stage I–II OA. The conclusion is that in order to create a treatment plan for patients with osteoarthritis (OA), an algorithm for coordinating specialists' interactions must be developed. This algorithm should involve therapists, orthopedists, rheumatologists, rehabilitologists, specialists in restorative medicine, and health care coordinators.

Keywords: Osteoarthritis, Endoprosthetic, Complications, Morphological examination, Histology

Introduction

With over 300 million cases globally, osteoarthritis (OA) is the most prevalent illness [1, 2]. The knee joint (KJ) is noteworthy as one of the disease's most frequent localizations [3, 4]. Treatment for knee osteoarthritis is provided by a variety of professionals, including rehabilitologists, rheumatologists, therapists, and orthopedic traumatologists. The procedure of choice for treating later stages of osteoarthritis nowadays is endoprosthetics of KJ (EKJ) [5]. But it's not always possible to view KJ arthroplasty outcomes favorably [6, 7].

The most recent research also offers these kinds of outcomes. For example, the validity of KJ endoprosthetics in older patients was investigated by Bork [8]. 40% of patients had excessively aggressive surgical techniques, making the surgery deemed unnecessary, according to the author. Weber et al. [9] have somewhat similar information. A third of people who have surgery nowadays have an unjustifiably executed KJ arthroplasty [10]. It has been observed by researchers that in 7–34% of instances, KJ arthroplasty is carried out without warrant [11]. Furthermore, according to some specialists, 82% of patients who have knee and hip arthroplasty do not resume physical activity and are compelled to continue living a "sedentary" lifestyle as they did prior to the procedure [12, 13].

The clinical and radiological stage of the illness, the clinical picture, the kind and severity of the concurrent pathology, the patient's desire, and a number of other factors were considered when deciding on EKJ as a therapeutic option [14-16]. After the joint is replaced with an implant, a morphological evaluation is often performed [17].

Consequently, the pathomorphological analysis of the excised knee joint components and the retrospective staging of the procedure with the detection of morphological and clinical correlations were the goals of this investigation.

Materials and Methods

Patients with osteoarthritis underwent 187 knee replacement procedures in the regional clinic in 2023. In order to perform the study, each patient was given informed consent. Fully upheld have been the moral guidelines outlined in the Helsinki Declaration [18]. For a lifetime pathoanatomical evaluation, materials from 30 patients, 19 women and 11 men, aged 40 to 76, were selected at random.

Following surgery, tibial condyle pieces were preserved throughout the day in a 10% buffered formalin solution. Then, bone material was sliced with a pair of saws for a later pathological investigation.

The normal protocol for bone tissue, including the decalcification stage, was followed in the creation of the histological preparations [19]. The examined bone tissue pieces were decalcified in an electrolyte decalcifying solution (Biovitrum, Russia) for eight hours at a volume ratio of 1:50 between the object's volume and the decalcifying liquid's volume, all the time using a needle to gauge the level of decalcification. The samples were washed with tap water for 60 minutes after the decalcification process was finished. Following the normal protocol, histological wiring, filling, and microtomy with a 5 µm slice thickness were carried out [20]. Safranin O, eosin, and hematoxylin were used to stain the preparations.

The state of subchondral bone, intertrabecular space tissue, and cartilage tissue was evaluated during microcoping. To evaluate injury to the articular surface and subchondral bone, the OOCHAS pathomorphological categorization was employed (Table 1) [21].

 

Table 1. Pathomorphological classification of OOCHAS

Stage

Substage

Related Criteria

Concomitant stage 0. Articular surface is intact, cartilage is intact criteria

Intact, uninjured cartilage

Stage 1. The articular surface is intact

1.0. Cellular elements are intact

Cartilage matrix: the surface area is intact, edema and/or fibrillation

1.5. Cellular elements are damaged

Cellular elements: active proliferation, hypertrophy

Stage 2. Surface tears/damages

2.0. Fibrillation in the surface area

As stated above

2.5. Abrasion of the articular surface with loss of cartilage matrix

± Roughness in the surface area

± Depletion of the cartilaginous matrix (stained with safranin O or toluidine blue) in the upper 1/3 of the cartilage (median zone)

± Disorientation of chondrocytic "columns"

Stage 3. Vertical cracks

3.0. Simple cracks

As stated above

3.5. Branched cracks

± Depletion of the cartilaginous matrix (stained with safranin O or toluidine blue) in the lower 2/3 of the cartilage (deep zone)

± Formation of new collagen (microscopy in polarized light, picrosirius red staining)

Stage 4. Erosion

4.0. Stratification of the surface area

Depletion of the cartilaginous matrix, formation of cysts

4.5. Extensive damage to the middle zone

in the cartilaginous matrix

Stage 5. Exposure of the subchondral bone

5.0. The subchondral bone is intact

The articular surface is a sclerosed bone and/or the beginnings of osteophytes, fibrous fibrous cartilage.

5.5. The presence of osteophyte rudiments

Stage 6. Joint deformity

6.0. Osteophytes in the marginal zones of the joint

Remodeling of the subchondral bone. Deformation with an increase in the contour of the articular surface (due to the formation of osteophytes)

6.5. Osteophytes in the marginal and central areas of the joint

Microfractures and remodeling sites

 

Results and Discussion

The information pertaining to 187 patients who had primary total knee arthroplasty at the regional clinic in 2023 due to osteoarthritis was examined. The patients ranged in age from 40 to 76 years old, with an average age of 59.3 ± 6.7 years. Table 2 lists the age and gender of 187 patients who were released from the clinic following EKJ.

 

Table 2. Distribution of patients who underwent primary total EKJ due to osteoarthritis, taking into account their age and gender

Age, years

Number of patients (%)

Male

Female

Total

absolute

%

absolute

%

absolute

%

18–44

8

4.3

15

8.0

23

12.3

45–64

32

17.1

57

30.5

89

47.6

≥65

22

11.8

53

28.3

75

40.1

Total

62

33.2

125

66.8

187

100

 

From the data in Table 2, it can be shown that women outnumbered males among young patients: 15 (8%) against 8 (4.3%) clinical observations. Women also dominated the groupings of elderly and middle-aged patients. In the meantime, the male-to-female ratio was 1:2 among the young and old patients, and it was 1:3 (11.8% and 28.3%, respectively) in the middle-aged group of patients (45 to 64 years old). It was discovered from the anamnesis that only 48 (25.7%) of the patients had received at least one session of conservative or minimally invasive surgical therapy for KJ osteoarthritis prior to the endoprosthesis. In most cases (139 cases – 74.3%), only outpatient treatment took place. All 187 patients underwent an X-ray examination of the knee joint before surgery. In 84 (44.9%) patients, magnetic resonance imaging was carried out. Following a routine examination prior to arthroplasty, 123 patients, or 65.8%, were diagnosed with "osteoarthritis of the knee joint of the III St." 64 observations (34.2%) revealed the presence of OA in the KJ of the II–III stage.

During the EKJ and in the initial postoperative phase following knee arthroplasty, local and general problems were confirmed. Most people thought that the outcomes of the arthroplasty were good. Simultaneously, problems during and after surgery were experienced by 18 patients (9.6%). Local postoperative sequelae included injuries to the KJ's ligamentous apparatus in 4 (2.1%) patients, including 2 cases of lateral ligament injury and 2 cases of quadriceps femoris injuries. Two (1.1%) incidences of superficial surgical site infections were identified during the postoperative complications study. The structure of general complications was dominated by cardiac diseases (4 instances, 2.1%). Remarkably, no fatalities were reported during the procedure or in the initial postoperative phase.

Thirty individuals were chosen at random from a total of 187 patients to undergo postoperative pathomorphological evaluation. We looked at the KJ's articular capsule and tibial condyle. Cases of osteoarthritis of the KJ and II and III stages as well as the early phases of the disease were found in the micropreparations investigation (Figure 1a).

The many stages of OA are depicted by the histograms that are shown, ranging from the disease's early symptoms to its stage III. It should be mentioned that 3 patients (10%) out of the 30 morphological examinations performed exhibited I-stage OA of KJ (Figure 1b). In 8 (26.7%) cases, II stage OA was diagnosed (Figure 1c), and in 19 (63.3%) osteoarthritis of III stage OA was diagnosed (Figure 1d).

 

 

b)

c)

a)

d)

Figure 1. Postoperative pathomorphological examination of 30 patients. a)  The appearance of the tissue material obtained by the pathology department after total knee replacement surgery. b) I stage OA of KJ (1 – hyaline cartilage tissue; 2 – subchondral lamellar bone tissue; 3 – intertrabecular spaces of the epiphysis filled with fatty bone marrow). Staining with safranin O, magnification ×100. c) Articular cartilage and subchondral bone of the medial condyle of the femur of a patient who underwent total knee replacement. II stages OA of KJ (1 – hyaline cartilage tissue with a biochemically altered matrix; 2 – subchondral lamellar bone tissue with signs of osteosclerosis (thickening); 3 – intertrabecular spaces of epiphysis filled with fatty bone marrow; * – vertical, horizontal cracks and erosion (defect) of cartilage).  Staining with safranin O, magnification ×100. d) Articular cartilage and sclerosed subchondral bone of the medial condyle of the femur of a patient who underwent total knee replacement. III stage OA of KJ (1 – fibrous cartilage tissue; 2 – sclerosed subchondral lamellar bone tissue and microcysts (*)). The red line is the boundary between the remaining cartilage and the underlying bone tissue. Staining with hematoxylin and eosin, magnification ×100.

 

Certainly, osteoarthritis specialists consider more than only the results of computed tomography or X-ray research techniques and the predicted degree of osteoarthritis when making decisions about knee replacements [22, 23]. The characteristics of the clinical picture (the severity of the pain syndrome, the efficacy of conservative therapy, the length of the illness), the outcomes of an investigation into the KJ's stability, and information on the state of the ligamentous apparatus were also considered [24]. It should be noted, therefore, that the majority of the time (139/74.3%) of the observations made out of 187 patients, complete knee replacement was the cause of the patient's initial inpatient therapy for OA of the KJ [25].

A knee replacement with an implant is not an organ-preserving procedure; it should be mentioned [26]. Like any other procedure, EKJ may also result in intra- or postoperative problems, some of which may be fatal [27, 28]. In addition, patients frequently disregard their physician's advice to limit their range of motion in the operated joint and adhere to a certain regimen, which can result in a number of problems [29-31]. Of particular note are the limited lifespan of the implant and the unsatisfactory outcomes of endoprosthetics [32]. The indications for endoprosthetics are also not ideal and are always being modified toward their restriction [33, 34]. Yet, a mechanism for medical assessment of individuals with osteoarthritis is not offered by the existing healthcare system [35]. Under mandatory health insurance, inpatient care is the least expensive for these patients, and there is currently no rigorous protocol governing the relationships between therapists, orthopedists, rheumatologists, rehabilitologists, and experts in restorative medicine [36].

Assuming that 11 (36.7%) of the patients with I or II stage OA underwent joint replacement surgery too soon without taking advantage of the possibility of conservative or minimally invasive surgical therapy for KJ OA is based on the findings from the morphological research. The outcomes that have been presented provide motivation for carrying out a unique scientific investigation focused on creating a treatment plan for individuals suffering from osteoarthritis of the knee joint. This plan should include conservative inpatient care, minimally invasive surgical methods, rehabilitation, and outpatient examination and treatment. After the creation and execution of an algorithm for the complicated treatment of OA of KJ, the study's findings will be taken into consideration and utilized as a control group in statistical analysis.

Conclusion

There is currently a growing body of research focused on the issue of knee replacements performed too soon in patients with osteoarthritis, despite the possibility of using conservative and less invasive surgical procedures. 48 patients, or one in four, who were admitted to the regional clinic for knee replacements received at least one session of inpatient conservative or minimally invasive surgical therapy for knee osteoarthritis. This is a 25.7% patient rate. The morphological analysis revealed that 19 (63.3%) individuals had definite stage III osteoarthritis. Stage I–II osteoarthritis was confirmed in 11 (36.7%) of the remaining patients who had arthroplasty procedures.

In order to establish a treatment plan for individuals suffering from osteoarthritis of the knee, an algorithm including the collaboration of therapists, orthopedists, rheumatologists, rehabilitologists, specialists in restorative medicine, and health care coordinators must be developed.

Acknowledgments: None

Conflict of interest: None

Financial support: None

Ethics statement: All patients received information consent to conduct the study. The ethical standards set out in the Helsinki Declaration have been fully respected.

References

  1. Chalian M, Pooyan A, Alipour E, Roemer FW, Guermazi A. What is new in osteoarthritis imaging? Radiol Clin North Am. 2024;62(5):739-53. doi:10.1016/j.rcl.2024.02.006
  2. Motyl G, Krupka WM, Maślińska M. The problem of residual pain in the assessment of rheumatoid arthritis activity. Reumatologia. 2024;62(3):176-86. doi:10.5114/reum/189779
  3. Femia M, Valenti Pittino C, Fumarola EM, Tramarin M, Papa M, Giurazza F, et al. Genicular artery embolization: A new tool for the management of refractory osteoarthritis-related knee pain. J Pers Med. 2024;14(7):686. doi:10.3390/jpm14070686
  4. Boyd SK. High-resolution peripheral quantitative computed tomography in rheumatic diseases: A new option for knee osteoarthritis. Radiol Clin North Am. 2024;62(5):903-12. doi:10.1016/j.rcl.2024.02.010
  5. Teoli A, Ippersiel P, Bussières A, Antoniou J, Robbins SM. Understanding the impact of physical activity level and sports participation on implant integrity and failure in patients following unicompartmental and total knee arthroplasty: A scoping review. Osteoarthr Cartil Open. 2024;6(3):100498. doi:10.1016/j.ocarto.2024.100498
  6. Liang ZJ, Koh DTS, Soong J, Lee KH, Bin Abd Razak HR. Severity of knee osteoarthritis does not affect clinical outcomes following proximal fibular osteotomy - A systematic review and pooled analysis. J Clin Orthop Trauma. 2024;54:102473. doi:10.1016/j.jcot.2024.102473
  7. Fu X, She Y, Jin G, Liu C, Liu Z, Li W, et al. Comparison of robotic-assisted total knee arthroplasty: An updated systematic review and meta-analysis. J Robot Surg. 2024;18(1):292. doi:10.1007/s11701-024-02045-y
  8. Bork H. Rehabilitation after hip and knee endoprosthetic treatment in the elderly. Orthopade. 2017;46(1):69-77. [In German]. doi:10.1007/s00132-016-3368-0
  9. Weber O, Goost H, Mueller M, Burger C, Wirtz D, Pagenstert G, et al. Mid-term results after post-traumatic knee joint replacement in elderly patients. Z Orthop Unfall. 2011;149(2):166-72. [In German]. doi:10.1055/s-0030-1249793
  10. Desouza C, Shetty V. Beyond one step: Unveiling optimal approach for bilateral knee arthroplasty - A comprehensive meta-analysis. Arch Orthop Trauma Surg. 2024:1-9. doi:10.1007/s00402-024-05454-8
  11. Wu KA, Therien AD, Kiwinda LV, Castillo CJ, Hendren S, Long JS, et al. Addressing meniscal deficiency part 2: An umbrella review of systematic reviews and meta-analyses on meniscal scaffold-based approaches. J Exp Orthop. 2024;11(3):e12108. doi:10.1002/jeo2.12108
  12. Sadiq S, Noor R, Akram R. Risk factors of post-discharge falls in patients undergoing total knee arthroplasty: An integrative review. J Back Musculoskelet Rehabil. 2024:1-3. doi:10.3233/BMR-230165
  13. Isaji Y, Uchino S, Inada R, Saito H. Effectiveness of psychological intervention following anterior cruciate ligament reconstruction: A systematic review and meta-analysis. Phys Ther Sport. 2024;69:40-50. doi:10.1016/j.ptsp.2024.07.003
  14. Zhao H, Ou L, Zhang Z, Zhang L, Liu K, Kuang J. The value of deep learning-based X-ray techniques in detecting and classifying K-L grades of knee osteoarthritis: A systematic review and meta-analysis. Eur Radiol. 2024:1-4. doi:10.1007/s00330-024-10928-9
  15. Sin A, Hollabaugh W, Porras L. Narrative review and call to action on reporting and representation in orthobiologics research for knee osteoarthritis. PM R. 2024. doi:10.1002/pmrj.13214
  16. Gabriel RA, Seng EC, Curran BP, Winston P, Trescot AM, Filipovski I. A narrative review of ultrasound-guided and landmark-based percutaneous cryoneurolysis for the management of acute and chronic pain. Curr Pain Headache Rep. 2024:1-8. doi:10.1007/s11916-024-01281-z
  17. Jia Z, Greven J, Hildebrand F, Kobbe P, Eschweiler J. Conservative treatment versus surgical reconstruction for ACL rupture: A systemic review. J Orthop. 2024;57:8-16. doi:10.1016/j.jor.2024.05.026
  18. Lopez-Valdes FJ, Mascareñas Brito A, Agnew AM, Cripton P, Kerrigan J, Masouros S, et al. The ethics, applications, and contributions of cadaver testing in injury prevention research. Traffic Inj Prev. 2024:1-14. doi:10.1080/15389588.2024.2376937
  19. Schendrigin IN, Timchenko LD, Rzhepakovsky IV, Avanesyan SS, Sizonenko MN, Grimm WD, et al. Clinical and pathogenetic significance of amylase level and microtomographic index of synovial fluid in various joint lesions. Sovrem Tekhnologii Med. 2022;14(6):42-9. doi:10.17691/stm2022.14.6.05
  20. Brockmeyer M, Orth P, Höfer D, Seil R, Paulsen F, Menger MD, et al. The anatomy of the anterolateral structures of the knee - A histologic and macroscopic approach. Knee. 2019;26(3):636-46. doi:10.1016/j.knee.2019.02.017
  21. Custers RJ, Creemers LB, Verbout AJ, van Rijen MH, Dhert WJ, Saris DB. Reliability, reproducibility, and variability of the traditional Histologic/Histochemical Grading System vs the new OARSI osteoarthritis cartilage histopathology assessment system. Osteoarthr Cartil. 2007;15(11):1241-8. doi:10.1016/j.joca.2007.04.017
  22. Hu X, Wang C, Zeng Y, Yang X, Min L. Clinical perspectives on surgical reconstruction of eccentric tumors at the distal femur with unicondylar resection. Orthop Surg. 2024. doi:10.1111/os.14119
  23. Rzhepakovsky I, Anusha Siddiqui S, Avanesyan S, Benlidayi M, Dhingra K, Dolgalev A, et al. Anti-arthritic effect of chicken embryo tissue hydrolyzate against adjuvant arthritis in rats (X-ray microtomographic and histopathological analysis). Food Sci Nutr. 2021;9(10):5648-69. doi:10.1002/fsn3.2529
  24. Simick Behera N, Duong V, Eyles J, Cui H, Gould D, Barton C, et al. How does osteoarthritis education influence knowledge, beliefs and behavior in people with knee and hip osteoarthritis? A systematic review. Arthritis Care Res (Hoboken). 2024. doi:10.1002/acr.25391
  25. Mapinduzi J, Ndacayisaba G, Verbrugghe J, Timmermans A, Kossi O, Bonnechère B. Effectiveness of mHealth interventions to improve pain intensity and functional disability in individuals with hip or knee osteoarthritis: A systematic review and meta-analysis. Arch Phys Med Rehabil. 2024:S0003-9993(24)01068-2. doi:10.1016/j.apmr.2024.06.008
  26. Chaiperm C, Ittiravivongs A, Waipanya P, Athikraimongkol B, Narinsorasak T. Simultaneous concurrent bilateral total knee replacement in a patient with bilateral lipoma arborescens with end-stage osteoarthritis. Arthroplast Today. 2024;27:101406. doi:10.1016/j.artd.2024.101406
  27. Daher M, Estephan M, Ghoul A, Tarchichi J, Mansour J. Hip strengthening after total knee arthroplasty: A meta-analysis and systematic review. Arch Bone Jt Surg. 2024;12(6):373-9. doi:10.22038/ABJS.2024.76202.3520
  28. Boopalan D, Vijayakumar V, Kalidas S, Ravi P, Balakrishnan A, Shanmugam P, et al. Effect of local mud application in patients with knee osteoarthritis - A systematic review and meta-analysis. Int J Biometeorol. 2024:1-2. doi:10.1007/s00484-024-02725-2
  29. Cao F, Xu Z, Li XX, Fu ZY, Han RY, Zhang JL, et al. Trends and cross-country inequalities in the global burden of osteoarthritis, 1990-2019: A population-based study. Ageing Res Rev. 2024;99:102382. doi:10.1016/j.arr.2024.102382
  30. Chen X, Zheng J, Yin L, Li Y, Liu H. Transplantation of three mesenchymal stem cells for knee osteoarthritis, which cell and type are more beneficial? A systematic review and network meta-analysis. J Orthop Surg Res. 2024;19(1):366. doi:10.1186/s13018-024-04846-1
  31. Santos ACG, Caiado VDS, Moreira-Marconi E, Teixeira-Silva Y, De Meirelles AG, Seixas A, et al. The influence of physical exercises on the flexibility of older individuals with knee osteoarthritis: A systematic review. Iran J Public Health. 2024;53(2):255-67. doi:10.18502/ijph.v53i2.14911
  32. Li G, Stampas A, Komatsu Y, Gao X, Huard J, Pan S. Proteomics in orthopedic research: Recent studies and their translational implications. J Orthop Res. 2024;42(8):1631-40. doi:10.1002/jor.25917
  33. Pfeil J, Höhle P, Rehbein P. Bilateral endoprosthetic total hip or knee arthroplasty. Dtsch Arztebl Int. 2011;108(27):463-8. doi:10.3238/arztebl.2011.0463
  34. Aurich M, Koenig V, Hofmann G. Comminuted intraarticular fractures of the tibial plateau lead to posttraumatic osteoarthritis of the knee: Current treatment review. Asian J Surg. 2018;41(2):99-105. doi:10.1016/j.asjsur.2016.11.011
  35. Beckmann J, Meier MK, Benignus C, Hecker A, Thienpont E. Contemporary knee arthroplasty: One fits all or time for diversity? Arch Orthop Trauma Surg. 2021;141(12):2185-94. doi:10.1007/s00402-021-04042-4
  36. Legnani C, Ventura A, Mangiavini L, Maffulli N, Peretti GM. Management of medial femorotibial knee osteoarthritis in conjunction with anterior cruciate ligament deficiency: Technical note and literature review. J Clin Med. 2024;13(11):3143. doi:10.3390/jcm13113143
Cite this article
Vancouver
Edelgirieva ME, Ulubaev TA, Papaev KB, Sherieva LR, Avagyan AS, Pyzhyanov VD, et al. Morphological Features of Osteoarthritis in Knee Arthroplasty. A Clinical Study. Pharmacophore. 2024;15(4):54-9. https://doi.org/10.51847/FVoKybLMM7
APA
Edelgirieva, M. E., Ulubaev, T. A., Papaev, K. B., Sherieva, L. R., Avagyan, A. S., Pyzhyanov, V. D., Radeva, E. A., & Nikoghosyan, M. S. (2024). Morphological Features of Osteoarthritis in Knee Arthroplasty. A Clinical Study. Pharmacophore, 15(4), 54-59. https://doi.org/10.51847/FVoKybLMM7

Related articles:
Study of the Toxicity of the Drug Monizen® Forte
Vol 12 Issue 2, 2021 | Engasheva Ekaterina Sergeevna
Most viewed articles:
QR code:

Short Link:
Views: 1068

Downloads: 126
Quick Access

Associations

Pharmacophore
ISSN: 2229-5402

Copyright © 2025 Pharmacophore. Authors retain copyright of their article if they are accepted for publication.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.