Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

Risk of Target Organ Damage in Patients with Masked Hypertension versus Sustained Hypertension:A Meta-analysis

Objective:To compare the risk of target organ damage in masked hypertension(MH)and sustained hypertension(SH).Methods:A systematic review and meta-analysis was performed.A search of PubMed,Embase,and the Cochrane Library of relevant case-control studies was performed from inception to December 2019,and articles on MH and SH selected according to the inclusion criteria were analyzed.The primary end point was target organ damage in the heart.The secondary end points were target organ damage in the kidneys and blood vessels.Results:Seventeen studies that met the screening criteria were included in the meta-analysis.Compared with the SH group,in the MH group carotid intima-media thickness(IMT)and E/A ratio were signifi cantly greater and the prevalence of left ventricular remodeling and the pulse wave velocity were signifi cantly lower.Other indicators in the heart,kidneys,and blood vessels were not statistically different between the two groups.IMT:P=0.01,E/A ratio:P=0.01,prevalence of left ventricular remodeling:P=0.02,pulse wave velocity:P=0.01.Conclusion:Our study has shown that MH may have almost the same degree of target organ damage as SH,so clinicians may need to consider target organ damage.

Metabolic syndrome in hypertensive patients:An unholy alliance

For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome(MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes.

Association of blood pressure variability with target organ damage in older patients with essential hypertension

Background:Although multiple measures of blood pressure variability(BPV)have been proposed,whether they are better than mean blood pressure in predicting target organs is unclear.We aimed to determine the relationship between short term BPV and target organ injury.Methods:This study was a retrospective study,and 635 inpatients in the Department of Cardiology from 2015 to 2020 were selected.We divided participants into four groups on the basis of the quartiles of BPV.One-way analysis of variance was used to compare the differences between the groups,and linear regression was used to analyze the relationship between BPV and target organ damage.Results:The average age of 635 patients was 74.36±6.50 years old.Among them,354 of 627 patients had diminished renal function(56.5%),221of 604 patients had associated left ventricular hypertrophy(36.6%),and 227 of 231 patients had carotid plaque formation(98.3%).The baseline data indicated significant differences in fasting glucose,total cholesterol,low-density lipoprotein,creatinine,glomerular filtration rate,sex,calcium channel blocker use,and the rate of diminished renal function.Multiple linear regression analysis showed that BPV was negatively correlated with renal injury(creatinine:r=0.306,p<0.01;estimated glomerular filtration rate:r=0.058,p<0.01),and BPV is positively correlated with cardiac injury(r=0.083,p<0.01).Elevated BPV was not found to be associated with vascularinjury.Conclusion:Renal function decreases with increasing BPV and left ventricular mass increases with increasing BPV.

Toxicological advances of traditional medicine in 2020

There were many researches concerning toxicology of traditional medicine and active natural products during the past 12 months.This annual toxicology review summarized different toxic analysis methods of traditional medicine,evaluated models,toxic target organs,toxic mechanisms,popular research issues and herbs in 2020.Caenorhabditis elegans came to use for the assessment of toxicity.Omics technology such as genomics,transcriptome,metabolomics and proteomics were applied extensively.2020 toxicology research demonstrated that liver,kidney and heart were the mainly toxic target organs of traditional medicine.Their toxic mechanisms included cell apoptosis,metabolic disorder,oxidative stress,inflammatory damage,liver and renal fibrosis and even inducing carcinogenesis.In addition,the safety assessment of Aconitum carmichaeli Debx.,Tripterygium wilfordii Hook.f.and Polygonum multiflorum Thunb.as well as their detoxification methods were still hot issue.Therefore,study on the toxicity mechanism of target organs,processing and extract methods,quality control and dose control,new models and methods should be used in the prevention of traditional medicine toxicology in the future.

Toxicological advances of traditional medicine in 2021

In 2021,there have been many studies on the toxicological evaluation of traditional medicine,as well as natural active ingredients.Among them,the toxicity evaluation of evodiamine,Gardenia Jasminoides J.Ellis,and anthraquinone in the liver,kidneys,heart,and other organs has become a popular topic.Their toxic mechanisms include oxidative stress,inflammatory response,apoptosis,mitochondrial damage,and disorders of lipid and amino acid metabolism.In response to the drawbacks of time-consuming,expensive,and ethical restrictions of animal models,a variety of techniques,such as 3D organoid models,metabolomics,toxicokinetics,bioprinting methods,and network toxicology methods,have been gradually employed in the toxicity evaluation of traditional medicine.This review summarizes the drug toxicity and safety assessment of traditional medicine in 2021.In the future,attention should be paid to preventing traditional medicine toxicity.

Toxicological advances of traditional medicine in 2019

There were many researches concerning toxicology of traditional medicine(TM)and active natural products during the past 12 months.This annual toxicology review summarized target organs of TM like liver,kidney and heart.Safety medication of TM has been concerned to different kinds of people,including infants,children,pregnancy and the postnatal period.Besides rodents,zebrafish embryoes have been regarded as common models to evaluate the safety of TM.New technologies in toxicology focus on rapidly screening and identification of toxins in TM.Multispectral optoacoustic tomography imaging the precise location of TM-induced liver injury with 3D information and integrating serum exosomal microRNA and liver microRNA profiles are used to explain the mechanism of TM-induced hepatotoxicity.Taken together,study on the toxicity mechanism of other target organs,drug safety in elders,new models and methods should be paid attention to in the prevention of TM toxicology in the future.

Effects of Mangiferin on the Expression of TNF-α,iNos,ICAM-1 and Its mRNA in the Heart,Brain and Kidneys of SHR

[Objectives] To study the effects of Mangiferin( MGF) on TNF-α,iNOS,ICAM-1 and its mRNA expression in the heart,brain and kidneys of spontaneously hypertensive rats( SHR),and reveal the mechanism of its anti-inflammatory injury in hypertension target organs.[Methods]SHRs were randomly divided into 5 groups: the model group,the high-dose,medium-dose,low-dose MGF groups and the Benazepril group,with 8 rats in each group,WKY rats were used for the normal control group. Besides,on-invasive blood pressure( BP) instruments were used to measure systolic blood pressure in the rats' tail artery,western blot was used to analyze the expression of TNF-α,iNOS,ICAM-1 and reverse transcription-polymerase chain reaction( RT-PCR) was used to analyze the expression of TNF-α,iNOS,ICAM-1 mRNA.[Results]Compared with the normal control group,the model group's BP level was significantly increased( P <0. 01)),but the MGF had no significant lowering BP effect( P > 0. 05); compared with the normal control group,the expression of TNF-α,iNOS,ICAM-1 and its' mRNA in the model group was significantly increased( P < 0. 05 or P < 0. 01),and MGF could reduce the level of expression of these inflammatory cytokines( P < 0. 05 or P < 0. 01); between the Benazepril group and high-dose,medium-dose,low-dose MGF groups,most of the indicators had no significant difference( P > 0. 05). [Conclusions]MGF had no significant lowering BP effect,SHR showed inflammatory injury in the heart,brain and kidneys,MGF showed improvement on the inflammatory injury,and the anti-inflammation mechanism may be associated with lowering TNF-α,i NOS and ICAM-1 and its mRNA expression.

A Pathological Study of GIFT Strain of Nile Tilapia(Oreochromis niloticus)Infected by Streptococcus agalactiae

[Objectives] This study aimed to determine the infection pathway and target organs of Streptococcus agalactiae in GIFT strain of Nile tilapia, thus providing theoretical basis for the breeding of disease-resistant tilapia and development of S. agalactiae vaccines.[Methods] GIFT strain of Nile tilapia was inoculated by S. agalactiae through intraperitoneal injection, oral gavage and in vitro immersion. The gill, spleen, liver and small intestine tissues of infected tilapia were collected for pathomorphological observation. Immunohistochemical localization was conducted using rabbit anti- S. agalactiae serum to identify the distribution pattern of S. agalactiae in various tissues of tilapia and its target organs via different infection pathways.[Results] GIFT strain of Nile tilapia could be infected by S. agalactiae via three artificial inoculation modes. Specifically, pathological changes occurred at 2 h post-inoculation in intraperitoneal injection and oral gavage groups, whereas tilapia in in vitro immersion group showed pathological changes at 5 h post-inoculation, and the lesion intensity in in vitro immersion group was slighter than that in intraperitoneal injection and oral gavage groups. Immunohistochemical localization indicated that the appearance time of positive signals in intraperitoneal injection group demonstrated an order of spleen→liver and gill→small intestine; positive signals in oral gavage group appeared in the order of small intestine→gill and spleen→liver; the appearance time of positive signals in in vitro immersion group showed an order of gill→spleen→liver and small intestine.[Conclusions] GIFT strain of Nile tilapia could be infected by S. agalactiae via intraperitoneal injection, oral gavage and in vitro immersion. The corresponding positive signals for pathogen infection were preferentially present in the spleen, intestine and gill tissues. Thus, preventing S. agalactiae contamination in aquaculture water and food sources is an effective measure to control the outbreak of S. agalactiae infections in tilapia under natural aquaculture conditions.

Toxic Effect of Different Neem Formulations against Pests and Mammals

Neem(Azadirachta indica A.Juss),prominently known as conventional medication is a local plant in India.Neem is regarded as a promising tree species which can be utilized in variety ways to benefit agricultural communities throughout the world.Neem based insect sprays were productive for the control of different insect species,yet their low lingering impact and absence of normalized definitions are issues for field application.Additionally,neem is fairly have harmful impact in nature.The use of nanotechnology as a mean for nanopesticides is in the beginning time of improvement.All things considered,the nanosphere definition demonstrated upgraded systemicity of the dynamic fixings and made its infiltration better in the plant,because of their little size.Nanoencapsulated pesticides can give controlled discharge energy,while proficiently upgrading piousness,dependability,and solvency.Nanoencapsulation can improve the vermin control proficiency over expanded spans by forestalling debasement of dynamic fixings under ecological conditions.This survey is hence composed to fundamentally evaluate the toxicological impacts i.e to examine the manifestations,systems and identifications of poisoning vertebrates particularly people.The prepared neem nano-plants contrasted with the bulk one have will be assessed on albino mice through two main approaches,i.e.determination of acute oral LD50 and study the toxic effect of sublethal dose(LD10)on some biochemical parameters.The effect of the prepared nano-formulations compared to the bulk one on various biomarkers,i.e.hematological,hepatotoxicity and nephrotoxicity in albino mice after an oral administration of sub-lethal dose during sub-acute treatment were taken in consideration.Hence,this review should thus offer an important guide for building up potential advantages are underlined,while little is known on security or the antagonistic impacts of nanoadvances in the agro-foodsystem.

Efficacy of Huoxue Qianyang Qutan Recipe on essential hypertension:A randomized,double-blind,placebo-controlled trial

Background:Hypertension,a prevalent disease,is a significant risk factor for coronary heart disease.Huoxue Qianyang Qutan Recipe (HQQR),a traditional Chinese herbal remedy,has been used for treating hypertension over several years.Objective:This study assesses HQQR’s efficacy for controlling blood pressure among patients with hypertension related to blood stasis,yang hyperactivity and phlegm.Design,setting,participants and interventions:A randomized controlled trial was conducted at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,China,from July 2020 to June 2022.Major components of HQQR were identified using thin-layer chromatography and high-performance liquid chromatography.Participants aged18–80 years,exhibiting traditional Chinese medicine syndromes of blood stasis,yang hyperactivity or phlegm,along with grades 1 or 2 hypertension,were randomly categorized into two groups.The intervention group was given HQQR granules alongside conventional hypertension treatment,while the control group was given placebo granules in addition to conventional treatment for 12 weeks.Main outcome measures:The primary outcome was clinic blood pressure,whereas secondary outcomes included metabolic indices (e.g.,homeostasis model assessment of insulin resistance[HOMA-IR],total cholesterol[TC],low-density lipoprotein cholesterol and triglyceride),target organ damage indices (left ventricular mass index and urinary albumin creatinine ratio[UACR]) and inflammation indices(interleukin-6[IL-6]and high-sensitivity C-reactive protein[hs-CRP]).Results:HQQR’s primary components were identified as salvianolic acid B,emodin and ferulic acid.Of the 216 participants (108 in each group),compared to the control,the intervention group exhibited significant improvements (P<0.001) in clinic systolic blood pressure ([136.24±7.63]vs[130.06±8.50]mmHg),clinic diastolic blood pressure ([84.34±8.72]vs[80.46±6.05]mmHg),home systolic blood pressure([131.64±8.74]vs[122.36±8.45]mmHg) and home diastolic blood pressure ([78.47±9.53]vs[71.79±6.82]mm Hg).HQQR demonstrated a reduction in ambulatory blood pressure (24-hour systolic blood pressure:[133.75±10.49]vs[132.46±8.84]mmHg and 24-hour diastolic blood pressure:[84.12±8.01]vs[82.11±7.45]mmHg) and an improvement in HOMA-IR ([4.09±1.72]vs[3.98±1.44]),TC ([4.66±1.47]vs[3.75±1.81]mmol/L) and UACR (75.94[5.12,401.12]vs 45.61[4.26,234.26]).Moreover,HQQR demonstrated a decrease in hs-CRP (1.46[0.10,10.53]vs 0.57[0.12,3.99]mg/L) and IL-6 (6.69[2.00,29.74]vs 5.27[2.00,9.73]pg/mL),with no reported side effects (P<0.001).Conclusion:This study highlights the therapeutic potential of HQQR use in ameliorating blood pressure,glycolipid metabolism,and inflammation in patients with hypertension.

Association factors of target organ damage： analysis of 17 682 elderly hypertensive patients in China

Background Hypertensive target organ damage （TOD） is the main reason for mortality or disability in elderly hypertensive patients. The studies on TOD of hypertension in Asia, especially in Chinese elderly hypertensive patients, are very limited. The aim of this study was to evaluate the prevalence and correlative factors of TOD in older Chinese hypertensive inpatients. Methods This is a retrospective survey and data were collected from the computerized medical files of hypertensive inpatients from January of 1993 to December of 2008. The analysis was done on 17 682 inpatients, aged 60 years or older, with a diagnosis of essential hypertension （EH）. The evidence of hypertensive TOD and associated factors with TOD were collected. Results The prevalence of any hypertensive target organ involvement among these subjects was high. In multivariable Logistic regressions adjusted for potentially confounding factors, older age, male gender, diabetes, EH grade 3, systolic blood pressure （SBP）, and low-density lipoprotein cholesterol （LDL-C）, were independently associated with coronary artery disease. Age, duration of EH, EH grade 3, SBP, pulse pressure （PP）, and homocysteine （Hcy） were independently associated with cerebrovascular disease. Age, diabetes, duration of EH, EH grade 3, SBP, PP and estimated glomerular filtration rate （eGFR） were independently associated with chronic kidney disease. Male gender, EH grade 3 and SBP were independently associated with aortic dissection. Conclusions The prevalence of hypertensive TOD is high in older Chinese hypertensive inpatients. Various cardiovascular risk factors are associated with hypertensive TOD. The level of SBP and severe hypertension （grade 3 hypertension） are common independent risk factors of TOD.

Relationships of Inflammatory Factors and Risk Factors with Different Target Organ Damage in Essential Hypertension Patients

Background： Atherosclerosis （AS） is an inflammatory disease. Inflammation was considered to play a role in the whole process of AS. This study aimed to analyze the relationships of inflammatory factors and risk factors with different target organ damages （TOD） in essential hypertension （EH） patients and to explore its clinical significance. Methods： A total of 294 EH patients were selected and divided into four groups according to their conditions of TOD. Forty-eight healthy subjects were selected as control. The clinical biochemical parameters, serum amyloid A, serum tryptase, and lipoprotein-associated phospholipase A2 （Lp-PLA2） in each group were detected, and the related risk factors were also statistically analyzed. Results： Fihrinogen （Fbg） was the most significant independent risk factor in acute coronary syndrome （ACS） group （odds ratio [OR]： 22.242, 95% confidence interval [CI]： 6.458-76.609, P 〈 0.001） with the largest absolute value of the standardized partial regression coefficient B＇ （b＇： 1.079）. Lp-PLA2 was the most significant independent risk factor in stroke group （OR： 13.699, 95% CI： 5.236-35.837, P 〈 0.001） with b＂ 0.708. Uric acid （UA） was the most significant independent risk factor in renal damage group （OR： 15.307, 95% CI：4.022 58.250, P〈0.001）with b＇= 1.026. Conclusions： Fbg, Lp-PLA2, and UA are the strongest independent risk factors toward the occurrence of ACS, ischemic stroke, and renal damage in EH patients, thus exhibiting the greatest impacts on the occurrence ofACS, ischemic stroke, and renal damage in EH patients, respectively.

Association between the rate of the morning surge in blood pressure and cardiovascular events and stroke

Background The exaggerated surge in morning blood pressure （BP） that many patients experience upon awakening may be closely related to target organ damage and may be a predictor of cardiovascular complications. However, no previous studies have evaluated the rate of this surge independently of the evening period. It remains unclear whether the rate of increase experienced during the surge is a significant or independent determinant of cardiovascular events. Methods We randomly selected 340 ambulatory BP monitoring （ABPM） patients. All subjects without type 2 diabetes mellitus were divided into two groups： hypertensive group （n=170） and normotensive group （n=170）. We analyzed ambulatory blood pressure recordings using a double logistic curve-fitting procedure to determine whether the magnitude of the surge in BP and heart rate （HR） in the morning is related to the level of BP in hypertensive individuals. We evaluated the association between the rate of the morning surge in systolic BP （SBP） and the incidence of myocardial infarction and stroke in normotensive and hypertensive subjects. Results Comparisons between hypertensive and normotensive subjects showed that the rates of the morning surges in SBP, mean BP （MBP）, and diastolic BP （DBP） were greater in the hypertensive group （P 〈0.05） than in the normotensive group. The rate of morning surge in BP was found to be correlated with the daytime SBP （r=0.236, P 〈0.01）, the difference between the day and night plateau （r=0.249, P 〈0.01）, and the night SBP （r---0.160, P 〈0.05）, respectively. After controlling for age, sex, and mean systolic pressure within 24 hours （24 h SBP）, the rate of morning surge in SBP was closely correlated with daytime SBP （r=0.463, P 〈0.001）, night SBP （r=-0.173, P 〈0.05）, and the difference between the day and night plateau （r=0.267, P 〈0.001）. Logistic regression analysis revealed that the rate of morning surge in SBP was an independent determinant of myocardial infarction （OR=1.266, 95% C1=1.153-1.389, P 〈0.001） and stroke （OR=1.367, 95% C/=1.174-1.591, P 〈0.001）. Conclusions The rate of the morning surge in BP is greater in hypertensive subjects than in normotensive subjects. Daytime SBP may be the best predictor of the rate of morning surge in SBP. The rate of the morning surge in BP is associated with cardiovascular and stroke events.