Percutaneous microwave ablation on management of hereditary renal cell carcinoma in Von Hippel-Lindau disease.

BACKGROUND: The effect of microwave ablation (MWA) for the renal cell carcinoma (RCC) in Von Hippel-Lindau (VHL) disease is unclear. OBJECTIVE: To assess the safety, Technique efficacy, renal function and oncological outcome of MWA for RCC in VHL patients. METHODS: Consecutive patients with RCCs in VHL disease treated by MWA were retrospectively collected from November 2009 to October 2020. The technical efficacy rate and complications were assessed. The outcomes of pre- and post-ablative eGFR were compared. The local recurrent-free survival (LRFS), renal-cancer-free survival (RCFS), cancer-specific survival (CSS), overall survival (OS) and complications were presented. RESULTS: A total of 10 patients (mean age, 39.0 years ± 10.7 [SD]; 3 women) with 28 RCCs (mean tumor size, 3.0 cm ± 0.34; mean tumor volume, 20.7 mL ± 43.3) treated with MWA were included. Th median follow-up time was 52 months(IQR:27-80). The overall technical efficacy rate was 100% with no major complications occurred. No significant statistical difference between pre-ablative and postablative creatinine level (102.0 µmol/L ± 30.4 vs 112.3 µmol/L ± 38.7, p = 0.06), but the pre-ablative eGFR level was significantly higher than the post-ablative eGFR (78.0 mL/(min*1.73m2) ± 28.6 vs 72 mL/(min*1.73m2) ± 31.4, p = 0.04), with the mean decrease of 5.86 ml/(min*1.73m2). The local recurrent-free survival(LRFS) and renal-cancer-free survival (RCFS) were 100% and 60%, respectively. The cancer specifical survival (CSS) and overall survival (OS) were 95.5% and 100%, respectively. CONCLUSION: Microwave ablation is a safe and feasible method for the treatment of RCC in VHL disease, preserving renal function and yielding satisfactory oncological outcomes.

The crosstalk between NLRP3 inflammasome and gut microbiome in atherosclerosis.

Atherosclerosis (AS) is chronic pathological process based on the inflammatory reaction associated with factors including vascular endothelial dysfunction, inflammation, and autoimmunity. Inflammasomes are known to be at the core of the inflammatory response. As a pattern recognition receptor of innate immunity, the NLRP3 inflammasome mediates the secretion of inflammatory factors by activating the Caspase-1, which is important for maintaining the immune system and regulating the gut microbiome, and participates in the occurrence and development of AS. The intestinal microecology is composed of a large number of complex structures of gut microbiota and its metabolites, which play an important role in AS. The gut microbiota and its metabolites regulate the activation of the NLRP3 inflammasome. Targeting the NLRP3 inflammasome and regulating intestinal microecology represent a new direction for the treatment of AS. This paper systematically reviews the interaction between the NLRP3 inflammasome and gut microbiome in AS, strategies for targeting the NLRP3 inflammasome and gut microbiome for the treatment of AS, and provides new ideas for the research and development of drugs for the treatment of AS.

Henoch-Schönlein Purpura With Scrotal Involvement: A Case Report and Literature Review.

Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood and affects the small blood vessels, leading to arthritis, abdominal pain, and renal involvement. However, scrotal involvement is a rare complication of HSP and scrotal pain. Swelling is the most frequent clinical presentation and can be easily confused with testicular torsion. If not treated in time, the scrotal inflammation will result in irreversible testicular necrosis. We report a 6-year-old male with HSP and scrotal involvement, characterized by swelling and pain on the left side of the scrotum, rashes on both lower extremities, and epididymitis. He was treated with conservative care, corticosteroids, and antibiotic therapy. We were able to avoid surgical intervention. On the 10 days of treatment, he recovered sufficiently well and was discharged. We have reviewed the literature related to HSP with scrotal involvement, identified 21 cases, and revealed that steroid therapy and/or antibiotics are the first-line of therapy in children with scrotal involvement. Vasculitis in the scrotum may predispose to testicular torsion, which is a complication that should not be overlooked. Clinicians should be aware of the atypical types of HSP. Timely diagnosis and appropriate treatment are essential for achieving the best results.

Optimized hydrolysis and analysis of Radix Asparagi polysaccharide monosaccharide composition by capillary zone electrophoresis.

Using orthogonal design, optimized conditions for the hydrolysis of the polysaccharide from Radix Asparagi were determined, as well as its monosaccharide composition. Optimized hydrolysis conditions were a temperature of 100°C in 1.5 M sulfuric acid solution for 5 h. The resulting monosaccharides were derivatized with 1-phenyl-3-methyl-5-pyrazolone, then separated by capillary zone electrophoresis in 40 mM sodium tetraborate buffer (pH 10.1), and detected by ultraviolet absorption at 245 nm. Results indicate that the polysaccharide from Radix Asparagi is composed of xylose, arabinose, glucose, rhamnose, mannose, galactose, glucuronic acid, and galacturonic acid, which differs from published findings. Moreover, xylose, glucuronic acid, and galacturonic acid have not been previously reported in Radix Asparagi polysaccharide. This method is simple, fast, and yields a highly efficient separation. As well, these findings can be applied to quality control of Radix Asparagi and for in-depth study of the biological activity of Radix Asparagi polysaccharide.

Triglyceride-glucose index's link to cardiovascular outcomes post-percutaneous coronary intervention in China: a meta-analysis.

Percutaneous coronary intervention (PCI) addresses myocardial ischaemia, but a significant subset of patients encounter major adverse cardiovascular events (MACE) post-treatment. This meta-analysis investigated the relationship between the post-PCI triglyceride-glucose (TyG) index and MACE. Comprehensive searches of the Embase, PubMed, Cochrane Library, and Web of Science databases were conducted up to 3 March 2023, using relevant keywords. The effect size was determined based on I2 statistic using random-effects models. Cluster-robust standard errors crafted the dose-response curve, and the GRADE Evaluation Scale was employed to rate the quality of evidence. The group with the highest TyG index had significantly higher post-PCI MACE rates than the lowest index group, with hazard ratios (HRs) of 2.04 (95% CI 1.65-2.52; I2 = 77%). Each unit increase in TyG index corresponded to HRs of 1.82 for MACE (95% CI 1.34-2.46; I2 = 92%), 2.57 for non-fatal MI (95% CI 1.49-4.41; I2 = 63%), and 2.06 for revascularization (95% CI 1.23-3.50; I2 = 90%). A linear relationship between TyG index and MACE risk was established (R2 = 0.6114). For all-cause mortality, the HR was 1.93 (95% CI 1.35-2.75; I2 = 50%), indicating a higher mortality risk with elevated TyG index. The GRADE assessment yielded high certainty for non-fatal MI but low certainty for all-cause mortality, revascularization, and MACE. The TyG index may predict risks of post-PCI MACE, all-cause mortality, non-fatal MI, and revascularization, with varied levels of certainty. A potential linear association between the TyG index and MACE post-PCI was identified. Future research should validate these findings.

Microwave Ablation for Refractory Giant Maxillofacial Arteriovenous Malformation: A Case Report.

Maxillofacial arteriovenous malformation located in the sensitive parts of the nose and lips has been an arduous challenge for doctors to meet a balance between resection and aesthetics in one time. In this report, one patient with a giant arteriovenous malformation covering the forehead, the nose, the lip, and bilateral cheeks and resulting in the appearance of the face like a lion's face, can not meet satisfactory outcomes by other therapeutic methods. We successfully reduced the size of vascular lesion using low-power and short-duration microwave ablation under real-time ultrasound guidance. In the two-year follow-up, the patient's face almost recovered to normality. Microwave ablation is expected to be a new alternative therapy for the treatment of maxillofacial arteriovenous malformations. Laryngoscope, 133:2984-2987, 2023.

Polydatin protects against atherosclerosis by activating autophagy and inhibiting pyroptosis mediated by the NLRP3 inflammasome.

ETHNOPHARMACOLOGICAL RELEVANCE: Polydatin is a bioactive ingredient extracted from the roots of the Reynoutria japonica Houtt, and it is a natural precursor of resveratrol. Polydatin is a useful inhibitor of inflammation and acts as a regulator of lipid metabolism. However, the specific mechanisms of action of polydatin in atherosclerosis (AS) remains poorly explained. AIM OF THE STUDY: The aim of this study was to assess the efficacy of polydatin on inflammation induced by the inflammatory cell death and autophagy in AS. MATERIALS AND METHODS: Apolipoprotein E knockout (ApoE-/-) mice were fed with a high-fat diet (HFD) for 12 weeks to induce the formation of atherosclerotic lesions. The ApoE-/- mice were then randomly divided into the following six groups: (1) model group, (2) simvastatin group, (3) MCC950 group, (4) low dose polydatin group (Polydatin-L), (5) medium dose polydatin group (Polydatin-M), (6) and high dose polydatin group (Polydatin-H). The C57BL/6J mice were treated as controls and administered a standard chow diet. All mice were gavaged once daily for 8 weeks. The distribution of aortic plaques was observed by En Oil-red-O staining and hematoxylin and eosin staining (H&E). Oil-red-O staining was used to observe lipid content in the aortic sinus plaque; Masson trichrome staining was used to gauge collagen content in the plaque; and immunohistochemistry was used to evaluate smooth muscle actin (α-SMA) and CD68 macrophages marker expression levels in the plaque, which were used to assess the vulnerability index of the plaque. The lipid levels were measured using an enzymatic assay with an automatic biochemical analyzer. The level of inflammation was detected by enzyme-linked-immunosorbent assay (ELISA). Autophagosomes were detected by transmission electron microscopy (TEM). Pyroptosis was detected by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL)/caspase-1 and other proteins related to the expression levels of autophagy and pyroptosis were detected by Western blot analysis. RESULTS: Nucleotide oligomerization (NOD)-like receptor (NLR) family pyrin domain-containing protein 3 (NLRP3) inflammasome activation leads to pyroptosis, including the cleavage of caspase-1, interleukin (IL)-1ß and IL-18 production, and the co-expression of TUNEL/caspase-1-all of these are inhibited by polydatin, whose inhibitory effect is similar to that of MCC950, a specific inhibitor of NLRP3. Further, polydatin decreased the protein expression of NLRP3 and the phosphorylated mammalian target of rapamycin (p-mTOR), and increased the number of autophagosomes as well as the increased the cytoplasmic microtubule-associated protein light chain 3 (LC3)/autophagosome membrane-type LC3 ratio. Moreover, the protein expression levels of p62 decreased, suggesting that polydatin can increase autophagy. CONCLUSIONS: Polydatin can inhibit the activation of the NLRP3 inflammasome and cleavage of caspase-1, thereby inhibiting pyroptosis and secretion of inflammatory cytokines, and promoting autophagy through NLRP3/mTOR pathway in AS.

Dual-quenching electrochemiluminescence resonance energy transfer system from CoPd nanoparticles enhanced porous g-C3N4 to FeMOFs-sCuO for neuron-specific enolase immunosensing.

For the diagnosis and therapy of small cell lung cancer (SCLC), the accurate and sensitive determination of neuron-specific enolase (NSE) content is crucial. This work outlines a dual-quenching electrochemiluminescence resonance energy transfer (ECL-RET) immunosensor based on the double quenching effects of iron base metal organic frameworks (FeMOFs) loaded with small sized CuO nanoparticles (FeMOFs-sCuO) towards CoPd nanoparticles (CoPdNPs) enhanced porous g-C3N4 (P-C3N4-CoPdNPs). To be specific, we prepared a porous g-C3N4 (P-C3N4) which has a rich porous structure, and significantly increased the specific surface area and the number of reaction sites of P-C3N4. Meanwhile, the CoPdNPs were loaded onto P-C3N4 to improve the ECL luminescence property of P-C3N4/K2S2O8 system through acting as a coreaction accelerator. In addition, the ultraviolet-visible (UV-vis) absorption spectra of FeMOFs and small sized CuO nanoparticles (sCuO) showed considerable overlap with the ECL emission spectra of P-C3N4 appropriately. Therefore, FeMOFs with high specific surface area were prepared and well combined with sCuO to effectively dual-quenching the ECL emission of P-C3N4 based on resonance energy transfer. Hence, a new type ECL-RET couple made up of P-C3N4-CoPdNPs (donor) and FeMOFs-sCuO (acceptor) were developed for the first time. A certain amount of P-C3N4-CoPdNPs, Ab1, BSA, NSE were modified layer by layer onto the electrode surface. Then FeMOFs-sCuO-Ab2 bioconjugates was incubated through the immune recognition binding. As a result, a sandwich-type ECL biosensor was manufactured successfully for NSE immunoassay. Under optimal experimental conditions, the limit of detection (LOD) and the limit of quantitation (LOQ) of the prepared ECL sensor for NSE analysis was 20.4 fg mL-1 and 7.99 fg mL-1, respectively, with the relative standard deviation (RSD) of 1.68%. The linear detection range was 0.0000500-100 ng mL-1. The studied immunosensor had satisfactory sensitivity, specificity and reproducibility, manifesting the suggested sensing strategy might offer a good technical means and theoretical basis for the sensitivity analysis of NSE and has a potential application in clinical diagnosis analysis.

Coplanarity Constrained Ultrasound Probe Calibration Based on N-Wire Phantom.

OBJECTIVE: N-wire phantom-based ultrasound probe calibration has been used widely in many freehand tracked ultrasound imaging systems. The calibration matrix is obtained by registering the coplanar point cloud in ultrasound space and non-coplanar point cloud in tracking sensor space based on the least squares method. This method is sensitive to outliers and loses the coplanar information of the fiducial points. In this article, we describe a coplanarity-constrained calibration algorithm focusing on these issues. METHODS: We verified that the out-of-plane error along the oblique wire in the N-wire phantom followed a normal distribution and used it to remove the experimental outliers and fit the plane with the Levenberg-Marquardt algorithm. Then, we projected the points to the plane along the oblique wire. Coplanarity-constrained point cloud registration was used to calculate the transformation matrix. RESULTS: Compared with the other two commonly used methods, our method had the best calibration precision and achieved 25% and 36% improvement of the mean calibration accuracy than the closed-form solution and in-plane error method respectively at depth 16. Experiments at different depths revealed that our algorithm had better performance in our setup. CONCLUSION: Our proposed coplanarity-constrained calibration algorithm achieved significant improvement in both precision and accuracy compared with existing algorithms with the same N-wire phantom. It is expected that calibration accuracy will improve when the algorithm is applied to all other N-wire phantom-based calibration procedures.

Protective effects of paeoniflorin on cardiovascular diseases: A pharmacological and mechanistic overview.

Background and ethnopharmacological relevance: The morbidity and mortality of cardiovascular diseases (CVDs) are among the highest of all diseases, necessitating the search for effective drugs and the improvement of prognosis for CVD patients. Paeoniflorin (5beta-[(Benzoyloxy)methyl] tetrahydro-5-hydroxy-2-methyl-2,5-methano-1H-3,4-dioxacyclobuta [cd] pentalen-1alpha (2H)-yl-beta-D-glucopyranoside, C23H28O11) is mostly derived from the plants of the family Paeoniaceae (a single genus family) and is known to possess multiple pharmacological properties in the treatment of CVDs, making it a promising agent for the protection of the cardiovascular system. Aim of the study: This review evaluates the pharmacological effects and potential mechanisms of paeoniflorin in the treatment of CVDs, with the aim of advancing its further development and application. Methods: Various relevant literatures were searched in PubMed, ScienceDirect, Google Scholar and Web of Science. All eligible studies were analyzed and summarized in this review. Results: Paeoniflorin is a natural drug with great potential for development, which can protect the cardiovascular system by regulating glucose and lipid metabolism, exerting anti-inflammatory, anti-oxidative stress, and anti-arteriosclerotic activities, improving cardiac function, and inhibiting cardiac remodeling. However, paeoniflorin was found to have low bioavailability, and its toxicology and safety must be further studied and analyzed, and clinical studies related to it must be carried out. Conclusion: Before paeoniflorin can be used as an effective therapeutic drug for CVDs, further in-depth experimental research, clinical trials, and structural modifications or development of new preparations are required.

[Ablation of segmental glissonian pedicle by ultrasound-guided radiofrequency in precision liver resection in a porcine model].

OBJECTIVE: To demonstrate the ablation of segmental glissonian pedicle by ultrasound-guided radiofrequency in precision liver resection in porcine model. METHODS: The study was carried out on 6 Bama miniature pigs. Coagulative desiccation of the vessels feeding the segment to be resected was induced by introduction of a "cooled-tip" radiofrequency electrode under intraoperative ultrasound guidance at the level of the vessels. Then, an area of marked discoloration on the surface of the liver became obvious. Liver parenchymal transection followed without any form of hepatic inflow occlusion. Three segments (segment 3, 5, and 6) were resected on each pig. The criteria studied the local and general tolerance, the change of blood flow parameters of each segmental arterial and portal branches, and the microscopic appearance of the segmental arterial, portal and biliary tract branches. Using t test as the statistical methods. RESULTS: Postoperative mortality and morbidity were 0 and all serum parameters had normalized by 14 days. Demarcation area was obtained in 15 segments. The flow rate of the resected segmental portal branches was 0 cm/s after radiofrequency and the value of the arterial branches was (28 ± 18) cm/s which was significantly lower than pre-radiofrequency, which were (10.2 ± 3.0) cm/s and (60 ± 17) cm/s (t = 14.439, 5.502; P = 0.000). There was no significant difference in the flow rate of the remnant segmental arterial and portal branches among pre-radiofrequency, post-radiofrequency and 14 days after operation. On microscopic observation, the mean ablated length of segmental portal, arterial and biliary tract branches were (1.6 ± 0.4) cm, (1.2 ± 0.4) cm, and (1.7 ± 0.3) cm respectively. CONCLUSIONS: The ablation of the segmental glissonian pedicle by ultrasound-guided radiofrequency is quick, safe and effective. The probe needs to be away from vessels feeding segments 1.5 cm at least to avoid thermal injuries.

[Surgical management and outcome of solid-pseudopapillary tumor of pancreas: a series of 58 cases].

OBJECTIVE: To study the surgical management of solid-pseudopapillary tumor of the pancreas (SPTP) and its characteristics of outcome. METHODS: Fifty-eight patients with SPTP of the pancreas admitted from January 2001 to December 2010 were retrospectively analyzed. There were 7 male and 51 female patients, with an average age of 30 years (ranging 9 to 70 years). Most patients were symptomatic before admission; the most common symptom was abdominal pain. Of the 58 patients, 21 patients underwent pancreaticoduodenectomy, 30 patients underwent distal pancreatectomy, 6 patients underwent central pancreatectomy, 1 patient underwent simple tumor enucleation, and 1 patients underwent duodenum-preserving pancreatic head resection. RESULTS: The average length of stay in hospital was 23.8 days (ranging 12 to 64 days). Thirteen patients (22.4%) developed postoperative complications, including grade A postoperative pancreatic fistula of 8 cases, gastrointestinal tract bleeding of 1 case, pleural effusion of 2 cases, wound infection and fat liquefaction of 2 cases. Two patients underwent reoperation due to gastrointestinal tract bleeding or wound infection. There was no hospital death. Forty-four patients were followed-up for 7 to 136 months with an average of 41 months. All the 44 patients were alive, while 8 patients developed dyspepsia and 4 patients developed diabetes mellitus. There were no tumor recurrences or metastasis. CONCLUSIONS: SPTP is found primarily in young women. Excellent prognosis would be achieved with surgical resection.

Targets of statins intervention in LDL-C metabolism: Gut microbiota.

Increasing researches have considered gut microbiota as a new "metabolic organ," which mediates the occurrence and development of metabolic diseases. In addition, the liver is an important organ of lipid metabolism, and abnormal lipid metabolism can cause the elevation of blood lipids. Among them, elevated low-density lipoprotein cholesterol (LDL-C) is related with ectopic lipid deposition and metabolic diseases, and statins are widely used to lower LDL-C. In recent years, the gut microbiota has been shown to mediate statins efficacy, both in animals and humans. The effect of statins on microbiota abundance has been deeply explored, and the pathways through which statins reduce the LDL-C levels by affecting the abundance of microbiota have gradually been explored. In this review, we discussed the interaction between gut microbiota and cholesterol metabolism, especially the cholesterol-lowering effect of statins mediated by gut microbiota, via AMPK-PPARγ-SREBP1C/2, FXR and PXR-related, and LPS-TLR4-Myd88 pathways, which may help to explain the individual differences in statins efficacy.

Improvement of spinosad production by overexpression of gtt and gdh controlled by promoter PermE* in Saccharopolyspora spinosa SIPI-A2090.

Spinosyns A and D are novel macrolide secondary metabolites containing two deoxysugars. Each of the sugars is derived from a common intermediate, which is biosynthesized sequentially by NDP-glucose synthase and glucose dehydratase. Systematical duplication of gtt and gdh was carried out by genetic engineering in Saccharopolyspora spinosa. Introduction of additional gtt and gdh genes under the control of PermE* promoter showed significant increase on their transcript levels. The production of spinosad was increased by over threefold to reach 800 µg/ml in the recombinant strain SIPI-M2093.

Deciphering the Protein, Modular Connections and Precision Medicine for Heart Failure With Preserved Ejection Fraction and Hypertension Based on TMT Quantitative Proteomics and Molecular Docking.

Background: Exploring the potential biological relationships between heart failure with preserved ejection fraction (HFpEF) and concomitant diseases has been the focus of many studies for the establishment of personalized therapies. Hypertension (HTN) is the most common concomitant disease in HFpEF patients, but the functional connections between HFpEF and HTN are still not fully understood and effective treatment strategies are still lacking. Methods: In this study, tandem mass tag (TMT) quantitative proteomics was used to identify disease-related proteins and construct disease-related networks. Furthermore, functional enrichment analysis of overlapping network modules was used to determine the functional similarities between HFpEF and HTN. Molecular docking and module analyses were combined to identify therapeutic targets for HFpEF and HTN. Results: Seven common differentially expressed proteins (co-DEPs) and eight overlapping modules were identified in HFpEF and HTN. The common biological processes between HFpEF and HTN were mainly related to energy metabolism. Myocardial contraction, energy metabolism, apoptosis, oxidative stress, immune response, and cardiac hypertrophy were all closely associated with HFpEF and HTN. Epinephrine, sulfadimethoxine, chloroform, and prednisolone acetate were best matched with the co-DEPs by molecular docking analyses. Conclusion: Myocardial contraction, energy metabolism, apoptosis, oxidative stress, immune response, and cardiac hypertrophy were the main functional connections between HFpEF and HTN. Epinephrine, sulfadimethoxine, chloroform, and prednisolone acetate could potentially be effective for the treatment of HTN and HFpEF.

Potential mechanisms of Guizhi decoction against hypertension based on network pharmacology and Dahl salt-sensitive rat model.

BACKGROUND: Guizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore the potential mechanisms and therapeutic effects of GZD on hypertension by integrating network pharmacology and experimental validation. METHODS: The active ingredients and corresponding targets were collected from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from the CTD, GeneCards, OMIM and Drugbank databases. Multiple networks were constructed to identify the key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD against hypertension. RESULTS: A total of 112 active ingredients, 222 targets of GZD and 341 hypertension-related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets for experimental verification, including interleukin 6 (IL-6), C-C motif chemokine 2 (CCL2), IL-1ß, matrix metalloproteinase 2 (MMP-2), and MMP-9. Pathway enrichment analysis results indicated that 56 overlapping targets were mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, Toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD could bind tightly to the key targets. Experimental studies revealed that the administration of GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL-6, CCL2, IL-1ß, MMP-2 and MMP-9 in rats. CONCLUSION: The potential mechanisms and therapeutic effects of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis.

Overexpression of aveBIV leading to the improvement of 4'-epidaunorubicin production in Streptomyces coeruleorubidus strain SIPI-A0707.

The 4'-epidaunorubicin is the semisynthesis precursor of epirubicin which is a clinically useful antitumor drug thought to have slightly less cardiotoxicity than doxorubin. The 4'-epidaunorubicin was formed by overexpression of heterologous Streptomyces avermitilis aveBIV in Streptomyces coeruleorubidus SIPI-A0707 dnmV mutant blocked in the biosynthesis of daunosamine, the deoxysugar component of daunorubicin. But there was a low-yield production of 4'-epidaunorubicin. In our study, product yields were enhanced considerably by increasing aveBIV gene copy number or changing means of aveBIV integration. The 4'-epidaunorubicin titer was improved by around threefold in the recombinant strain DYG1006 with the aveBIV increased threefold copy numbers. The transcript levels of aveBIV gene meet the expectation of fermentation levels of 4'-epidaunorubicin. The method described here provides the means to produce 4'-epidaunorubicin efficiently on an industrial scale.

[Determinants of long-term survival after pancreaticoduodenectomy for ampulla of Vater carcinoma].

OBJECTIVE: To investigate the determinants of long-term survival for ampulla of Vater carcinoma treated by pancreaticoduodenectomy. METHODS: A total of 77 patients with ampulla of Vater carcinoma undergoing pancreaticoduodenectomy were reviewed. Kaplan-Meier method was used to analyze the survival rate. Independent t test was used for statistical comparison and COX regression model for multivariate analysis. RESULTS: No patient died as a result of surgery. The overall 5-year survival was 40.7%. Univariate analysis showed that perioperative serum carcinoembryonic antigen (CEA) level (P = 0.012), tumor invasion depth (P = 0.000), UICC stage (P = 0.000) and tumor size (P = 0.001) were significant prognostic factors of ampulla of Vater carcinoma; in multivariate analysis, only the tumor size (P = 0.000) was an independent prognostic factor of ampulla of Vater carcinoma. CONCLUSION: Pancreaticoduodenectomy is associated with significant survival. Tumor size is the most important influencing factor of outcome after pancreaticoduodenectomy; in addition, perioperative serum CEA level, tumor invasion depth and UICC stage may also influence the survival rate, there exists a need for further follow-up studies.

Xiao-Qing-Long Tang Prevents Cardiomyocyte Hypertrophy, Fibrosis, and the Development of Heart Failure with Preserved Ejection Faction in Rats by Modulating the Composition of the Gut Microbiota.

BACKGROUND: Changes in the gut microbiota are associated with cardiovascular disease progression. Xiao-Qing-Long Tang (XQLT), a traditional herbal formula, has an anti-inflammatory effect and regulates the steady state of the immune system, which is also associated with the progression of heart failure with preserved ejection faction (HFpEF). In this study, we investigated whether XQLT could contribute to prevent the development of HFpEF and whether the modulation of the gut microbiota by this herbal formula could be involved in such effect. METHODS: The gut microbiota, SCFAs, the histology/function of the heart, and systolic blood pressure were examined to evaluate the effect of XQLT on the gut microbiota and the progression of HFpEF after oral administration of XQLT to model rats. Furthermore, we evaluated, through fecal microbiota transplantation experiments, whether the favorable effects of XQLT could be mediated by the gut microbiota. RESULTS: Oral administration of XQLT contributed to the reduction of elevated blood pressure, inflammation, and compensatory hypertrophy, features that are associated with the progression of HFpEF. The gut microbiota composition, SCFA levels, and intestinal mucosal histology were improved after treatment with XQLT. Moreover, fecal transfer from XQLT-treated rats was sufficient to prevent the progression of HFpEF. CONCLUSIONS: These data suggested that XQLT prevented the development of HFpEF in model rats by regulating the composition of the gut microbiota.