Design, Synthesis, and Biological Evaluation of Phenyloxadiazole Sulfoxide Derivatives as Potent Pseudomonas aeruginosa Biofilm Inhibitors.

With the development of antimicrobial agents, researchers have developed new strategies through key regulatory systems to block the expression of virulence genes without affecting bacterial growth. This strategy can minimize the selective pressure that leads to the emergence of resistance. Quorum sensing (QS) is an intercellular communication system that plays a key role in the regulation of bacterial virulence and biofilm formation. Studies have revealed that the QS system controls 4-6% of the total number of P. aeruginosa genes, and quorum sensing inhibitors (QSIs) could be a promising target for developing new prevention and treatment strategies against P. aeruginosa infection. In this study, four series of phenyloxadiazole and phenyltetrazole sulfoxide derivatives were synthesized and evaluated for their inhibitory effects on P. aeruginosa PAO1 biofilm formation. Our results showed that 5b had biofilm inhibitory activity and reduced the production of QS-regulated virulence factors in P. aeruginosa. In addition, silico molecular docking studies have shown that 5b binds to the P. aeruginosa QS receptor protein LasR through hydrogen bond interaction. Preliminary structure-activity relationship and docking studies show that 5b has broad application prospects as an anti-biofilm compound, and further research will be carried out in the future to solve the problem of microbial resistance.

Discovery of 2,5-disubstituted furan derivatives featuring a benzamide motif for overcoming P-glycoprotein mediated multidrug resistance in MCF-7/ADR cell.

P-glycoprotein (P-gp) is one of the drug efflux transporters that triggers multidrug resistance (MDR) in cells. Herein, by utilizing the strategies of active skeleton splicing and structural optimization on the lead compound 5 m, a total of 50 novel 2,5-disubstituted furan derivatives were designed, synthesized, and screened for P-gp inhibitory activity. The structure-activity relationship analysis enabled the identification of an important pharmacophore N-phenylbenzamide, which resulted in the discovery of a promising drug lead compound Ⅲ-8. Ⅲ-8 possesses broad-spectrum reversal activity and low toxicity in MCF-7/ADR cells. Western blot and Rh123 accumulation assay demonstrated that Ⅲ-8 displayed the reversal activity by inhibiting P-gp efflux. Molecular docking analysis indicated a potent affinity of Ⅲ-8 to P-gp by forming H-bond interactions with residues Asn 721 and Met 986. Ⅲ-8 was determined to be a highly effective and safe P-gp inhibitor in an MCF-7/ADR xenograft mouse model.

Design, synthesis, and biological evaluation of benzoheterocyclic sulfoxide derivatives as quorum sensing inhibitors in Pseudomonas aeruginosa.

Six series of benzoheterocyclic sulfoxide derivatives were designed and synthesised as Pseudomonas aeruginosa (P. aeruginosa) quorum sensing inhibitors in this paper. We experimentally demonstrated that 6b significantly inhibited the formation of P. aeruginosa PAO1 biofilm without affecting the growth. Further mechanistic studies showed that 6b affected the luminescence of quorum sensing reported strain PAO1-lasB-gfp and the production of P. aeruginosa PAO1 elastase virulence factor which was regulated by las system. These experimental results indicate that 6b acts as a quorum sensing inhibitor mainly through the las system. Furthermore, silico molecular docking studies demonstrated that 6b and the P. aeruginosa quorum sensing receptor LasR were molecularly bound via hydrogen bonding interactions. Preliminary structure-activity relationship and docking studies illustrated that 6b shows great promise as anti-biofilm compounds for further studies in order to solve the problem of microbial resistance in future.

Research progress of different minimally invasive spinal decompression in lumbar spinal stenosis / 中国修复重建外科杂志

OBJECTIVE@#To review the application and progress of different minimally invasive spinal decompression in the treatment of lumbar spinal stenosis (LSS).@*METHODS@#The domestic and foreign literature on the application of different minimally invasive spinal decompression in the treatment of LSS was extensively reviewed, and the advantages, disadvantages, and complications of different surgical methods were summarized.@*RESULTS@#At present, minimally invasive spinal decompression mainly includes microscopic bilateral decompression, microendoscopic decompression, percutaneous endoscopic lumbar decompression, unilateral biportal endoscopy, and so on. Compared with traditional open surgery, different minimally invasive spinal decompression techniques can reduce the operation time, intraoperative blood loss, and postoperative pain of patients, thereby reducing hospital stay and saving treatment costs.@*CONCLUSION@#The indications of different minimally invasive spinal decompression are different, but there are certain advantages and disadvantages. When patients have clear surgical indications, individualized treatment plans should be formulated according to the symptoms and signs of patients, combined with imaging manifestations.

The Molecular Architecture of Pseudomonas aeruginosa Quorum-Sensing Inhibitors.

The survival selection pressure caused by antibiotic-mediated bactericidal and bacteriostatic activity is one of the important inducements for bacteria to develop drug resistance. Bacteria gain drug resistance through spontaneous mutation so as to achieve the goals of survival and reproduction. Quorum sensing (QS) is an intercellular communication system based on cell density that can regulate bacterial virulence and biofilm formation. The secretion of more than 30 virulence factors of P. aeruginosa is controlled by QS, and the formation and diffusion of biofilm is an important mechanism causing the multidrug resistance of P. aeruginosa, which is also closely related to the QS system. There are three main QS systems in P. aeruginosa: las system, rhl system, and pqs system. Quorum-sensing inhibitors (QSIs) can reduce the toxicity of bacteria without affecting the growth and enhance the sensitivity of bacterial biofilms to antibiotic treatment. These characteristics make QSIs a popular topic for research and development in the field of anti-infection. This paper reviews the research progress of the P. aeruginosa quorum-sensing system and QSIs, targeting three QS systems, which will provide help for the future research and development of novel quorum-sensing inhibitors.

Electroacupuncture versus sham electroacupuncture in the treatment of postoperative ileus after laparoscopic surgery for colorectal cancer: study protocol for a multicentre, randomised, sham-controlled trial.

INTRODUCTION: Postoperative ileus (POI) is an inevitable complication of almost all abdominal surgeries, which results in prolonged hospitalisation and increased healthcare costs. Various treatment strategies have been developed for POI but with limited success. Electroacupuncture (EA) might be a potential therapy for POI. However, evidence from rigorous trials that evaluated the effectiveness of EA for POI is limited. Thus, the aim of this study was to examine whether EA can safely reduce the time to the first defecation after laparoscopic surgery in patients with POI. METHODS AND ANALYSIS: This multicentre randomised sham-controlled trial will be conducted in four hospitals in China. A total of 248 eligible participants with colorectal cancer who will undergo laparoscopic surgery will be randomly allocated to an EA group and a sham EA group in a 1:1 ratio. Treatment will be performed starting on postoperative day 1 and continued for four consecutive days, once per day. If the participant is discharged within 4 days after surgery, the treatment will cease on the day of discharge. The primary outcome will be the time to first defecation. The secondary outcome measures will include time to first flatus, tolerability of semiliquid and solid food, length of postoperative hospital stay, postoperative nausea and vomiting, abdominal distension, postoperative pain, postoperative analgesic, time to first ambulation, blinding assessment, credibility and expectancy and readmission rate. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of Beijing University of Chinese Medicine (number 2020BZHYLL0116) and the institutional review board of each hospital. The results will be disseminated through peer-reviewed publications. This study protocol (V.3.0, 6 March 2020) involves human participants and was approved by the ethics committees of Beijing University of Chinese Medicine (number 2020BZHYLL0116), Beijing Friendship Hospital Affiliated to Capital Medical University (number 2020-P2-069-01), Beijing Chao-Yang Hospital Affiliated to Capital Medical University (number 2020-3-11-2), National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (number 20/163-2359), and the Affiliated Hospital of Qingdao University (number QYFYKYLL711311920). The participants gave informed consent to participate in the study before taking part. TRIAL REGISTRATION NUMBER: ChiCTR2000038444.

Clinical observation of selective nerve block combined with percutaneous posterior endoscopic cervical discectomy in the treatment of cervical spondylotic radiculopathy / 西安交通大学学报(医学版)

【Objective】 To observe the short-term clinical effect of selective nerve block combined with percutaneous posterior endoscopic cervical discectomy （PPECD） in the treatment of cervical spondylotic radiculopathy. 【Methods】 We reviewed 22 patients who received selective nerve block combined with percutaneous posterior endoscopic cervical discectomy （PPECD） for cervical spondylotic radiculopathy from June 2018 to January 2020. We recorded Japanese Orthopaedic Association （JOA） score for treatment evaluation， visual analogue scale （VAS）， the neck disability index score （NDI） preoperative 1 day， postoperative 1 day， 1 month， 3 months， 6 months and 1 year. All data were imported into SPSS26.0 software for analysis and processing. Quantitative data are expressed as mean ± standard deviation. The scores of neck VAS， arm VAS， JOA and NDI were compared at different time points by repeated measurement analysis of variance. Paired t-test was used to compare each time point after operation and the first day before operation. P<0.05 was considered statistically significant， and the modified MacNab standard was used to evaluate the clinical effect at the last follow-up. 【Results】 All operations were successfully completed under ultrasound-guided selective nerve block combined with endoscopic operation. The average operation time was 125.6 minutes. The intraoperative blood loss was 2-100 mL and the average blood loss was 19.1 mL. All patients were followed up for 15-33 months， with an average follow-up of 24.1 months. No patients had spinal cord， nerve root and vascular injury， dural tear or other complications. Compared with the preoperative VAS score， the VAS score of neck and upper arm decreased significantly （P<0.05）， while the JOA score increased significantly （P<0.05）， and the preoperative NDI score decreased significantly （P<0.05）. At the last follow-up， the modified Macnab criteria showed there were 15 excellent cases， 5 good cases， 2 medium cases and 0 poor case. The excellence rate was 91%. Postoperative magnetic resonance imaging and 3D computed tomography reconstruction of the cervical spine showed that the disc had been fully removed and the nerve root compression at the surgical segment was relieved. 【Conclusion】 Ultrasound-guided selective nerve block combined with percutaneous posterior endoscopic cervical discectomy is a safe and effective minimally invasive surgical method for the treatment of cervical spondylotic radiculopathy with reliable short-term efficacy.

Effect of intervertebral foramina formation on the biomechanics of lumbar spine under finite element simulation spinal endoscopy / 西安交通大学学报(医学版)

【Objective】 To analyze the effect of different range and location of foramen formation on the biomechanics of lumbar spine by three-dimensional finite element analysis （D-FEA）. 【Methods】 A complete model of the lumbar spine （L5）， M0， was developed using the finite element method， and the models M1， M2， M3， M4 and M5 were obtained by sequentially simulating the apical， medial 1/4， 2/4， 3/4 and 4/4 graded resections of the left superior articular process of L5 under a lateral posterior approach with full spinal endoscopy. The displacements were recorded in six conditions： forward flexion， back extension， left and right lateral bending， and left and right lateral rotation. The results were compared between the resected models and the unresected group M0. 【Results】 The three-dimensional finite model of the L4-L5 segment developed in this experiment was valid. Compared with the unresected group M0， the differences in ROM were statistically significant for M1 under forward flexion load （all P<0.05）， M2 under forward flexion and back extension load （all P<0.05）， M3 and M4 under forward flexion， back extension and left and right lateral bending load （all P<0.05）. The differences were statistically significant for M3 and M4 under anterior flexion， posterior extension， left and right lateral flexion， and right rotation loads （all P<0.05）； and for M5 under anterior flexion， posterior extension， left and right lateral flexion and right rotation loads （all P<0.05）. Compared with M0 in the unresected group， the differences were statistically significant for M1 under anterior flexion loads （all P<0.05）， M2 under anterior flexion and left and right rotation loads （all P<0.05）. The differences were statistically significant for M3， M4 and M5 in forward flexion and extension， left and right lateral flexion， and left and right rotational loading （all P<0.05）. 【Conclusion】 In the process of foramen formation， removal of the tip or the medial quarter of the unilateral single segment of the upper articular process of the lumbar spine will affect the stability of the lumbar spine， and increase the maximum value of the stress of the intervertebral disc during the activities of the lumbar spine. Removal of one half or more will significantly damage the biomechanics of the lumbar spine. In order to avoid damaging the normal biomechanics of the lumbar spine， the upper articular process should be protected as much as possible during the whole spinal endoscopic foraminal reconstruction.

Ultrasensitive electrochemical genosensor for detection of CaMV35S gene with Fe3O4-Au@Ag nanoprobe.

We report an attomolar sensitive electrochemical genosensor for the detection of cauliflower mosaic virus 35S (CaMV35S) gene. The sandwich-type genosensor uses gold-silver core-shell (Au@Ag)-loaded iron oxide (Fe3O4) nanocomposite (Fe3O4-Au@Ag) as label of signal DNA probe (sDNA). Electrochemical sensing is accomplished at interface of electrodeposited AuNPs and carboxylated multiwalled carbon nanotubes-modified glassy carbon electrode through the specific interaction between the capture probe and target CaMV35S (tDNA), and tDNA and the labeled sDNA. The detection sensitivity was improved by the amplified reduction signal of hydrogen peroxide (H2O2), which takes advantage of the enhanced electrocatalytic activity of Fe3O4-Au@Ag. Under the optimal experimental conditions, an ultralow limit of detection was calculated to be 1.26 × 10-17 M (S/N = 3), and the blank value subtracted reduction signal of H2O2 of the sensor increased linearly with the logarithm of CaMV35S concentration over a wide range (1 × 10-16 M to 1 × 10-10 M). This genosensor displayed excellent stability, selectivity and reproducibility, and was successful in detecting the target CaMV35S in genetically modified tomato samples.

Accuracy of endoscopic ultrasound in rectal cancer and its use in transanal endoscopic microsurgery.

Introduction: This study evaluated the accuracy of endoscopic ultrasound (EUS) for preoperative staging of rectal cancer and guiding the treatment of transanal endoscopic microsurgery (TEM) in early rectal cancer.Material and methods: One-hundred-twenty-six patients with rectal cancer were staged preoperatively using EUS and the results were compared with postoperative histopathology results. Radical surgeries, including low anterior resection (LAR), abdominal-perineal resection (APR) and Hartmann surgeries, were performed on patients with advanced rectal cancers, and TEM was performed on patients with stage T1. The Kappa statistic was used to determine agreement between EUS-based staging and pathology staging.Results: The overall accuracies of EUS for T and N stage were 90.8% (Kappa = 0.709) and 76.7% (Kappa = 0.419), respectively. The accuracies of EUS for uT1, uT2, uT3, and uT4 stages were 96.8%, 92.1%, 84.1%, and 88.9%, respectively, and for uN0, uN1, and uN2 stages, they were 71.9%, 64.9%, and 93.0%, respectively. Twelve patients underwent TEM and received confirmed pathology results of early rectal cancer. After postoperative follow-up, there were no local recurrences or distant metastases.Conclusion: EUS is a good and comparable technique for postoperative staging of rectal cancer. Moreover, EUS is used as indicator for preoperative staging and tumor assessment strategy when considering TEM.

Shunt products of aminoansamycins from aas1 overexpressed mutant strain of Streptomyces sp. S35 / 中国天然药物

Constitutively expression of the pathway-specific activators is an effective method to activate silent gene clusters and improve natural product production. In this study, nine shunt products of aminoansamycins (1-9) were identified from a recombinant mutant strain S35-LAL by overexpressed the large-ATP-binding regulator of the LuxR family (LAL) gene aas1 in Streptomyces sp. S35. All the compounds showed no anti-microbial, anti-T3SS and cytotoxic activities.

A new briarane-type diterpenoid from the South China Sea gorgonian Junceella fragilis / 药学学报

The chemical constituents of gorgonian Junceella fragilis Ridley, collected from Ximao Island, the South China Sea, were investigated. A new briarane-type diterpenoid, named fragilide Y (1), together with five known compounds (2–6), namely fragilide D (2), cholesterol (3), ergosterol peroxide (4), 2'-deoxythymidine (5) and cis-thyminenol (6), were isolated from the acetone extract of J. fragilis. The structure of the new compound 1 was elucidated by extensive spectroscopic analysis, while the known compounds were identified by comparison with the reported data. In bioassay, none of these compounds displayed obvious anti-inflammatory and cytotoxic effects.

Enhancing the Contact Area of Ti Wire as Photoanode Substrate of Flexible Fiber-Type Dye-Sensitized Solar Cells Using the TiO2 Nanotube Growth and Removal Technique.

The fiber-type dye-sensitized solar cell (FDSSC) with flexible and dim-light workable features is one of the promising energy generation devices for soft electronics. A novel TiO2 nanotube (TNT) growth and removal technique is proposed in this study to enhance the contact area of the Ti wire substrate using anodization and ultrasonication processes. Smaller and denser imprints of TNT on the surface of Ti wire are obtained when a smaller voltage was applied for anodization. The thickness of the TiO2 nanoparticle layer coated on the Ti wire is also optimized by varying the dip-coating layers. With the smallest diameter and densest distribution of TNT imprints on the Ti wire, the FDSSC with the TiO2/TNT-printed Ti wire photoanode, prepared using 30 V as the anodization voltage, shows the highest photon-to-electricity efficiency of 2.37% as a result of the rough surface of Ti wire substrate, which provides more contact, as well as the suitable thickness of the TiO2 nanoparticle layer, which promotes charge generation and transportation. The smallest charge-transfer resistance and the highest electron collection efficiency are also obtained in this case, as examined using the electrochemical impedance spectroscopy and intensity modulated photocurrent spectroscopy/intensity modulated photovoltage spectroscopy. This facile TNT growth and removal technique is expected to be able to be applied to other fields for enhancing the contact area of the titanium substrate and promoting the generation of electrochemical reactions.

Madelung's Disease: Is Insobriety the Chief Cause?

BACKGROUND: Madelung's disease (MD) is a rare disease of unknown etiology that is characterized by massive fatty deposits distributed in a symmetrical pattern mainly in the head, neck, and upper trunk. Here, we sought to explore the pathogeny and treatment of MD. METHODS: We enrolled ten patients who underwent surgical operations and one patient who refused an operation at our hospital between January 2009 and December 2016. We collected their medical histories and the preoperative and postoperative serological indices. The serum chemistry clinical outcomes were compared between the preoperative and postoperative states. RESULTS: The mean alcohol intake of the eleven patients exceeded 450 g daily. Ten patients underwent open excisions, and the other patient refused an operation. No significant differences were observed between the preoperative and postoperative serum chemistry results. No recurrence has yet been observed in any of the ten operated patients. CONCLUSIONS: All of the patients in our study had associated alcoholism. Thus, insobriety might be one of the causes of MD. We believe that open operations may be an effective treatment based on the outcomes of the surgeries. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Rupture of sigmoid colon caused by compressed air.

Compressed air has been generally used since the beginning of the 20(th) century for various applications. However, rupture of the colon caused by compressed air is uncommon. We report a case of pneumatic rupture of the sigmoid colon. The patient was admitted to the emergency room complaining of abdominal pain and distention. His colleague triggered a compressed air nozzle against his anus as a practical joke 2 h previously. On arrival, his pulse rate was 126 beats/min, respiratory rate was 42 breaths/min and blood pressure was 86/54 mmHg. Physical examination revealed peritoneal irritation and the abdomen was markedly distended. Computed tomography of the abdomen showed a large volume of air in the abdominal cavity. Peritoneocentesis was performed to relieve the tension pneumoperitoneum. Emergency laparotomy was done after controlling shock. Laparotomy revealed a 2-cm perforation in the sigmoid colon. The perforation was sutured and temporary ileostomy was performed as well as thorough drainage and irrigation of the abdominopelvic cavity. Reversal of ileostomy was performed successfully after 3 mo. Follow-up was uneventful. We also present a brief literature review.

Spontaneous perforation of pyometra presenting as acute abdomen: a rare condition with considerable mortality.

Pyometra is an uncommon and potentially lethal disease that occurs mainly in postmenopausal women. Spontaneous perforation of pyometra presenting as acute abdomen is an extremely rare complication of pyometra, and the patients are always admitted to the emergency department. An additional case is reported herein. In addition, a literature review was performed between 1949 and 2015. A correct preoperative diagnosis was made in 21.05% of all the cases. Of all cases, 25.71% were associated with malignant disease. The mortality rate of spontaneous perforation of pyometra is 31.88%. Thus, it should be considered in the differential diagnosis of acute abdomen in elderly women. Total hysterectomy along with bilateral salpingo-oophorectomy is the preferred treatment. Administration of broad-spectrum antibiotics and postoperative intensive care support are essential to reduce the high mortality.

Iridium-catalyzed asymmetric hydrogenation of 2-pyridyl cyclic imines: a highly enantioselective approach to nicotine derivatives.

A highly efficient asymmetric hydrogenation of cyclic imines containing a pyridyl moiety was established by using iridium catalysts with chiral spiro phosphine-oxazoline ligands. This process will facilitate the development of new nicotine-related pharmaceuticals. The introduction of a substituent at the ortho position of the pyridyl ring to reduce its coordinating ability ensures the success of the hydrogenation and excellent enantioselectivity.

Siderochelins with anti-mycobacterial activity from Amycolatopsis sp. LZ149 / 中国天然药物

Three new compounds, namely siderochelins D (2), E (3), and F (4), together with one known siderochelin A (1), were isolated from Amycolatopsis sp. LZ149 and elucidated by spectroscopic analyses including1D- and 2D-NMR and X-ray single crystal diffraction. Compounds 1-3 showed antibacterial activity against Mycobacterium smegmatis.

Chemical constituents of the aerial parts of Emilia sonchifolia (II) / 中国药学杂志

OBJECTIVE: To study the chemical constituents of the aerial parts of Emilia sonchifolia. METHODS: The chemical constituents were isolated and purified by chromatographies on silica gel, MCI gel, ODS, and Sephadex LH - 20 columns, as well as RP-HPLC. And their structures were identified on the basis of physicochemical properties and spectral data. RESULTS: Eighteen compounds were obtained from the aerial parts of E. sonchifolia and identified as isorhamnetin-3-O-α-L-rhamnopyranoside(1), afzelin (2), quercetin-7-O-α-L-rhamnopyranoside(3), 5, 2', 6'-trihydroxy-7-methoxyflavone 2'-O-β-D-glucopyranoside(4), quercetin-3-O- α-L-rhamnopyranoside(5), diosmin(6), isorhamnetin-3-O-rutinoside(7), linarin(8), vitexin(9), quercetin-7-O-β-D-glucopyranoside(10), vicenin-2(11), methyl 4-hydroxybenzeneacetate(12), 3, 4-dihydroxybenzeneacetic acid(13), brevifolin(14), chlorogenic acid(15), methyl chlorogenate(16), pedatisectine E(17), and uridine(18), respectively. CONCLUSION: All compounds are isolated from this genus for the first time except compounds 5 and 11.