A dereplication strategy for identifying triterpene acid analogues in Poria cocos by comparing predicted and acquired UPLC-ESI-QTOF-MS/MS data.

INTRODUCTION: Triterpene acids from the dried sclerotia of Poria cocos (Schw.) Wolf (poria) were recently found to possess anti-cancer activities. Identification of more triterpene acid analogues in poria is worthwhile for high throughput screening in anti-cancer drug discovery. OBJECTIVE: To establish an efficient dereplication strategy for identifying triterpene acid analogues in poria based on ultra-performance liquid chromatography with electrospray ionisation quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-QTOF-MS/MS). METHODOLOGY: The structural characteristics and mass spectrometric data profiles of known triterpene acids previously reported in poria were used to establish a predicted-analogue database. Then, the quasi-molecular ions of components in a poria extract were automatically compared with those in the predicted-analogue database to highlight compounds of potential interest. Tentative structural identification of the compounds of potential interest and discrimination of isomers were achieved by assessing ion fragmentation patterns and chromatographic behaviour prediction based on structure-retention relationship. RESULTS: A total of 62 triterpene acids were unequivocally or tentatively characterised from poria, among which 17 triterpene acids were tentatively identified for the first time in poria. CONCLUSION: This study provided more structure information of triterpene acids in poria for future high throughput screening of anti-cancer candidates. It is suggested that this semi-automated approach in which MS data are automatically compared to a predictive database may also be applicable for efficient screening of other herbal medicines for structural analogues of proven bioactives.

[Thought and method of classic formulae in treatment of chronic cough].

Chronic cough is a common clinical disease with complex etiology, which is easily misdiagnosed and mistreated. Chronic cough guideline has been developed based on the modern anatomical etiology classification, and it may improve the level of diagnosis and treatment. Common causes of chronic cough are as follows: cough variant asthma, upper airway cough syndrome, eosinophilic bronchitis, gastroesophageal reflux-related cough, post-infectious cough, etc. There is a long history and rich experience in treatment of cough in traditional Chinese medicine which is characterized by syndrome differentiation. The four elements of pathogenesis for chronic cough include wind, phlegm, fire, and deficiency. Classic formula is widely used in the treatment of chronic cough, and the focus is on prescriptions corresponding to syndromes. This article attempts to explore the thought and method of classic formulae in treatment of chronic cough based on three perspectives: differentiation of etiology, pathogenesis and formula-syndrome. Three medical cases are selected at last in order to prove its correction.

Risk factors for and causes and treatment of recurrence of inferior vena cava type of Budd-Chiari syndrome after stenting in China: A retrospective analysis of a large cohort.

OBJECTIVES: To explore the risk factors for recurrence of inferior vena cava (IVC)-type Budd-Chiari syndrome (BCS) after stenting and evaluate the feasibility and primary outcomes of endovascular therapies for recurrent BCS. METHODS: A retrospective analysis of 219 patients was performed to identify risk factors for recurrence. The images of the recurrent patients during follow-up duration and interventional surgery were also reviewed to find the possible reasons of recurrence. The outcome of endovascular therapies for recurrent BCS was evaluated by Kaplan-Meier analysis. RESULTS: Among the 219 patients, 172 patients with primary IVC-type BCS underwent stenting and 28 patients experienced recurrence. Multivariate analysis identified age, Child-Pugh score, MELD and total bilirubin as independent recurrent indicators. Possible causes of recurrence include thrombosis in the stent, re-obstruction in or above the stent, and stent-related hepatic vein obstruction. Twenty-five patients with recurrent BCS underwent endovascular therapies with a few complications and achieved a high level of short- and mid-term patency. CONCLUSION: Age, total bilirubin and severity of liver function are the main risk factors for BCS recurrence. These risks might contribute to thrombosis or subsequent fibrous obstruction. Endovascular therapies are effective and safe management options that yield positive outcomes for recurrent BCS. KEY POINTS: • Risk factors for recurrent Budd-Chiari syndrome were identified by multivariate analysis. • Causes of recurrent Budd-Chiari syndrome were investigated by assessing radiological images. • There is a correlation between risk factors and causes of recurrence. • Endovascular therapies for recurrent Budd-Chiari syndrome are effective and safe.

[Endovascular therapy of superior mesenteric artery embolism].

OBJECTIVE: To explore the safety and immediate efficacy of endovascular treatment for superior mesenteric artery embolism. METHODS: From November 2007 to October 2012, 18 cases of superior mesenteric artery embolism were treated by thrombus extraction and/or catheter-directed thrombolysis. There were 13 males and 5 females with an age range of 44-91 years. The concurrent conditions included atrial fibrillation (n = 8) and rheumatic valve disease (n = 3). All diagnoses were made with abdominal enhanced computed tomography (CT) examination. Embolism was predominantly located at 3 to 10 cm away from opening. The procedures included thrombus extraction plus system thrombosis (n = 3), thrombus extraction and catheter-directed thrombolysis (n = 6), catheter-directed thrombolysis (n = 5) and thrombus extraction, catheter-directed thrombolysis and PTA (n = 2). RESULTS: The technical success rate was 100%. Two cases had new embolism in popliteal artery. Another case with peritoneal irritation syndrome died after automatic discharge. The other 17 patients obtained satisfactory results and were followed up after 6 months by color Doppler ultrasound or abdominal enhanced CT. It showed that superior mesenteric arteries were unobstructed, but local stenosis occurred in 2 cases. CONCLUSION: Endovascular interventional therapy is both safe and efficacious in the treatment of superior mesenteric artery embolization. And its immediate effect is satisfactory.

[Analysis of cause and treatment of acute limb ischemia complicated in peripheral endovascular interventions].

OBJECTIVE: To discuss the cause and treatment of acute limb ischemia in endovascular therapy of the lower extremity arterial occlusive disease. METHODS: Clinical data of 54 cases of acute limb ischemia in the endovascular treatment of 685 cases of lower extremity arterial occlusive disease from June 2003 to April 2012 was analyzed retrospectively. There were 43 male and 11 female patients, with a mean age of 72.3 years (ranging from 56 to 82 years). The major causes which resulted in acute limb ischemia included: arterial embolization of 43 cases, arterial thrombosis of 8 cases, arterial dissection of 3 cases. The acute limb ischemia occurred in the process of balloon angioplasty/stent in 36 cases, catheter-directed thrombolysis in 17 cases, Silverhawk atherectomy in 1 cases. Thirty-two cases were treated by endovascular treatment, 9 cases by surgical procedures (bypass or embolectomy), 13 cases by the combination of endovascular therapy and surgical procedures. RESULTS: Treatment were successfully accomplished in 50 of 54 cases, and failed in 4 cases which had surgical amputation. There were no deaths in all the patients. Forty-five of 54 cases were followed up for the average of 40.3 months. Six cases had ischemic symptoms recurrence in 43 artery embolization patients, in whom 4 cases were cured by endovascular treatment, 2 cases were cured by toe amputation. One case of bypass anastomotic stenosis and one case of stent restenosis were successfully cured by endovascular treatment in 8 arterial thrombosis patients. One cases of below-knee artery stent occlusion in 3 arterial dissection patients was cured by medical treatment. Four cases of amputation patients were followed up in good condition. CONCLUSIONS: Most patients of acute limb ischemia complicated in endovascular therapy could be treated by endovascular therapy. Surgical procedures in time is still the best choice for the patients in whom the endovascular therapy was not satisfied.

A novel method for assessing cardiac function in patients with coronary heart disease based on wrist pulse analysis.

BACKGROUND: The timely assessment of B-type natriuretic peptide (BNP) marking chronic heart failure risk in patients with coronary heart disease (CHD) helps to reduce patients' mortality. OBJECTIVE: To evaluate the potential of wrist pulse signals for use in the cardiac monitoring of patients with CHD. METHODS: A total of 419 patients with CHD were assigned to Group 1 (BNP < 95 pg/mL, n = 249), 2 (95 < BNP < 221 pg/mL, n = 85), and 3 (BNP > 221 pg/mL, n = 85) according to BNP levels. Wrist pulse signals were measured noninvasively. Both the time-domain method and multiscale entropy (MSE) method were used to extract pulse features. Decision tree (DT) and random forest (RF) algorithms were employed to construct models for classifying three groups, and the models' performance metrics were compared. RESULTS: The pulse features of the three groups differed significantly, suggesting different pathological states of the cardiovascular system in patients with CHD. Moreover, the RF models outperformed the DT models in performance metrics. Furthermore, the optimal RF model was that based on a dataset comprising both time-domain and MSE features, achieving accuracy, average precision, average recall, and average F1-score of 90.900%, 91.048%, 90.900%, and 90.897%, respectively. CONCLUSIONS: The wrist pulse detection technology employed in this study is useful for assessing the cardiac function of patients with CHD.

Gut Microbiota Mediates the Protective Effects of Traditional Chinese Medicine Formula Qiong-Yu-Gao against Cisplatin-Induced Acute Kidney Injury.

Our previous study found that Qiong-Yu-Gao (QYG), a traditional Chinese medicine formula derived from Rehmanniae Radix, Poria, and Ginseng Radix, has protective effects against cisplatin-induced acute kidney injury (AKI), but the underlying mechanisms remain unknown. In the present study, the potential role of gut microbiota in the nephroprotective effects of QYG was investigated. We found that QYG treatment significantly attenuated cisplatin-induced AKI and gut dysbiosis, altered the levels of bacterial metabolites, with short-chain fatty acids (SCFAs) such as acetic acid and butyric acid increasing and uremic toxins such as indoxyl sulfate and p-cresyl sulfate reducing, and suppressed histone deacetylase expression and activity. Spearman's correlation analysis found that QYG-enriched fecal bacterial genera Akkermansia, Faecalibaculum, Bifidobacterium, and Lachnospiraceae_NK4A136_group were correlated with the altered metabolites, and these metabolites were also correlated with the biomarkers of AKI, as well as the indicators of fibrosis and inflammation. The essential role of gut microbiota was further verified by both the diminished protective effects with antibiotics-induced gut microbiota depletion and the transferable renal protection with fecal microbiota transplantation. All these results suggested that gut microbiota mediates the nephroprotective effects of QYG against cisplatin-induced AKI, potentially via increasing the production of SCFAs, thus suppressing histone deacetylase expression and activity, and reducing the accumulation of uremic toxins, thereby alleviating fibrosis, inflammation, and apoptosis in renal tissue. IMPORTANCE Cisplatin-induced acute kidney injury is the main limiting factor restricting cisplatin's clinical application. Accumulating evidence indicated the important role of gut microbiota in pathogenesis of acute kidney injury. In the present study, we have demonstrated that gut microbiota mediates the protective effects of traditional Chinese medicine formula Qiong-Yu-Gao against cisplatin-induced acute kidney injury. The outputs of this study would provide scientific basis for future clinical applications of QYG as prebiotics to treat cisplatin-induced acute kidney injury, and gut microbiota may be a promising therapeutic target for chemotherapy-induced nephrotoxicity.

Protective effects of Poria cocos and its components against cisplatin-induced intestinal injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos (Schw.) Wolf (Poria) is a well-known traditional medicinal fungus. It has been considered to possess spleen-invigorating (Jianpi) effects in traditional Chinese medicine, and is used clinically to treat spleen deficiency (Pixu) with symptoms of intestinal disorders such as diarrhea, indigestion, mucositis and weight loss. THE AIM OF THIS STUDY: To investigate the protective effects of Poria and its three component fractions (Water-soluble polysaccharides, WP; alkali-soluble polysaccharides, AP; triterpene acids, TA) on cisplatin-induced intestinal injury and explore the underlying mechanisms. MATERIALS AND METHODS: C57BL/6 mice were treated with Poria powder (PP), WP, AP and TA by oral gavage respectively for 13 days, and intraperitoneally injected with 10 mg/kg of cisplatin on day 10 to conduct a cisplatin-induced intestinal injury model. Pathological changes of ileum and colon were examined using H&E staining. The composition of gut microbiota and the alteration of host metabolites were characterized by 16S rDNA amplicon sequencing and UPLC-QTOF-MS/MS based untargeted metabolomics analysis. RESULTS: PP and WP attenuated the cisplatin-induced ileum and colon injury, and WP alleviated the weight loss and reversed the elevation of IL-2, IL-6 in serum. Both PP and WP could mitigate cisplatin-induced dysbiosis of gut microbiota, in particular PP and WP decreased the abundance of pathogenic bacteria including Proteobacteria, Cyanobacteria, Ruminococcaceae and Helicobacteraceae, while WP promoted the abundance of probiotics, such as Erysipelotrichaceae and Prevotellaceae. Moreover, WP attenuated the cisplatin-induced alteration of metabolic profiles. The levels of potential biomarkers, including xanthine, L-tyrosine, uridine, hypoxanthine, butyrylcarnitine, lysoPC (18:0), linoleic acid, (R)-3-hydroxybutyric acid, D-ribose, thiamine monophosphate, indolelactic acid and plamitic acid, showed significant correlations with intestinal flora. CONCLUSIONS: PP and WP possess protective effects against cisplatin-induced intestinal injury via potentially regulating the gut microbiota and metabolic profiles.

[Studies on the chemical constituents from Cissus assamica].

OBJECTIVE: To study the chemical constituents from Cissus assamica and obtain a more comprehensive understanding of its effective components. METHODS: Compounds were isolated by various column chromatographies with silica gel. Their structures were elucidated by spectral analysis (IR, MS, 1H-NMR, 13C-NMR) and chemical evidence. RESULTS: Eight compounds were isolated and elucidated as ursolic acid (I), lupeol (II), n-hexacosinc acid (III), isolariciresinol-9-O-beta-D-glucopyranoside (IV), dauco sterin (V), 3,3'-dimethyl ellagic acid (VI), beta-Sitosterol (VII), bergenin (VIII). CONCLUSION: Among these compounds, I-V are isolated from this plant for the first time.

Pathophysiologic Mechanisms And Management Of Large Granular Lymphocytic Leukemia Associated Pure Red Cell Aplasia.

Large granular lymphocytic leukemia (LGLL) is a chronic clonal lymphoproliferative disease of mature T or NK cells, and produces a variety of hematological abnormalities. Pure red cell aplasia (PRCA) is a rare haematological disease and is one of the most common complications of LGLL. LGLL-associated PRCA may represent a relatively indolent type and may be more common than reported, but its natural history and clinical course have not been well described. The ethnic origin of the patients is an important consideration in determining the relationship between PRCA and LGLL. Guidelines and progresses for management of LGLL-associated PRCA rely on accumulation of empirical experiences, integrative analyses of several cases and clinical trials. The purpose of this review is to evaluate occurrence, possible mechanisms, diagnosis, clinical features, treatments and outcomes of LGLL-associated PRCA.

Chemical markers for quality control of bran-fried sulfur-fumigated Paeoniae Radix Alba.

In traditional Chinese medicine practice, crude herbs are often subjected to traditional processing (Paozhi in Chinese) for a special medicinal purpose. Bran-frying is one of processing methods for Paeoniae Radix Alba (PRA). Previous studies found that paeoniflorin and paeoniflorin sulfonate, a principle bioactive compound and its sulfur-fumigation induced characteristic sulfur-containing derivative, could be used together with sulfur dioxide residue as chemical markers for the quality control of sulfur-fumigated PRA crude material. In this paper, the feasibility of these three markers used for the quality control of bran-fried sulfur-fumigated PRA was further investigated. First, homemade samples of sulfur-fumigated PRA with different sulfur-fumigation duration (0.5-6 h) were bran-fried, and stored for 12 months. Second, the contents of sulfur dioxide residue, paeoniflorin and paeoniflorin sulfonate were dynamically quantified respectively. Third, the variation of the marker contents and their correlation during bran-frying and storage was evaluated. A validation was conducted using commercial bran-fried PRA samples. The results showed that bran-frying caused an averaged reduction of 20% in the content of sulfur dioxide residue, and during the first two months of storage the content of sulfur dioxide residue was decreased by up to 27%, then the content was tending towards stability for the subsequent ten months of storage (RSD = 3.92%). Meanwhile, paeoniflorin and paeoniflorin sulfonate were relatively stable, the contents of which were not affected by bran-frying processing and 12 months of storage. The correlations between the contents of sulfur dioxide residue and paeoniflorin/paeoniflorin sulfonate were obviously influenced by storage duration. Since sulfur dioxide residue is a safety marker, while paeoniflorin and paeoniflorin sulfonate can reflect the inner quality and the impact extent of sulfur-fumigation on the quality of bran-fried PRA respectively, these three chemicals might be used together as markers for the quality control, and consequently to ensure the safety and efficacy of bran-fried PRA.

T-cell large granular lymphocytic leukemia associated with renal cell carcinoma: A case report.

RATIONALE: T-cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative neoplasm of cytotoxic T cells and renal cell carcinoma (RCC) is the most common form of kidney cancer, but T-LGLL associated with RCC has never been reported. PATIENT CONCERNS: A 58-year-old Chinese male presented with general fatigue and intermittent-remittent fever, accompanied by palpitations and dizziness. DIAGNOSIS: Radical nephrectomy was performed, and a diagnosis of clear cell carcinoma (T1N0M0, I phase) was made based on the postoperative pathology findings. With typical cellular morphology, immunophenotype and T-cell receptor gene rearrangement, a diagnosis of T-LGLL was established. INTERVENTIONS: After radical nephrectomy, this patient remained asymptomatic without any treatment. OUTCOMES: To date, the patient is generally in good condition, without complaints of discomfort. LESSONS: The coexistence of these 2 entities may not be coincidental, and it is likely that they may share a common pathogenic pathway related to immune dysregulation.

Large granular lymphocytosis after transplantation.

Post-transplant lymphoproliferative disorders (PTLD) represent a heterogeneous group of diseases that occur following transplantation. Large granular lymphocytic (LGL) lymphocytosis is one type of PTLD, ranging from reactive polyclonal self-limited expansion to oligo/monoclonal lymphocytosis or even to overt leukaemia. LGL lymphocytosis in transplant recipients may present as a relatively indolent version of the condition and may be more common than reported, but its natural history and clinical course have not been well described, and the lack of a reliable classification system has limited studies on this disease. Patients with unexplained cytopenias, autoimmune manifestations, or unexpected remissions may be mislabelled. The purpose of this review was to evaluate the clinical features, immunophenotypes, etiopathogenesis, diagnosis, outcomes and treatment of post-transplantation LGL lymphocytosis. In conclusion, LGL lymphocytosis is a frequent occurrence after transplantation that correlates with certain procedural variables and post-transplant events. LGL lymphocytosis should be considered in patients with unexplained lymphocytosis or when pancytopenia develops after transplantation. The diagnosis of LGL lymphocytosis requires a demonstration of monoclonality, but clonality does not indicate malignancy. Additional studies are necessary to further delineate the potential effects of large granular lymphocytes in the long-term prognosis of post-transplant patients.

Paeonifiorin sulfonate as a characteristic marker for specifically inspecting Chinese patent medicine Liu-Wei-Di-Huang-Wan contained sulfur-fumigated Moutan Cortex.

Sulfur fumigation can induce chemical transformation of bioactive components, consequently the alteration of bioactivities or even toxicities of medicinal herbs. Inspecting Chinese patent medicines (CPM) contained sulfur-fumigated constituent herbs is crucial for ensuring the safety and efficacy of CPM. Paeonifiorin sulfonate is a sulfur-fumigation induced compound of Moutan Cortex (MC), one of the main constituent herbs of a commonly used CPM Liu-Wei-Di-Huang-Wan (LWDHW). Herein, we investigated the approach of paeonifiorin sulfonate as a characteristic marker for specifically inspecting LWDHW potentially contained sulfur-fumigated MC (SFMC). First, mimic LWDHW samples contained SFMC (SFMC-LWDHW) and non-fumigated MC (NFMC-LWDHW) were prepared respectively. Second, an LC-MS method was developed and validated to qualitatively and quantitatively determine paeonifiorin sulfonate in the mimic LWDHW samples. Third, the established method was applied to analyze the commercial LWDHW samples. The results showed that paeoniflorin sulfonate could only be detectable in SFMC-LWDHW, but not in NFMC-LWDHW samples. The CPM matrix could enhance the response of paeoniflorin sulfonate in mass spectrometry analysis. In addition, the LOQ, linearity, precision, accuracy and stability were also demonstrated to be acceptable for quantifying paeoniflorin sulfonate in LWDHW. Commercial samples analysis indicated that paeoniflorin sulfonate were detectable in 9 of 10 commercial LWDHW samples, with the content varied between 105.53µg/g and 438.61µg/g. All the results suggested that paeoniflorin sulfonate could be used as a characteristic and reliable chemical marker for specifically inspecting commercial LWDHW contained SFMC. This study also provides a new strategy for the quality control of other CPMs potentially produced from sulfur-fumigated constituent herbs.

Efficacy and safety of Re-Du-Ning injection in the treatment of seasonal influenza: results from a randomized, double-blinded, multicenter, oseltamivir-controlled trial.

OBJECTIVE: To assess the efficacy and safety of RDNI in the treatment of seasonal influenza. RESULTS: 1575 participants were screened and 229 completed the study and had a RT-PCR laboratory confirmation of influenza virus infection. Fever alleviation time was 2 and 6 hours, and fever clearance time was 27 and 47 in RDNI and oseltamivir, with significant difference between two groups. Total scores of influenza symptoms descended more in RDNI than oseltamivir on day 2 and day 3. Single symptom such as fever, aversion to cold, sore throat and nasal obstruction score descended more in RDNI than oseltamivir on different days. 20 subjects used aspirin during the trial, and there was no significant difference between two groups. MATERIALS AND METHODS: We conducted a randomized, double-blind, double-dummy, oseltamivir controlled clinical trial. Patients with a positive influenza rapid test diagnosis were enrolled and randomized to receive RDNI or oseltamivir. Primary outcome was the median fever alleviation and clearance time. Secondary outcomes were total 8 influenza symptom scores, the single influenza symptom score, and the frequency of aspirin usage. CONCLUSIONS: The effect of RDNI was not worse than oseltamivir on the alleviation of influenza symptoms. RDNI was well tolerated, with no serious adverse events noted during the study period.