The History of Controlling and Treating Infectious Diseases in Ancient China

Infectious diseases are the common enemies of mankind.In the course of historical development,they persistently threaten human health and safety.Even today,despite the developments in medical science,we cannot escape the fear and suffering caused by infectious diseases.Whether in ancient or modern times,the source of infection,route of transmission,and a susceptible population are the three key conditions for the prevalence and spread of infectious diseases.All factors closely related to these three conditions can affect the prevalence of infectious diseases.China is one of the cradles of world civilization.The ancient people accumulated a great deal of experience and lessons in the long struggle against infectious diseases.In the face of the current threat posed by widespread infectious disease,it is imperative to review and summarize ancient Chinese ideas and health policies on epidemic prevention and control to inspire contemporary efforts in the prevention and control of infectious disease.The combination of prevention-oriented epidemic prevention ideology and traditional medicine provides valuable insights,especially for impoverished and medically underserved regions.

Effectiveness of a new approach to minimally invasive surgery in palliative treatment of patients with distal malignant biliary obstruction

BACKGROUND Palliative endoscopic biliary drainage is the primary treatment option for the management of patients with jaundice which results from distal malignant biliary obstruction(DMBO).In this group of patients,decompression of the bile duct(BD)allows for pain reduction,symptom relief,chemotherapy administration,improved quality of life,and increased survival rate.To reduce the unfavorable effects of BD decompression,minimally invasive surgical techniques require continuous improvement.AIM To develop a technique for internal-external biliary-jejunal drainage(IEBJD)and assess its effectiveness in comparison to other minimally invasive procedures in the palliative treatment of patients with DMBO.METHODS A retrospective analysis of prospectively collected data was performed,which included 134 patients with DMBO who underwent palliative BD decompression.Biliary-jejunal drainage was developed to divert bile from the BD directly into the initial loops of the small intestine to prevent duodeno-biliary reflux.IEBJD was carried out using percutaneous transhepatic access.Percutaneous transhepatic biliary drainage(PTBD),endoscopic retrograde biliary stenting(ERBS),and internal-external transpapillary biliary drainage (IETBD) were used for the treatment of studypatients. Endpoints of the study were the clinical success of the procedure, the frequency andnature of complications, and the cumulative survival rate.RESULTSThere were no significant differences in the frequency of minor complications between the studygroups. Significant complications occurred in 5 (17.2%) patients in the IEBJD group, in 16 (64.0%)in the ERBS group, in 9 (47.4%) in the IETBD group, and in 12 (17.4%) in the PTBD group.Cholangitis was the most common severe complication. In the IEBJD group, the course ofcholangitis was characterized by a delayed onset and shorter duration as compared to other studygroups. The cumulative survival rate of patients who underwent IEBJD was 2.6 times higher incomparison to those of the PTBD and IETBD groups and 20% higher in comparison to that of theERBS group.CONCLUSIONIEBJD has advantages over other minimally invasive BD decompression techniques and can berecommended for the palliative treatment of patients with DMBO.

Crosstalk between gut microbiota and antidiabetic drug action

Type 2 diabetes (T2D) is a disorder characterized by chronic inflated blood glucose levels (hyperglycemia), at first due to insulin resistance and unregulated insulin secretion but with tendency towards global spreading. The gut microbiota is recognized to have an influence on T2D, although surveys have not formed a clear overview to date. Because of the interactions between gut microbiota and host homeostasis, intestinal bacteria are believed to play a large role in various diseases, including metabolic syndrome, obesity and associated disease. In this review, we highlight the animal and human studies which have elucidated the roles of metformin,α-glucosidase inhibitors, glucagon-like peptide-1 agonists, peroxisome proliferator-activated receptors γ agonists, inhibitors of dipeptidyl peptidase-4, sodium/glucose cotransporter inhibitors, and other less studied medications on gut microbiota. This review is dedicated to one of the most widespread diseases, T2D, and the currently used antidiabetic drugs and most promising new findings. In general, the gut microbiota has been shown to have an influence on host metabolism, food consumption, satiety, glucose homoeostasis, and weight gain. Altered intestinal microbiota composition has been noticed in cardiovascular diseases, colon cancer, rheumatoid arthritis, T2D, and obesity. Therefore, the main effect of antidiabetic drugs is on the microbiome composition, basically increasing the short-chain fatty acids-producing bacteria, responsible for losing weight and suppressing inflammation.

Insulin resistance and liver steatosis in chronic hepatitis C infection genotype 3

Hepatitis C virus(HCV) infection is a common chronic liver disease worldwide.Non-alcoholic fatty liver disease and insulin resistance(IR) are the major determinants of fibrosis progression and response to antiviral therapy.The pathogenetic link between IR and chronic HCV infection is complex,and is associated with HCV genotype.Liver steatosis is the most common in the patients infected with genotype 3 virus,possibly due to direct effects of genotype 3 viral proteins.To the contrary,hepatic steatosis in the patients infected with other genotypes is thought to be mostly due to the changes in host metabolism,involving IR.In HCV genotype 3,liver steatosis correlates with viral load,reverts after reaching the sustained virologic response and reoccurs in the relapsers.A therapeutic strategy to improve IR and liver steatosis and subsequently the response to antiviral treatment in these patients is warranted.

Intestinal-borne dermatoses significantly improved by oral application of Escherichia coli Nissle 1917

AIM: To evaluate the effect of oral Escherichia coli(E. coli) Nissle application on the outcome of intestinalborne dermatoses.METHODS: In a randomized, controlled, non-blinded prospective clinical trial 82 patients with intestinal-borne facial dermatoses characterized by an erythematous papular-pustular rash were screened. At the initiation visit 37 patients entered the experimental arm and 20 patients constituted the control arm. All 57 patients were treated with a vegetarian diet and conventional topical therapy of the dermatoses with ointments containing tetracycline, steroids and retinoids. In the experimental arm patients received a one month therapy with oral E. coli Nissle at a maintenance dose of 2 capsules daily. The experimental group was compared to a non-treatment group only receiving the diet and topical therapy. The primary outcome parameter was improvement of the dermatoses, secondary parameters included life quality and adverse events. In addition the immunological reaction profile(Ig A, interleucin-8 and interferon-a) was determined. Furthermore the changes of stool consistency and the microbiota composition over the time of intervention were recorded.RESULTS: Eighty-nine percent of the patients with acne, papular-pustular rosacea and seborrhoic dermatitis responded to E. coli Nissle therapy with significant amelioration or complete recovery in contrastto 56% in the control arm(P < 0.01). Accordingly, in the E. coli Nissle treated patients life quality improved significantly(P < 0.01), and adverse events were not recorded. The clinical improvement was associated with a significant increase of Ig A levels to normal values in serum as well as suppression of the proinflammatory cytokine IL-8(P < 0.01 for both parameters). In the E. coli Nissle treated group a shift towards a protective microbiota with predominance of bifidobacteria and lactobacteria(> 107 CFU/g stool) was observed in 79% and 63% of the patients, respectively(P < 0.01), compared to no change in the control group without E. coli Nissle. Moreover, the detection rate of a pathogenic flora dropped from 73% to 14 % of the patients in the experimental arm(P < 0.01) with no significant change in the control arm(accounting 80% before and 70% after the observation period, P > 0.05). Accordingly, stool consistency, color and smell normalized in the E. coli Nissle treated patients. CONCLUSION: E. coli Nissle protects the mucus barrier by overgrowth of a favorable gut microbiota with less immunoreactive potential which finally leads to clinical improvement of intestinal borne dermatoses.

Mechanisms of regulation of PFKFB expression in pancreatic and gastric cancer cells

Enzymes 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 and-4(PFKFB-3 and PFKFB-4)play a significant role in the regulation of glycolysis in cancer cells as well as its proliferation and survival.The expression of these mRNAs is increased in malignant tumors and strongly induced in different cancer cell lines by hypoxia inducible factor(HIF)through active HIF binding sites in promoter region of PFKFB-4 and PFKFB-3 genes.Moreover,the expression and hypoxia responsibility of PFKFB-4 and PFKFB-3 was also shown for pancreatic(Panc1,PSN-1,and MIA PaCa-2)as well as gastric(MKN45 and NUGC3)cancer cells.At the same time,their basal expression level and hypoxia responsiveness vary in the different cells studied:the highest level of PFKFB-4 protein expression was found in NUGC3 gastric cancer cell line and lowest in Panc1 cells,with a stronger response to hypoxia in the pancreatic cancer cell line.Overexpression of different PFKFB in pancreatic and gastric cancer cells under hypoxic condition is correlated with enhanced expression of vascular endothelial growth factor(VEGF)and Glut1 mRNA as well as with increased level of HIF-1αprotein.Increased expression of different PFKFB genes was also demonstrated in gastric,lung,breast,and colon cancers as compared to corresponding nonmalignant tissue counterparts from the same patients,being more robust in the breast and lung tumors.Moreover,induction of PFKFB-4 mRNA expression in the breast and lung cancers is stronger than PFKFB-3mRNA.The levels of both PFKFB-4 and PFKFB-3 proteins in non-malignant gastric and colon tissues were more pronounced than in the non-malignant breast and lung tissues.It is interesting to note that Panc1and PSN-1 cells transfected with dominant/negative PFKFB-3(dnPFKFB-3)showed a lower level of endogenous PFKFB-3,PFKFB-4,and VEGF mRNA expressions as well as a decreased proliferation rate of these cells.Moreover,a similar effect had dnPFKFB-4.In conclusion,there is strong evidence that PFKFB-4 and PFKFB-3 isoenzymes are induced under hypoxia in pancreatic and other cancer cell lines,are overexpressed in gastric,colon,lung,and breast malignant tumors and undergo changes in their metabolism that contribute to the proliferation and survival of cancer cells.Thus,targeting these PFKFB may therefore present new therapeutic opportunities.

Effect of a specific Escherichia coli Nissle 1917 strain on minimal/mild hepatic encephalopathy treatment

BACKGROUND Hepatic encephalopathy(HE)can be considered a result of dysregulated gutliver-brain axis function,where cognitive impairment can be reversed or prevented by the beneficial effects induced by"gut-centric"therapies,such as the administration of nonabsorbable disaccharides,nonabsorbable antibiotics,probiotics and prebiotics.AIM To assess the short-term efficacy and safety of the probiotic Escherichia coli Nissle(EcN)1917 strain compared to lactulose and rifaximin in patients with minimal/mild HE.METHODS From January 2017 to March 2020,a total of 45 patients with HE were enrolled in this prospective,single-centre,open-label,randomized study.Participants were randomly assigned at a ratio of 1:1:1 to one of the treatment groups:The EcN group(n=15),lactulose group(n=15)or rifaximin group(n=15)for a 1 mo intervention period.The main primary outcomes of the study were changes in serum ammonia and Stroop test score.The secondary outcomes were markers of a chronic systemic inflammatory response(ІL-6,ІL-8,and IFN-γ)and bacteriology of the stool flora evaluated by specialized nonculture techniques after a 1 mo intervention period.RESULTS Patients who were given rifaximin or EcN showed a more significant reduction in serum ammonia and normalization of Bifidobacteria and Lactobacilli abundance compared to the lactulose group.However,the most pronounced restoration of the symbiotic microflora was associated with EcN administration and characterized by the absence of E.coli with altered properties and pathogenic enterobacteria in patient faeces.In the primary outcome analysis,improvements in the Stroop test parameters in all intervention groups were observed.Moreover,EcN-treated patients performed 15%faster on the Stroop test than the lactulose group patients(P=0.017).Both EcN and rifaximin produced similar significant reductions in the proinflammatory cytokines INF-γ,IL-6 and IL-8.EcN was more efficient than lactulose in reducing proinflammatory cytokine levels.CONCLUSION The use of the probiotic EcN strain was safe and quite efficient for HE treatment.The probiotic reduced the ammonia content and the level of serum proinflammatory cytokines,normalized the gut microbiota composition and improved the cognitive function of patients with HE.The application of the EcN strain was more effective than lactulose treatment.

Consensus on management of hepatitis C virus infection in resource-limited Ukraine and Commonwealth of Independent States regions

Globally, 69.6 million individuals were infected with hepatitis C virus (HCV) infection in 2016. Of the six major HCV genotypes (GT), the most predominant one is GT1, worldwide. The prevalence of HCV in Central Asia, which includes most of the Commonwealth of Independent States (CIS), has been estimated to be 5.8% of the total global burden. The predominant genotype in the CIS and Ukraine regions has been reported to be GT1, followed by GT3. Inadequate HCV epidemiological data, multiple socio-economic barriers, and the lack of regionspecific guidelines have impeded the optimal management of HCV infection in this region. In this regard, a panel of regional experts in the field of hepatology convened to discuss and provide recommendations on the diagnosis, treatment, and pre-, on-, and posttreatment assessment of chronic HCV infection and to ensure the optimal use of cost-effective antiviral regimens in the region. A comprehensive evaluation of the literature along with expert recommendations for the management of GT1-GT6 HCV infection with the antiviral agents available in the region has been provided in this review. This consensus document will help guide clinical decision-making during the management of HCV infection, further optimizing treatment outcomes in these regions.

Introduction of antineoplastic drug NSC631570 in an inpatient and outpatient setting:Comparative evaluation of biological effects

The aim of this study is to evaluate the effect of moderate physical exercise and treatment time on the organism’s response to NSC631570. The sensitivity of circulating phagocytes to the drug at different times of day was estimated in in vitro experiments. NSC631570 was administered intravenously to healthy volunteers (eleven men, 23 ± 2 years) in a single therapeutic dose in an inpatient and an outpatient setting. Blood samples were obtained before the drug administration, 30 min after the drug injection and every fourth hour throughout the 24 hour period. Biochemical parameters were determined using the hematological analyzer. Flow cytometry was used to evaluate phagocyte metabolism. Treatment of circulating phagocytes with NSC631570 in vitro resulted in an increase in ROS production along with a decrease in their phagocytic activity, most expressed in the morning time. Drug injection to sedentary persons resulted in pro-inflammatory metabolic polarization of circulating phagocytes. Introduction of NSC631570 to active persons was accompanied by a significant increase in phagocyte endocytosis along with a decrease in the daily mean of ROS generation. Significant oscillation (but in the normal ranges) of urea, creatinine, alanine aminotransferase and aspartate aminotransferase after NSC631570 introduction in the outpatient setting was shown during the day. Physical activity interferes with immunomodulatory action of NSC631570 and abrogates pro-inflammatory shift of circulating phagocytes. Biochemical parameters of blood from patients treated with NSC631570 in the outpatient setting must be interpreted cautiously considering the effect of physical activity on some metabolic biomarkers.

Proactive psychological and psychiatric support of patients with chronic noncommunicable diseases in a randomised trial:a Ukrainian experience

Background Presently, approaches for the early treatment of pathological anxiety in patients with chronic non-communicable diseases are lacking, thus delaying the initiation of symptom management at the early onset of the illness. Proactive psychological and psychiatric support, to alleviate subclinical symptoms of anxiety and to improve the quality of life in patients with chronic non-communicable diseases, is a promising candidate for the role of such therapy.Aims To investigate and determine the effectiveness of proactive psychological and psychiatric support for alleviating subclinical symptoms of anxiety and improving quality of life, in patients with chronic non-communicable diseases.Methods The study design was a monocentric randomised controlled trial with parallel groups. The study, involving 193 inpatients with chronic non-communicable diseases, complied with the ethical and deontological norms in accordance with the principles set out in the Declaration of Helsinki. Instruments used in the study included the Hamilton Anxiety Scale (HAM-A) to assess subclinical symptoms, the Scale of Somatic Symptoms and the Chaban Quality of Life Scale. Block randomisation was used to randomise patients to a 2-month-long study group with a proactive counselling psychiatry model care or a control group with standard regulated treatment for chronic non-communicable diseases. The allocation ratio was 1.15:1 owing to the expectancy of a higher percentage of dropout in the intervention group.Results After 60 days of treatment (T2), there was a statistically significant difference in all clinical parameters between the study and control groups. The median HAM-A value differed between the groups by 4.87 points, with statistically significant lower results in the study group. The comparison of the study group’s scale values on day 1 and day 60 demonstrated statistically significant changes in all three indicators.Conclusions Our results support existing evidence for the effectiveness of proactive psychological and psychiatric support to reduce subclinical anxiety and somatisation symptoms and to improve the quality of life for patients with common chronic non-communicable diseases. However, continued research on the effectiveness of proactive psychological and psychiatric support for patients with chronic non-communicable diseases is needed.

Energy Aspects of Sodium Thiopental Action on Nervous Activity

Sodium thiopental, used in a narcotic dose, makes it possible to identify the nervous processes that underlie consciousness and establish the causes of its disorder. When studying the cortical EEG activity, the impulses of individual nerve cells and the electromyographic activity of the muscles of the forelimb, it was found that thiopental blocks a number of neuronal reactions requiring energy support: tonic activating reactions to acetylcholine, applied to neurons, cease;the rate of spontaneous neuronal activity drops;the stage of non-specific activation in response to electrocutaneous stimulation disappears. So, thiopental blocks consciousness by significant limitation of the brain energy metabolism. This results in a loss of the adaptive function of the central nervous system. At the same time, glutamatergic excitation, the formation of which does not depend on energy support, is resistant to the action of thiopental. The blocking of the brain’s energy supply caused by thiopental, in accordance with its depth, develops in two stages—hypoxic and narcotic. The hypoxic stage is accompanied by hyperactivity in the nervous system, which is manifested by epileptiform discharges on the EEG and powerful unmotivated movement;the narcotic stage is associated with blockade of motor activity and flattening of EEG oscillations. The post-narcotic state associated with the consequence of the hypoxic effect of thiopental leads to the loss of ionic homeostasis and is accompanied by a steady drop in the amplitude of cortical neuron spikes.

Histological differentiation impacts the tumor immune microenvironment in gastric carcinoma:Relation to the immune cycle

BACKGROUND Various histological types of gastric carcinomas(GCs)differ in terms of their pathogenesis and their preexisting background,both of which could impact the tumor immune microenvironment(TIME).However,the current understanding of the immune contexture of GC is far from complete.AIM To clarify the tumor-host immune interplay through histopathological features and the tumor immune cycle concept.METHODS In total,50 GC cases were examined(15 cases of diffuse GC,31 patients with intestinal-type GC and 4 cases of mucinous GC).The immunophenotype of GC was assessed and classified as immune desert(ID),immune excluded(IE)or inflamed(Inf)according to CD8+cell count and spatial pattern.In addition,CD68+and CD163+macrophages and programmed death-ligand 1(PD-L1)expression were estimated.RESULTS We found that GCs with different histological differentiation demonstrated distinct immune contexture.Most intestinal-type GCs had inflamed TIMEs rich in both CD8+cells and macrophages.In contrast,more aggressive diffuse-type GC more often possessed ID characteristics with few CD8+lymphocytes but abundant CD68+macrophages,while mucinous GC had an IE-TIME with a prevalence of CD68+macrophages and CD8+lymphocytes in the peritumor stroma.PD-L1 expression prevailed mostly in intestinal-type Inf-GC,with numerous CD163+cells observed.Therefore,GCs of different histological patterns have specific mechanisms of immune escape.While intestinal-type GC was more often related to PD-L1 expression,diffuse and mucinous GCs possessing more aggressive behavior demonstrated low immunogenicity and a lack of tumor antigen recognition or immune cell recruitment into the tumor clusters.CONCLUSION These data help to clarify the links between tumor histogenesis and immunogenicity for a better understanding of GC biology and more tailored patient management.

Low-intensity Microwave Radiation of Natural Substances for Physiotherapy

The mechanisms of influence of physiotherapy procedures in ozokeriteparaffin therapy are considered in this paper.It is shown that microwave electromagnetic radiation formed by heated ozokerite-paraffin mixture is an important component of physiotherapy procedures.Using the experimental setup developed by the authors,the radiative abilities of ozokerite,paraffin and their mixtures in the microwave range were investigated.It was found that in the process of cooling the ozokerite-paraffin mixture,during the procedure,negative microwave fluxes occur,affecting the inflammatory processes in the patient’s body.The dependences of the microwave radiation level on the composition of the ozokerite-paraffin mixture are investigated.The results of experimental studies allowed us to evaluate the interaction of electromagnetic radiation of ozokerite-paraffin mixtures with human own electromagnetic radiation and to approach the choice of modes of therapeutic interaction more carefully.

Low Intensity Microwave Fields and Radiation and Their Interaction with the Human Body

Sources of low-intensity microwave signals formation,which affect the metabolism processes when they interact with human body,are considered in the article.It’s noticed that increasing intensity level of the technogenic signals in environment significantly exceeds natural electromagnetic fields and radiation(EMR).The peculiarities of the registration and measurement of low-intensity signals parameters of the microwave range are considered.The processes of the interaction of the microwave signals and human organism are analyzed.Formation mechanisms of the positive and negative microwave flows of the electromagnetic radiation are revealed.Particularly,possible formation mechanism of the microwave EMR fluxes of implants in the human body.The results of the experimental study of the EMR signals levels of the objects contacting with human body,partly materials for bone defects replacement and soft tissues regeneration so as materials for physiotherapy,are given.The use of the term“electromagnetic compatibility”for materials which contacting the human body,is proposed.The expediency of its use is proven.Microwave properties of materials for clothes,minerals and building materials,which can affect the human body and environment,have been also studied.