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Ethnopharmacological Relevance: The adverse effects of Fructus Psoraleae (FP), especially liver injury, have attracted wide attention in recent years., Aim of the Study: To establish a system to explore potential hepatotoxic targets and the chief culprit of liver injury based on clinical experience, network pharmacological method, molecular docking, and in vitro and in vivo experiments., Materials and Methods: Clinical applications and adverse reactions to FP were obtained from public literatures. Components absorbed in the blood were selected as candidates to search for potential active targets (PATs) of FP. Subsequently, potential pharmacological core targets (PPCTs) were screened through the "drug targets-disease targets" network. Non-drug active targets (NPATs) were obtained by subtracting the PPCTs from the PATs. The potential hepatotoxic targets (PHTs) of FP were the intersection targets obtained from Venn analysis using NPATs, hepatotoxic targets, and adverse drug reaction (ADR) targets provided by the databases. Then, potential hepatotoxic components and targets were obtained using the "NPATS-component" network relationship. Molecular docking and in vitro and in vivo hepatotoxicity experiments were performed to verify the targets and related components., Results: Overall, 234 NPATs were acquired from our analysis, and 6 targets were identified as PHTs. Results from molecular docking and in vitro and in vivo experiments showed that angelicin is the leading cause of liver injury in FP, and VKORC1 plays an important role., Conclusion: The results indicate that six targets, especially VKORC1, are associated with the PHTs of FP, and angelicin is the leading culprit involved in FP liver injury via inhibition of VKORC1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intrauterine device(IUD)migrating to the bladder is rare,especially the migration far away from the uterus into the bladder wall.Due to no obvious clinical symptom in the early stage and being far away from the uterus,the IUD totally embedded in the bladder wall is prone to misdiagnosis and delay in treatment.We reported one case of such migration,aiming to improve the clinical management of the IUD totally embedded in the bladder wall.

Background: Infected pancreatic necrosis (IPN) accounts for 30% mortality in severe acute pancreatitis (SAP). Early prediction of IPN occurrence is critical for prophylactic measures to be taken. This study aimed to evaluate the predicting value for IPN of combined markers at early stages of SAP., Methods: The clinical records of 324 SAP patients admitted within 48 h after disease onset were retrospectively analyzed. As potential predictors, the neutrophil to lymphocyte ratio (NLR), blood procalcitonin (PCT) concentration on the 1st, 4th, and 7th day post admission, as well as modified computerized tomography severity index (MCTSI) on the 5-7th day post admission, were extracted. Correlations between these features with IPN were analyzed using logistic regression, and predictive values were estimated using the receiver operating characteristic curve analyses., Results: NLR, PCT, body mass index, and MCTSI were significantly higher in the IPN group (p < 0.001) compared to the control, among which NLR, PCT, and MCTSI were identified as independent predictors for IPN in logistic regression model. Combination of these parameters yielded significant predicting values with an area under curve of 0.92, sensitivity of 97.2%, and specificity of 77.2% in receiver operating characteristic curve analysis., Conclusion: Combination of NLR, PCT, MCTSI might facilitate the prediction of IPN occurrence in SAP patients., (© 2023 S. Karger AG, Basel.)

Purpose: To explore the relationship between the genotype and renal phenotype in a Chinese cohort and guide clinical decision-making for treating tuberous sclerosis complex (TSC)., Materials and Methods: We reviewed 173 patients with definite TSC at three centers in China from September 2014 to September 2020. All the patients underwent TSC1 and TSC2 genetic testing as well as renal phenotypic evaluation. All analyses were performed using the SPSS software, version 19.0, with a cut-off P value of 0.05 considered statistically significant., Results: We identified variants in 93% (161/173) cases, including 16% TSC1 and 77% TSC2 variants. Analysis of the relationship between the genotype and renal phenotype, revealed that those with TSC2 variants were more likely to develop severe renal AML (> 4) (P = 0.044). In terms of treatment, TSC2 variants were more likely to undergo nephrectomy/partial nephrectomy (P = 0.036) and receive mTOR medication such as everolimus (P < 0.001). However, there was no significant difference between the two groups in terms of their response to the everolimus treatment., Conclusion: Patients with TSC2 variants exhibit more severe renal phenotypes, especially those associated with renal angiomyolipomas (AML), and they often require nephrectomy/partial nephrectomy or mTOR medication. Detection of the genotype is helpful in TSC management., (© 2022. The Author(s).)

When the drug induces the organism to produce a type Ⅰ allergic reaction, the combination of IgE and mast cells results in the degranulation of the mast cells. Release of vasoactive substances, increase in vascular permeability, and exudation of intravascular substances outside the blood vessels. Based on this pathophysiological mechanism, a mouse model that can objectively and quantitatively assess the allergic response to the injection has been established. ICR mice were sensitised by intraperitoneal injection of different doses of OVA once every two days for three times. 14 days after the last sensitization, a combination OVA solution of 4 times the sensitizing dose and Evans blue were injected intravenously into mice for the challenge. Compared with the normal group, OVA 0.625/2.5, 1.25/5, 2.5/10, 5/20 mg·kg~(-1) sensitized and challenged can induce allergic reactions mainly manifested by blue staining of the auricle in mice. Direct injection of OVA intravenously did not cause an auricular blue colouration reaction in mice. The passive cutaneous anaphylaxis reaction in mice was conducted with the aforementioned OVA-sensitized mouse serum, and there were obvious blue spots on the mouse's back. In addition, the content of anti-OVA-IgE in 5 mg·kg~(-1) OVA-sensitized mice was significantly increased. Ears and lungs of mice sensitized to OVA showed evident exudation inflammation. Significantly elevated inflammatory factors(VEGF and IL-10) were also detected in the serum of OVA-sensitized mice. The equivalent dose of OVA caused obvious allergic reactions in both guinea pigs and mice. Compared with nude mice, ICR and BALB/c mice are more sensitive to OVA sensitization. Injections of selected TCMI did not induce type Ⅰ allergic reactions in mice and guinea pigs, but there was a risk of inducing pseu-doallergic reactions in mice. The model is problematic and may well reflect the sensitization effect of allergens. It obtains the benefits of simple operation, accuracy, low cost, easy extension, and high repeatability. It is suitable for predicting and researching for IgE-dependent type Ⅰ allergic reactions.

Background: Bladder cancer is the 10th most common cancer and most common urothelial malignancy worldwide. Prognostic biomarkers for bladder cancer patients are required for individualized treatment. Monocarboxylate transporter 4 (MCT4), encoded by SLC16A3 gene, is a potential biomarker for bladder cancer because of its crucial role in the lactate efflux in the aerobic glycolysis process. We aimed to study the association between MCT4 expression and the overall survival (OS) of bladder cancer patients., Methods: The published single-cell RNA sequencing data of 49,869 bladder cancer cells and 15,827 normal bladder mucosa cells and The Cancer Genome Atlas (TCGA) bladder cancer cohort data were used to explore the mRNA expression of SLC16A3 in bladder cancer. Eighty-nine consecutive bladder cancer patients who had undergone radical cystectomy were enrolled as a validation cohort. The expression of MCT4 proteins in bladder cancer specimens was detected using immunohistochemistry staining. The Kaplan-Meier survival analysis and Cox regression were performed to analyze the association between MCT4 protein expression and OS in bladder cancer patients., Results: SLC16A3 mRNA was upregulated in bladder cancer cells. The upregulated genes in SLC16A3-positive epithelial cells were enriched in the glycolysis process pathway and monocarboxylic acid metabolic process pathway. Patients with high SLC16A3 mRNA expression showed significantly poor OS (p = 0.016). High MCT4 protein expression was also found to be an independent predictor for poor OS in bladder cancer patients (HR: 2.462; 95% CI: 1.202~5.042, p = 0.014). A nomogram was built based on the results of the multivariate Cox analysis., Conclusion: Bladder cancer with high SLC16A3 mRNA expression has a poor OS. High MCT4 protein expression is an independent prognostic factor for bladder cancer patients who had undergone radical cystectomy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Zhao, Yan, Xia, Wang, Zheng, Wang and Zhang.)

There has been no research on applying gene detection to differential diagnosis of adrenocortical carcinoma (ACC). We attempted to explore a novel auxiliary method for differential diagnosis between ACC with benign adrenocortical adenoma (ACA), based on mutations of target genes in tissues. Nine genes were chosen as target genes, including TP53, CTNNB1, ARMC5, PRKAR1A, ZNRF3, RB1, APC, MEN1, and RPL22. Exons sequencing of target genes were performed in 98 cases of tissue samples by FastTarget technology, including 41 ACC tissues, 32 ACA tissues, and 25 normal adrenal gland tissues. Significant mutations were detected and identified, and the clinical information was collected, for further comparative analysis and application to assist differential diagnosis of ACC. We identified 132 significant gene mutations and 227 significant mutation sites in 37 ACC tissues, much more than ACA and normal adrenal gland tissues. Mutation rates of 6 genes in ACC tissues were obviously higher than ACA tissues, including ZNRF3, ARMC5, TP53, APC, RB1, and PRKAR1A, regarded as high-risk genes. The sum of mutated high-risk genes detected in each sample was denominated sum of high-risk gene mutation (SHGM), and the rates of SHGM > 0 and SHGM > 1 in ACC tissues were 73.0% and 62.2%, respectively, both obviously higher than those in ACA tissues, with significant statistic differences. Especially for 8 cases of ACC with diameter < 5 cm, SHGM > 0 and SHGM > 1 were found in 6 samples (75%) and 4 samples (50%), respectively. However, no relevance was found between SHGM and clinical characteristics of ACC. We identified 6 high-risk genes in ACC tissues, with significantly higher mutation rates than ACA or normal adrenal gland tissues. The sum of mutated high-risk genes detected in ACC tissues was denominated SHGM, which was potential to assist the differential diagnosis of ACC with ACA, especially for the small-size ACC.

Purpose: To evaluate the efficacy and safety of everolimus and sirolimus in patients with tuberous sclerosis complex-associated angiomyolipomas (TSC-AML)., Materials and Methods: We performed a multi-institutional retrospective study of TSC-AML patients treated with oral everolimus 10 mg or sirolimus 2 mg per day for at least 3 months. Angiomyolipoma volume was estimated using orthogonal measurements by MRI or CT. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events. All analyses were performed using SPSS 19.0 software., Results: Response rates were high in both groups. With the prolonged medication durations, the therapeutic efficacy of both agents became more significant. The TSC-AML volume reduction after 6 and 12 months was more pronounced in patients with everolimus than those with sirolimus. More than half of the patients treated with everolimus had ≥ 50% reduction, and approximately 80% of them had ≥ 30% reduction, which was higher than that in patients treated with sirolimus. Regarding safety, there was no significant difference in the incidence of AEs between the two groups., Conclusions: Both everolimus and sirolimus are excellent therapeutic options for TSC-AML. However, everolimus has a better therapeutic efficacy than sirolimus, particularly in reducing TSC-AML volume. Everolimus is therefore recommended as the first choice of therapy for TSC-AML.

Objectives Transmuscular quadratus lumborum block (TQLB) may provide postoperative analgesia in patients undergoing intraperitoneal surgeries. The purpose of this study was to examine the potential efficacy of TQLB among patients undergoing retroperitoneal procedures, such as the laparoscopic partial nephrectomy (LPN). Methods This prospective, randomized, controlled study was conducted from August 2017 to November 2018 at Peking Union Medical College Hospital (Beijing, China). Patients who were scheduled for a LPN, aged 18-70 years old with an ASA physical status score of I - II were randomly assigned to receive either TQLB with 0.6 ml/kg of 0.5% ropivacaine plus general anesthesia (TQLB group) or general anesthesia alone (control group). Patient-controlled intravenous analgesia with morphine was initiated immediately upon surgery completion. The primary outcome was the cumulative consumption of morphine within 8 h after surgery. The secondary outcome included postoperative consumptions of morphine at other time points, pain score at rest and during activity, postoperative nausea and vomitting (PONV), and recovery related parameters. Results Totally 30 patients per group were recruited in the study. The 8 h consumption of morphine was lower in the TQLB group than in the control group (median, 0.023 mg/kg vs . 0.068 mg/kg, U=207.5, P <0.001). No significant differences were observed in postoperative pain scores between the two groups. Patients in the TQLB group had fewer episodes of PONV (20% vs. 47%, χ 2 =4.8, P =0.028) in the first 24 h after surgery and higher scores for quality of recovery (mean, 138.6 vs. 131.9, t =-2.164, P =0.035) 120 h after surgery than the controls. Conclusions TQLB resulted in an opioid-sparing effect during the early postoperative period following LPN, as well as a lower incidence of PONV and improved quality of recovery.

Objective Accumulated evidence has suggested that there is a close association between preoperative neutrophil-to-lymphocyte ratio (NLR) and prognosis of various malignant tumors. However, the relationship between NLR and surgically resectable urinary cancers remains contradictory. Therefore, we performed this systematic review and meta-analysis to explore whether preoperative NLR could predict the prognosis of surgically resectable urinary cancers. Methods After searching the Embase, PubMed/MEDLINE and Cochrane databases and screening the articles, we finally included 25 studies involving 15950 patients. Hazard ratios ( HR s) and their 95% confidence intervals ( CI s) were extracted to assess the association between preoperative NLR and the overall survival (OS) and cancer-specific survival (CSS) of surgically resectable urinary cancers. Results The pooled results revealed that an elevated preoperative NLR could predict a worse OS ( HR =1.40, 95% CI : 1.26-1.54, P <0.001) and CSS ( HR =1.43, 95% CI : 1.27-1.59, P <0.001) in urinary cancers. In addition, our analyses also suggested that high preoperative NLR was associated with worse prognosis in renal cell carcinoma (OS: HR =2.06, 95% CI : 1.54-2.76, P =0.131; CSS: HR =2.46, 95% CI : 1.46-4.16, P =0.178), upper tract urothelial carcinoma (OS: HR =1.91, 95% CI : 1.50-2.42, P =0.616; CSS: HR =1.84, 95% CI : 1.41-2.39, P =0.001), bladder cancer (OS: HR =1.09, 95% CI : 1.02-1.17, P <0.001; CSS: HR =1.05, 95% CI : 1.01-1.09, P =0.163) and prostate cancer (OS: HR =1.69, 95% CI : 1.19-2.41, P =0.714). Regardless of the participants' race or the cutoff value of the preoperative NLR, the results remained valid. Conclusion Elevated preoperative NLR could predict a worse prognosis in surgically resectable urinary cancers, namely, renal cell carcinoma, bladder cancer, prostate cancer and upper tract urothelial carcinoma.

The outbreak caused by 2019 novel coronavirus(2019-nCoV) is still spreading, posing a great threat to the safety and health of general population. However, there have not been any effective drugs for treatment, with symptomatic treatment and prevention prevailing. The treatment plans of severe acute respiratory syndrome(SARS) and Middle East respiratory syndrome(MERS) are often used for reference in clinic. The advantages of traditional Chinese medicine(TCM) in treating SARS and MERS are that it can intervene and block the progression of disease in early stage, significantly reduce symptoms, shorten the treatment duration of patients, reduce complications and side effects caused by hormone therapy. The coronavirus disease 2019(COVID-19) belongs to the category of TCM epidemic diseases. Chinese patent medicines and prescriptions in medical observation and clinical treatment were recommended in the &quot;pneumonia diagnosis and treatment plan for new coronavirus infection&quot;(trial version fifth) of the National Health Commission of the People's Republic of China. Qingfei Paidu Decotion was recommended for the treatment of COVID-19 by the National Health Commission of the People's Republic of China and National Administration of Traditional Chinese Medicine. TCM shows good clinical efficacy and great potential in the treatment of COVID-19. Previous studies of TCM have shown broad-spectrum antiviral activity, providing a variety of sources for the discovery of new antiviral drugs. In this paper, we reviewed traditional Chinese medicines and its active ingredients in the hope of bringing novel inspirations to the drug screening and clinical treatment for COVID-19.

Renal cell carcinoma(RCC)is one of the most common malignant tumors in the urinary system.Many patients have already been in the advanced stage at the first medical consultation and the prognosis is dismal.Metabonomics searches for differential metabolomes through high-throughput analysis of endogenous metabolites showing high potential in the early diagnosis of RCC and the investigations on its pathophysiological mechanisms.Metabonomics techniques are also useful for identifying tumor markers,which will help to enable early diagnosis and improve clinical prognosis of RCC.

A high incidence of hypersensitivity reactions (HSRs) largely limits the use of paclitaxel injection. Currently, these reactions are considered to be mediated by histamine release and complement activation. However, the evidence is insufficient and the molecular mechanism involved in paclitaxel injection-induced HSRs is still incompletely understood. In this study, a mice model mimicking vascular hyperpermeability was applied. The vascular leakage induced merely by excipients (polyoxyl 35 castor oil) was equivalent to the reactions evoked by paclitaxel injection under the same conditions. Treatment with paclitaxel injection could cause rapid histamine release. The vascular exudation was dramatically inhibited by pretreatment with a histamine antagonist. No significant change in paclitaxel injection-induced HSRs was observed in complement-deficient and complement-depleted mice. The RhoA/ROCK signaling pathway was activated by paclitaxel injection. Moreover, the ROCK inhibitor showed a protective effect on vascular leakage in the ears and on inflammation in the lungs. In conclusion, this study provided a suitable mice model for investigating the HSRs characterized by vascular hyperpermeability and confirmed the main sensitization of excipients in paclitaxel injection. Histamine release and RhoA/ROCK pathway activation, rather than complement activation, played an important role in paclitaxel injection-induced HSRs. Furthermore, the ROCK inhibitor may provide a potential preventive approach for paclitaxel injection side effects.

Objective: To explore the dynamic impacts of simulated microgravity (SM) on different vital brain regions of rats., Methods: Microgravity was simulated for 7 and 21 days, respectively, using the tail-suspension rat model. Histomorphology, oxidative stress, inflammatory cytokines and the expression of some key proteins were determined in hippocampus, cerebral cortex and striatum., Results: 21-day SM decreased brain derived neurotrophic factor and induced neuron atrophy in the cerebral cortex. Strong oxidative stress was triggered at day 7 and the oxidative status returned to physiological level at day 21. Inflammatory cytokines were gradually suppressed and in striatum, the suppression was regulated partially through c-Jun/c-Fos., Conclusion: The results revealed that the significant impacts of SM on rat brain tissue depended on durations and regions, which might help to understand the health risk and to prevent brain damage for astronauts in space travel., (Copyright © 2019 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Objective: This study aimed to provide rational guidelines for patients with subclinical Cushing syndrome (SCS), who are undergoing laparoscopic adrenalectomy, in order to avoid the risk of overtreatment., Methods: A total of 59 patients diagnosed with SCS caused by unilateral adrenal adenoma, who underwent laparoscopic adrenalectomy from 2010 to 2017, were included into the study. These patients did not receive prophylactic steroid treatment. After discharge, patients with adrenal insufficiency (AI) were treated with glucocorticoid. Then, cortisol levels were reevaluated at three months after surgery by morning serum cortisol., Results: No severe perioperative complications occurred. After unilateral laparoscopic adrenalectomy, no patient developed AI and was readmitted. In the first week after surgery, 10 patients (16.9%) received steroid therapy at the clinic because of mild symptoms of AI. The probability of developing AI was greater in patients with 1-mg dexamethasone midnight suppression test (1 mg-DST) >5 μg/dL than patients with mg-DST ranging within 1.8 to 5.0 μg/dL (P=0.042). The initial dose of hydrocortisone was 20.00±6.67 mg/d (range, 10 to 30), and the duration of treatment was 6.90±3.51 weeks (range, 3 to 12 wk). At three months after surgery, morning cortisol was >5 μg/dL in all patients., Conclusions: After laparoscopic adrenalectomy, the probability of AI is small in patients with adrenal SCS, and the symptoms of AI were mild. Meanwhile, the HPA axis rapidly recovered. Therefore, prophylactic steroid treatment is not mandatory. Given that AI is more frequent in patients with higher cut-offs of 1 mg-DST, a more precise definition of SCS is necessary to better manage these patients.

Sinomenine (SIN) is widely used in China to treat a variety of rheumatic diseases (RA), and has various pharmacological effects such as anti-inflammatory, analgesic, and anti-tumor effects. However, due to the histamine release characteristics of SIN, its adverse reactions such as allergic reactions, gastrointestinal reactions, and circulatory systemic reactions have been drawing increasing attention. We present here a systematic review of the chemical structure, pharmacological effects, clinical application, and adverse reactions of SIN, a detailed discussion on the relationship between histamine/histamine receptor and mechanism of action of SIN. In addition, we simulated the binding of SIN to four histamine receptors by using a virtual molecular docking method and found that the bonding intensity between SIN and receptors varied in the order shown as follows: H1R > H2R ~ H3R > H4R. The docking results suggested that SIN might exhibit dual regulatory effects in many processes such as cyclooxygenase-2 (COX-2) expression, NF-κB pathway activation, and degranulation of mast cells to release histamine, thereby exhibiting pro-inflammatory (adverse reactions)/anti-inflammatory effects. This study provides a theoretical basis for the clinical treatment of inflammations seen such as in RA using SIN, and also suggests that SIN has great potential in the field of cancer treatment and will have very important social and economic significance.

Animal traditional Chinese medicine has a long history of application in China, and its clinical application is very extensive. Due to the complex chemical composition in animal traditional Chinese medicine, the basis of chemical research is relatively weak, which leads to the unclear composition and toxic components of many animal Chinese medicines. The relationship between the medicinal and toxic components of animal Chinese medicine has not yet been elucidated. The non-clinical safety evaluation of animal traditional Chinese medicine mainly includes acute toxicity, long-term toxicity, safety pharmacology, reproductive toxicity, genotoxicity experiments, and experimental studies such as carcinogenicity are needed when necessary. The current preclinical safety research on animal traditional Chinese medicine is mainly based on the study for toxic animal traditional Chinese medicines. Most animal Chinese medicines have not carried out systematic preclinical and clinical safety studies. The research method is mainly focused on acute toxicity test. It is necessary to carry out systematic preclinical safety studies on animal traditional Chinese medicines, to clarify the possible side effects and its characteristics, its toxic target organs, toxic doses and poisoning mechanisms induced by different animal traditional Chinese medicines. Finally, this paper suggests that in the preclinical safety study of animal traditional Chinese medicine, in-depth research and comparison should be carried out in combination with chemical substance foundation, origin, and collection season, and the safety of "non-toxic" animal traditional Chinese medicine should be carried out when necessary. In addition, it is necessary to rationally use the cutting-edge technologies and methods of toxicology research to fully clarify the preclinical safety information of animal Chinese medicines., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Animal medicine injection is an important part of traditional Chinese medicine (TCM) injections. All or part of animals with a significant curative effect and little side reactions as raw materials as well as modern technology are used to produce traditional Chinese medicine injections with a reliable and rapid drug efficacy and high bioavailability. Due to the complex composition of traditional Chinese medicine injections, imperfect quality standards, and unreasonable clinical use, the incidence of adverse reactions of traditional Chinese medicine injections has been significantly higher than that of traditional Chinese medicine for oral use. Animal medicine injections contain rich protein and fat, and heteroproteins are the main sensitization source in animal medicine injections. At present, the adverse reactions of animal medicine injections are mainly manifested in the anaphylaxis-like reactions at skin, mucous membranes and organ systems. The adverse reactions that occur during the first medication are more common. Specific causes for allergic-like adverse reactions in animal injections and related substances in traditional Chinese medicine injections made of animals that induce allergies or anaphylactoid reactions are currently not specifically reported. This article reviews the current adverse reactions of animal TCM injections, allergies and pseudoallergic reactions of animal TCM injections, the pharmacokinetics of animal TCM injections, and the combined use of drugs, in order to improve the quality standards of Chinese medicine injections for animals and provide reference for further safety related research., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

The aim of this study was to investigate the renal toxicity of rhubarb and its mechanism. The SD rats were randomly divided into three groups: normal group and two rhubarb extract groups (16, 2 g·kg⁻¹). According to the dose conversion method between human and animal, rhubarb 16 g·kg⁻¹ and 2 g·kg⁻¹ were equivalent to 10 times and 1.25 times of human clinical dose respectively. Rhubarb extract was administered by a gastric gavage to rats once daily for 30 days. Serum urea nitrogen （BUN）, creatinine （CRE） and urine KIM-1, NGAL and renal morphology were analyzed. The expressions of OAT1, OAT3 and clusterin mRNA in kidney were measured. The results showed that the low dose of rhubarb had no obvious renal toxicity. The high dose group showed mild and moderate renal injury and a down-regulation of clusterin mRNA expression in the kidney tissue. The renal toxicity in male animals was heavier than that in female animals. There was no significant change in blood BUN and CRE in the high dose group. But urine NGAL level of the high dose group increased by 51.53% compared with normal group, of which male animals increased more significantly ( P <0.05, compared with the normal group). The expressions of renal OAT1 and OAT3 mRNA in the low dose group were obviously higher than that in the normal group. The results indicated that the high dose of rhubarb could cause the renal toxicity. The dosage should be controlled reasonably in the clinical use. OAT1 and OAT3 mRNA related to anionic transport in kidney tissue played a compensatory protective role in rhubarb-induced renal injury. But the compensatory effect is relatively weak at the high dose level. In addition, routine renal function indicators BUN and CRE had limitation for monitoring the kidney toxicity of rhubarb. It is suggested that urine NGAL detection might be helpful for monitoring the renal toxicity of rhubarb., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

In this study, different batches of Xingnaojing injection products were first selected for pseudoallergic mice test, and the results showed that after injection of 6.6-fold clinical dose Xingnaojing injection, the mice showed a slight pseudoallergic reaction, while other mice injected with other batches of injections showed no obvious pseudoallergic reaction. Therefore, it is preliminarily believed that this mice model can effectively indicate the risk of pseudoallergic reactions in the clinical application of Xingnaojing injections. In addition, by changing some of the processes, a high concentration of Xingnaojing injection was prepared for mice pseudoallergic test and guinea pig systemic allergy test. The results showed no significant type Ⅰ allergic reaction in guinea pigs. Mild pseudoallergic reactions occurred in mice after a 6.6-fold clinical dose injection. Therefore, it is considered that for sensitive or idiosyncratic people, the concentration of certain chemical components in Xingnaojing injection will increase after entering the body, which may increase the risk of pseudoallergic reaction. However, due to the limitations of test models, the risk of Xingnaojing injection to induce allergic reactions cannot be ruled out. Finally, by increasing the content of borneol and Tween and (or) sodium chloride in Xingnnaojing Injection and testing its pseudoallergic reactions, the results showed that the combination of these three ingredients may produce new trace sensitization substance and induce pseudoallergic reactions., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Purpose: To compare the long-term clinical and oncologic outcomes in patients treated with laparoscopic partial nephrectomy (LPN) and laparoscopic radial nephrectomy (LRN) for clinical T1b renal cell carcinoma., Materials and Methods: We retrospectively reviewed the records of all patients who underwent LPN or LRN for a single clinical T1b tumor between January 2005 and January 2012, an actual follow-up of 2-year or greater was available in 39 and 160 after LPN and LRN, respectively. Survival was calculated using the Kaplan-Meier method. Multivariable Cox regression analysis was done to assess predictors of survival., Results: The two cohorts of patients were similar in age, sex, body-mass index and preoperative eGFR. There were no differences in tumors size (4.97 vs 5.29cm, P = .08), and pathological stage distribution between the two cohorts. The median follow-up after LPN and LRN were 67 (range: 18-118) and 70 (19-120) months, respectively. For LPN versus LRN, 5-years overall and cancer specific survival rates were 93.33% vs 85.69% and 96.00% vs 91.35%, respectively. For LPN versus LRN, 10-years overall and cancer specific survival rates were 85.56% vs73.41% and 88.00% vs 82.85%, respectively. On multivariate analysis, patients' age, ASA score and pathological stage were the major factors affecting overall survival, and patients' age and pathological stage were associated with cancer specific survival. The percent decrease in glomerular filtration rate was significantly lower in the LRN group at early and last followup., Conclusion: LPN is an effective treatment option in appropriately selected patients with cT1b RCC. It provides 5-year, 10-year overall survival and cancer specific survival comparable to those of LRN as well as better preservation of renal function than LRN. Overall survival and cancer specific survival are associated with nonmodifiable factors but not by the choice of operative technique.

Objective: To assess whether adrenalectomy may improve biochemical and metabolic impairment for patients with subclinical Cushing syndrome (SCS) due to adrenal incidentaloma (AI) compared with conservative management., Methods: A total of 87 patients with SCS due to AI in Peking Union Medical College Hospital between September 2011 and January 2016 have been treated. Forty-eight patients underwent laparoscopic adrenalectomy (operative group), whereas 39 were managed conservatively (control group)., Results: The duration of follow-up was 32.5 ± 10.6 months in operative group, and 30.1 ± 13.1 months in control group, respectively. In the operative group, laboratory corticosteroid parameters normalized in all patients but not in the control group. In the operative group, BP of hypertensive patients improved or normalized (22 of 48); to the contrary, in the control group, cure or improvement was never achieved among the patients with hypertension, whereas a worsening was observed in 5 patients (P= 0.004). No significant difference was found in glycemic control and blood lipid change between the two groups. However, a decrease in triglyceridaemia and HBA1c was found in operative group compared with the control group (P= 0.011 and P= 0.017, respectively). Substitutive corticosteroid treatment was administered in 3 patients due to postoperative adrenal insufficiency during hospital stay, and the duration of treatment was 9 weeks, 10 weeks and 12 weeks, respectively., Conclusions: Laparoscopic adrenalectomy should be performed for patients with SCS due to AI.

This study aimed to explore the characteristics and the influencing factors of Qingkailing injection (QKLI) pseudoallergic reaction, and screen out the possible pseudoallergenic substances. The results showed that ICR and Kunming mice had stronger pseudoallergic reactions than BALB/c and C57 mice after being injected with the same dose of QKLI. The pseudoallergic reaction induced by QKLI that was prepared with 0.9% saline was stronger than that prepared with 5% glucose. When the dose was twice of the clinical dose, some batches of QKLI could cause significant or suspected pseudoallergic reactions; when the dose dropped to clinically equal times, all of the batches did not induce pseudoallergic reactions in mice. Different batches of QKLI induced different pseudoallergic reactions in mice. Therefore, QKLI's pseudoallergic reactions might have a certain relationship with different body constitutions. Different solvents might affect the safety of QKLI. QKIL-induced pseudoallergic reactions had the different characteristics between batches, and the dosage should be strictly controlled in clinical use. After the comparison of pseudoallergic reactions induced by different components and different intermediates of QKLI in mice, it was preliminary believed that pseudoallergenic substances might exist in intermediate Isatidis Radix extracts and Gardenia extracts, but specific pseudoallergens shall be furthered studied in subsequent experiences., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective To evaluate the application of weak cation exchange (WCX) magnetic bead-based Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) in detecting differentially expressed proteins in the urine of renal clear cell carcinoma (RCCC) and its value in the early diagnosis of RCCC.Methods Eleven newly diagnosed patients (10 males and 1 female, aged 46-78, mean 63 years) of renal clear cell carcinoma by biopsy and 10 healthy volunteers (all males, aged 25-32, mean 29.7 years) were enrolled in this study. Urine samples of the RCCC patients and healthy controls were collected in the morning. Weak cation exchange (WCX) bead-based MALDI-TOF MS technique was applied in detecting differential protein peaks in the urine of RCCC. ClinProTools2.2 software was utilized to determine the characteristic proteins in the urine of RCCC patients for the predictive model of RCCC. Results The technique identified 160 protein peaks in the urine that were different between RCCC patients and health controls; and among them, there was one peak (molecular weight of 2221.71 Da) with statistical significance (P=0.0304). With genetic algorithms and the support vector machine, we screened out 13 characteristic protein peaks for the predictive model. Conclusions The application of WCX magnetic bead-based MALDI-TOF MS in detecting differentially expressed proteins in urine may have potential value for the early diagnosis of RCCC.

In this study, by the means of the active systemic allergy test in guinea pigs, passive skin allergy test in rats and pseudoallergic test in mice, it was determined that the "allergic reaction" of Shuxuening injection(SXNI) may not be a true IgE-mediated allergic reactions, but mainly of pseudoallergic reaction. Further pseudoallergic test proved that the pseudoallergic reactions of SXNI had difference between batches and showed dose dependence, so it was recommended to establish SXNI pseudoallergic reaction detection method for timely detecting and controlling the product risk of each batch products. In addition, as the pseudoallergic reactions of SXNI were dose-dependent, the dose and concentration of SXNI should be strictly controlled in clinical use. Then the main pseudoallergenic reaction test was conducted for the main monomer components in SXNI and the different fractions of Ginkgo biloba extract in mice, and the results showed that the sensitizing substances may mainly exist in YXY-3 fractions containing flavonol glycosides. By further chemically separating YXY-3, we got four chemical components. Among these four components, YXY-3-1 and YXY-3-2 were testified as the main allergenic components in SXNI through pseudoallergic test in mice. To make sure the specific chemical constituent that is responsible for the pseudoallergic reaction, in-depth study in follow-up experiments should be needed., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Rho GTPases belong to Ras superfamily, which is reported to involve in cell migration, phagocytosis, contraction and adhesion. ROCK (also known as Rho-associated kinase) is considered to be one of the most important downstream targets of Rho that is widely investigated. Rho/ROCK signal pathway induces cytoskeletal reorganization, cell migration and stress fiber formation, affects endothelial permeability, tissue constriction and growth, involves in diabetic nephropathy, eye disease, cancer, heart disease, nerve injury disease, hypertension, radiation injury and leukemia. As a novel drug research target, Rho/ROCK signal pathway has received more and more attention. This review provides the basic characteristics and physiological effects of Rho/ROCK signal pathway, the relationships between Rho/ROCK signal pathway and diseases, and the therapeutic methods based on the Rho/ROCK signal pathway.

We describe the clinical presentation, diagnosis, treatment, and follow-up data of a 39-year-old woman with asymptomatic right kidney tumor, which was later histopathologically diagnosed as metanephric adenoma (MA). Macroscopically, the tumor had integrity tegument with homogeneous and gray cutting surface. Microscopically, the tumor cells were formed in adenoid or papillary pattern and contained psammoma bodies, without distinctive atypia. Immunohistochemistry results showed they were negative for creatine kinase 7, epithelial membrane antigen, and renal cell carcinoma, and positive for AE1/AE3, vimentin, and Wilms Tumor 1. Pathological diagnosis was MA. The 48 months' follow-up information was available without recurrence.According to this case and literature review, we figured that it is difficult to make a definite diagnosis of MA only by image examination. Nephron-sparing surgery is eligible to treat MA. Long-term active surveillance is necessary because of the uncertainty of the biological behavior and cellular origin of MA.

IgG4-related disease is a recently recognized clinical entity. It is characterized by diffuse organ swelling or mass formation, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells with fibrosis and typically an increased serum IgG4 concentration, which may affect various organs. An 80-year-old woman with an otherwise unremarkable previous medical history was revealed to have a renal mass that was indicative of renal malignant carcinoma, for which a radical nephrectomy was performed. The mass was diagnosed as an IgG4-related inflammatory pseudotumor, which was histopathologically confirmed. The patient is currently well without evidence of IgG4-related disease at 3 months post-surgery, and did not require any additional therapy.

Purpose: To compare the characteristics of primary tumors, sites distribution of metastases and the metastasis-free interval (MFI) between metastatic upper tract urothelial carcinoma (UTUC) and urothelial bladder cancer (UBC), and evaluate the clinicopathological factors associated with MFI., Methods: We retrospectively reviewed 153 metastatic urothelial carcinoma patients consecutively registered at our hospital from 1997 to 2015, including 71 UTUC and 82 UBC, with a median follow-up of 18.3 months. MFI indicators were assessed by univariate and multivariate logistic regression analysis., Results: There were significant differences in median age at metastatic disease (p = 0.016), gender (p = 0.018), primary tumor size (p = 0.003), growth pattern (p < 0.001), grade (p < 0.001) and stage (p < 0.001) between metastatic UTUC and UBC. The median MFI of UTUC was dramatically shorter than that of UBC (6.1 vs. 17.4 months, p < 0.001). Univariate analysis revealed pathological stage was the only factor associated with the MFI of UTUC. Multivariate analysis showed that primary tumor grade was an independent inferior predictor for the MFI of UBC (HR 6.384, 95% CI 3.21-12.69, p < 0.001), while recurrence was an independent favorable factor for the MFI of UBC (HR 0.384, 95% CI 0.18-0.82, p = 0.014)., Conclusions: Compared to metastatic UBC, the primary tumors of metastatic UTUC were more invasive and the MFI was significantly shorter. Pathological stage was the only factor associated with the MFI in UTUC, while primary tumor grade and recurrence were independent factors for the MFI of UBC.

A direct and catalyst-free method for the intramolecular aminoboration of unfunctionalized olefins is reported. In the presence of BCl3 (1 equiv) as the sole boron source, intramolecular aminoboration of sulfonamide derivatives of 4-penten-1-amines, 5-hexen-1-amines, and 2-allylanilines proceeded readily without the use of any catalyst. The boronic acids obtained after hydrolysis could be converted into the corresponding pinacol borates in a straightforward manner by treatment with pinacol under anhydrous conditions., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Paragangliomas (PGLs) are rare neuroendocrine neoplasms of the autonomic nervous system dispersed from the skull base to the pelvic floor. We reported an extremely rare case with coexisting PGL of the retroperitoneum and urinary bladder. The patient complained of episodes of severe headache and palpitation during micturition, with a 1-year history of uncontrolled hypertension. The (131)I-metaiodobenzylguanidine ((131)I-MIBG) scintigraphy revealed high uptake in both of the retroperitoneum and urinary bladder mass accompanied with increasing 24 hour urinary norepinephrine and epinephrine. The patient received 6 doses of high-specific activity (131)I-MIBG from October 2009 to April 2015, each treatment dose was 400 mCi. The patient got symptomatic, hormonal, and radiographic tumor complete response without life-threatening adverse events.Intermediate-dose (131)I-MIBG therapy may be an alternative choice for patients with multicentric PGLs with positive MIBG scintigraphy.

Drug allergy and pseudoallergic reactions are main adverse drug reactions. Allergy is mainly induced by the immunogenicity of drug, drug metabolic products or drug additive. Pseudoallergic reactions may result from the irritation or activation of inflammatory material release. Pre-clinical evaluation of drug allergy and pseudoallergic reactions is included in immunotoxicity evaluation. Now there is no in vivo or in vitro method that could predict all kinds of allergy or pseudoallergic reactions due to the different mechanisms. In the past few years, FDA, SFDA OECD, ICH and WHO have published several guidelines on per-clinical immunotoxicity evaluation, however, no agreement has been reached on allergy and pseudoallergic reactions evaluation. This article reviews the requirements of allergy and pseudoallergic reactions in pre-clinical evaluation.

Pseudoallergic reactions occured after the first administration of patients, and the pathogenic mechanisms of them were different from the allergic reactions which needed excitation after antigen sensitization. To provide a basis for evaluation, clinical use and drug development of pseudoallergic reactions, the models were established by two kinds of Chinese herbal injections (CHI) both on different strain or gender mice. With the use of ICR, Kunming, BALB/C, C57 mice, pseudoallergic tests of two CHI were conducted to compare the sensitivity of four strains mice, and compared the differences in male and female animals. Test substances contain 0.8% Evans blue (EB) were intravenously injected into different strain and gender mice. Scores of ear blue staining and quantitation of ear EB exudation were the parameters for pseudoallergic reaction. Results of strain difference indicated that both CHI A and B could cause severe pseudoallergic reactions indicated by obvious vascular hyperpermeability on ICR mice. The pseudoallergic reactions in ICR mice are more obvious under the the same dose of injection, which stated the sensibility of ICR mice. And the reactions of KM mice and BALB/C mice were slightly reduced which compared to ICR mice, even alomost nothing on C57 mice. Comparison results of gender difference showed that one CHI was not have significant difference in male and female animals, but male animals were more susceptible than females on another CHI. Therefore, ICR mice were preferable experimental strain on the model of pseudoallergic reactions induced by CHI A and B. Because of female animals were easily influenced by estrous cycle, the pseudoallergic reactions induced by CHI A and B select and use male mice befittingly.

To evaluated the pseudo-allergic reactions of cordate houttuynia, pulse-activating and Qingkailing injection in mice, the ICR mouse were divided into different test groups, then were intravenously injected with three traditional Chinese medicine injections, positive control compound 48/80 and physiological saline as normal control. All test substances were mixed with 0.4% Evans blue. The reaction and vascular permeability of the ears were observed and measured 30 min after injection. At the same time, the mechanisms of the traditional Chinese injections' pseudo-allergic reactions was studyed. ICR mice were injected with the test substances as above without EB, blood in a part of mice were collected after 5 min, and the level of histamine in the plasma were measured. Blood in the other part of mice were collected after 30 min, and the level of VEGF, TNF-α and IL-10 in the serum were measured. The reasults showed that except the cordate houttuynia injection, pulse-activating injection in 1. 5 times clinical concentration and Qingkailing injection in 3.3 times clinical concentration caused mild pseudo-allergic reactions mainly for vascular permeability, no pseudo-allergic reactions occurred when the concentration of the two injections was below the concentration metioned above; 5 minutes after intravenous injection of the three TCM injections into ICR mice with the highest dose, the levels of histamine in plasma of pulse-activating injection and Qingkailing injection groups were increased significantly, 30 minutes later, the levels of VEGF, TNF-α and IL-10 in the serum of all groups were no significant change compared to normal group. The mouse of pulse-activating and Qingkailing injection groups showed inflammatory changes in ear and lung tissues. It can be conluded that when the dose or concentration increased to a certain extent, pulse-activating and Qingkailing injection could induce pseudo-allergic reactions on ICR mice, the increased histamine realease maybe the main reason for pseudo-allergic reactions of the two traditional Chinese medicine injections. In addition the author preliminary thought that inflammatory mechanisms leading to hyperpermeabilities were the main reason of the traditional Chinese medicine injection's pseudo-allergic reaction.

Choosing the right solvent and timely use is the basis of rational drug use and the most direct and efficient way to improve the safety of traditional Chinese medicine injections. This study aimed to evaluate the influence of solvent and drug preparation time on Shuanghuanglian injection inducing pseudo-allergic reactions with mouse mode. The two tests were carried out: (1) Comparative experiment between different solvent: Shuanghuanglian injection preparation to the appropriate concentration with 0.9% sodium chloride injection and 5% dextrose injection, mixed with Evans blue, at one time intravenous injected into mice, 30 minutes later, the mouse ears vascular permeability were observed and compared. (2) Comparative experiment among different preparation time: placed 10 min, 2.5 h, 6 h and 24 h after Shuanghuanglian injection were prepared and then to detect the pseudo-allergic reactions in mice using the same methods as in (1). The results showed that there was no significant difference in the pseudo-allergic reactions in mice which induced by the same dose of Shuanghuanglian injection, respectively with 0.9% sodium chloride injection and 5% dextrose injection preparation, and with the extension of preparation time, the degree of pseudo-allergic reactions of Shuanghuanglian injection was gradually severe.

In this study, chemistry, biology and pharmacology were combinated to screen pseudoallergenic substances of Shuang-huanglian injection (SHLI) so that to establish a scientific and systematic approach to screen pseudoallergenic substances of traditional Chinese medicine injections. The mouse pseudoallergic reaction models were used to screen the pseudoallergic reaction of SHLI's intermediate extract and the intermediate extract's component or ingredient. Among the three intermediates of Shuanghuanglian injection (extract of Scutellaria baicalensis, extract of Lonicera japonica, extract of Forsythia suspensa) , pseudoallergic action of Forsythia suspensa was the strongest, Forsythia suspesnsa's pseudoallergic reaction mainly associated with the composition with largerchemical polarity. Further it was found that forsythiaside A and arctiin which existed in the the composition with largerchemical polarity caused obvious pseudoallergic reactions. SHLI with removal forsythoside A with the technology of HPLC-MS displayed reduced pseudoallergic reaction and a significant improved safety. This study provided a scientific basis for SHLI process improvements and also offered idea and research foundation for screening pseudoallergenic substances injections in other TCM injections.

Genotoxicity research takes an important place in traditional Chinese medicine safety evaluation. Genotoxicity test on traditional Chinese medicine has been paid great attention since 1970s. Currently, the most developed genotoxicity test methods included: bacterial reverse mutation test and mouse lymphoma assay which are used to detect relevant genetic changes, micronucleus test and chromosomal analysis which are used to measure chromosomal aberration, and single cell electrophoresis assay which is used to test DNA damage. This article reviews research progress on genotoxicity of traditional Chinese medicine, evaluation methods of genotoxicity, the problems and solutions on genotoxicity evaluation of traditional Chinese medicine, and new technique used in genotoxicity test.

Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem-ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data obtained in this study showed that the application of ethosomal technology to antimalarial cataplasm could improve the transdermal delivery of drug, enhance the efficacy, and facilitate practical application in clinic.

Objective: To explore the diagnostic and therapeutic principles of the rare adrenal schwannoma., Methods: We objectively analyzed the detailed clinical data of 19 patients with adrenal schwannoma treated in a large comprehensive medical center in China between January 2009 and March 2014, including general information, clinical manifestations, imaging, adrenal-related endocrine tests, treatment, pathology, and follow-up records., Results: Patients included 16 females and 3 males ranging from 23 to 66 years of age (mean, 48.3 ± 12.6 years), of whom 15 were discovered incidentally. Four patients reported mild abdominal discomfort. Each patient had one unilateral lesion, ranging in diameter from 4.0 to 8.8 cm (mean, 6.2 ± 1.2 cm). Lesions were hypoechoic in 16 patients and cystic-solid in 3 patients. Computed tomography (CT) scanning revealed soft tissue density, mostly with calcifications and clear boundaries. Average values in normal and enhanced CT were 28.7 ± 7.2 Hounsfield units (HU) and 59.7 ± 5.4 HU, respectively. Indicators of adrenal-related endocrine tests were normal, except that catecholamines levels were slightly low in 2 patients with excessively large lesions. All patients underwent uncomplicated retroperitoneal laparoscopic surgery, with subsequent pathology confirmation of adrenal schwannoma. The patients have been followed for 6 months to 4 years, with no recurrence., Conclusion: Our results demonstrate that the onset of adrenal schwannoma is always occult, without typical clinical manifestations and adrenal-related endocrine abnormalities, and the pre-operative diagnosis depends primarily on imaging features of hypoechoic calcifications and mild enhancement. Diagnosis can be confirmed by postoperative pathology. Even with large diameter lesions, retroperitoneal laparoscopic surgery is still the preferred approach, with good prognosis.

Reproductive toxicity research takes an important place in traditional Chinese medicine pre-clinical safety evaluation. Modern reproductive toxicity experiment includes drug-related miscarriage, fetal death, teratism, and adverse effects on fertility, genital system, embryonic development and fetus, which is different from contraindicated in pregnancy in traditional Chinese medicine theory. Now the three-phases reproductive toxicity study is the method mainly applied in traditional Chinese medicine reproductive toxicity evaluation. Besides that, alternative methods of whole embryos culture and embryonic stem cell test are also used in traditional Chinese medicine embryo toxicity evaluation. This article reviews research progress and pre-clinical evaluation on reproductive toxicity of traditional Chinese medicine.

The purpose of this study is to evaluate the embryotoxicity of alkaloids in Senecionis Scandentis Hebra on in vitro cultured mouse embryos. Mouse whole embryo culture (WEC) was applied in this study. Post-implantation (8.5 d) mouse embryos were isolated from their mothers, and cultured in medium of immediately centrifuged serum (ICS) with different concentrations of seneciphylline (target concentrations were 100, 50, 25 and 12.5 μg x mL(-1)) or senkirkine (target concentrations were 50, 25 and 12.5 μg x mL(-1)) for 48 h. After culturing completed, the development and organic morphodifferentiation of the cultured embryos were evaluated microscopically. Treatment with seneciphylline and senkirkine had adverse effects on the development and organic morphodifferentiation of embryos. The effect also had clear dose-response. Alkaloidals in Senecionis Scandentis Hebra had embryotoxicity on cultured embryos, which indicated that pregnant people exposed to Senecionis Scandentis Hebra may get potential risk on fetus.

Pseudoallergic reactions of Qingkailing injection (QKLI) was assessed by vascular hyperpermeability which were indicated by ear blue staining in ICR mice after single intravenous injection of QKLI mixed with Evans blue (EB) and skin blue spot formation in SD rats after intradermal injection of QKLI and intravenous injection of EB. In addition, QKLI-induced histamine, VEGF, TNF-alpha release was measured after ICR mice received the single dosing of QKLI iv. The mild vascular hyperpermeability characterized by ear blue staining could be observed in mice after intravenous injection of QKLI and EB. Intracutaneous injection of 50 micro L of test solution containing QKLI (25,50 microL) in rat back skin caused obvious local vascular hyperpermeability at the injection sites so as to result the larger diameters of blue spots than that in negative control group (P <0. 01). QKLI induced a significant increase of VEGF and a slight elevation of histamine in mice after intravenous administration, while TNF-alpha showed no change after QKLI iv. The results in this study indicated that both intravenous injection and intracutanous injection of QKLI could induce vascular hyperpemeability so as to cause pseudoallergic reaction in mice and rats. QKLI-induced pseudoallergic reaction may be associated with the release of histamine and VEGF.

Objective: To discuss perioperative treatment and cardiac function changes after medicine and surgical treatment of pheochromocytoma patients with severe catecholamine cardiomyopathy., Methods: Five pheochromocytoma patients with severe catecholamine cardiomyopathy in our hospital for the past 5 years were studied, their general characteristics, clinical manifestations, diagnosis tests summarized and the cardiac function changes before and after the treatment evaluated., Results: All the 5 patients were diagnosed definitely before operation. After medication, left ventricular ejection fraction (LVEF) of the 5 patients improved and 4 patients' LVEF increased 7-10 days after operation compared with after medication, and one patient's LVEF improved after 3 months., Conclusion: Pheochromocytoma patients with severe catecholamine cardiomyopathy should have adequate medication, and their abnormal cardiac function would be reversed after surgical treatment.

Objective: To analyze the complications of laparoscopic surgery for the past 11 years in the Urology Department of Peking Union Medical College Hospital., Methods: The laparoscopic surgery of 5 386 cases from Jan. 2002 to Dec. 2012 was statistically analyzed. The patient's gender, age, surgery mode, blood loss, complications, total length of hospital stay, postoperative hospital stay and other data were analyzed., Results: There were 5 386 cases in this group aged 8-86 years (the mean age: 49.0 years; 2 651 cases were male and 2 735 female). Of all the cases, 2 411 were of adrenal surgery, accounting for 44.7%, 167 of retroperitoneal tumor resection , accounting for 3.1%, 763 of radical nephrectomy surgery, accounting for 14.2%, 441 of partial nephrectomy surgery, accounting for 8.2%, 784 of renal cyst surgery, accounting for 14.6%; 279 of semi-urinary tract resection, accounting for 5.2%; 74 of renal pelvis and ureter plasty, accounting for 1.4%; 141 of radical prostatectomy surgery, accounting for 2.6%, 71 of cystectomy surgery, accounting for 1.3% and 255 of other surgery, accounting for 4.7%. The blood loss was 10-3 000 mL (average: 97.5 mL ) and the surgery requiring blood transfusion treatment involved 270 patients. The total hospital stay was 3-133 days (average: 18 days) and postoperative hospital stay was 2-35 days (average: 6.3 days). All kinds of complications occured in 346 cases (6.42%), of which 198 were of peritoneal injury, 12 of pleural injury; 72 of subcutaneous emphysema, 24 of urinary fistula, 15 of inferior vena cava injury, 6 of pancreatic fistula 10,of lymphatic fistula, 8 of wound delayed healing and 1 of, intestinal fistula. The incidence of the complications and blood transfusion showed a downward trend according to stratified analysis each year., Conclusion: The laparoscopic surgery coveres almost all treatment of urological diseases. The complications are different in different types of surgery at different times, but generally no serious complications occurr. The incidence of complications is in a downward trend as the laparoscopic technique level improves.

To investigate the clinicopathological characteristics of metanephric adenoma (MA), we analyzed the clinical and pathological data of metanephric adenoma. A 39-year old woman with asymptomatic right kidney tumor for 4 years was admitted to the hospital. A tumor with the largest diameter of 28 mm in the right kidney was homogeneously enhanced on CT. The tumor was distinctly increased as compared with 4 years before. The diagnosis was right kidney tumor. Nephron-sparing surgery was given after general anaesthesia. And the relative literature was reviewed. The tumor was homogeneous, with integrity tegument, and a grey cutting surface. Histopathologically, the tumor cells formed an adenoid or papillary pattern and contained psammoma bodies. Immunohistologically, they were positive for AE1/AE3, vimentin and WT1, negative for CK7, EMA and RCC. Pathological diagnosis was metanephric adenoma. The follow-up data of 24 months were available and without recurrence. MA is peculiar. It is difficult to get the final diagnosis of MA only by imaging characters. Nephron-sparing surgery is eligible for the treatment of MA. Considering the uncertainty of the biological behavior and cellular origin of MA, a long-term active surveillance is necessary.

Objective: To explore the diagnosis and treatment of tuberous sclerosis complex complicated with renal angiomyolipoma., Methods: The clinical data of 22 patients with tuberous sclerosis complex complicated with renal angiomyolipoma were analyzed retrospectively., Results: There were 12 males and 10 females with a mean age of 23 (1-46) years. All of them had bilateral multiple renal angiomyolipomas. The mean tumor size was 8.5 (0.7-18.0) cm in diameter. The presence or absence of clinical symptoms showed a significant correlation with tumor size.Eight patients with angiomyolipoma under 4 cm in diameter were continuously monitored at an outpatient clinic. There were 8 patients with lesions of 4-10 cm.Five of them underwent nephron-sparing surgeries and another 3 monitored at an outpatient clinic. There were 6 patients with tumor over 10 cm. Three of them underwent transcatheter arterial embolization and one case took rapamycin after embolization.One patient with concurrent renal cell carcinoma underwent partial nephrectomy. Chronic renal failure occurred in one case dying of pulmonary lymphangiomyomatosis with serious hemoptysis. During a mean follow-up of 25 months, neither severe renal hemorrhage nor symptomatic aggravation was found.In the case of rapamycin, there was 10% reduction in the size of angiomyolipoma., Conclusions: Most cases of tuberous sclerosis complex are complicated with bilateral multiple renal angiomyolipoma. The small lesions under 4 cm in diameter may be monitored at an outpatient clinic.For those larger (>4 cm) or symptomatic ones, medication, embolization or surgery is necessary.

Objective: To explore the significance of succinate dehydrogenase B (SDHB) mutation and EPAS1 overexpression in Zuckerkandl paragangliomas (PGL) and examine their correlations with malignant infiltration and metastasis., Methods: From March 2008 to July 2011, the clinical profiles of 16 Zuckerkandl PGL patients were analyzed retrospectively. For increased diagnostic specificity, a complex immunohistochemical panel of tissue microarray was performed for SDHB, EPAS1 and MIB-1. Positive expression identified as a granular cytoplasmic staining. Greater than or equal to 50% as strongly positive (+++), 1% to 10% as weakly positive (+)., Results: Tissue microarray immunohistochemical staining showed SDHB immunoreactivity in the cytoplasm, whereas EPAS1 and MIB-1 in the nuclear of tumor cells. Positive expression of EPAS1 in which 13 cases of Zuckerkandl PGL. And high expression strongly associated with malignancy. SDHB mutation of 7 cases are all EPAS1 positive staining. Non-gene mutation 9 cases tumor specimens, 6 cases were EPAS1 positive expression (P < 0.05). CgA positive expression in 11 cases benign Zuckerkandl PGL, strongly positive in 4 malignant cases (4/4). MIB-1 below 1% in 12 cases of benign Zuckerkandl PGL. And in 4 malignant cases, MIB-1 was about 3%. Malignant neoplasms had significantly higher EPAS1, CgA and MIB-1 expression compared to benign counterparts (P < 0.05)., Conclusions: The SDHB mutation causes the EPAS1 over expression in PGL and correlation with higher positive expression of CgA and MIB-1. It may be one of the mechanisms of malignant invasiveness and metastasis in PGL.

Objective: To screen for the differential protein peaks of renal cell carcinoma (RCC) using magnetic beads-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS)., Methods: Serum proteins were profiled by magnetic beads (WCX) from 62 RCC patients and 37 patients with benign renal space-occupying lesions. Protein peaks were identified by MALDI-TOF-MS. Data were analyzed with Biomarker Wizard 3.1 and Biomarker Patterns Software 5.0. Diagnostic model for RCC was constructed based on 47 RCC cases and 26 patients with benign renal space-occupying lesions. The remaining 26 cases were evaluated with blind method., Results: Seven differential protein peaks related to RCC were identified (Pβ0.05). The diagnostic model for RCC constructed by the differential protein peaks (m/z 2945.35, 15340.8, 6984.51, and 5819.23) generated excellent separation between the RCC and control groups, with a sensitivity of 83.0% and the specificity of 84.6%. As validated by blind method, the model had a sensitivity of 80.0% and a specificity of 81.8%., Conclusion: Differential protein peaks for RCC can be identified in serum by magnetic beads-based MALDI-TOF-MS, which is also valuable for the establishment of a RCC diagnostic model with a high sensitivity and specificity.

Background and Objective: Functional paraganglioma of the urinary bladder (FPUB) is a rare tumor. Misdiagnosis of FPUB before operation can lead to serious intraoperative consequences. In this article, we reported our experience in preoperative diagnosis and surgical treatment of FPUB., Methods: Clinical data of nine patients with FPUB treated between June 1985 and January 2009 at Peking Union Medical College Hospital were analyzed., Results: All patients underwent urinary catecholamine (CA) detection, B-ultrasound, CT and/or MRI scan; 5 underwent nailfola microcirculation inspection; 4 underwent 131I-metaiodobenzyl guanidine (MIBG) detection; and 6 underwent 111In-DTPA-Octreotide (OCT) scintiscan. According to the UICC bladder tumor classification, 5 patients had T2, 3 had T3, and 1 had T4 disease. All patients underwent surgical treatment, and 1 received 131I-MIBG therapy. All patients had paroxysmal hypertension and palpitation and six had cold sweat, headache, and dizziness after emphatic urination. The definitive diagnosis was made by histopathologic examination of the removed tumors and was confirmed in 7 cases by the immunohistochemical staining of chromogranin A, Ki-67 and S100 protein. The tumor consisted of discrete aggregates of zellballen cells separated by a network of vascular channels. One patient had metastases in the pelvic lymph nodes, liver and colon. Follow-up ranged from 7 to 289 months (mean, 127.2 ± 34.2). Six of the nine cases reported here were found in the usual locations. One patient had multiple tumors. The catecholamine level was elevated under basal conditions in 8 patients and during endoscopic resection of the tumor in 1 patient; it returned to normal after surgery in 8 patients. Three patients had recurrence and 1 had metastasis following surgery., Conclusions: Early preoperative diagnosis of FPUB is difficult, but it should be suspected in patients with typical tetrad symptoms: headache and micturition syncope, sweating, palpitation and hematuria. In those patients with unresectable multiple tumors, medicine and 131I-MIBG therapy may be helpful for controlling hypertension and delaying disease progression. Advanced classification (≥T3), multifocal tumors and CgA expression are risk factors of recurrence and metastasis.

Objective: To evaluate the application of nephron-sparing surgery (NSS) in the treatment of renal cell carcinoma (RCC)., Methods: The clinical data of 221 RCC patients who received nephron-sparing surgery were retrospectively reviewed. Open surgery was performed for 203 cases and laparoscopic surgery for 18 cases. The renal arteries were blocked and ice fragments were used for 115 patients. Biopsy was performed on renal tissue adjacent the tumor for 136 patients. After operation 156 patients were treated with interferon and interleukin II. Among these 221 patients, 132 patients (59.7%) were followed for 3-56 months (mean: 28 months)., Results: The mean distance from the edge of normal tissue to the tumor was 0.4 cm (0.2-1.0 cm). The mean volume of blood loss was 180 ml (50-1 000 ml). Pathological examination showed clear cell carcinoma (n = 195), chromophobe renal carcinoma (n = 12), papillary renal carcinoma (n = 7), cystic renal carcinoma (n = 6), and sarcomatoid clear cell carcinoma (n = 1). Biopsies in 136 patients showed negative results. Post-operative complications included leakage of urine (n = 1), hemorrhage or hematuria (n = 5), and infarction of blood vessel of lower limbs (n = 2). During the follow-up, no patients died for this reason, although tumor recurrence (n = 4, 1.8%) and metastasis (n = 3, 1.4%) were noted., Conclusion: NSS is a safe and effective method to treat carefully selected RCC patients.