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Stochastic differential equation is established by solving some stochastic phenomenon. Square-mean asymptotically almost periodic solutions of the equations are used more widely than square-mean almost periodic solutions. In order to study the applications of square-mean asymptotically almost periodic processes in the stochastic differential equations, the existence and uniqueness of square-mean asymptotically almost periodic solutions to a class of stochastic integro-differential equations are discussed using the properties of square-mean asymptotically almost periodic functions and Banach fixed point theorem. [ABSTRACT FROM AUTHOR]

Three new lycopodium alkaloids, huperserramines A-C ( 1- 3, resp.), along with 15 known ones, lycopodine-6 α,11 α-diol ( 4), lycoposerramine H ( 5), lycoposerramine I ( 6), lycopodine-6 α-ol ( 7), lycoposerramine M ( 8), diphaladine A ( 9), lycoposerramine K ( 10), lycoposerramine W ( 11), huperzine M ( 12), luciduline ( 13), phlegmariuine N ( 14), huperzine A ( 15), huperzine B ( 16), lycodine ( 17), and lycoposerramine R ( 18), were isolated from the whole plant of Huperzia serrata. Their structures were established by spectroscopic methods, including 2D-NMR and MS analyses. All the isolates were evaluated for their inhibitory effects on acetylcholinesterase (AChE) and α-glucosidase. As a result, lycopodine-6 α,11 α-diol ( 4) exhibited more potent α-glucosidase inhibitory activity ( IC50 148±5.5 μ M) than the positive control acarbose ( IC50 376.3±2.7 μ M). [ABSTRACT FROM AUTHOR]

Three new metabolites, norcyclocitrinol A ( 1), erythro-11 α-hydroxyneocyclocitrinol ( 2), and pesudocyclocitrinol A ( 3), along with six known analogs, i.e., neocyclocitrinols A-D ( 4- 7, resp.), cyclocitrinol ( 8), and 24-epicyclocitrinol ( 9), were isolated and identified from the culture broth of Penicillium chrysogenum P1X, a fungal endophyte of Huperzia serrata. Compounds 1- 9 were identified by spectroscopic methods to share the same C25-steroid skeleton featuring an unusual bicyclo[4.4.1] A/ B ring system. In particular, 1 represents the first example of a C25 steroid with a bisnor C-atom side chain. All compounds were evaluated for their cytotoxic activities against HeLa and HepG2 cell lines. However, none of them exhibited a significant cytotoxicity at a concentration of 20 μ M. [ABSTRACT FROM AUTHOR]

Aim:To investigate the effects of ginsenoside Rg1 on the radiation-induced aging of hematopoietic stem/progenitor cells (HSC/HPCs) in mice and the underlying mechanisms.Methods:Male C57BL/6 mice were treated with ginsenoside Rg1 (20 mg·kg−1·d−1, ip) or normal saline (NS) for 7 d, followed by exposure to 6.5 Gy X-ray total body irradiation. A sham-irradiated group was treated with NS but without irradiation. Sca-1+ HSC/HPCs were isolated and purified from their bone marrow using MACS. DNA damage was detected on d 1. The changes of anti-oxidative activities, senescence-related markers senescence-associated β-galactosidase (SA-β-gal) and mixed colony-forming unit (CFU-mix), P16INK4a and P21Cip1/Waf1 expression on d 7, and cell cycle were examined on d 1, d 3, and d 7.Results:The irradiation caused dramatic reduction in the number of Sca-1+ HSC/HPCs on d 1 and the number barely recovered until d 7 compared to the sham-irradiated group. The irradiation significantly decreased SOD activity, increased MDA contents and caused DNA damage in Sca-1+ HSC/HPCs. Moreover, the irradiation significantly increased SA-β-gal staining, reduced CFU-mix forming, increased the expression of P16INK4a and P21Cip1/Waf1 in the core positions of the cellular senescence signaling pathways and caused G1 phase arrest of Sca-1+ HSC/HPCs. Administration of ginsenoside Rg1 caused small, but significant recovery in the number of Sca-1+ HSC/HPCs on d 3 and d 7. Furthermore, ginsenoside Rg1 significantly attenuated all the irradiation-induced changes in Sca-1+ HSC/HPCs, including oxidative stress reaction, DNA damage, senescence-related markers and cellular senescence signaling pathways and cell cycle, etc.Conclusion:Administration of ginsenoside Rg1 enhances the resistance of HSC/HPCs to ionizing radiation-induced senescence in mice by inhibiting the oxidative stress reaction, reducing DNA damage, and regulating the cell cycle. [ABSTRACT FROM AUTHOR]

In consideration of the problem of visible nearest neighbors for uncertain objects, the characteristics of uncertain-voronoi diagram are analyzed. The concepts such as multilayer adjacent generator and multilayer uncertain-voronoi region are proposed. The theories that evaluate the probabilistic visible nearest neighbors are put forward, and the algorithm is presented which deals with the probabilistic visible nearest neighbor queries based on uncertain-voronoi diagram. The algorithm can directly determine the scope of probabilistic visible nearest neighbors participated in query processing and the range of obstruction sets participating in visual judgment, which reduced a large number of calculation and pruning operation when traversing index. The performance of the algorithm is analyzed by using both real and synthetic data sets, and the experimental results show that the algorithm presented can deal with the queries of visible nearest neighbors for uncertain objects effectively. [ABSTRACT FROM AUTHOR]

Two new polyketide derivatives, huaspenones C and D ( 1 and 2, resp.), were isolated from the cultures of an endophytic fungus Peyronellaea sp. HS-12, derived from the stems of Huperzia serrata. They share N-bearing furan-3(2 H)-one backbone, and 2 has an unprecedented furo[3,2- c]pyridine skeleton. Their structures including the absolute configuration were elucidated by extensive spectroscopic analysis combined with quantum-chemical calculations. (2 E,4 E)-6-hydroxy-2-methylocta-2,4-dienoic acid ( 3), a key intermediate of the biosynthesis of 1 and 2, was also obtained from the endophyte. [ABSTRACT FROM AUTHOR]

Drug solubility plays a significant role in the development of drug formulation. The objectives of this work are to improve the solubility and dissolution rate of vortioxetine (VT) by preparing its inclusion complexes (ICs) with β‐Cyclodextrin (β‐CD) and γ‐Cyclodextrin (γ‐CD). The ICs were prepared in 1:1 M ratio via recrystallization method and characterized by P‐XRD, FT‐IR, 1H NMR, 2D NOESY, and DSC. Further, the crystal structure of VT‐β‐CD was analyzed by SC‐XRD. P‐XRD data obtained for ICs describe the crystalline pattern. The DSC analysis shows change in the thermal behavior of VT, CDs and ICs. FT‐IR analysis shows shifting of frequencies in ICs when compared with the pristine VT drug and CDs. The 2D NOESY in DMSO‐d6 indicates weak interaction between the VT and CD molecules. The crystal structure of VT‐β‐CD consists of one guest VT, one host CD, and nine water molecules in the crystal lattice. The solubility of ICs was significantly improved in distilled water, pH 1.2 acidic, and phosphate buffer pH 6.8 medium, as compared with the solubility of the pristine VT drug. The in vitro dissolution rate of ICs in different dissolution media was investigated, which was higher than that of the commercial product of VT. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate the role of reparative membrane as a barrier in nerve regeneration during parotidectomy in rats. METHODS: The bilateral parotids of 40 male SD rats were resected partially. The left parotids of rats were used as experimental sides, in which reparative membranes were sutured on the surface of remaining parotids during parotidectomy; the right parotids were performed as control, in which the remaining parotids were covered with subcutaneous tissue and skin directly. The rats were divided into group A and B. Facial nerves were protected carefully in group A and the buccal branch of facial nerve was cut off in group B. 4 rats were sacrificed in each group at 1 week, 2-week, 4-week, 3-month and 6-month postoperatively. The tissue blocks in the bilateral parotid -masseter region were obtained to perform hematoxylin-eosin staining and PGP9.5 immunostaining. The healing process of operative regions was examined. Paired sample t test in SPSS 13.0 software package was used to compare the intraepidermal nerve fiber density and dermis nerve fiber density between the left and right sides in all rats, rats in group A and group B, respectively. RESULTS: The inflammation cells infiltrated more severely in the experimental sides than in the control sides during healing process. The reparative membranes were replaced by tissue at 4- week after surgery. Neuroma formation could be observed in group B at 1 week, 2-week and 4-week after surgery. The dermis nerve fiber density of group B was less than that of group A, which had significant difference (P<0.05). CONCLUSIONS: By mimicking parotidectomy in rats, this study found that the inserted reparative membrane could reduce the dermis nerve fiber density of the rat whose facial nerve was cut off. The results showed that the reparative membrane could prevent nerve growing to a certain extent, and be used as a barrier in nerve regeneration. [ABSTRACT FROM AUTHOR]

According to the local characteristics of network nodes, a simple measure method to quantify node is proposed. The principle of this method lies in that the importance of network nodes is not only related to the degree of the nodes themselves, but also related to the degrees of their neighborhood nodes. The experimental results show that the presented method is still valid in the condition that it lacks the global topological structure information of the network. It could well describe the differences among nodes and its time complexity is only o(m+n). Hence, this method could acquire a high performance when dealing with the large scale complex network. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the efficacy and safety of laparoscopic resection (LR) for rectal cancer.Methods: A case-control study involving three Chinese medical centers was conducted. Rectal cancer patients undergoing LR were compared with open resection (OR) cases simultaneously from January 2004 to December 2005. Data were collected, and basic characteristics, conversion rate, recovery, complications, adjuvant therapy, and recurrence rate were compared. Analysis was by intention to treat.Results: A total of 335 rectal cancer procedures (115 LR and 220 OR) met the inclusion criteria. The patients' basic characteristics were similar in the two groups (p>0.05). Total mesorectal excision was performed for 85.59% of the patients (201/235), who received anal sphincter preservation. Compared with OR, LR had a shorter incision length, less blood loss, and less need for transfusion, but the operation time was longer (p<0.05). No significant differences were observed between the two groups in positive rates of longitudinal resection margins, numbers of harvested lymph nodes, complication rates during operation and postoperation, and perioperative reoperation and morbidity rates (p>0.05). Postoperative parenteral narcotics were used less in LR than in OR (47.8% vs 62.7%; chi(2)=6.867; p=0.009). The median time until first flatus; resumption of diet, defecation, micturition, and ambulation; and discharge were reduced in LR (p<0.05). Conversion from LR to OR was required by 11.3% of the patients (13/115). The intraoperative complication rate was 30.8% for the patients who underwent conversion. The operation time and postoperative complication rate were the same as for LR alone (p>0.05). The local recurrence rate was 3.7% for the LR group and 4.9% for the OR group (chi (2)=0.209; p=0.647) during the 20-month median follow-up period.Conclusions: The findings showed that LR for rectal cancer was safe and effective, resulting in faster recovery and a similar complication rate compared with OR. Conversion did not alter the patients' outcomes. [ABSTRACT FROM AUTHOR]

Human-induced fish introduction in aquaculture always be considered the most important driver of biological invasions in freshwater ecosystems, yet most introduced species fail to establish though having great economic benefits. Explaining the varying success of introduced fish species is a central question both in invasion biology and aquaculture management. Southern China is a good region to test the invasion hypotheses where lots of non-native fish species were cultured and invaded. In this study, we used four human activities related to aquaculture to test their effects on the establishment of non-native fish species in the rivers of southern China. Our results showed that: open-water aquaculture significantly increased the establishment probabilities of non-native species relative to standardised aquaculture in ponds; the establishment and spread of non-native fish species in rivers had no significant correlation to their production and distribution in standardised aquaculture; non-native fish species with low economic value were more prone to escape and establishment in natural rivers, and had higher establishment probabilities in rivers due to the lower fishing pressure. These results indicate that standardised aquaculture and cultivated species with high economic value do not always result in biological invasions. To mitigate the invasion of exotic species caused by aquaculture, stricter management practices and more optimized economic assessments should be implemented for the introduction and cultivation of non-native fish species. • Open-water aquaculture promote the establishment of exotic species; • Invasion of exotic fish not related to their production in standard aquaculture; • Fish species with high economic value do not always result in biological invasion. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is a common pediatric malignancy associated with poor outcomes. Recent studies have shown that murine double minute2 homolog (MDM2) protein inhibitors are promising anticancer agents. MI-773 is a novel and specific antagonist of MDM2, however, the molecular mechanism of its anti-NB activity remains unclear. NB cell viability was measured by Cell Counting Kit-8 assay following MI-773 treatment. Cell cycle progression was analyzed using PI staining and apoptosis was assessed using Annexin V/PI staining. The molecular mechanisms by which MI-773 exerted its effects were investigated using a microarray. The results showed that disturbance of the MDM2/p53 axis by MI-773 resulted in potent suppression of proliferation, induction of apoptosis and cell cycle arrest in NB cells. In addition, microarray analysis showed that MI-773 led to significant downregulation of genes involved in the G2/M phase checkpoint and upregulation of hallmark gene associated with the p53 pathway. Meanwhile, knockdown of insulinoma-associated 1 decreased proliferation and increased apoptosis of NB cells. In conclusion, the present study demonstrated that MI-773 exhibited high selectivity and blockade affinity for the interaction between MDM2 and TP53 and may serve as a novel strategy for the treatment of NB. [ABSTRACT FROM AUTHOR]

Ageing often results in insulin resistance (IR) and chronic inflammation, and adipose is one of the tissues in which inflammation and IR occur earliest during this process. The present study investigated the effect and underlying mechanisms of ursolic acid (UA) on adipose IR and inflammation in ageing rats. Specific pathogen-free male Sprague-Dawley rats were randomly divided into 4 groups: i) Young normal (young); ii) untreated ageing (aged); and groups supplemented with UA either iii) low-UA 10 mg/kg (UA-L) or iv) high-50 mg/kg (UA-H). Animals in the UA-treated groups received 10 or 50 mg/kg UA (suspended in 5% Gum Arabic solution). The rats in the corresponding aged group and young groups received vehicle (5% Gum Arabic) alone. All rats were intragastrically treated once daily by oral gavage for 7 weeks. The day before the experiment terminated, overnight fasting blood (~700 µl) was collected and plasma was prepared to measure biochemical indicators; western blotting was performed to analyze the expression of insulin signaling proteins [(insulin receptor substrate 1 (IRS-1), phosphorylated (p)-IRS-1, PI3K, glucose transporter 4 (GLUT4), Akt and p-Akt)] and inflammatory factors (NF-κB, IL-6 and IL-1β) in the epididymis white adipose tissue (eWAT). The results revealed that treatment with UA-H decreased eWAT weight, the ratio of eWAT weight/body weight, fasted insulin and triglyceride levels, the homeostasis model assessment of insulin resistance and adipose tissue insulin resistance index in ageing rats, indicating the amelioration of systemic and adipose tissue IR, compared with the aged group. Mechanistically, UA-H administration upregulated p-protein kinase B, the ratio of p-Akt to protein kinase B and total and cellular membrane GLUT4 protein levels in eWAT of ageing rats. Conversely, UA inhibited the increase in NF-κB expression and proinflammatory cytokines IL-6 and IL-1β. However, these alterations were not observed in the rats of the aged group. Taken together, the findings of the present study indicated that UA may ameliorate adipose IR, which is associated with activation of the Akt-GLUT4 signaling pathway and inhibition of inflammation in ageing rats. These data provide a basis for the development of effective and safe drugs or functional substances, such as UA, for the prevention and treatment of metabolic diseases. [ABSTRACT FROM AUTHOR]

The study objective was to study the therapeutic effect of surgical treatment for hepatocellular carcinoma (HCC) originating from the caudate lobe. From 1995 to 2003, caudate lobe resection was carried out for 97 cases; among them 39 were for HCC, who were divided into two groups. Group A consisted of 19 cases undergoing isolated caudatectomy, and group B consisted of 20 cases undergoing caudatectomy combined with other liver resections. The factors that might influence postoperative recovery were compared between the two groups. A special instrument, Peng''s Multifunctional Operative Dissector, was used for surgical dissection. All tumors were resected successfully. One patient died of postoperative renal failure. Hydrothorax occurred in three patients, ascites occurred in four patients, and bile leakage occurred in one patient. Thirty cases received long-term follow-up with survival rates at 1, 3, and 5 years of 53%, 50%, and 39%, respectively. Caudate lobectomy is an effective therapeutic method for HCC originating in the caudate lobe. Isolated caudatectomy should be performed as the first choice whenever possible. Anterior transhepatic approach is appropriate in some cases. Peng''s Multifunctional Operative Dissector is a very useful instrument for surgical dissection. [Copyright &y& Elsevier]

Since there is a lack of the reference to price real estates, this paper points out the first step is to determine the influence range of the project based on the districted market theory. Then, the average price of the same type of buildings needs to be found so that the final price can be adjusted according to the trait of this project. Finally, according to the required sale cost and time, the quantity-price strategies for different sale stages can be determined by using the dynamic programming method, thus achieving the maximum of comprehensive effectiveness. [ABSTRACT FROM AUTHOR]

The stochastic resonance (SR) phenomenon for a bistable system subject to signal-modulated noise and to multiplicative and additive noise is investigated. The signal is modelled as a random-phase asymmetric square-wave one. Based on adiabatic approximation condition and two-state theory, the system output signal-to-noise ratio (SNR) is deduced. It is found that double SR phenomenon occurs when the SNR varies with the asymmetry of the square-wave signal. One resonance peak appears when the SNR changes with the amplitude of the square-wave signal. Traditional SR can be observed on the curves of the SNRs vs. the strength of the signal-modulated noise and vs. the intensities of the multiplicative and additive noise. The non-monotonous dependence of the SNR on the system parameter is discussed. [ABSTRACT FROM AUTHOR]

Understanding the host–guest chemistry of α-/β-/γ- cyclodextrins (CDs) and a wide range of organic species are fundamentally attractive, and are finding broad contemporary applications toward developing efficient drug delivery systems. With the widely used β-CD as the host, we herein demonstrate that its inclusion behaviors toward an array of six simple and bio-conjugatable adamantane derivatives, namely, 1-adamantanol (adm-1-OH), 2-adamantanol (adm-2-OH), adamantan-1-amine (adm-1-NH2), 1-adamantanecarboxylic acid (adm-1-COOH), 1,3-adamantanedicarboxylic acid (adm-1,3-diCOOH), and 2-[3-(carboxymethyl)-1-adamantyl]acetic acid (adm-1,3-diCH2COOH), offer inclusion adducts with diverse adamantane-to-CD ratios and spatial guest locations. In all six cases, β-CD crystallizes as a pair supported by face-to-face hydrogen bonding between hydroxyl groups on C2 and C3 and their adjacent equivalents, giving rise to a truncated-cone-shaped cavity to accommodate one, two, or three adamantane derivatives. These inclusion complexes can be terminated as (adm-1-OH)2⊂CD2 (1, 2:2), (adm-2-OH)3⊂CD2 (2, 3:2), (adm-1-NH2)3⊂CD2 (3, 3:2), (adm-1-COOH)2⊂CD2 (4, 2:2), (adm-1,3-diCOOH)⊂CD2 (5, 1:2), and (adm-1,3-diCH2COOH)⊂CD2 (6, 1:2). This work may shed light on the design of nanomedicine with hierarchical structures, mediated by delicate cyclodextrin-based hosts and adamantane-appended drugs as the guests. [ABSTRACT FROM AUTHOR]

With the development of dye and printing, production wastewater has become one of the most primary pollution sources of water and soil pollution. Most of the dyes are toxic substances, which have the "three-way" effect of carcinogenic, teratogenic and mutagenic. Therefore, it is a very difficult but significant issue to deal with the dye in the wastewater. Here, we report a study on low-cost, high-capacity hydrogels that remove water-soluble dyes. The hydrogel is prepared by crosslinking the β-cyclodextrin and functional monomer: acrylamido and 2-acrylamide-2-methylpropane sulfonic acid by aqueous solution polymerization, meanwhile, alkaline hydrolysis is also an important step for adsorption performance. After alkaline hydrolysis, the amide and sulfonic groups in the hydrogel were converted into carboxylate and sulfonate, which was beneficial to the adsorption of cationic dyes. This polymer could remove 96.58% methylene blue (400 mg/L) and only requires 0.02 wt%. Its maximum adsorption capacity for methylene blue could reach 2638.22 mg/g under equilibrium condition. It is the most powerful adsorbent used to treat dye wastewater, according to the report. It also provides some references for hydrogel treatment of dye wastewater. [Display omitted] • With the introduction of β-CD and graft polymerization with AM and AMPS, a novel hydrogel was successfully prepared and used for MB removal. • The alkaline hydrolysis process of β-CD-A-A hydrogel is beneficial to further improve the adsorption performance of MB. The maximum adsorption capacity of MB can reach 2638.22 mg/g, which is attributed to the internal hydrophobic cavities of β-CD and the adsorption of MB by -COO- and –SO 3 - groups after hydrolysis. • The MB adsorption is mainly due to the affinity of the hydrophobic cavities with the hydrophobic groups on MB molecules and the electrostatic attraction of between -COO- and –SO 3 - groups, and the positively charged groups on MB molecules. • In addition, it was also found that β-CD-A-A has a much higher adsorption capacity for MB under alkaline conditions. [ABSTRACT FROM AUTHOR]

Puerarin (PUE) is a Chinese traditional medicine known to enhance glucose uptake into the insulin cells to downregulate the blood glucose levels in the treatment of type II diabetes. Nevertheless, the bioavailability of pristine PUE is limited due to its poor solubility and low intestinal permeability. In this work, we demonstrate that the solubility of PUE can be significantly enhanced via its co-crystallization with L-Proline (PRO). Two crystalline phases, namely, the solvate-free form [PUE][PRO] (I) and the solvated form [PUE]2[PRO]∙EtOH∙(H2O)2 (II) are isolated. These two phases are characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), Fourier-transformed infrared (FT-IR) spectra, nuclear magnetic resonance (NMR), and thermogravimetric analysis in association with differential scanning calorimetry (TGA-DSC). The solubility and dissolution rate of both I and II in water, gastrointestinal tract at pH 1.2, and phosphate buffer at pH 6.8 indicates a nearly doubled increase as compared to the pristine PUE. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine PUE, I and II against murine colon cancer cell lines CT-26 and human kidney cell lines HEK-293 indicated that neither compound exhibits obvious cytotoxicity after 24 h. This work showcases that the readily available and biocompatible PRO can be a promising adjuvant to enhance the physicochemical properties of PUE toward orally administered drug formulation with improved pharmacokinetics. [ABSTRACT FROM AUTHOR]

Correction for 'Super-large dendrites composed of trigonal PbO2 nanoplates with enhanced performances for electrochemical devices' by Liang-Xin Ding et al., Chem. Commun., 2012, 1275–1277, DOI: 10.1039/C2CC15271A. [ABSTRACT FROM AUTHOR]

Tenofovir alafenamide (TAF) is a prodrug of tenofovir as a potent nucleotide reverse transcriptase inhibitor. It serves as the key component of Genvoya® for the first-line treatment of human immunodeficiency virus infection (HIV) and is the active component of Vemlidy® for the treatment of chronic hepatitis B. Vemlidy® is also a monotherapeutic regimen formulated as TAF hemifumarate (1; TAF:fumarate = 2:1). In this work, we report for the first time the single-crystal structure of TAF fumarate hemihydrate (2, TAF:fumarate:H2O = 2:2:1). Compound 2 is initially documented as a salt in which one proton of the fumaric acid migrates to the amine group of the adenine moiety in TAF. It was recently proposed that ca. 20–30% proton is transferred to the N atom on the aromatic adenine backbone. We herein provide definitive single-crystal X-ray diffraction results to confirm that 2, though phase pure, is formed as a mixture of co-crystal (75%) and salt (25%). It features two pairs of TAF fumarates, wherein one of the four H atoms on the fumaric acid is transferred to the N atom of the adjacent adenine moiety while the other three carboxylates remain in their intrinsic acid form. Compound 2 is a metastable phase during the preparation of 1 and can be isolated by halting the reaction during the refluxing of TAF and fumaric acid in acetonitrile (MeCN). Our report complements the previous characterizations of TAF monofumarate, and its elusive structural patterns are finally deciphered. [ABSTRACT FROM AUTHOR]

The aim of this work was to determine whether locally advanced rectal cancer (LARC) with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiation therapy treatment. This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6 to 12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathologic [CRM] circumferential margins were subjected to chemoradiotherapy [CRT] and those with negative CRM underwent adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients underwent subsequent surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS). A total of 275 patients were randomly assigned to the intervention (n = 140) and control (n = 135) groups, in which 33.57% and 28.15% patients were at clinical T4 stage and 85.92% and 80.45% patients were at "bad" or "ugly" risk in the intervention and control groups, respectively. There were 2 patients (1.52%) and 1 patient (0.77%) with positive CRM in the intervention and control groups, respectively (P >.05). The non-adherence rates for the intervention and control groups were 3.6% and 23.7%, respectively. After a median follow-up of 34.6 months (IQR, 18.2-45.7), 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were 6 patients (4.4%) with local recurrence in the intervention group and none in the control group, which led to the termination of the trial. The 3-year DFS rate was 81.82% in the intervention group (95% CI, 78.18%-85.46%) and 85.37% in the control group (95% CI, 81.75%-88.99%), with a difference of –3.55% (95% CI, –3.71% to –3.39%; hazard ratio, 1.76; 95% CI, 0.94-3.30). In the per-protocol data set, the difference between 3-year DFS rates was –5.44% (95% CI, –5.63% to –5.25%; hazard ratio, 2.02; 95% CI, 1.01-4.06). Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy compared with preoperative CRT followed by surgery and cannot be recommended for patients with LARC. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients.Methods: This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment.Results: A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11-17 days) vs. 23.5 days (IQR, 15-42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7-91.5%) vs. 87.1% (95% CI, 80.8-91.4%), P = 0.7420].Conclusions: The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer.Trial Registration: ClinicalTrials.gov: NCT01080547 , registered on March 4, 2010. [ABSTRACT FROM AUTHOR]