Electrochemical reactor dictates site selectivity in N-heteroarene carboxylations.

Pyridines and related N-heteroarenes are commonly found in pharmaceuticals, agrochemicals and other biologically active compounds1,2. Site-selective C-H functionalization would provide a direct way of making these medicinally active products3-5. For example, nicotinic acid derivatives could be made by C-H carboxylation, but this remains an elusive transformation6-8. Here we describe the development of an electrochemical strategy for the direct carboxylation of pyridines using CO2. The choice of the electrolysis setup gives rise to divergent site selectivity: a divided electrochemical cell leads to C5 carboxylation, whereas an undivided cell promotes C4 carboxylation. The undivided-cell reaction is proposed to operate through a paired-electrolysis mechanism9,10, in which both cathodic and anodic events play critical roles in altering the site selectivity. Specifically, anodically generated iodine preferentially reacts with a key radical anion intermediate in the C4-carboxylation pathway through hydrogen-atom transfer, thus diverting the reaction selectivity by means of the Curtin-Hammett principle11. The scope of the transformation was expanded to a wide range of N-heteroarenes, including bipyridines and terpyridines, pyrimidines, pyrazines and quinolines.

Dimensionality reduction approach for many-objective epistasis analysis.

In epistasis analysis, single-nucleotide polymorphism-single-nucleotide polymorphism interactions (SSIs) among genes may, alongside other environmental factors, influence the risk of multifactorial diseases. To identify SSI between cases and controls (i.e. binary traits), the score for model quality is affected by different objective functions (i.e. measurements) because of potential disease model preferences and disease complexities. Our previous study proposed a multiobjective approach-based multifactor dimensionality reduction (MOMDR), with the results indicating that two objective functions could enhance SSI identification with weak marginal effects. However, SSI identification using MOMDR remains a challenge because the optimal measure combination of objective functions has yet to be investigated. This study extended MOMDR to the many-objective version (i.e. many-objective MDR, MaODR) by integrating various disease probability measures based on a two-way contingency table to improve the identification of SSI between cases and controls. We introduced an objective function selection approach to determine the optimal measure combination in MaODR among 10 well-known measures. In total, 6 disease models with and 40 disease models without marginal effects were used to evaluate the general algorithms, namely those based on multifactor dimensionality reduction, MOMDR and MaODR. Our results revealed that the MaODR-based three objective function model, correct classification rate, likelihood ratio and normalized mutual information (MaODR-CLN) exhibited the higher 6.47% detection success rates (Accuracy) than MOMDR and higher 17.23% detection success rates than MDR through the application of an objective function selection approach. In a Wellcome Trust Case Control Consortium, MaODR-CLN successfully identified the significant SSIs (P < 0.001) associated with coronary artery disease. We performed a systematic analysis to identify the optimal measure combination in MaODR among 10 objective functions. Our combination detected SSIs-based binary traits with weak marginal effects and thus reduced spurious variables in the score model. MOAI is freely available at https://sites.google.com/view/maodr/home.

Cu-Catalyzed Asymmetric Dicarboxylation of 1,3-Dienes with CO2.

Dicarboxylic acids and derivatives are important building blocks in organic synthesis, biochemistry, and the polymer industry. Although catalytic dicarboxylation with CO2 represents a straightforward and sustainable route to dicarboxylic acids, it is still highly challenging and limited to generation of achiral or racemic dicarboxylic acids. To date, catalytic asymmetric dicarboxylation with CO2 to give chiral dicarboxylic acids has not been reported. Herein, we report the first asymmetric dicarboxylation of 1,3-dienes with CO2 via Cu catalysis. This strategy provides an efficient and environmentally benign route to chiral dicarboxylic acids with high regio-, chemo-, and enantioselectivities. The copper self-relay catalysis, that is, Cu-catalyzed boracarboxylation of 1,3-dienes to give carboxylated allyl boronic ester intermediates and subsequent carboxylation of C-B bonds to give dicarboxylates, is key to the success of this dicarboxylation. Moreover, this protocol exhibits broad substrate scope, good functional group tolerance, easy product derivatizations, and facile synthesis of chiral liquid crystalline polyester and drug-like scaffolds.

Enantioselective Nickel-Electrocatalyzed Reductive Propargylic Carboxylation with CO2.

The exploitation of carbon dioxide (CO2) as a sustainable, plentiful, and harmless C1 source for the catalytic synthesis of enantioenriched carboxylic acids has long been acknowledged as a pivotal task in synthetic chemistry. Herein, we present a current-driven nickel-catalyzed reductive carboxylation reaction with CO2 fixation, facilitating the formation of C(sp3)-C(sp2) bonds by circumventing the handling of moisture-sensitive organometallic reagents. This electroreductive protocol serves as a practical platform, paving the way for the synthesis of enantioenriched propargylic carboxylic acids (up to 98% enantiomeric excess) from racemic propargylic carbonates and CO2. The efficacy of this transformation is exemplified by its successful utilization in the asymmetric total synthesis of (S)-arundic acid, (R)-PIA, (S)-chizhine D, (S)-cochlearin G, and (S,S)-alexidine, thereby underscoring the potential of asymmetric electrosynthesis to achieve complex molecular architectures sustainably.

Multiobjective optimization-driven primer design mechanism: towards user-specified parameters of PCR primer.

Primers are critical for polymerase chain reaction (PCR) and influence PCR experimental outcomes. Designing numerous combinations of forward and reverse primers involves various primer constraints, posing a computational challenge. Most PCR primer design methods limit parameters because the available algorithms use general fitness functions. This study designed new fitness functions based on user-specified parameters and used the functions in a primer design approach based on the multiobjective particle swarm optimization (MOPSO) algorithm to address the challenge of primer design with user-specified parameters. Multicriteria evaluation was conducted simultaneously based on primer constraints. The fitness functions were evaluated using 7425 DNA sequences and compared with a predominant primer design approach based on optimization algorithms. Each DNA sequence was run 100 times to calculate the difference between the user-specified parameters and primer constraint values. The algorithms based on fitness functions with user-specified parameters outperformed the algorithms based on general fitness functions for 11 primer constraints. Moreover, MOPSO exhibited superior implementation in all experiments. Practical gel electrophoresis was conducted to verify the PCR experiments and established that MOPSO effectively designs primers based on user-specified parameters.

MOAI: a multi-outcome interaction identification approach reveals an interaction between vaspin and carcinoembryonic antigen on colorectal cancer prognosis.

Identifying and characterizing the interaction between risk factors for multiple outcomes (multi-outcome interaction) has been one of the greatest challenges faced by complex multifactorial diseases. However, the existing approaches have several limitations in identifying the multi-outcome interaction. To address this issue, we proposed a multi-outcome interaction identification approach called MOAI. MOAI was motivated by the limitations of estimating the interaction simultaneously occurring in multi-outcomes and by the success of Pareto set filter operator for identifying multi-outcome interaction. MOAI permits the identification for the interaction of multiple outcomes and is applicable in population-based study designs. Our experimental results exhibited that the existing approaches are not effectively used to identify the multi-outcome interaction, whereas MOAI obviously exhibited superior performance in identifying multi-outcome interaction. We applied MOAI to identify the interaction between risk factors for colorectal cancer (CRC) in both metastases and mortality prognostic outcomes. An interaction between vaspin and carcinoembryonic antigen (CEA) was found, and the interaction indicated that patients with CRC characterized by higher vaspin (≥30%) and CEA (≥5) levels could simultaneously increase both metastases and mortality risk. The immunostaining evidence revealed that determined multi-outcome interaction could effectively identify the difference between non-metastases/survived and metastases/deceased patients, which offers multi-prognostic outcome risk estimation for CRC. To our knowledge, this is the first report of a multi-outcome interaction associated with a complex multifactorial disease. MOAI is freely available at https://sites.google.com/view/moaitool/home.

Application of propofol-remifentanil intravenous general anesthesia combined with regional block in pediatric ophthalmic surgery.

OBJECTIVE: The aim of this study is to observe the anesthetic effect and safety of intravenous anesthesia without muscle relaxant with propofol-remifentanil combined with regional block under laryngeal mask airway in pediatric ophthalmologic surgery. METHODS: A total of 90 undergoing ophthalmic surgery were anesthetized with general anesthesia using the laryngeal mask airway without muscle relaxant. They were randomly divided into two groups: 45 children who received propofol-remifentanil intravenous anesthesia combined with regional block (LG group), and 45 children who received total intravenous anesthesia (G group). The peri-operative circulatory indicators, awakening time after general anesthesia, postoperative analgesic effect and the incidence of anesthesia-related adverse events were respectively compared between the two groups. RESULTS: All the children successfully underwent the surgical procedure. The awakening time after general anesthesia and removal time of laryngeal mask were significantly shorter in the LG group than in the G group (P < 0.05). There was no statistically significant difference in the heart rates in the perioperative period between the two groups (P > 0.05). There was no statistically significant difference in the incidence of intraoperative physical response, respiratory depression, postoperative nausea and vomiting (PONV) and emergence agitation (EA) between the two groups (P > 0.05). The pain score at the postoperative hour 2 was lower in the LG group than in the G group (P < 0.05). CONCLUSION: Propofol-remifentanil intravenous anesthesia combined with long-acting local anesthetic regional block anesthesia, combined with laryngeal mask ventilation technology without muscle relaxants, can be safely used in pediatric eye surgery to achieve rapid and smooth recovery from general anesthesia and better postoperative analgesia. This anesthesia scheme can improve the comfort and safety of children in perioperative period, and has a certain clinical popularization value.

[Comparison of Two Methods With a Left-Sided Double-Lumen Tube for Endobronchial Intubation].

Objective To compare the success rates of two methods for endobronchial intubation:the left-sided double-lumen tube(DLT) rotated 90° counter-clockwise with the patient head at the mid positon and the tube rotated 180° counter-clockwise with the patient head turned to the right. Methods Six hundred and forty-eight patients were enrolled in this study,who were to undergo elective thoracic surgery by left-sided DLT intubation in the Peking Union Medical College Hospital from December 2021 to June 2022.They were randomized into a 90° group and a 180° group,with 324 patients in each group.In the 90° group,with the patient head kept at the mid position,the left-sided DLT was advanced until the bronchial cuff passed the vocal cords and then rotated 90° counter-clockwise.In the 180°group,with the left mandible angle of each patient in the straight line with the sternum,the tube was advanced until the bronchial cuff passed the vocal cords and then rotated 180° counter-clockwise.The intubation success rate and the intubation-related complications such as carina mucosal injuries were compared between the two groups. Results The 648 patients included 336 males and 312 females,with the age ranging from 39.0 to 75.0 years old and the average age of(54.6±9.0) years old.The success rate of first intubation was 80.3% in the 90° group and 75.0% in the 180° group,which showed no significant difference(P=0.109).The success rate of second intubation was higher in the 180° group than in the 90° group(P<0.001).The rate of carina mucosal injuries was 23.8% in the 90° group and 25.6% in the 180° group,which showed no significant difference(P=0.585). Conclusions Compared with the conventional method(90°),the intubation of the left-sided DLT rotated 180° counter-clockwise with the patient head turned to the right cannot improve the success rate of the first intubation.However,it could improve the success rate of reintubation as a remedy.

Atropisomeric Carboxylic Acids Synthesis via Nickel-Catalyzed Enantioconvergent Carboxylation of Aza-Biaryl Triflates with CO2.

Upgrading CO2 to value-added chiral molecules via catalytic asymmetric C-C bond formation is a highly important yet challenging task. Although great progress on the formation of centrally chiral carboxylic acids has been achieved, catalytic construction of axially chiral carboxylic acids with CO2 has never been reported to date. Herein, we report the first catalytic asymmetric synthesis of axially chiral carboxylic acids with CO2, which is enabled by nickel-catalyzed dynamic kinetic asymmetric reductive carboxylation of racemic aza-biaryl triflates. A variety of important axially chiral carboxylic acids, which are valuable but difficult to obtain via catalysis, are generated in an enantioconvergent version. This new methodology features good functional group tolerance, easy to scale-up, facile transformation and avoids cumbersome steps, handling organometallic reagents and using stoichiometric chiral materials. Mechanistic investigations indicate a dynamic kinetic asymmetric transformation process induced by chiral nickel catalysis.

Robotic thyroidectomy using gas-insufflation one-step single-port transaxillary (GOSTA) approach.

BACKGROUND: We conducted this study to report our novel robotic thyroidectomy using gas-insufflation one-step single-port transaxillary (GOSTA) approach and compare it with a conventional transaxillary (CTA) approach using a retraction method for intraoperative and postoperative outcomes. METHODS: We retrospectively analyzed 354 patients who underwent robotic thyroidectomy between January 2019 and April 2023. Of these patients, 143 underwent the procedure through the GOSTA approach, which involves a small incision of 3 cm along the axillary folds with both arms down and a gas-insufflation, from skin flap creation to the completion of thyroidectomy as a one-step single-port procedure without the need for a retractor. The remaining 211 patients underwent the CTA approach. We analyzed the GOSTA approach and compared the surgical outcomes of the GOSTA (n = 100) and CTA (n = 167) approaches in patients with differentiated thyroid cancer who underwent thyroid lobectomy. RESULTS: Out of the 143 patients who underwent the GOSTA approach, 12 underwent total thyroidectomy and 9 underwent lateral neck lymph node dissection with total thyroidectomy. GOSTA-thyroid lobectomy was performed on 122 patients; of these, 100 were diagnosed with differentiated thyroid carcinoma. A comparative study with the CTA approach was only conducted in patients who underwent thyroid lobectomy. No significant differences were found in operative time, hospital stay, or complications between the two groups. CONCLUSIONS: Despite proceeding in one-step with a single smaller incision, from skin flap creation to the completion of thyroidectomy, the GOSTA approach is as feasible and safe as the CTA approach. Additionally, the GOSTA approach allows for thyroidectomy without using a retractor and reduces the workload for the surgeon and assistants.

Increased risk of suicidality in patients with psoriasis: A Nationwide cohort study in Korea.

BACKGROUND: Psoriasis has a devastating psychological impact on patients' quality of life. However, the relationship between suicidality and psoriasis remains unclear. OBJECTIVE: This study analysed and compared the risk of suicidality (suicidal ideation, suicide attempt and completed suicide) between patients with psoriasis and the general population. METHODS: This nationwide, population-based, retrospective, cohort study analysed the Korean National Health Insurance Service claim data from 2005 to 2018. RESULTS: The study included 348,439 patients with psoriasis aged over 18 years and with age- and sex-matched controls. The risk of suicidality was higher in the psoriasis group than in the control group [adjusted hazard ratio (aHR) 1.21; 95% confidence interval (CI), 1.18-1.24]. The aHR of suicidality was higher in the psoriatic arthritis group (aHR, 1.46; 95% CI, 1.39-1.54) than in the psoriasis-alone group (aHR, 1.17; 95% CI, 1.13-1.20). However, the severity of psoriasis and suicidality showed no correlation (mild psoriasis group: aHR, 1.22; 95% CI, 1.18-1.25; moderate-to-severe psoriasis group: aHR, 1.16; 95% CI, 1.10-1.23). CONCLUSION: Patients with psoriasis have an increased risk of suicidality. In particular, the presence of arthritis in patients had a more significant effect on the risk of suicidality.

FAM64A aggravates proliferation, invasion, lipid droplet formation, and chemoresistance in gastric cancer: A biomarker for aggressiveness and a gene therapy target.

FAM64A is a mitogen-induced regulator of the metaphase and anaphase transition. Here, we found that FAM64A messenger RNA (mRNA) and protein expression levels were higher in gastric cancer tissue than in normal mucosa (p < .05). FAM64A methylation was negatively correlated with FAM64A mRNA expression (p < .05). The differentially expressed genes of FAM64A were mainly involved in digestion, potassium transporting or exchanging ATPase, contractile fibers, endopeptidase, and pancreatic secretion (p < .05). The FAM64A-related genes were principally categorized into ubiquitin-mediated proteolysis, cell cycle, chromosome segregation and mitosis, microtubule binding and organization, metabolism of amino acids, cytokine receptors, lipid droplet, central nervous system, and collagen trimer (p < .05). FAM64A protein expression was lower in normal gastric mucosa than intestinal metaplasia, adenoma, and primary cancer (p < .05), negatively correlated with older age, T stage, lymphatic and venous invasion, tumor, node, metastasis stage, and dedifferentiation (p < .05), and associated with a favorable overall survival of gastric cancer patients. FAM64A overexpression promoted proliferation, antiapoptosis, migration, invasion, and epithelial-mesenchymal transition via the EGFR/Akt/mTOR/NF-κB, while the opposite effect was observed for FAM64A knockdown. FAM64A also induced chemoresistance directly or indirectly through lipid droplet formation via ING5. These results suggested that upregulation of FAM64A expression might induce aggressive phenotypes, leading to gastric carcinogenesis and its subsequent progression. Thus, FAM64A could be regarded as a prognosis biomarker and a target for gene therapy.

Photocatalytic Carboxylation of C-N Bonds in Cyclic Amines with CO2 by Consecutive Visible-Light-Induced Electron Transfer.

Visible-light photocatalytic carboxylation with CO2 is highly important. However, it still remains challenging for reluctant substrates with low reduction potentials. Herein, we report a novel photocatalytic carboxylation of C-N bonds in cyclic amines with CO2 via consecutive photo-induced electron transfer (ConPET). It is also the first photocatalytic reductive ring-opening reaction of azetidines, pyrrolidines and piperidines. This strategy is practical to transform a variety of easily available cyclic amines to valuable ß-, γ-, δ- and ϵ-amino acids in moderate-to-excellent yields. Moreover, the method also features mild and transition-metal-free conditions, high selectivity, good functional-group tolerance, facile scalability and product derivations. Mechanistic studies indicate that the ConPET might be the key to generating highly reactive photocatalysts, which enable the reductive activation of cyclic amines to generate carbon radicals and carbanions as the key intermediates.

Electroreductive Dicarboxylation of Unactivated Skipped Dienes with CO2.

Carboxylation of easily available alkenes with CO2 is highly important to afford value-added carboxylic acids. Although dicarboxylation of activated alkenes, especially 1,3-dienes, has been widely investigated, the challenging dicarboxylation of unactivated 1,n-dienes (n>3) with CO2 remains unexplored. Herein, we report the first dicarboxylation of unactivated skipped dienes with CO2 via electrochemistry, affording valuable dicarboxylic acids. Control experiments and DFT calculations support the single electron transfer (SET) reduction of CO2 to its radical anion, which is followed by sluggish radical addition to unactivated alkenes, SET reduction of unstabilized alkyl radicals to carbanions and nucleophilic attack on CO2 to give desired products. This reaction features mild reaction conditions, broad substrate scope, facile derivations of products and promising application in polymer chemistry.

Electrochemical Ring-Opening Dicarboxylation of Strained Carbon-Carbon Single Bonds with CO2: Facile Synthesis of Diacids and Derivatization into Polyesters.

Diacids are important monomers in the polymer industry to construct valuable materials. Dicarboxylation of unsaturated bonds, such as alkenes and alkynes, with CO2 has been demonstrated as a promising synthetic method. However, dicarboxylation of C─C single bonds with CO2 has rarely been investigated. Herein we report a novel electrochemical ring-opening dicarboxylation of C─C single bonds in strained rings with CO2. Structurally diverse glutaric acid and adipic acid derivatives were synthesized from substituted cyclopropanes and cyclobutanes in moderate to high yields. In contrast to oxidative ring openings, this is also the first realization of an electroreductive ring-opening reaction of strained rings, including commercialized ones. Control experiments suggested that radical anions and carbanions might be the key intermediates in this reaction. Moreover, this process features high step and atom economy, mild reaction conditions (1 atm, room temperature), good chemoselectivity and functional group tolerance, low electrolyte concentration, and easy derivatization of the products. Furthermore, we conducted polymerization of the corresponding diesters with diols to obtain a potential UV-shielding material with a self-healing function and a fluorine-containing polyester, whose performance tests showed promising applications.

Radical Carboxylative Cyclizations and Carboxylations with CO2.

Carbon dioxide (CO2) is not only a greenhouse gas and a common waste product but also an inexpensive, readily available, and renewable carbon resource. It is an important one-carbon (C1) building block in organic synthesis for the construction of valuable compounds. However, its utilization is challenging owing to its thermodynamic stability and kinetic inertness. Although significant progress has been achieved, many limitations remain in this field with regard to the substrate scope, reaction system, and activation strategies.Since 2015, our group has focused on CO2 utilization in organic synthesis. We are also interested in the vast possibilities of radical chemistry, although the high reactivity of radicals presents challenges in controlling selectivity. We hope to develop highly useful CO2 transformations involving radicals by achieving a balance of reactivity and selectivity under mild reaction conditions. Over the past 6 years, we along with other experts have disclosed radical-type carboxylative cyclizations and carboxylations using CO2.We initiated our research by realizing the Cu-catalyzed radical-type oxytrifluoromethylation of allylamines and heteroaryl methylamines to generate valuable 2-oxazolidones with various radical precursors. Apart from Cu catalysis, visible-light photoredox catalysis is also a powerful method to achieve efficient carboxylative cyclization. In these cases, single-electron-oxidation-promoted C-O bond formation between benzylic radicals and carbamates is the key step.Since carboxylic acids exist widely in natural products and bioactive drugs and serve as important bulk chemicals in industry, we realized further visible-light-promoted carboxylations with CO2 to construct such chemicals. We have achieved the selective umpolung carboxylations of imines, enamides, tetraalkylammonium salts, and oxime esters by successive single-electron-transfer (SSET) reduction. Using this strategy, we have also realized the dearomative arylcarboxylation of indoles with CO2. In addition to the incorporation of 1 equiv of CO2 per substrate, we have recently developed a visible-light photoredox-catalyzed dicarboxylation of alkenes, allenes, and (hetero)arenes via SSET reduction, which allows the incorporation of two CO2 molecules into organic compounds to generate valuable diacids as polymer precursors.In addition to the two-electron activation of CO2, we sought to develop new strategies to realize efficient and selective transformations via single-electron activation of CO2. Inspired by the hypothetical electron-transfer mechanism of iron-sulfur proteins, we have realized the visible-light-driven thiocarboxylation of alkenes with CO2 using catalytic iron salts as promoters. The in-situ-generated Fe/S complexes are likely able to reduce CO2 to its radical anion, which could react with alkenes to give a stabilized carbon radical. Moreover, we have also disclosed charge-transfer complex (CTC) formation between thiolate and acrylate/styrene to realize the visible-light-driven hydrocarboxylation of alkenes with CO2 via generation of a CO2 or alkene radical anion. On the basis of this novel CTC, the visible-light-driven organocatalytic hydrocarboxylation of alkenes with CO2 has also been realized using a Hantzsch ester as an effective reductant.

Forecasting groundwater level of karst aquifer in a large mining area using partial mutual information and NARX hybrid model.

Predicting the groundwater level of karst aquifers in North China Coalfield is essential for early warning of mine water hazards and regional water resources management. However, the dynamic changes of strata structure and hydrogeological parameters driven by coal mining activity cause challenges to the process-oriented groundwater model. In order to achieve accurate prediction of groundwater level in large mining areas, this study was the first to use the data-driven Nonlinear Autoregressive with External Input (NARX) model to predict the groundwater level of six karst aquifer observation wells in Pingshuo Mining Area. Three variable input scenarios were set up, solely considering meteorological factors, anthropogenic disturbance factors, and considering both meteorological and anthropogenic disturbance factors. The novel partial mutual information (PMI) screening algorithm was adopted to determine optimized input variables in each scenario. The input and feedback delay coefficients of NARX model were determined by using Seasonal-trend Decomposition Procedure Based on Loess (STL) algorithm and auto- and cross-correlation functions. The results showed that PMI algorithm can effectively screen out the optimal input variables for predicting groundwater level, the NSE coefficients of the PMI-NARX models under the three scenarios were 38.81%, 4.26% and 41.46% higher than those of the corresponding control experiments, respectively. In addition, the prediction performance of the PMI-NARX built on the basis of meteorological factors is poor (NSE <0.63). However, in scenarios which solely use anthropogenic disturbance factors and both use meteorological and anthropogenic disturbance factors, the PMI-NARX coupling models exhibit good prediction performance (NSE and R2 are all greater than 0.8). Especially under solely considering anthropogenic disturbance factors scenario, the model still exhibited good prediction accuracy with a negligible number of input variables. The results can provide technical and theoretical support for the prediction of groundwater level in other mining areas.

Lower Incidence of Postoperative Urinary Retention in Robotic Total Mesorectal Excision for Low Rectal Cancer Compared with Laparoscopic Surgery.

INTRODUCTION: The incidence and clinical significance of postoperative urinary retention (POUR) remain high. This study aimed to evaluate the incidence of POUR and related risk factors in patients who underwent total mesorectal excision (TMR) for low rectal cancer. METHODS: This study is a retrospective review of a prospectively collected colorectal database from a single center. Data from patients who underwent surgery for low rectal cancer between September 2006 and May 2017 were analyzed to assess the risk factors of POUR. POUR was considered inability to void after urinary catheter removal requiring catheter reinsertion and difficulty in bladder emptying requiring intermittent catheterization. RESULTS: Of 555 patients with low rectal cancer, 78 (14.1%) developed POUR. Based on multivariate logistic regression analysis, laparoscopic TMR (odds ratio [OR]; 2.114, 95% confidence interval [CI]; 1.212-3.689, p = 0.008) and postoperative ileus (OR; 2.389, 95% CI; 1.282-4.450, p = 0.006) were independent risk factors of POUR. Male gender, advanced age, neoadjuvant chemoradiation, longer operative time, abdominoperineal resection, and lateral pelvic lymph node dissection were not associated with POUR. Advanced age over 65 years also failed to show statistical significance (OR; 1.604, 95% CI; 0.965-2.668, p = 0.068). CONCLUSION: Laparoscopic approach and postoperative ileus are risk factors for POUR after low rectal cancer surgery. We postulate that the benefits of robotic surgical systems compared to a laparoscopic approach may reduce the incidence of POUR.

Occurrence, source tracking and removal of antibiotics in recirculating aquaculture systems (RAS) in southern China.

The recirculating aquaculture system (RAS) has attracted much attention in China as a way to rapidly transform and upgrade aquaculture ponds to realize zero-emissions of pollutants in aquaculture tail water. Tail water purification ponds (TWPPs) play an important role in the treatment of aquaculture wastewater. However, until now, there have been few reports on the occurrence of antibiotics in RAS and the removal of antibiotics from the TWPPs of RAS. Therefore, this study focused on the occurrence of antibiotics in a typical ecological RAS. For comparison, the same measurements were simultaneously carried out in nearby open aquaculture ponds and rivers. The pollution level and spatial distribution of antibiotics in the RAS and the removal of antibiotics in the TWPPs were explored. The results showed that (1) eleven and twelve antibiotics were detected in water and sediment samples in the RAS, respectively, but no antibiotics were found in fish muscles and feed. Erythromycin (ERY), lincomycin (LIN), and ciprofloxacin (CFX) were the three main types of antibiotics found in water and sediment samples. (2) The TWPPs of the RAS can effectively remove antibiotics in aquaculture water. The antibiotic concentration in recirculating aquaculture ponds of the RAS was as high as 180 ng/L. After treatments in the TWPPs, the antibiotic concentration of aquaculture water decreased to 81.6 ng/L (3) The antibiotic concentrations in recirculating aquaculture ponds (25.2-180 ng/L) were lower than those in the nearby open aquaculture ponds (126-267.3 ng/L), and the concentration of antibiotics in the sediments of recirculating aquaculture ponds was up to 22.9 ng/g, while that in TWPPs was as high as 56.1 ng/g. In conclusion, the antibiotic residues in the RAS were low after antibiotics were banned in feed in China, and the removal of antibiotics in the TWPPs was more pronounced. Furthermore, cross-contamination was found between the RAS, surrounding open aquaculture ponds and the river, and the water supply of the RAS was likely to be the main contributor of antibiotics in the aquaculture environments. This study can help the government formulate discharge standards for antibiotics in aquaculture and also provide a reference for the transformation and upgrading of aquaculture ponds to achieve a zero-emission aquaculture mode.

The effects of REG4 expression on chemoresistance of ovarian cancer.

Although ovarian cancer usually responds well to platinum- and taxane-based first-line chemotherapy, most patients develop recurrence and chemoresistance. Regenerating gene 4 (REG4) is a secretory protein involved in cell differentiation and proliferation. We found higher REG4 expression in ovarian cancer than in normal tissues (p < .05). Regenerating gene 4 expression was negatively associated with overall, progression-free or post-progression survival rates of patients with ovarian cancer receiving platinum or paclitaxel treatment (p < .05) according to a Kaplan-Meier plotter. Regenerating gene 4 overexpression resulted in either cisplatin or paclitaxel resistance, and apoptosis resistance in CAOV3 ovarian cancer cells (p < .05). REG4-transfected ovarian cancer cells showed stronger migration and invasion treated with cisplatin or paclitaxel (p < .05). Additionally, cisplatin or paclitaxel exposure led to the overexpression of phosphorylated phosphoinositide 3-kinase (p-PI3K), p-Akt, phosphorylated mammalian target of rapamycin (p-mTOR), glutathione S-transferase-π, survivin, and B-cell lymphoma 2 in REG4 transfectants compared with control cells (p < .05). These findings suggested that REG4 expression was up-regulated in ovarian cancer, and associated with poor survival and chemotherapy resistance. REG4 promoted the occurrence, development, and chemotherapy resistance of ovarian cancer by regulating cell proliferation, apoptosis, migration, and invasion, and PI3K/Akt/m-TOR signalling pathways. IMPACT STATEMENTWhat is already known on this subject? REG4 mRNA expression is up-regulated in many digestive cancers. High REG4 expression was associated with an adverse prognosis, high tumour and nodal stages, poor differentiation, and hepatic and peritoneal metastases of digestive cancers. REG4 expression conferred cancer cells with increased resistance to chemoradiotherapy, especially 5-FU-based treatment, by activating the MAPK/Erk/Bim signalling pathway.What do the results of this study add? REG4 was highly expressed in ovarian cancer. The expression of p-PI3K, p-AKT, p-mTOR, GST-π, survivin, and Bcl-2 was increased in REG4-overexpressing cells. High REG4 expression was significantly associated with inferior OS, PFS, and PPS rates in patients with ovarian cancer receiving platinum chemotherapy. REG4 mediated cisplatin and paclitaxel resistance in CAOV3 ovarian cancer cells. The percentage of apoptotic cells was markedly lower in REG4-transfected compared to mock-transfected cells after cisplatin or paclitaxel treatment.What are the implications of these findings for clinical practice and/or further research? This study aimed to evaluate the prognostic significance of REG4 expression in ovarian cancer treated with platinum and paclitaxel, to explore REG4 chemoresistance mechanisms to platinum and paclitaxel, and to provide a scientific experimental basis for the clinical treatment and outcome evaluation of ovarian cancer. In order to provide comprehensive clinical treatment of ovarian cancer, it is helpful to improve our understanding of multi-drug resistance and identify new cancer diagnostic biomarkers.