Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases

Autophagy is a cellular catabolic process characterized by the formation of double-membrane autophagosomes.Transmission electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation.A large number of studies have shown that autophagy is closely related to the digestion,secretion,and regeneration of gastrointestinal(GI)cells.However,the role of autophagy in GI diseases remains controversial.This article focuses on the morphological and biochemical characteristics of autophagy in GI diseases,in order to provide new ideas for their diagnosis and treatment.

Corrigendum to“Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review”[J.Pharm.Anal.14(2024)100919]

Original statement in the Section 2:2.Literature search Our primary screening of 180 articles yielded the relevant data for this study.2.1.Study selection A total of 180 articles spanning from 1960 to the present day,including original research,reviews,case reports and studies reporting nitrosamine impurities above the no-observed-adverse-effect levels(NOAEL)established by regulatory agencies,were initially screened.During the primary screening,we considered factors such as relevance,publication date,access to the full article text,and content.

Comparison of da Vinci 5 with previous versions of da Vinci and Sina:A review

Robotic systems have become popular in modern surgical procedures.The option of telesurgery has effectively addressed geographic limitations.These systems are offered by numerous companies worldwide.In this review article,we discuss four models of robotic systems to determine their advantages:the Sina flex system from Iran and the da Vinci Xi,SP,and 5 systems from the USA.We compared aspects such as architecture,instruments,visualizations,clinical use,and costs.Our findings suggest that the da Vinci robot,which was introduced earlier than the Sina system,utilizes proprietary and limited-use EndoWrist instruments with diameters ranging from 8 to 12 mm and features advanced imaging capabilities,including three-dimensional optical,tomographic,and fluorescence imaging.It is well established and widely utilized in various surgical procedures.Conversely,the Sina flex system employs single-use 5 mm instruments and is equipped with two-dimensional optical imaging as a standard,with optional three-dimensional and fluorescence imaging upgrades available.Despite its affordability,the Sina flex system is relatively new and has not yet been clinically tested.Additionally,the Sina flex system is more user-friendly.

Changes in renal function and morphological variations of kidney diseases in rheumatoid arthritis patients

Objective:Rheumatoid nephropathy is one of the most severe extra-articular manifestations of rheumatoid arthritis(RA)associated with a very unfavorable prognosis.This study aimed to identify changes in renal function and morphological variations of kidney diseases in RA patients.Methods:The study enrolled patients(126 patients)between 18 and 55 years of age with a confirmed active RA of more than 12 months.Each patient underwent the following range of laboratory and instrumental research methods:general clinical analysis of blood and urine,performing urinalysis according to Nechiporenko method;determining daily proteinuria;determining the blood content of glucose,urea,creatinine,uric acid,total bilirubin,liver transaminase level,ionogram,lipidogram,and coagulogram;determining the blood content of rheumatoid factor,anti-streptolysin O,and C-reactive protein;and X-ray of the joints of hands and feet.Renal function was examined by estimating glomerular filtration rate,tubular reabsorption index,and renal functional reserve.For studying the morphological changes in the kidneys under ultrasound examination,renal biopsy was performed in 31 patients with RA with urinary syndrome(proteinuria more than 0.3 g per day and hematuria).Results:Nephropathy in RA is characterized by impaired renal function and manifested by an increased blood creatinine and a decrease in glomerular filtration rate and renal functional reserve.Among morphological variations of nephropathy at RA,mesangial proliferative glomerulonephritis prevails,accounting for 48.4%of patients.Other disorders include the secondary amyloidosis(29.0%of patients),tubulointerstitial nephritis(16.1%),membranous glomerulonephritis(3.2%),and focal-segmental glomerulosclerosis(3.2%).Conclusion:Kidney damage is a common systemic manifestation of RA with a long and active course,a major nephropathy trigger.

Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review

The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

Orbital reconstruction:From simple materials to bioengineered solutions

Orbital fractures are a frequent and serious problem for practicing ophthalmologists. The complexity of the pathology is explained by the combined nature of the injuries(often associated with craniofacial injuries), multistage treatments, results that are often unsatisfactory, and a wide range of complaints about functional and cosmetic limitations. Over the years, significant progress has been made in the field of orbital reconstruction,allowing the transition from traditional methods using simple materials to innovative bioengineering solutions.This evolution has been driven by advances in surgical technologies, imaging techniques, and biomaterials aimed at optimizing the restoration of the shape and function of the orbital region. Traditional approaches are based on the use of autologous tissues such as bone grafts and muscle flaps, which provide biocompatibility and natural integration, but have limitations in terms of customization and accessibility. The advent of patient-specific implants and 3D printing technology has revolutionized the reconstruction of the orbit, allowing implants to be precisely adapted to a patient's anatomy. Biocompatible materials, such as porous polyethylene, titanium, and silicone, have become the basis for orbital reconstruction, ensuring durability and compatibility while minimizing long-term complications. Bioengineered solutions hold promise for further advancements in orbital reconstruction. We searched Pub Med, Cyberleninka, and other verified databases for published articles on orbital reconstruction reported in the literature between 1960 and January 2024. In this article, we consider the advantages and disadvantages of each category of reconstruction materials and provide up-to-date information on the methods for modifying their properties using modern processing technologies.

Effectiveness of negative pressure wound therapy in complex surgical treatment of necrotizing fasciitis of the upper limb

BACKGROUND Necrotizing fasciitis(NF)of the upper extremities is a severe surgical pathology,and the incidence of this disease has been steadily increasing in recent decades.Surgical treatment is accompanied by the formation of extensive wounds,which can be treated with significant difficulties.In recent years,negative pressure wound therapy(NPWT)has proven to be highly effective.It is also promising for the treatment of NF.AIM To explore the effectiveness of NPWT in the treatment of NF of the upper extremities.METHODS The results of the treatment of 36 patients with NF of the upper extremities in two groups(NPWT group and control group;2022−2023)were retrospectively analyzed.In the NPWT group,the NPWT method(120 mmHg;constant mode)was used after surgical treatment.The number of vacuum-assisted dressings in patients ranged from 1 to 3,depending on the dynamics of the wound process.The duration of fixation of one bandage was up to 2−3 d.In the control group,conventional methods of local wound treatment were used.The following indicators were analyzed:The treatment delay,the prevalence of inflammation,the microbial landscape,the number of debridements,the duration of wound preparation for surgical closure,and the nature of skin plastic surgery.RESULTS Most patients experienced a significant treatment delay[4 d,interquartile range(IQR):2–7 d],which led to the spread of the pathological process to the forearm and shoulder.The most common pathogens were Staphylococcus aureus(14;38.9%)and Streptococcus pyogenes(22;61.1%).The average number of debridements per patient was 5(IQR:3–7),with no difference between groups.The average time to prepare wounds for surgical closure was 11±4 d in the NPWT group and 29±10 d(P=0.00001)in the control group.In the NPWT group,the wounds were more often closed with local tissues(15;83.3%),and in the control group,split-thickness skin grafts were more often used(4;50%).CONCLUSION The predominant isolation of Staphylococcus aureus and/or Streptococcus pyogenes from the lesions allowed us to classify these patients as NF type II.Multiple debridement procedures have become a feature of this disease treatment.The use of NPWT has significantly reduced the time required to prepare wounds for surgical closure.Early closure of wounds allows for more frequent use of local tissue repair,which ensures better results.NPWT is a highly effective way to prepare wounds for early surgical closure in patients with upper extremity NF.

Characteristics of gut microbiota in anastomotic leakage patients in cold zones post-colorectal cancer surgery: A high-throughput sequencing and propensity-score matching study

Objective:The study aimed to explore the association between gut microbiota and anastomotic leakage(AL)after surgery in colorectal cancer(CRC)patients from a frigid zone,based on high-throughput sequencing.Methods:A total of 98 CRC patients admitted to the Second Affiliated Hospital of Harbin Medical University from July 2018 to February 2019,who met the inclusion criteria,were included.Among these,10 patients were diagnosed as AL.After propensity-score matching of baseline characteristics,10 patients from the anastomotic leakage group(AG)and 10 patients from the normal group(NG)were finally included in this study.Fecal samples were collected,and total DNA was extracted for high-throughput sequencing and bioinformatic analysis.Results:Alpha diversity analysis showed no significant difference between the two groups,while beta diversity analysis revealed significant differences in principal components.Differential microbiota were classified as Proteobacteria at the phylum level(P=0.021).At the genus level,the abundances of Streptococcus(P=0.045),Citrobacter(P=0.008)and Klebsiella(P=0.002)were significantly different between the two groups.LEfSe analysis indicated that these genera contributed most to the differences between the groups.Conclusion:The characteristics of the gut microbiota in the AG and NG were significantly different,and these differences might be associated with AL in CRC patients from frigid zones.

Assessment of Mercury in Diagnostic Biomaterials of Different Population Groups in Urban Areas of the Moscow Region

The results of a survey of different population groups in urban areas of the Moscow Region (industry workers, residents of areas with increased anthropogenic load of mercury and conditionally pristine areas, cohorts of pregnant women and children) to assess the contents of mercury in samples of various diagnostic biomaterials taken during the course of research are presented. Mercury concentrations in venous and umbilical cord blood, urine, hair, and nails were determined by means of instrumental neutron activation analysis and cold vapor atomic absorption spectrometry. Peculiarities of selection, transportation, storage, and preparation for analysis of samples of hair, nails, urine and umbilical venous blood are described. The determined concentrations of mercury in the studied diagnostic biomaterials are compared with normal and thresholds values. Although increased mercury concentrations were observed in some cases, no significant exposure of mercury was evident in general in the study towns. A positive correlation between the degree of consumption of seafood during pregnancy and a high content of mercury in the analyzed diagnostic biomaterials was shown.

Revealing True and False Brain States Based on Wavelet Analysis of Electroencephalogram

Statement of the Problem: As you know, there exist two different states in the brain’s mental activity: true and false. In recent years, a progressive method of wavelet transformation of the electroencephalogram (EEG) has been developed, which enabled us to establish the fundamental possibility of direct objective registration of the human brain’s mental activity. Earlier, we created an experimental model and software for recognizing true and false mental responses of a person based on the EEG wavelet transformation and described it in the article. The developed experimental model and information software made it possible to compare the two mental states of brain activity by electroencephalographic indicators, one of which is false and the other is true. The goal is to develop a fundamentally new information technology for recognizing true and false states in the brain’s mental activity based on the wavelet transformation of the electroencephalogram. Results: It was revealed that the true and false states of the brain can be distinguished using the method of continuous wavelet transformation and calculation of the EEG wavelet energy. It is shown that the main differences between true and false mental responses are observed in the delta and alpha ranges of the EEG. In the EEG delta rhythm, the wavelet energy is reliably higher in case of a false answer compared to a true one. In the EEG alpha rhythm, the wavelet energy is significantly higher with a true answer than a false one. Practical significance of the research: The data obtained open up the fundamental possibility of identifying true and false mental states of the brain on the basis of continuous wavelet transformation and calculation of the EEG wavelet energy.

Clostridioides difficile infection in patients with nonalcoholic fatty liver disease-current status

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,leading to fibrosis,cirrhosis and hepatocellular carcinoma and also associated with increased cardiovascular disease mortality.The pathogenesis of NAFLD is not fully understood,although NAFLD is thought to be a hepatic form of metabolic syndrome.There is an increasing understanding of the role of microbiota disturbances in NAFLD pathogenesis,and as with many other conditions affecting the microbiota,NAFLD may be a novel risk factor for Clostridioides difficile(C.difficile)colonization(CDC)and C.difficile infection(CDI).CDI is an emerging nosocomial disease,and community-acquired cases of infection are growing,probably due to an increase in CDC rates.The association of NAFLD with CDI has been shown in only 4 studies to date,three of which included less than 1000 patients,although the frequency of NAFLD in these studies was observed in almost 20%of the total patient cohort.These data revealed that NAFLD is a risk factor for CDI development and,moreover,is a risk factor for intestinal complications of CDI.More studies are needed to investigate this association and move forward CDC and CDI screening efforts for this group of patients.

Prospects for the use of olfactory mucosa cells in bioprinting for the treatment of spinal cord injuries

The review focuses on the most important areas of cell therapy for spinal cord injuries.Olfactory mucosa cells are promising for transplantation.Obtaining these cells is safe for patients.The use of olfactory mucosa cells is effective in restoring motor function due to the remyelination and regeneration of axons after spinal cord injuries.These cells express neurotrophic factors that play an important role in the functional recovery of nerve tissue after spinal cord injuries.In addition,it is possible to increase the content of neurotrophic factors,at the site of injury,exogenously by the direct injection of neurotrophic factors or their delivery using gene therapy.The advantages of olfactory mucosa cells,in combination with neurotrophic factors,open up wide possibilities for their application in threedimensional and four-dimensional bioprinting technology treating spinal cord injuries.

Identifying sex-specific injury predictors as a key factor in maintaining optimal physical activity levels

BACKGROUND Optimal physical activity is known to reduce cardiovascular,respiratory and endocrine system diseases and,as a consequence,improve quality of life.An important risk factor for reinjuries during normal exercise is the initial connective tissue pathology.The variety of clinical dysplastic manifestations significantly complicate the timely diagnosis of this comorbidity.AIM To establish pathognomonic sex-specific dysplasia phenotypes that indicate a particular sensitivity to physical exertion.METHODS The study involved 117 participants with recurrent musculoskeletal injuries that occurred during normal exercise.There were 67 women(57.26%)and 50 men(42.74%),which made it possible to compare the presence of the identified signs between sexes.A validated questionnaire was used to screen their connective tissue status.RESULTS Ranking the most commonly revealed dysplasia signs depending on their clinical significance made it possible to establish pathognomonic sex-specific phenotypes that indicated a particular susceptibility to injuries.Individualized programs of optimal physical activity are necessary for men with chest deformities,flat-valgus feet,dolichostenomelia,arachnodactylia,hemorrhoids,abdominal muscle diastasis and recurrent hernias.In women,special sensitivity to physical exertion was associated with a combination of signs such as asthenic body,joint hypermobility,overly soft auricles,thin hyperelastic skin,atrophic striae,telangiectasias and varicose veins.Of particular importance were universal signs such as gothic palate,scoliosis,kyphosis,leg deformities,temporomandibular joint crunching,and moderate to high myopia.CONCLUSION Participants’connective tissue condition should be considered when designing optimal physical activity programs.Identifying the established sex-specific dysplasia phenotypes will allow timely optimization of training loads,thus reducing the risk of injury.

Identification of a three-gene prognostic signature for radioresistant esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens.The prognostic role of genes responsible for the acquisition of radioresistance in ESCC has not been fully elucidated.AIM To establish a prognostic model by studying gene expression patterns pertinent to radioresistance in ESCC patients.METHODS Datasets were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases.The edgeR,a Bioconductor package,was used to analyze mRNA expression between different groups.We screened genes specifically responsible for radioresistance to estimate overall survival.Pearson correlation analysis was performed to confirm whether the expression of those genes correlated with each other.Genes contributing to radioresistance and overall survival were assessed by the multivariate Cox regression model through the calculation ofβi and risk score using the following formula:∑^(n)_(i=1)βi×PSI.RESULTS We identified three prognostic mRNAs(cathepsin S[CTSS],cluster of differentiation 180[CD180],and SLP adapter and CSK-interacting membrane protein[SCIMP])indicative of radioresistance.The expression of the three identified mRNAs was related to each other(r>0.70 and P<0.05).As to 1-year and 3-year overall survival prediction,the area under the time-dependent receiver operating characteristic curve of the signature consisting of the three mRNAs was 0.716 and 0.841,respectively.When stratifying patients based on the risk score derived from the signature,the high-risk group exhibited a higher death risk and shorter survival time than the low-risk group(P<0.0001).Overall survival of the low-risk patients was significantly better than that of the highrisk patients(P=0.018).CONCLUSION We have developed a novel three-gene prognostic signature consisting of CTSS,CD180,and SCIMO for ESCC,which may facilitate the prediction of early prognosis of this malignancy.

A comprehensive approach to the delayed treatment of post-burn facial scars

Background:Damage to the skin and underlying tissues due to thermal burns is relevant.Despite the success of modern medicine,repairing thermal damage to the skin is a difficult task in reconstructive plastic surgery because of the nature of the damage and the regenerative features.Characteristic post-burn changes are associated with different depths of damage when areas of deep damage are combined with more superficial areas.Methods:We described a clinical case of the staged surgical treatment of a cicatricial deformity of the buccalperiorbital-perioral region resulting from a childhood burn injury from a hot object.The 44-year-old patient complained of an aesthetic and functional deformity of the buccal-periorbital-perioral region and had previously undergone repeated nonsurgical corrections.Results:A comprehensive approach to the surgical treatment of a patient with post-burn deformities using a diplene adhesive membrane directly affected the stage of the surgical treatment and contributed to improved functional and aesthetic results.Conclusion:The positive treatment results with preserved contraction and relaxation processes of the facial muscles as well as satisfactory aesthetic results allow us to recommend the use of a biodegradable diplene film during facial reconstructive operations.

Eyelid reconstruction methods:A 10-year review

In ophthalmological practice,eyelid reconstruction is often needed because of the presence of defects that arise after the excision of a tumor or after injuries.Various methods for reconstructing these defects have been previously described.However,it is important to understand the basic principles underlying these techniques and their advantages and disadvantages to ensure the choice of the optimal technique in a particular case.We have analyzed the recent literature on new methods or modifications of existing ones to provide a brief overview of the reconstructive methods of the century for comparison.We searched PubMed and CyberLeninka for articles on restoring eyelid defects reported in the literature over the past 10 years.Most techniques can be considered modified classical reconstruction methods.Postoperative complications included aesthetic defects,such as scarring of the upper or lower eyelid,trichiasis,entropion,and lagophthalmos.Surgeons continue to search for the best methods for complex reconstructive surgery to achieve good cosmetic and aesthetic outcomes.

New classification for septic arthritis of the hand

The severity of septic arthritis of the hand and the prospects for restoration of joint function are determined by a complex of factors. Among them, the leading role belongs to local changes in tissue structures. This includes the destruction of articular cartilage and bone tissue with the development of osteomyelitis, the involvement of paraarticular soft tissues in the purulent process, and the destruction of the flexor/extensor tendons of the fingers. The currently missing specialized classification of septic arthritis could help in systematizing the diseases, determining treatment tactics, and predicting the results of treatment.The classification of septic arthritis of the hand proposed for discussion is based on the following principle: Joint-Wound-Tendon(Jx Wx Tx);Jx characterizes damage to the osteochondral structures of the joint, Wx is the presence of paraarticular purulent wounds or fistulas, and Tx is destruction of the flexor/extensor tendons of the finger. The classification of the diagnosis makes it possible to assess the nature and severity of damage to the structures of the joint and may also be useful when comparing the results of treatment of septic arthritis of the hand.

Reconstruction of eyelid defects using the diplene adhesive membrane

Background The abundance of closely packed vital structures in the periocular and palpebral regions makes resection and subsequent reconstructive interventions extremely difficult.Methods In this novel article,we described a method for closing lower eyelid defects after tumor excision using a skin-muscle flap from the upper eyelid along with the use of an adhesive diplene biodegradable membrane.The membrane was used for seamless fixation of the flap and to prevent the development of lower eyelid deformity.Results The case presented herein demonstrated that using diplene adhesive biodegradable membranes has excellent functional and aesthetic results.Conclusion Our findings suggest that an adhesive biodegradable diplene membrane can be used for the reconstruction of the lower eyelid to prevent the occurrence of retraction,for the surgical treatment of ectropion including recurrent cases,and for seamless fixation of flaps to wound surfaces in patients with a tendency to form keloids and hypertrophic scars.

The association of type and number of high-risk criteria with cancer-specific mortality in prostate cancer patients treated with radical prostatectomy

Objectives:This study aimed to test the association between of type and number of D'Amico high-risk criteria(DHRCs)with cancer-specific mortality(CSM)in high-risk prostate cancer patients treated with radical prostatectomy.Materials and methods:In the Surveillance,Epidemiology,and End Results database(2004–2016),we identified 31,281 radical prostatectomy patients with at least 1 DHRC,namely,prostate-specific antigen(PSA)>20 ng/mL(hrPSA),biopsy Gleason Grade Group(hrGGG)score of 4 and 5,or clinical tumor stage≥T3(hrcT).Multivariable Cox regression models and competing risks regression models(adjusting for other cause mortality)tested the association between DHRCs and 5-year CSM.Results:Of 31,281 patients,14,394(67%)exclusively harbored hrGGG,3189(15%)harbored hrPSA,and 1781(8.2%)harbored hrcT.Only 2132 patients(6.8%)harbored a combination of the 2 DHRCs,and 138(0.6%)had all 3 DHRCs.Five-year CSMrates ranged from 0.9%to 3.0%when any individual DHRC was present(hrcT,hrPSA,and hrGGG,in that order),1.6%to 5.9%when 2 DHRCs were present(hrPSA-hrcT,hrcT-hrGGG,and hrPSA-hrGGG,in that order),and 8.1%when all 3 DHRCs were present.Cox regression models and competing risks regression confirmed the independent predictor status of DHRCs for 5-year CSM that was observed in univariable analyses,with hazard ratios from 1.00 to 2.83 for 1 DHRC,2.35 to 5.88 for combinations of 2 DHRCs,and 7.13 for all 3 DHRCs.Conclusions:Within individual DHRCs,hrcT and hrPSA exhibited weaker effects than hrGGG did.Moreover,a dose-response effect was identified according to the number of DHRCs.Accordingly,the type and number of DHRCs allow further risk stratification within the high-risk subgroup.