Targeted temperature management, warm alkaline hydrogen peroxide solutions, and dilute solutions of local anesthetics as safety factors for circumcision

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1. Introduction

Circumcision represents the oldest surgical procedure known to mankind. It is still part of Muslim and Jewish cultures and is performed on healthy boys and men [1-6]. In addition to this, circumcision is a surgical treatment option for phimosis, balanitis and balanoposthitis, that is used regardless of religion [7]. Foreskin circumcision is reported to be a relatively safe procedure [6]. However, sometimes circumcision can lead to complications that are most often localized in nature [3, 5]. Possible complications include bleeding, post-injection bruising, hematoma, erythema, inflammation, necrosis, abscess, wound infection, as well as penile amputation, meatal stenosis, cutaneous urethral fistula, urethral erosion and iatrogenic hypospadias [8-10]. These complications worsen the aesthetic outcome of circumcision, the mood of patients and their relatives, and increase costs to the health care system [9]

Since circumcision is not a completely safe procedure, the need to reduce the risks of complications accompanying circumcision, especially in children, remains urgent. It has been reported that this requires a thorough study of the etiology and pathogenesis of the most likely localized complications [10-15]. It has been shown that one part of complications arises from poor surgical quality [16-19], and another part of complications arises from insufficient efficacy and safety of the drug solutions used [20, 21]. In this regard, the current priority is to improve the safety of surgical interventions and drug solutions of the following pharmacological groups: anesthetics (intra-venous anesthesia agents), local anesthetics, detergents (sanitizers), antiseptic and an-ti-inflammatory agents [22, 23]. The fact is that these are the medicated solutions that are most commonly used in circumcision. In this case, a targeted change in local temperature becomes very relevant, since local complications of surgical and drug nature are manifested by local hyperthermia, and the intensity of the processes of ischemia and inflammation depends on tissue temperature. 

In our opinion, the new understanding of surgical and drug factors of local complications arising from circumcision may be reflected not only in scientific articles, but also in inventions aimed at improving the efficacy and safety of surgical procedures and appropriate drugs for local use in various fields of medicine. 

2. Materials and methods

The methodology of the study was built on the search and analysis of existing inventions and articles. The study was conducted on selected databases up to 29.02.2024. Ethical approval was not required for the study as only published literature (articles and inventions) was used in this study. Articles were searched in electronic databases Web of Science, SCOPUS, PudMed, Crossref, Google and E-Library. Inventions were searched in electronic databases BYPATENTS, EAPATIS, DEPATISnet, PATENTSCOPE, DWPI, Espacenet, USPTO, CIPO, RUPTO, KIPRIS, CNIPA, TPO, PatSearch, J-PlatPat and Google Patents. 

The criteria for inclusion in the study were local mechanical and physical-chemical factors of surgical intervention and similar factors of local interaction of drug solutions. The exclusion criterion from the study was the absence of a patent for an invention that ensures the safety of a surgical procedure or the local use of drugs. The risk of individual judgment bias was reduced by using the essence of the invention as a generally accepted novelty criterion. A total of 33 inventions were identified, of which 6 were evaluated for consideration.

3.Results

Foreskin circumcision in boys and men is one of the most commonly performed surgical procedures worldwide and a topic that is at the center of considerable debate [24]. The medical benefits of neonatal circumcision have been reported to outweigh the risks [25].  Infancy has been shown to be the optimal time for clinical circumcision because the infant's low mobility facilitates the use of local anesthesia, sutures are not required, and the risk of foreskin trauma, inflammatory foreskin diseases such as balanoposthitis, phimosis, and paraphimosis is reduced [26, 27]. Foreskin circumcision in adolescence or adulthood has been reported to cause fear of pain, require leave from work or school, increase the cost of the surgical procedure and risks of complications. Healing is slower and sutures or tissue adhesive must be used [26].

The American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, the Centers for Disease Control and Prevention, and the American Academy of Family Physicians recognize that there are health benefits of newborn male circumcision but do not universally recommend the procedure [28]. The three most common techniques for newborn male circumcision utilize the Mogen clamp, the Gomco clamp, or the Plastibell device [29-33]. Complications after circumcision have been reported to be rare and may include bleeding, penile trauma, adhesions, excessive skin removal, phimosis, penile stenosis, ischemia, necrosis and Fournier’s gangrene of penil [26, 32]. Therefore, physicians should provide information to the child's parents about the potential benefits and risks of circumcision, rather than refusing or recommending it. To do this, providers should have information about the pros and cons of both the circumcision procedure itself and the medications used in the procedure [6]. In this regard, it is pointed out that one of the gaps is the lack of comprehensive information on the safety of medicines used in circumcision [35-38]. The fact is that sometimes drug solutions considered to be of high quality cause post-injection local complications [20, 21, 39-41]. In particular, sometimes these complications can be allergic in nature, sometimes they can occur due to mechanical damage to blood vessels by injection needles, or due to physical-chemical damage to tissues by the drug solutions [20, 21, 39]. Moreover, the cause of drug complications such as post-injection bruising, hematoma, erythema, local inflammation, necrosis, abscess, post-injection pain syndrome, Nicolau syndrome, and Steven-Johnson syndrome are not fully understood [39, 42-45] (Table 1).

 

Table 1. A list of local genital complications of foreskin circumcision related to surgical errors and drugs used

 

	Complications related to surgical factors	Complications related to drug factors
1	Bleeding	Post-injection bleeding
2	Penis trauma	Post-injection bruising
3	Amputation of the glans penis	Post-injection hematoma
4	Adhesions	Post-injection erythema
5	Excessive skin removal	Local aseptic inflammation of soft tissues of allergic nature
6	Wound infection	Local aseptic inflammation of soft tissue due to mechanical and/or physical-chemical local irritant action
7	Phimosis	Post-injection necrosis
8	Penile stenosis	Post-injection abscess
9	Penil ischemia	Infection of tissue at the injection site
10	Fournier's gangrene of the penis.	Post-injection pain syndrome
11	Meatal stenosis	Nicolau syndrome
12	Cutaneous urethral fistula	Stevens–Johnson syndrome
13	Urethral erosion

 

It is reported that the procedure of foreskin circumcision in healthy boys and men consists of several steps [46, 47]. These steps are illustrated in Figure 1.

 

Figure 1. List of steps in the standard of surgical circumcision for healthy boys and men

 

It should be added that, in contrast to the norm, circumcision can also be used in case of pathology, namely, in the presence of purulent-inflammatory processes in the penile region. These include phimosis (inability to fully retract the foreskin and expose the head of the penis due to congenital or acquired narrowing of the foreskin), paraphimosis (when the foreskin is not pulled over the head after retraction, resulting in a tight bandage that causes swelling of the distal penis and acute discomfort), balanoposthitis (erythema and swelling of the foreskin and glans), and balanitis (inflammation limited to the glans; the foreskin is usually not retracted) [48-50]. In such cases, the scheme of surgical treatment is more complicated. In particular, in localized purulent-inflammatory processes in the genital area, preliminary conservative treatment with local hypertonic solutions of sodium chloride and/or local glucocorticoids is recommended [48-54]. In addition, conservative treatment may include the use of new medical tubing (Phimostop™) to gently widen the foreskin [52, 55, 56]. The following groups of drugs have been reported to be indicated for foreskin circumcision for phimosis, balanitis, and balanoposthitis: detergent solutions, antiseptics, local anesthetics, antibiotics, and glucocorticoids. These drug solutions are administered as injections and/or as irrigations [57-60]. Infusions of pentoxifylline solution, heparin injections and skin lubrication with nitroglycerin ointment are used to treat penile ischemia [61-65] (Table 2).

Table 2. Drugs and application techniques used in foreskin circumcision.

	Drugs	Application technology
1	Local anesthetic solutions	Injections into the penile nerve area for dorsal blockade
2	Creams with local anesthetics (lidocaine and prilocaine)	Lubrication of the skin of the penis and/or glans penis mucosa for superficial anesthesia
3	Hypertensive sodium chloride solutions	Washing of penile skin and mucous membrane of glans penis in the presence of limited purulent-inflammatory processes of genitalia
4	Glucocorticoid ointments	Lubrication of the glans penis mucosa for phimosis
5	Creams with antibiotics	Lubrication of the glans penis mucosa for phimosis
6	Pentoxifylline solution	Infusion administration for penile ischemia
7	Nitroglycerin ointment	Lubrication of the affected surface of the penis for penile ischemia
8	Heparin solution	Subcutaneous injections for penile ischemia
9	Oxygen gas	As part of the hyperbaric oxygenation procedure

 

In turn, the gold standard of foreskin circumcision is recognized as circumcision in which tissue fusion after foreskin removal is achieved using barbed sutures, fibrin glues, or staples. In addition, foreskin circumcision can be performed using laser circumcision [52, 66].

Medications that provide general or local anesthesia have been shown to be recommended for pain relief during foreskin circumcision [67-72]. It is reported that typical medicines are the following: cream with lidocaine 4%, cream with lidocaine 2.5% and prilocaine 2.5% and injectable local anesthetics, for example, lidocaine solution without adrenaline and bupivacaine [73-75]. It has been shown that the use of lidocaine-prilocaine cream provided less pain relief than the use of injectable local anesthetics. The most well-studied pharmacological intervention for pain relief during circumcision is blockade of the dorsal nerve of the penis (DPNB) by injection of lidocaine solution (lignocaine). At the same time, the incidence of drug-induced local post-injection complications is 6.7% [67-76].

4. Discussion

A review of the scientific literature has shown that foreskin circumcision in newborns, boys and men in normal and pathologic conditions (phimosis, paraphimosis, balanoposthitis and balanitis) is an ancient and relatively safe surgical procedure. The current standard of foreskin circumcision includes 7 steps (Figure 1).  These steps include examination of the genitals by eye, irrigation of their surface with solutions of local antiseptics or wiping the surface with wipes soaked in antiseptic solutions, anesthesia of the foreskin through the use of drugs that provide general or local anesthesia, monitoring the effectiveness of anesthesia, surgical excision of the foreskin, stopping wound bleeding, suturing the wound edges with surgical sutures and applying an aseptic dressing to the wound. However, adhering to the standard of circumcision does not guarantee that it is completely safe for the patient [77-81].  It has been reported that sometimes the circumcision procedure may worsen the aesthetic outcome, the patient's health, and increase the health care costs associated with the treatment of complications encountered [9, 82-86]. Analysis of complications arising from circumcision shows that they can be divided into 2 groups: surgical and medications (Table 1). Complications associated with surgical factors may include bleeding, penile trauma, glans penis amputation, adhesions, excessive skin removal, wound infection, phimosis, penile stenosis, penile ischemia, and Fournier's gangrene of the penis, meatal stenosis, cutaneous urethral fistula and urethral erosion.  It has also been reported that surgical factors can cause iatrogenic hypospadias [8-10]. Complications associated with topical application of drugs may include post-injection bleeding, bruising, hematoma, erythema, inflammation, necrosis, abscess, post-injection pain, Nicolau's syndrome, Steven-Johnson syndrome, and infection. Of these, the most unfortunate local complications are post-injection soft tissue necrosis and post-injection abscess. The point is that these local complications cause irreversible damage to soft tissues, delay the healing process and leave a scar at the site of drug injection.  At the same time, other local complications of drug nature can sometimes also end up with local inflammation of the skin and subcutaneous fatty tissue of irreversible nature, which also delays recovery, worsens the aesthetic result and leaves a scar at the site of the complication.

Literature review showed that the list of drugs used in circumcision is very small (Table 2). In this surgical procedure performed in healthy patients, local anesthetics are more commonly used than other drugs. They are used in the form of solutions for injection and in the form of creams for lubrication of the skin and mucous membranes. When circumcision, which is part of the complex treatment of purulent-inflammatory and ischemic processes of the penis, additionally used antiseptics in the form of hypertonic solutions of sodium chloride, pentoxifylin in the form of solutions for injection, as well as ointments with glucocorticoids or with nitroglycerin or antibiotics. To eliminate ischemia and prevent infarction (necrosis) of the soft tissues of the penis, oxygen gas under increased pressure (in the form of a universal procedure known as hyperbaric oxygenation) is used. Nevertheless, even such a small list of medicines in use does not guarantee drug safety. Analysis of the literature has shown that the problem of complete drug safety has not been solved yet. The truth is that today no one knows which drug will cause a complication and in which patient [20, 21, 39, 43-45].   

The circumcision standard does not include thermal imaging of foreskin circumcision and drug injections, as is common today in various medical fields to monitor local temperature to assess peripheral circulation and diagnosing post-injection inflammation. In addition, the standard of foreskin circumcision does not include infrared imaging of the genitalia for the prevention, diagnosis, and treatment of localized post-injection complications. At the same time, it has been reported that surgical circumcision procedure may cause both unexpected penile ischemia and inflammation of the penile soft tissues, since local temperature monitoring is not currently performed [87-91]. In this regard, the diagnosis of penile ischemia is not made in a timely manner. On the other hand, some drug solutions considered to be of good quality today may have excessively high hypertonic activity because the osmotic activity of drugs is not controlled [20, 21, 39, 43-45], or may have excessively high acid activity, as pharmacopoeial requirements allow drug solutions to have acid activity up to pH 3.0, and sometimes even below this value [76-80]. In this regard, injections of such drugs have an excessively strong local hyperosmotic and acidic effect on soft tissues, which is manifested by their inflammation of reversible or irreversible nature. Moreover, the process of post-injection inflammation becomes irreversible within the first 5 minutes after drug injection [20, 21].  Therefore, in the absence of skin temperature monitoring at the injection site in the first 5 minutes after drug administration, the diagnosis of post-injection inflammation, necrosis and abscess is delayed.

This is surprising, but it turned out that the standard of foreskin circumcision does not include special topical antiseptics developed for antiseptic treatment of the skin of the genital organ both normally and in the presence of focal purulent inflammatory processes in it [45, 52, 58, 92-97]. At the same time, in recent years, special antiseptics have been developed that have the ability to dissolve purulent masses and convert them into a soft oxygenated foam. Such antiseptics were developed by physicochemical repurposing of hydrogen peroxide solution. They were named pyolytics and were initially recommended for the treatment of focal purulent-inflammatory processes such as chronic wounds (diabetic foot, pressure sores, and shin ulcer) [98-106]. It has been reported that pyolytics are warm alkaline solutions of hydrogen peroxide, which, when applied locally, have not only an aniseptic and pyolytic effect, but also an antihypoxic effect. Therefore, local application of such pyolytics not only cleans the wound surface from infectious agents and pathological tissues (pus, mucus, blood clots), but also provides tissues with oxygen, eliminating their ischemia. 

In addition, a review of the scientific literature has shown that the modern standard of foreskin circumcision and circumcision schemes, established in the practice of surgical treatment of limited purulent-inflammatory processes in the penis, do not provide for the registration of the dynamics of the local temperature of the penis and the amputated part of the glans penis, even in the case of long-term storage of the severed part and after its subsequent transplantation [16, 17, 92]. It is reported that ischemia is observed in the penis and in the severed part of the glans penis. Therefore, hyperbaric oxygenation is used to treat penile ischemia, as well as intravenous pentoxifylline and lubrication of the penile skin with nitroglycerin ointment to dilate blood vessels in the area of ischemia. However, this does not cool the penis and glans penis to a specific temperature. Therefore, controlled therapeutic hypothermia of the penis after glans penis transplantation is not properly performed [107-116].

Hyperbaric oxygenation and intravenous pentoxifylline have been reported to treat glans penis ischemia. However, cooling is not used for glans penis ischemia. At the same time, in the field of transplantology, preservation of organs and tissues, as well as in protecting various parts of the body from ischemic-hypoxic damage, the effectiveness of therapeutic hypothermia and the diagnostic value of thermal imaging monitoring of local temperature have no alternative [117-122]. It has been reported that cold preservation is a key component of organ procurement and transplantation. It has been shown that keeping biological organs and tissues in the cold slows down their metabolic activity and causes a period known as the cold ischemia time (CIT) [123-132].

Consequently, the literature review showed that not only the schemes of surgical treatment of limited purulent inflammatory processes of the genital organ, established in the practice of physicians, but also the standard of surgical circumcision, focused on healthy boys and men, do not include infrared thermography and recent advances in pharmaceutical modernization of antiseptics. 

In particular, in recent years it has been found that standard antiseptics, saline solutions and detergents continue to be used in surgical practice at pH less than 7.0, i.e. acidic, and at a temperature of +24 - +26 °C, i.e. cold. Acidic and cold solutions have been shown to be ineffective in dissolving purulent masses and in sanitizing the surfaces covered by them [98, 99]. In this regard, a new group of antiseptics was developed for rapid and effective dissolution of thick purulent masses, which was called "pyolytics" [100]. Pyolytics were obtained by physical-chemical repurposing of antiseptic hydrogen peroxide solution [101-103]. It has been reported that pyolytics are solutions of 0.3 - 3% hydrogen peroxide and 2 - 10% sodium bicarbonate heated to +37 - +45 °С. Such solutions were called "warm alkaline hydrogen peroxide solutions" (WAHPSs) [104]. In local interaction with pus masses WAHPSs urgently dissolve pus due to alkaline saponification of lipid and protein-lipid complexes and "explode" it, turning pus into soft oxygen foam. Foam formation occurs due to the rapid release of oxygen gas due to catalase cleavage of hydrogen peroxide into water and molecular oxygen. The fact is that pus masses contain the enzyme catalase. In recent years, there has been a proposal to saturate WAHPSs with gas under overpressure, which potentiates the pyolytic action. For this purpose, carbon dioxide, oxygen or inert gases under overpressure of 0.2 - 4 atm can be used for hypergasification of WAHPSs [105, 106].

Therefore, there are reasons to modernize surgical circumcision schemes for phimosis, paraphimosis, balanoposthitis, and balanitis. For this purpose, the list of drugs that are recommended for conservative treatment of limited purulent inflammatory processes of the penis, it is advisable to expand it to include warm alkaline hydrogen peroxide solutions (WAHPSs), which are called "piolitics".

In addition, previously unknown critical factors in the development of post-injection infiltrates, necroses and abscesses have been discovered in recent years. It turned out that the modern quality standard of drugs in the dosage form "Solution for injection" allows the presence of their acidic activity and does not include control of their osmotic activity and local irritant effect on the skin, subcutaneous fatty tissue, vascular wall and even blood [43]. Therefore, some drugs in the "solution for injection" dosage form considered to be of high quality today may have excessive acidic and/or hypertonic activity, which may be the cause of uncontrolled local irritation as well as post-injection infiltration, necrosis and abscess. It has been shown that the likelihood of post-injection complications is greater the greater the total concentration of ingredients in the drug solution. Moreover, drug solutions with a total concentration of more than 10% have excessively high hypertonic activity, which can cause postinjection necroses and abscesses. On this basis, to prevent local post-injection complications, it was suggested to eliminate the hypertonic activity of drug solutions by diluting them with water for injection by 2 or more times [39, 123].

In addition, it was found that the precursor to the formation of post-injection necrosis is a focus of local inflammation that develops if the drug solution has a local irritant effect. It was shown that the diagnostic symptom of local irritant action and local inflammation is local hyperthermia, which was recommended to be detected using a thermal imager [125, 126, 128-137]. It was recommended to use a thermal imager in parallel for infrared imaging of cold local anesthetic solution inside soft tissues after injection into them. It has been reported that thermal imaging monitoring of local genital temperature dynamics can provide thermal imaging navigation of the process of drug-induced tissue infiltration and subsequent resorption of the drug-induced infiltrate [127]. Finally, a solution of 3% hydrogen peroxide and 4% sodium bicarbonate at +37 - +42 °C was recommended as an effective pyolytic for effective perineal skin sanitation, and a solution of 1% lidocaine hydrochloride at +18 - +20 °C was recommended as a safe local anesthetic for local anesthesia under thermal imaging navigation of penile soft tissue infiltration process during injections [124]. Therefore, it is hoped that improved pre- and postoperative care may improve surgical circumcision outcomes [138].

On this basis, in order to improve the safety of surgical circumcision, there is reason to modernize the standard for surgical circumcision. For this purpose, it is necessary to include an instruction to dilute the drug solutions selected for injection with water for injection several times to eliminate hypertonic and local irritating effect of drugs to the minimum values. In addition, targeted temperature management and infrared imaging should be included to improve the safety and efficacy of local anesthetics, prevent post-injection complications, and increase the viability of ischemic parts and tissues of the penis.

Thus, a review of the scientific literature revealed some shortcomings of the current foreskin circumcision procedure (Table 3).

Table 3. A list of gaps in the modern foreskin circumcision procedure that reduce the prevention and timely diagnosis of localized surgical and drug-related complications 

	Gaps in procedure	Advantages of use
1	Infrared monitoring of local penile and skin temperature at injection sites of drug solutions	Early non-invasive diagnosis of localized inflammation; Evaluation of drug infiltration of soft tissue and drug absorption process; Diagnosis of ischemia of the genital organ at a distance without physical contact with it; Real-time evaluation of regional blood circulation in the penis and the efficacy of applied vasodilator drugs; Real-time monitoring of therapeutic penile hypothermia.
2	Washing the penile surface with pyolytics, which are warm alkaline hydrogen peroxide solutions (WAHPSs)	Quick and effective destruction of infectious agents, removal of purulent masses, mucus, blood clots and necrotic tissues from the penile surface and wound; Local oxygen enrichment of the wound surface and granulation; Thermal stimulation of the wound healing process.
3	Before injection, dilute drug solutions 2 - 3 times with water for injection	Prevention of post-injection necrosis, abscess, pain syndrome, erythema, Nicolau syndrome
4	Therapeutic penile hypothermia	Prevention of ischemic damage to the soft tissues of the penis; Prevention of infarction (necrosis) of the soft tissues of the penis and gangrene of the glans penis; Extending the viability of the severed glans penis during preservation, transportation and transplantation.

The table above shows that 4 major shortcomings of the current surgical procedure of foreskin circumcision have been identified: lack of infrared monitoring of the local temperature of the penis and the surface of the injection sites of drug solutions, lack of dilution of drug solutions before injection by 2 to 3 times with water for injection, lack of antiseptic pyolytics, which are warm alkaline hydrogen peroxide solutions (WAHPSs), and lack of therapeutic hypothermia. These shortcomings can be addressed today. There are all the conditions for this.  Therefore, it is hoped that the safety of the most ancient surgical procedure of foreskin circumcision will be significantly improved in the near future through effective prevention and timely diagnosis of local complications associated with surgical and drug factors.   

On this basis, in order to improve the safety of surgical circumcision, there is a rationale for adding the following recommendations to the surgical circumcision standard:

1. For early diagnosis of penile ischemia and post-injection inflammation of tissues at the sites of injection of drug solutions, it is advisable to perform infrared monitoring of local penile temperature before and after circumcision of the foreskin and skin at the sites of drug injection.
2. To prevent local postinjection necroses and abscesses, it is advisable to supplement the instructions for the use of local anesthetic solutions and other drug solutions with the recommendation to dilute them before injection with water for injections 2 or more times.
3. In order to increase the viability of the penis in case of its ischemia and the severed area of the glans penis after circumcision, it is advisable to cool them by applying therapeutic hypothermia.
4. To prevent infection of the wound and accelerate its healing after circumcision, which is part of the complex treatment of phimosis, paraphimosis, balanoposthitis and balanitis, it is advisable to wash the surface with antiseptic pyolytics, namely warm alkaline solutions of hydrogen peroxide.
5. Conclusion

A review of the literature showed that the established circumcision procedure is sometimes complicated by penile ischemia, wound infection, and post-injection necrosis and abscesses. It is reasoned that the risk of these complications can be reduced by infrared monitoring of penile and skin temperature at the injection sites, as this provides early detection of localized hyperthermia for inflammation and localized hypothermia for ischemia. It has been shown that the risk of ischemic soft tissue injury in trauma and amputation can be reduced by therapeutic hypothermia because cooling increases tissue resistance to ischemia; the risk of wound infection in phimosis, paraphimosis, balanitis and balanopostitis can be reduced by surface sanation with warm alkaline hydrogen peroxide solutions, and the risk of necrosis and abscess after injection can be reduced by pre-dilution of the drug solution with water for injection by 2 or more times.    

Author contributions. All authors confirm that their authorship meets the ICMJE international criteria (all authors contributed substantially to the conceptualization, research and preparation of the article, read and approved the final version before publication).

Conflict of interest. The authors declare that they have no apparent and potential conflicts of interest related to the publication of this article.

Funding source. The authors state that there was no external funding in the conduct of the study.

About the authors

Aleksandr L. Urakov

Izhevsk State Medical Academy, Izhevsk

Author for correspondence.
Email: alurakov@bk.ru
ORCID iD: 0000-0002-9829-9463
SPIN-code: 1613-9660
Scopus Author ID: 56915840000

Dr. Sci. (Med.), Professor, Head of the Department of General and Clinical Pharmacology

Russian Federation, Kommunarov street, 281, 426034, Izhevsk, Russia

Ilina R. Sagidullina

Izhevsk State Medical Academy

Email: ildar.sagidullin@gmail.com
ORCID iD: 0009-0005-3465-2634

Студентка

Russian Federation, 426034б, Kommunarov street, 281,Izhevsk, Russia

Petr D. Shabanov

Institute of Experimental Medicine

Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
Russian Federation

References