Preclinical therapy of benign prostatic hyperplasia with neuropeptide hormone antagonists

Benign prostatic hyperplasia(BPH)is a pathologic condition of the prostate described as a substantial increase in its number of epithelial and stromal cells.BPH may significantly reduce the quality of life due to the initiation of bladder outlet obstruction and lower urinary tract syndromes.Current medical therapies mostly consist of inhibitors of 5α-reductase orα1-adrenergic blockers;their efficacy is often insufficient.Antagonistic analogs of neuropeptide hormones are novel candidates for the management of BPH.At first,antagonists of luteinizing hormone-releasing hormone(LHRH)have been introduced to the therapy aimed to reduce serum testosterone levels.However,they have also been found to produce an inhibitory activity on local LHRH receptors in the prostate as well as impotence and other related side effects.Since then,several preclinical and clinical studies reported the favorable effects of LHRH antagonists in BPH.In contrast,antagonists of growth hormone-releasing hormone(GHRH)and gastrin-releasing peptide(GRP)have been tested only in preclinical settings and produce significant reduction in prostate size in experimental models of BPH.They act at least in part,by blocking the action of respective ligands produced locally on prostates through their respective receptors in the prostate,and by inhibition of autocrine insulin-like growth factors-Ⅰ/Ⅱand epidermal growth factor production.GHRH and LHRH antagonists were also tested in combination resulting in a cumulative effect that was greater than that of each alone.This article will review the numerous studies that demonstrate the beneficial effects of antagonistic analogs of LHRH,GHRH and GRP in BPH,as well as suggesting a potential role for somatostatin analogs in experimental therapies.     

Obstructive uropathy-acute and chronic medical management

Obstructive uropathy is an important cause of acute and chronic kidney disease. Decompression of the urinary tract is an essential aspect of treatment. The cause and aetiology of obstruction typically determine the surgical approach. Acute relief of obstruction is frequently complicated by fluid and electrolyte imbalance. Standard therapeutic interventions for acute or chronic renal failure also apply for cases of obstructive uropathy. This narrative review summarises the early and long-term med...     

Psoriasis:Biologic treatment and liver disease

Patients with moderate or severe psoriasis have a high prevalence of chronic liver disease. Chronic liver disease in these patients is related to metabolic syndrome, alcohol abuse or viral infections. Therefore,treatment of these patients is challenging. Classic systemic treatments may be contraindicated because of their immunosuppressive and hepatotoxic potential.First-line therapy in this setting is generally ultraviolet B phototherapy combined with topical treatment, but its feasibility and efficacy are sometimes limited. The therapeutic options are further restricted by concomitant psoriatic arthritis. Biologic treatments have shown to be effective in psoriasis and psoriatic arthritis, and they are largely devoid of liver toxicity. Anti-tumor necrosis factor-alpha(TNF-α) treatments have proven to be effective and safe in patients with chronic hepatitis C virus(HCV) infections and other non-infectious chronic liver disorders, including alcoholic and non-alcoholic liver diseases. However, in chronic hepatitis B virus(HBV), anti-TNF-α treatments carry a high risk of HBV reactivation. Anti-interleukin-12/23 treatments are also effective in patients with psoriasis, but data regarding their safety in chronic hepatitis infections are still limited. Safety reports in patients with psoriasis and chronic HCV infection are contradictory, and in chronic HBVevidence indicate a potential risk of viral reactivation. Moreover, concerns remain about the long-term safety of both TNF-α antagonists and ustekinumab. Non-viral liver diseases such as alcoholic and non-alcoholic liver diseases are more prevalent in patients with psoriasis than in the general population. TNF-α antagonists have also been prescribed in these patients. Although data are still scarce in this setting, results suggest a favorable profile in patients with psoriasis and non-alcoholic liver diseases. We review the literature regarding all these aspects.     

Benefits and risks of erythrocyte-stimulating agents

Chronic kidney disease(CKD)is a common and serious clinical problem.Anemia in patients with advanced CKD,frequently called renal anemia,causes disabling fatigue and diminishes patients’quality of life.Frequent and excess transfusions or iron supplementation are potentially hazardous.Although it remains unclear whether the main factor in the development of renal anemia is the failure of erythropoietin(EPO)production in the kidney or a dysfunction in oxygen sensing exogenous EPO administration is considered a rational treatment.The advent of recombinant human erythropoietin(r Hu-EPO)products has dramatically changed the therapeutic strategy for renal anemia.Although rH u-EPO therapy has improved patients’quality of life and decreased the need for blood transfusions,some potential adverse effects have been reported till date.This brief review discusses the treatment of renal anemia with regard to the following:(1)historical background;(2)effectiveness of r Hu-EPO;(3)some topics regarding the treatment of anemia,including EPO resistance,hemoglobin(Hb)cycling,and adequate Hb levels;(4)major adverse effects of rH u-EPO,including hypertension,thrombotic complications,and pure red cell aplasia;and(5)future problems to be resolved.     

梅毒非特异性类脂质反应素抗体试验操作的改进及应用评价

Objective To estimate the application value of a standard operating procedure (SOP) in the detection of syphilitic anticardiolipin reagin. Methods Clinical laboratories from 9 local hospitals in Shanghai participated the program. Quality control samples with unknown target value were qualitatively and quantitatively examined according to the uniform SOP in these laboratories with the same reagent and facility of horizontal reaction. External quality assessment (EQA) was carried out by using seven serum samples with no, or low (1∶ 128 dilution) to high (1∶1 dilution) concentrations of target before and after the implementation of SOP. The test results were statistically analyzed and the reasons for the detecting error were assessed. Results A total of 388 tests were performed in the 9 clinical laboratories. The total accuracy rate was 93.0%, including 40.2% in the detection of samples with 1 ∶ 8 dilution of target, 49.2% in the detection of samples with 1 ∶ 16 dilution of target, and 3.6% in the detection of samples with 1 ∶ 32 dilution of target. No forward bias was observed in these tests. There was a significant difference in the accuracy rate between the two times of EQA before and after the implementation of SOP (x2 = 4.17, P < 0.05). Conclusions The improved standard procedure for nontreponemal antigen test is beneficial to the decrease of testing error, and may provide a basis for the establishment of SOP and implementation of internal quality assessment.     

梅毒非特异性类脂质反应素抗体试验操作的改进及应用评价

Objective To estimate the application value of a standard operating procedure (SOP) in the detection of syphilitic anticardiolipin reagin. Methods Clinical laboratories from 9 local hospitals in Shanghai participated the program. Quality control samples with unknown target value were qualitatively and quantitatively examined according to the uniform SOP in these laboratories with the same reagent and facility of horizontal reaction. External quality assessment (EQA) was carried out by using seven serum samples with no, or low (1∶ 128 dilution) to high (1∶1 dilution) concentrations of target before and after the implementation of SOP. The test results were statistically analyzed and the reasons for the detecting error were assessed. Results A total of 388 tests were performed in the 9 clinical laboratories. The total accuracy rate was 93.0%, including 40.2% in the detection of samples with 1 ∶ 8 dilution of target, 49.2% in the detection of samples with 1 ∶ 16 dilution of target, and 3.6% in the detection of samples with 1 ∶ 32 dilution of target. No forward bias was observed in these tests. There was a significant difference in the accuracy rate between the two times of EQA before and after the implementation of SOP (x2 = 4.17, P < 0.05). Conclusions The improved standard procedure for nontreponemal antigen test is beneficial to the decrease of testing error, and may provide a basis for the establishment of SOP and implementation of internal quality assessment.     

梅毒非特异性类脂质反应素抗体试验操作的改进及应用评价

Objective To estimate the application value of a standard operating procedure (SOP) in the detection of syphilitic anticardiolipin reagin. Methods Clinical laboratories from 9 local hospitals in Shanghai participated the program. Quality control samples with unknown target value were qualitatively and quantitatively examined according to the uniform SOP in these laboratories with the same reagent and facility of horizontal reaction. External quality assessment (EQA) was carried out by using seven serum samples with no, or low (1∶ 128 dilution) to high (1∶1 dilution) concentrations of target before and after the implementation of SOP. The test results were statistically analyzed and the reasons for the detecting error were assessed. Results A total of 388 tests were performed in the 9 clinical laboratories. The total accuracy rate was 93.0%, including 40.2% in the detection of samples with 1 ∶ 8 dilution of target, 49.2% in the detection of samples with 1 ∶ 16 dilution of target, and 3.6% in the detection of samples with 1 ∶ 32 dilution of target. No forward bias was observed in these tests. There was a significant difference in the accuracy rate between the two times of EQA before and after the implementation of SOP (x2 = 4.17, P < 0.05). Conclusions The improved standard procedure for nontreponemal antigen test is beneficial to the decrease of testing error, and may provide a basis for the establishment of SOP and implementation of internal quality assessment.     

Intraoperative magnetic resonance imaging in neurosurgery and anesthetic considerations

Currently, magnetic resonance imaging(MRI) is the only imaging modality available which is capable of acquiring intra-operative images frequently with acceptable spatial and contrast resolution. However, the incorporation of MRI technology into the operating room requires special anesthetic considerations. It may include various aspects such as transport, remote location anesthesia, strong electromagnetic field, use of approved items, equipment counts, possible emergencies, and surgery in awake patients. The patient safety may be compromised by health-related, equipment-related, and procedure-related risks. Direct patient observation may be compromised by acoustic noise, darkened environment, obstructed line of sight, and distractions along with difficult access to the patient for airway management. Most often, the patient's head will be 180° away from the anesthesiologist during the procedure. Several monitors exist that are designed for conditional use in a MR environment. The general design criterion in these monitors is to eliminate conductors that carry electrical signals for monitoring physiologic parameters of the patient. General anesthesia requires an extended anesthetic circuit for ventilation maintenance and drug administration because the patient is located farther from the anesthesia machine than in traditional operating room settings. Dead space creates a time delay before the volatile anesthetic and drugs are administered and when expected effects can be observed. Therefore, the attending anaesthesiologists must understand the above aspects for safe conduct of neurosurgical procedures by minimizing MRI associated accidents while assuring optimal patient vigilance.     

Does steroid-free immunosuppression improve the outcome in kidney transplant recipients compared to conventional protocols?

Steroids continue to be the cornerstone of immune suppression since the early days of organ transplantation.Steroids are key component of induction protocols,maintenance therapy and in the treatment of various forms of rejection.Prolonged steroid use resulted in significant side effects on almost all the body organs owing to the presence of steroid receptors in most of the mammalian cells.Kidney allograft recipients had to accept the short and long term complications of steroids because of lack of effective alternatives.This situation changed with the introduction of newer and more effective immune suppression agents with a relatively more acceptable side effect profile.As a result,the clinicians have been contemplating if it is the time to abandon the unquestionable reliance on maintenance steroids in modern transplantation practice.This review aims to evaluate the safety and efficacy of various steroid-minimization approaches(steroid avoidance,early steroid withdrawal,and late steroid withdrawal)in kidney transplant recipients.A meticulous electronic search was conducted through the available data resources like SCOPUS,MEDLINE,and Liverpool University library e-resources.Relevant articles obtained through our search were included.A total number of 90 articles were eligible to be included in this review[34 randomised controlled trials(RCT)and 56 articles of other research modalities].All articles were evaluating the safety and efficacy of various steroidfree approaches in comparison to maintenance steroids.We will cover only the RCT articles in this review.If used in right clinical context,steroid-free protocols proved to be comparable to steroid-based maintenance therapy.The appropriate approach should be tailored individually according to each recipient immunological challenges and clinical condition.     

Use of intralesional collagenase in the treatment of peyronie's disease: A review

AIM:To review the relevant literature in an effort to examine the body of evidence available to date.METHODS:Ovid MEDLINE search database was queried using MeS H terms"penile induration","peyronie’s disease","Collagenases"and"Collagenase"using various permutations.No temporal parameters were employed.RESULTS:In all,5 relevant clinical trials were isolated from 34 results.These trials were analyzed using the Oxford Centre for Evidence-Based Medicine criteria.They were further examined based on study design and methods;the primary and secondary outcomes were reviewed for treatment efficacy and collagenase-related side effects.CONCLUSION:Intralesional collagenase appears to be safe and effective in the non-surgical treatment of Peyronie’s disease.However,the data remains limited and further inquiries into the safety of collagenase,treatment standardization and standardized outcomesreporting remain necessary.Furthermore,studies comparing intralesional collagenase to alternative medical and surgical therapy will be important in guiding the future treatment decision process.     

新生隐球菌荚膜毒力作用的研究进展

新生隐球菌是重要的机会致病真菌,其胞外包裹的荚膜被公认为隐球菌关键的毒力因子.近年来,研究初步证明荚膜有抗吞噬细胞吞噬作用.另外,荚膜在新生隐球菌感染扩散过程中以及诱导宿主细胞凋亡中均发挥了关键的作用.概述荚膜的抗吞噬作用及荚膜在感染扩散中的作用等,对这些机制的探讨将有助于理解新生隐球菌的致病机制,同时为治疗新生隐球菌病提供新的靶位点.

Abstract：

Cryptococcus neoformans is an important conditional pathogenic fungus and capsule is widely acknowledged to be a key virulence factor of it. It has been proved that capsule posseses antiphagocytosis acitivity, and plays an essential role in the dissemination of C. neoformans infection and induction of apoptosis in host cells. The review describes the roles of capsule in antiphagocytic process and dissemination of C. neoformans infection, which will help to better understand the pathogenic mechanism of cryptococcosis and to provide new therapeutic targets for cryptococcosis.     

Impact of donor-specific antibodies on the outcomes of kidney graft: Pathophysiology,clinical, therapy

Allo-antibodies, particularly when donor specific, are one of the most important factors that cause both early and late graft dysfunction. The authors review the current state of the art concerning this important issue in renal transplantation. Many antibodies have been recognized as mediators of renal injury. In particular donorspecific-Human Leukocyte Antigens antibodies appear to play a major role. New techniques, such as solid phase techniques and Luminex, have revealed these antibodies from patient sera. Other new techniques have uncovered alloantibodies and signs of complement activation in renal biopsy specimens. It has been acknowledged that the old concept of chronic renal injury caused by calcineurine inhibitors toxicity should be replaced in many cases by alloantibodies acting against the graft. In addition, the number of patients on waiting lists with preformed anti-human leukocyte antigens(HLA) antibodies is increasing, primarily from patients with a history of renal transplant failure already been sensitized. We should distinguish early and late acute antibody-mediated rejection from chronic antibody-mediated rejection. The latter often manifets late during the course of the posttransplant period and may be difficult to recognize if specific techniques are not applied. Different therapeutic strategies are used to control antibody-induced damage.These strategies may be applied prior to transplantation or, in the case of acute antibody-mediated rejection, after transplantation. Many new drugs are appearing at the horizon; however, these drugs are far from the clinic because they are in phase Ⅰ-Ⅱ of clinical trials. Thus the pipeline for the near future appears almost empty.     

Donor defects after lymph vessel transplantation and free vascularized lymph node transfer:A comparison and evaluation of complications

BACKGROUND Secondary lymphedema after surgical interventions is a progressive,chronic disease that is still not completely curable.Over the past years,a multitude of surgical therapy options have been described.AIM To summarize the single-center complications in lymph vessel(LVTx)and free vascularized lymph node transfer(VLNT).METHODS In total,the patient collective consisted of 87 patients who were undergoing treatment for secondary leg lymphedema during the study period from March 2010 to April 2020.The data collection was performed preoperatively during consultations,as well as three weeks,six months and twelve months after surgical treatment.In the event of complications,more detailed follow-up checks were carried out.In total n=18 robot-assisted omental lymph node transplantations,n=33 supraclavicular lymph node transplantations and n=36 Lymph vessel transplantations were analyzed.An exemplary drawing is shown in Figure 1.A graphical representation of patient selection is shown in Figure 2.Robotic harvest was performed with the Da Vinci Xi Robot Systems(Intuitive Surgical,CA,United States).RESULTS In total,11 male and 76 female patients were operated on.The mean age of the patients at study entry was:omental VLNT:57.45±8.02 years;supraclavicular VLNT:49.76±4.16 years and LVTx:49.75±4.95 years.The average observation time postoperative was:omental VLNT:18±3.48 mo;supraclavicular VLNT:14.15±4.9 and LVTx:14.84±4.46 mo.In our omental VLNT,three patients showed a slight abdominal sensation of tension within the first 12 postoperative days.No other donor side morbidities occurred.No intraoperative conversion to open technique was needed.Our supraclavicular VLNT collective showed 10 lift defect morbidities with one necessary surgical intervention.In our LVTx collective,12 cases of donor side morbidity were registered.In one case,surgical intervention was necessary.CONCLUSION Concerning donor side morbidity,robot-assisted omental VLNT is clearly superior to supraclavicular lymph node transplantation and LVTx.     

Role of β2-microglobulin in uremic patients may be greater than originally suspected

The role of beta2-microglobulin(β2M) in dialysisrelated amyloidosis as a specific amyloid precursor was defined in the 1980 s. Studies in those years were largely related to β2M amyloidosis. In 2005, for what was probably the first time in the available literature, we provided data about the association betweenβ2M and early-onset atherosclerosis in hemodialysis patients without co-morbidities. In recent years, the role of uremic toxins in uremic atherosclerosis and the interest in β2M as a marker of cardiovascular(CV) and/or mortality risk have grown. In the current literature,clinical studies suggest that β2M is an independent, significant predictor of mortality, not only in dialysis patients, but also in predialysis patients and in the highrisk portion of the general population, and it seems to be a factor strongly linked to the presence and severity of CV disease. It is still unknown whether β2M is only a uremic toxin marker or if it also has an active role in vascular damage, but data support that it may reflect an increased burden of systemic atherosclerosis in a setting of underlying chronic kidney disease. Thus, although there have been some inconsistencies among the various analyses relating to β2M, it promises to be a novel risk marker of kidney function in the awareness and detection of high-risk patients. However, more research is required to establish the pathophysiological relationships between retained uremic toxins and further biochemical modifications in the uremic milieu to get answers to the questions of why and how. In this review, the recent literature about the changing role of β2M in uremic patients will be examined.     

伴Kasabach-Merritt现象卡波西形血管内皮瘤和丛状血管瘤的临床及病理特征

Objective To investigate the clinical and pathological features of Kasabach-Merritt phenomenon(KMP)associated with Kaposiform hemangioendothelioma(KHE)and tufted angioma(TA).Methods Clinical presentations and pathological features of seven patients with KHE or TA complicated by KMP were analyzed retrospectively and a literature review was made.Results Five patients were diagnosed with KHE and two with TA,and all of them exhibited a decrease in platelet count(less than 100×109/L).In all patients,lesions were present or developed on the trunk or limbs at birth or wimin one month after birth.The lesions showed a rapid growth in two patients,slow expansion in two patients,kept stable or regressed gradually in three patients.Lesion appearance varied in KHE and TA,and characteristic manifestation was dark-erythematous or prunosus tumors or patches involving the skin or subcutis.Histopathologically.both KHE and TA were composed of numerous fusiform endothellal cell clumps arranged in a lobular fashion.The nodules of KHE had an indistinct boundary usually with erythrocyte stasis or hemosiderin deposition,and TA was characterized by rounded,well-defined nodules distributed in a crater-like fashion within the dermis.A satisfactory outcome was achieved in two patients treated with oral dehydrocortisone and one patient with surgical resection plus skin grafting;the other four patients remained untreated and no progress was observed during follow-up.Conclusions KMP is pathologically associated with KHE or TA.KHE is an intermediate tumor with local aggressiveness while TA is a benign tumor.Both of them can regress spontaneously and should be difierentiated from other types of vascular tumors.     

Update summarising the conclusions of the international consultation on male lower urinary tract symptoms

The International Consultation on Urological Disease have recently published comprehensive conclusions, based on evidence reviewed by eight committees, on aspects of male lower urinary tract symptoms(LUTS). In this review, we summarise the conclusions from fourof the committees, namely, the evidence regarding the epidemiology of male LUTS, patient assessment, nocturia and medical management. It is indisputable that with an expanding and ageing global population the prevalence of male LUTS is likely to increase. Therefore symptom prevention and preservation of quality of life(Qo L) feature highly in the guidelines. There are now a number of different medical options, proven to lead to significant improvements in symptom scores, flow rate and Qo L available to men with LUTS. Metaanalyses have shown the benefits for alpha blockers, antimuscarinics, 5-α reductase and phosphodiesterase-5 inhibitors. High level evidence also exists for combinations of all of the above with alpha blockers and so men with concomitant storage symptoms, prostate volume 30 mL, PSA 1.4 or erectile dysfunction may be considered for combination treatment of an alpha blocker with an antimuscarinic, 5-α reductase inhibitor or phosphodiesterase-5 inhibitor respectively. In an era of personalised medicine, appropriate patient selection is likely to provide the key to the most effective clinical management strategy.     

Perioperative hypothermia: Causes,consequences and treatment

Perioperative hypothermia, core temperature below 36.0 ℃, transpires due to disruption of thermoregulationby anesthesia coupled with cold exposure to procedural surroundings and cleansing agents. Although most publications have focused on thermoregulation disruption with general anesthesia, neuraxial anesthesia may also cause significant hypothermia. The clinical consequences of perioperative hypothermia are multiple and include patient discomfort, shivering, platelet dysfunction, coagulopathy, and increased vasoconstriction associated with a higher risk of wound infection. Furthermore, postoperative cardiac events occur at a higher rate; although it is unclear whether this is due to increased oxygen consumption or norepinephrine levels. Hypothermia may also affect pharmacokinetics and prolong postoperative recovery times and hospital length of stay. In order to combat perioperative hypothermia, many prevention strategies have been examined. Active and passive cutaneous warming are likely the most common and aim to both warm and prevent heat loss; many consider active warming a standard of care for surgeries over one hour. Intravenous nutrients have also been examined to boost metabolic heat production. Additionally, pharmacologic agents that induce vasoconstriction have been studied with the goal of minimizing heat loss. Despite these multiple strategies for prevention and treatment, hypothermia continues to be a problem and a common consequence of the perioperative period. This literature review presents the most recent evidence on the disruption of temperature regulation by anesthesia and perioperative environment, the consequences of hypothermia, and the methods for hypothermia prevention and treatment.     

ACE and ACE2 in kidney disease

Renin angiotensin system(RAS) activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme(ACE)-angiotensin Ⅱ(Ang Ⅱ)-Ang Ⅱ type 1(AT1) axis is considered to control the effects of RAS activation on renal disease.However, since its discovery in 2000 ACE2 has also been demonstrated to have a significant impact on the RAS.The synthesis and catabolism of Ang Ⅱ are regulated via a complex series of interactions, which involve ACE and ACE2. In the kidneys, ACE2 is expressed in the proxima tubules and less strongly in the glomeruli. The synthesisof inactive Ang 1-9 from Ang Ⅰ and the catabolism of Ang Ⅱ to produce Ang 1-7 are the main functions of ACE2. Ang 1-7 reduces vasoconstriction, water retention, salt intake, cell proliferation, and reactive oxygen stress, and also has a renoprotective effect. Thus, in the nonclassical RAS the ACE2-Ang 1-7-Mas axis counteracts the ACE-Ang Ⅱ-AT1 axis. This review examines recent human and animal studies about renal ACE and ACE2.