A Joint Model Based on Post-Treatment Longitudinal Prognostic Nutritional Index to Predict Survival in Nasopharyngeal Carcinoma.

BACKGROUND: a low PNI in patients with NPC is linked to poor survival, but prior studies have focused on single-timepoint measurements. Our study aims to employ joint modeling to analyze longitudinal PNI data from each routine visit, exploring its relationship with overall survival. METHODS: In this retrospective study using data from the Chang Gung Research Database (2007-2019), we enrolled patients with NPC undergoing curative treatment. We analyzed the correlation between patient characteristics, including the PNI, and overall survival. A joint model combining a longitudinal sub-model with a time-to-event sub-model was used to further evaluate the prognostic value of longitudinal PNI. RESULTS: A total of 2332 patient were enrolled for the analysis. Separate survival analyses showed that longitudinal PNI was an independent indicator of a reduced mortality risk (adjusted HR 0.813; 95% CI, 0.805 to 0.821). Joint modeling confirmed longitudinal PNI as a consistent predictor of survival (HR 0.864; 95% CI, 0.850 to 0.879). An ROC analysis revealed that a PNI below 38.1 significantly increased the risk of 90-day mortality, with 90.0% sensitivity and 89.6% specificity. CONCLUSIONS: Longitudinal PNI data independently predicted the overall survival in patients with NPC, significantly forecasting 90-day survival outcomes. We recommend routine PNI assessments during each clinic visit for these patients.

[Chemical composition and antioxidant activity of different parts of Prunella vulgaris by UPLC-Q-TOF-MS/MS and UPLC].

Prunellae Spica is the dried spica of Prunella vulgaris belonging to Labiatae and it is widely used in pharmaceutical and general health fields. As a traditional Chinese medicine cultivated on a large scale, it produces a large amount of non-medicinal parts, which are discarded because they are not effectively used. To analyze the chemical constituents in the different samples from spica, seed, stem, and leaf of P. vulgaris, and explore the application value and development prospect of these parts, this study used ultrahigh performance liquid chromatography-tandem quadrupoles time of flight mass spectrometry(UPLC-Q-TOF-MS/MS) to detect chemical constituents in different parts of P. vulgaris. As a result, 117 compounds were detected. Among them, 87 compounds were identified, including 32 phenolic acids, 8 flavonoids, and 45 triterpenoid saponins. Some new triterpenoid saponins containing the sugar chain with 4-6 sugar units were found. Further, multivariate statistical analysis was conducted on BPI chromatographic peaks of multiple batches of different parts, and the results showed that spica had the most abundant chemical constituents, including salviaflaside and linolenic acid highly contained in the seed and phenolic acids, flavonoids, and triterpenoid saponins in the stem and leaf. In general, the constituents in the spica were composed of those in the seed, stem, and leaf. UPLC was used to determine the content of 6 phenolic acids(danshensu, protocatechuic acid, protocatechuic aldehyde, caffeic acid, salviaflaside, and rosmarinic acid) in different parts. The content of other phenolic acids in the seed was generally lower than that in the spica except that of salviaflaside. The content of salviaflaside in the spica was higher than that in the stem and leaf, but the content of other phenolic acids in the spica was not significantly different from that in the stem. The content of protocatechuic aldehyde and caffeic acid in the spica was lower than that in the leaf. DPPH free radical scavenging method was used to detect the antioxidant activity of four parts, and there was no significant difference in the antioxidant activity between the spica and the stem and leaf, but that was significantly higher than the seed. Moreover, the antioxidant activity of these parts was correlated with the content of total phenolic acids. Based on the above findings, the stem and leaf of P. vulgaris have potential application value. Considering the traditional medication rule, it is feasible to use the whole plant as a medicine. Alternatively, salviaflaside, occurring in the seed, can be used as a marker compound for the quality evaluation of Prunellae Spica, if only using spica as the medicinal part of P. vulgaris, as described in the Chinese Pharmacopoeia(2020 edition).

Optimization of Extraction and Separation Process of Notoginsenoside Fc from Panax notoginseng Leaves.

Response surface methodology (RSM) was used to determine the optimal conditions for ultrasound-assisted extraction (UAE) of Notoginsenoside Fc (Fc) from panax notoginseng leaves. The experiment utilized a Box-Behnken design (BBD) and separation conditions were optimized. The optimum extraction conditions were as follows: extraction time = 1.5 h, ethanol concentration = 86%, liquid-to-solid ratio = 19:1. The experimentally obtained values were in accordance with the values predicted by the RSM model. We determined that the RSM model was able to successfully simulate the optimal extraction of Fc from the leaves. Further, Fc was enriched from Panax notoginseng through nine macroporous resins, and HPD-100 macroporous resins were selected for preliminary enrichment of Fc due to its economic costs and benefits. Subsequently, octadecyl silane (ODS) column chromatography was used to improve the purity of Fc to over 90% after separation by ODS column chromatography. Fc with a purity greater than 95% can be obtained by recrystallization. This is the first study that has focused on the extraction and enrichment of Fc from Panax notoginseng leaves using macroporous resin combined with ODS column chromatography, which provides the possibility for further application of Fc.

Antimicrobial secondary metabolites from an endophytic fungus Aspergillus polyporicola.

Two new nucleoside derivatives, kipukasins O (1) and P (2), one new cyclohexenone derivative, arthropsadiol D (5), and one new natural product, (+)-2,5-dimethyl-3(2H)-benzofuranone (6), together with eleven known compounds (3, 4, 7-15), were obtained from the culture broth of the endophytic fungus Aspergillus polyporicola R2 isolated from the roots of Synsepalum dulcificum. Among them, the absolute configuration of compound 5 was determined by quantum chemical calculations of NMR chemical shifts and ECD spectrum. The antimicrobial activities of these compounds were evaluated. Compound 11 exhibited obvious inhibitory activity against MRSA, Staphylococcus aureus, Salmonella typhimurium, Botrytis cinerea, and Fusarium graminearum with MIC values of 4, 4, 4, 32, and 16 µg/mL, respectively. Compound 12 exhibited antibacterial activity against S. typhimurium and MRSA with MIC values of 4 and 16 µg/mL. Compound 6 exhibited antifungal activity against F. graminearum with MIC value of 32 µg/mL.

New paeonol derivative C302 reduces hypertension in spontaneously hypertensive rats through endothelium-dependent and endothelium-independent vasodilation.

Hypertension is a major risk factor for cardiovascular disease and Chinese herb monomers could provide new structural skeletons for anti-hypertension new drug development. Paeonol is a Chinese herbal monomer extracted from Cortex moutan, exhibited some anti-hypertensive activity. The study focused on the structural optimization of paeonol to provide promising lead compounds for anti-hypertension new drug development. Herein, twelve new paeonol derivatives (PD) were designed and synthesized and their vasodilation activity was evaluated by in vitro vasodilation drug screening platform based on Myograph. Its anti-hypertension activity, PD-C302 (2-hydroxy-4-methoxyvalerophenone) as a representative with the optimal vasodilation activity, was determined by its response to blood pressure in spontaneously hypertensive rats (SHR) in vivo. Moreover, its molecular mechanism was probed by the vasodilation activity of rat superior mesenteric artery rings with or without endothelium pre-contracted by potassium chloride (KCl) or phenylephrine hydrochloride (PE). It was indicated that PD-C302 significantly reduced the blood pressure in SHR, which would involve in PD-C302-induced vasodilation. Furthermore, endothelium-dependent pathways and endothelium-independent pathways both contributed importantly to PD-C302-induced vasodilation at low concentration of PD-C302. Endothelium-independent pathways (vascular smooth muscle cell-mediated vasodilation), were mainly responsible for the PD-C302-induced vasodilation at high concentration of PD-C302, which involved in opening multiple K+ channels to restrain Ca2+ channels, and then triggered vasodilation to reduce blood pressure. PD-C302 has a simple structure and favorable anti-hypertensive activity in vivo, which could be a promising lead compound for anti-hypertension new drug development.

Exploring the genes involved in biosynthesis of dihydroquercetin and dihydromyricetin in Ampelopsis grossedentata.

Dihydroquercetin (DHQ), an extremely low content compound (less than 3%) in plants, is an important component of dietary supplements and used as functional food for its antioxidant activity. Moreover, as downstream metabolites of DHQ, an extremely high content of dihydromyricetin (DHM) is up to 38.5% in Ampelopsis grossedentata. However, the mechanisms involved in the biosynthesis and regulation from DHQ to DHM in A. grossedentata remain unclear. In this study, a comparative transcriptome analysis of A. grossedentata containing extreme amounts of DHM was performed on the Illumina HiSeq 2000 sequencing platform. A total of 167,415,597 high-quality clean reads were obtained and assembled into 100,584 unigenes having an N50 value of 1489. Among these contigs, 57,016 (56.68%) were successfully annotated in seven public protein databases. From the differentially expressed gene (DEG) analysis, 926 DEGs were identified between the B group (low DHM: 210.31 mg/g) and D group (high DHM: 359.12 mg/g) libraries, including 446 up-regulated genes and 480 down-regulated genes (B vs. D). Flavonoids (DHQ, DHM)-related DEGs of ten structural enzyme genes, three myeloblastosis transcription factors (MYB TFs), one basic helix-loop-helix (bHLH) TF, and one WD40 domain-containing protein were obtained. The enzyme genes comprised three PALs, two CLs, two CHSs, one F3'H, one F3'5'H (directly converts DHQ to DHM), and one ANS. The expression profiles of randomly selected genes were consistent with the RNA-seq results. Our findings thus provide comprehensive gene expression resources for revealing the molecular mechanism from DHQ to DHM in A. grossedentata. Importantly, this work will spur further genetic studies about A. grossedentata and may eventually lead to genetic improvements of the DHQ content in this plant.

Retrospective observation of the efficacy and safety of prostatic artery embolization combined with transurethral resection of the prostate and simple transurethral resection of the prostate in the treatment of large (> 100 mL) benign prostatic hyperplasia.

PURPOSE: To retrospectively compare the efficacy and safety of prostatic artery embolization (PAE) combined with transurethral resection of the prostate (TURP) and simple TURP in treating large (> 100 mL) benign prostatic hyperplasia (BPH). METHODS: We retrospectively analyzed the clinical data of 13 and 17 patients with large BPH who underwent TURP and PAE + TURP, respectively, from January 2016 to January 2020. The changes in various indices before and after surgery were compared between the two groups. RESULTS: In the PAE + TURP group, the operation time (OT), intraoperative blood loss (BL), postoperative bladder flushing time (PBFT), and postoperative catheter retention time (PCRT) were lower, and the speed of the excised lesion (SEL) was higher than that in the TURP group (P < 0.05). Following-up for 12 months, the prostatic volume (PV), maximum urinary flow rate (Qmax), postvoid residual volume (PVR), International Prostate Symptom Score (IPSS), quality of life (QoL) score, total prostate-specific antigen (T-PSA), and free prostate-specific antigen (F-PSA) in each group improved as compared to before the surgery (P < 0.05), and the above improved indicators, IPSS ratio, and obstructive symptoms in the PAE + TURP group were higher than those in the TURP group (P < 0.05). The incidence of postoperative complications in the PAE + TURP group was lower than that in the TURP group. We obtained the pathological picture of a prostate biopsy after PAE for the first time. CONCLUSION: Compared to TURP alone, PAE + TURP should be promoted, because of its greater efficacy and safety in treating large BPH and fewer post-surgical complications.

Effects of Dingchuan Decoction on Lung Function and Clinical Effectiveness Rate in Children with Asthma: A Systematic Review and Meta-Analysis.

Dingchuan decoction (DCD) is a traditional Chinese prescription for asthma that remains popular today. To systematically evaluate the effect of DCD on lung function, clinical effectiveness rate, and safety in children with asthma, significant databases were searched for randomized controlled trials from their inception to September 9, 2019. Randomized controlled trials assessing the effect of DCD on lung function and clinical effectiveness rate in children with asthma were included in this meta-analysis. The methodological quality of the included trials was assessed using the Cochrane risk of bias tool. RevMan 5.3 was used for data analysis. Fourteen studies with 1,384 children were reviewed. FEV1 improvement rate (mean difference [MD] 12.50, 95% confidence interval [CI] 8.72-16.29), PEF improvement rate (MD 14.28, 95% CI 11.08-17.49), and clinical effectiveness rate (relative risk 1.19, 95% CI 1.14-1.25) significantly increased in the DCD group when compared to simple conventional medication. Four trials suggest that DCD is safe for children. In conclusion, the use of DCD combined with conventional medication improves lung function and clinical effectiveness rate better than simple conventional medication. However, the selected trials lack blinding and large-scale studies. Therefore, to better manage DCD in clinical practice, more randomized controlled trials and large-scale studies are required for further evaluation.

Activity Components from Gynostemma pentaphyllum for Preventing Hepatic Fibrosis and of Its Molecular Targets by Network Pharmacology Approach.

Hepatic fibrosis would develop into cirrhosis or cancer without treating. Hence, it is necessary to study the mechanism and prevention methods for hepatic fibrosis. Gynostemma pentaphyllum is a traditional medicinal material with a high medicinal and health value. In this study, nineteen compounds obtained from G. pentaphyllum were qualitative and quantitative by HPLC-FT-ICR MS and HPLC-UV, respectively. Among them, the total content of 19 gypenosides accurately quantified reaches 72.21 mg/g and their anti-proliferation against t-HSC/Cl-6 cells indicated compound 19 performed better activity (IC50: 28.1 ± 2.0 µM) than the other compounds. Further network pharmacology study demonstrated that compound 19 mainly plays an anti-fibrosis role by regulating the EGFR signaling pathway, and the PI3K-Akt signaling pathway. Overall, the verification result indicated that compound 19 appeared to be nontoxic to LO2, was able to modulate the PI3K/Akt signal, led to subG1 cells cycle arrest and the activation of mitochondrial-mediated apoptosis of t-HSC/Cl-6 cells for anti-hepatic fibrosis.

Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial.

BACKGROUND: Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma. METHODS: In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18-60 years with previously untreated, non-keratinising stage III-IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68-70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62-68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30-32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed. FINDINGS: From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9-81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7-80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69-1·39; log-rank p=0·92), with a difference of 0·5% (95% CI -7·1 to 8·1; pnon-inferiority=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (-6·1 to 9·3; pnon-inferiority=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3-4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported. INTERPRETATION: Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma. FUNDING: National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

A meta-analysis of randomized clinical trials on the impact of oral vitamin C supplementation on first-year outcomes in orthopedic patients.

This meta-analysis aimed at investigating the impact of oral vitamin C supplementation on the post-procedural recovery of orthopedic patients, including functional outcomes and complex regional pain syndrome type I (CRPS I). Literature search using the Medline, Cochrane Library, and Embase databases from inception till March 2021 identified seven eligible randomized controlled trials with 1,361 participants. Forest plot revealed no significant difference in the functional outcomes at 6-12 months [standardized mean difference (SMD) = -0.00, 95% CI - 0.19 to 0.18, 467 patients], risk of overall complications (RR = 0.98, 95% CI 0.68 to 1.39, 426 patients), and pain severity at 3-6 months (SMD = - 0.18, 95% CI - 0.49 to 0.12, 486 patients) between patients with and without oral vitamin C supplementation. Pooled analysis showed that vitamin C treatment reduced the risk of CRPS I regardless of dosage (RR = 0.46, 95% CI 0.25 to 0.85, 1143 patients). In conclusion, the current meta-analysis demonstrated that oral vitamin C supplementation may reduce the risk of complex regional pain syndrome type I but did not improve the functional outcomes in orthopedic patients. Nevertheless, because of the small number of trials included in the present study, further large-scale clinical studies are warranted to support our findings.

The Effect of Perioperative Vitamin C on Postoperative Analgesic Consumption: A Meta-Analysis of Randomized Controlled Trials.

Because the analgesic effect of vitamin C against acute pain remains poorly addressed, this meta-analysis aimed at investigating its effectiveness against acute postoperative pain. A total of seven randomized controlled trials with placebo/normal controls were identified from PubMed, Cochrane Library, Medline, Google Scholar, and Embase databases. Pooled analysis showed a lower pain score (standardized mean difference (SMD) = -0.68, 95% CI: -1.01 to -0.36, p < 0.0001; I2 = 57%) and a lower morphine consumption (weighted mean difference (WMD) = -2.44 mg, 95% CI: -4.03 to -0.86, p = 0.003; I2 = 52%) in the vitamin group than that in the placebo group within postoperative 1-2 h. At postoperative 24 h, a lower pain score (SMD = -0.65, 95% CI: -1.11 to -0.19, p = 0.005; I2 = 81%) and lower morphine consumption (WMD = -6.74 mg, 95% CI: -9.63 to -3.84, p < 0.00001; I2 = 85%) were also noted in the vitamin group. Subgroup analyses demonstrated significant reductions in pain severity and morphine requirement immediately (1-2 h) and 24 h after surgery for patients receiving intravenous vitamin C but not in the oral subgroup. These findings showed significant reductions in pain score and opioid requirement up to postoperative 24 h, respectively, suggesting the effectiveness of perioperative vitamin C use. Further large-scale trials are warranted to elucidate its optimal intravenous dosage and effectiveness against chronic pain in the postoperative pain control setting.

Diagnostic potential of ionomic profile in the plasma of cervical cancer patients receiving neoadjuvant chemoradiotherapy.

BACKGROUND AND AIM: Major and trace elements play an important role in human body, and it has been reported that ionomic distribution differ greatly in tumor patients. The aim of the present study was to investigate the effects of cisplatin-based neoadjuvant chemoradiotherapy on the ionomic profile in human plasma as a potential biomarker for the therapeutic effects of cervical cancer. METHOD: Thirty-seven patients with cervical cancer receiving neoadjuvant chemoradiotherapy were included in this study, pretherapy and post-treatment blood samples were collected and concentrations of 24 ions were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: The results showed that after cisplatin chemotherapy and radiotherapy, patients' plasma Pt level significantly increased, Na, Mg, P, K, Ca, Se, Cu, Zn, Se, Sr, Ba levels significantly decreased (P < 0.01), and Al, Cu ions were significantly correlated with the treatment effect (P < 0.05). In addition, the pattern of elemental correlations changed dramatically after the neoadjuvant chemoradiotherapy. CONCLUSION: The results indicated that the plasma ionomic profile may serve as a quick and convenient tool to reflect the therapeutic effect of cisplatin-based chemoradiotherapy in cervical cancer patients, and supplement of certain essential elements may be of great importance for the maintenance of ion homeostasis in human body and for the reduction of adverse effect of chemotherapy and radiotherapy.

Electrogram dispersion-guided driver ablation adjunctive to high-quality pulmonary vein isolation in atrial fibrillation of varying durations.

OBJECTIVE: To investigate the role of driver mechanism and the effect of electrogram dispersion-guided driver mapping and ablation in atrial fibrillation (AF) at different stages of progression. METHODS: A total of 256 consecutive patients with AF who had undergone pulmonary vein isolation (PVI) plus driver ablation or conventional ablation were divided into three groups: paroxysmal atrial fibrillation (PAF; group A, n = 51); persistent atrial fibrillation (PsAF; group B, n = 38); and long standing-persistent atrial fibrillation (LS-PsAF; group C, n = 39). PVI was performed with the guidance of the ablation index. The electrogram dispersion was analyzed for driver mapping. RESULTS: The most prominent driver regions were at roof (28.0%), posterior wall (17.6%), and bottom (21.3%). From patients with PAF to those with PsAF and LS-PsAF: the complexity of extra-pulmonary vein (PV) drivers including distribution, mean number, and area of dispersion region increased (P < .001). Patients who underwent driver ablation vs conventional ablation had higher procedural AF termination rate (76.6% vs 28.1%; P < .001). With AF progression, the termination rate gradually decreased from group A to group C, and the role of PVI in AF termination was also gradually weakened from group A to group C (39.6%, 7.4%, and 4.3%; P < .001) in patients with driver ablation. At the end of the follow-up, the rate of sinus rhythm maintenance was higher in patients with driver ablation than those with conventional ablation (89.1% vs 70.3%; P < .001). CONCLUSION: The formation of extra-PV drivers provides an important mechanism for AF maintenance with their complexity increasing with AF progression. Electrogram dispersion-guided driver ablation appears to be an efficient adjunctive approach to PVI for AF treatment.

Randomized Trial on Comparison of the Efficacy of Extracorporeal Shock Wave Therapy and Dry Needling in Myofascial Trigger Points.

OBJECTIVE: The aim of the study was to compare the efficacy of radial extracorporeal shock wave therapy and dry needling in the treatment of myofascial trigger points in the upper trapezius muscle. DESIGN: A total of 65 patients with myofascial trigger points were randomly divided into extracorporeal shock wave therapy group (n = 32) and dry needling group (n = 33). Patients received 3 wks of treatment at 1-wk intervals (in both groups). Visual analog scale, pressure pain threshold, Neck Disability Index, and shear modulus were evaluated before treatment, immediately after the first therapy, 1 mo, and 3 mos after the completion of the third therapy. RESULTS: Significant improvements of visual analog scale, pressure pain threshold, and Neck Disability Index scores were observed at all time points after treatment (P < 0.01) in both treatment groups. The shear modulus of myofascial trigger points was reduced in both dry needling group (P < 0.05) and extracorporeal shock wave therapy group (P < 0.01) immediately after the first treatment. Significant reductions in shear modulus were maintained up to 3-mo posttreatment in both groups (P < 0.01). There were no significant differences between the radial extracorporeal shock wave therapy group and dry needling group. CONCLUSIONS: The extracorporeal shock wave therapy is as effective as dry needling for relieving pain, improving function, and reducing shear modulus for patients with myofascial trigger points after a series of three treatments.

A new phthalazinone derivative and a new isoflavonoid glycoside from lichen-associated Amycolatopsis sp.

A new phthalazinone derivative, named amycophthalazinone A (1), and a new isoflavonoid glycoside, 7-O-methyl-5-O-α-L-rhamnopyranosylgenestein (2), along with an isoflavonoid glycoside, 7-O-α-D-arabinofuranosyl daidzein (3) firstly found from natural sources, and eight known compounds (4-11), were isolated from the culture broth of the lichen-associated Amycolatopsis sp. YIM 130642. The structures of new compounds were elucidated on the basis of spectroscopic analysis. Compound 1 was the first example of naturally occurring phthalazinone derivative. The antimicrobial activities of all compounds towards five pathogenic strains were evaluated by a broth microdilution assay. Compound 1 exhibited the most potent inhibitory activity against Staphylococcus aureus, Salmonella typhi, and Candida albicans with MIC values of 32, 32, and 64 µg/mL, respectively.

Extra pulmonary vein driver mapping and ablation in paroxysmal atrial fibrillation by electrogram dispersion analysis.

BACKGROUND: The adjunctive approach is still unknown for atrial fibrillation (AF), which cannot be terminated after pulmonary vein isolation (PVI). We hypothesized that the driver ablation plus PVI was superior to PVI alone. METHODS AND RESULTS: A total of 98 patients with paroxysmal AF were enrolled in this study and were divided into two groups, with one group undergoing PVI (n = 49) and the other group undergoing PVI + driver ablation (n = 49). The driver regions were defined as clusters of bipolar electrograms that displayed spatial dispersion spread over mean AF cycle length at a minimum of three adjacent bipolars of a PentaRay catheter. During the procedure, the most prominent driver regions before PVI were the roof (n = 27; 55.1%), PV antrum (n = 23; 46.9%), and the inferoposterior wall (n = 11; 22.4%). PVI can eliminate all drivers at PV antrum, but only terminate 30.4% of AF in the driver group. The AF termination rate in the driver ablation group was significantly higher than that in conventional ablation (93.9% vs 40.6%; P < 0.001). The rate of freedom from atrial tachyarrhythmia episodes by a single procedure at 6 months was significantly higher in the driver group than in the conventional group (91.6% vs 72.4%; P = 0.02). CONCLUSION: The present method is effective for AF driver identification. It guided ablation adjunctive to PVI increasing the rate of AF termination and improving the outcomes in patients with paroxysmal AF.

The bioenergetics mechanisms and applications of sulfate-reducing bacteria in remediation of pollutants in drainage: A review.

Sulfate-reducing bacteria (SRB), a group of anaerobic prokaryotes, can use sulfur species as a terminal electron acceptor for the oxidation of organic compounds. They not only have significant ecological functions, but also play an important role in bioremediation of contaminated sites. Although numerous studies on metabolism and applications of SRB have been conducted, they still remain incompletely understood and even controversial. Fully understanding the metabolism of SRB paves the way for allowing the microorganisms to provide more beneficial services in bioremediation. Here we review progress in bioenergetics mechanisms and application of SRB including: (1) electron acceptors and donors for SRB; (2) pathway for sulfate reduction; (3) electron transfer in sulfate reduction; (4) application of SRB for economical and concomitant treatment of heavy metal, organic contaminants and sulfates. Moreover, current knowledge gaps and further research needs are identified.

Polyoxygenated Cyclohexenoids with Promising α-Glycosidase Inhibitory Activity Produced by Phomopsis sp. YE3250, an Endophytic Fungus Derived from Paeonia delavayi.

Seven new polyoxygenated cyclohexenoids, namely, phomopoxides A-G (1-7), were isolated from the fermentation broth extract of an endophytic fungal strain Phomopsis sp. YE3250 from the medicinal plant Paeonia delavayi Franch. The structures of these compounds were established by spectroscopic interpretation. The absolute configurations of compounds 1 and 4 were confirmed by X-ray crystallographic analysis and chemical derivative approach. All isolated compounds showed weak cytotoxic activities toward three human tumor cell lines (Hela, MCF-7, and NCI-H460) and weak antifungal activities against five pathogenic fungi (Candida albicans, Aspergillus niger, Pyricularia oryzae, Fusarium avenaceum, and Hormodendrum compactum). In addition, compounds 1-7 showed a promising α-glycosidase inhibitory activity with IC50 values of 1.47, 1.55, 1.83, 2.76, 2.88, 3.16, and 2.94 mM, respectively, as compared with a positive control of acarbose (IC50 = 1.22 mM).

Capsaicin-loaded folic acid-conjugated lipid nanoparticles for enhanced therapeutic efficacy in ovarian cancers.

In this study, folic acid-conjugated lipid nanoparticles were successfully prepared to enhance the active targeting of capsaicin (CAP) in ovarian cancers. The particles were nanosized and exhibited a controlled release of drug in the physiological conditions. The folic acid (FA)-conjugated system exhibited a remarkably higher uptake of nanoparticles in the cancer cells compared to that of non-targeted system. The folate-conjugated CAP-loaded lipid nanoparticles (CFLN) upon interacting with cancer cells were internalized via receptor-mediated endocytosis mechanism and resulted in higher concentration in the cancer cells. Consistently, CFLN showed a remarkably higher toxic effect compared to that of non-targeted nanoparticle system. CFLN showed significantly higher cancer cell apoptosis with nearly 39% of cells in apoptosis chamber (early and late) compared to only ∼21% and ∼11% for CAP-loaded lipid nanoparticles (CLN) and CAP. The loading of drug in the lipid nanoparticle system extended the drug retention in the blood circulation and allowed the active targeting to specific cancer cells. The prolonged circulation of drug attributed to the antifouling property of polyethylene glycol molecule in the structure. Overall, study highlights that using targeting moiety could enhance the therapeutic response of nanomedicines in the treatment of solid tumors.