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Background Surgery is an important component in the treatment of esophageal cancer. For patients not eligible for R0 resection, defined as locally advanced unresectable esophageal cancer, a new approach is to transform the cancer into a resectable state by preoperative treatment. However, preoperative chemo/radiation is unsatisfactory. Therefore, the aim of this study was to assess the safety and efficacy of chemo/radiotherapy combined with a programmed cell death protein 1 (PD‐1) inhibitor in the preoperative transformation of unresectable esophageal cancer. Methods Patients were evaluated as having unresectable, locally advanced esophageal cancer at baseline and were re‐evaluated as possible R0 resection candidates after PD‐1 inhibitor treatment. Patient data were derived from the prospective database of Peking University Cancer Hospital Thoracic Surgery I. Preoperative chemotherapy plus PD‐1 inhibitor treatment was defined as “transformation treatment.” The objective response rate, operation rate (proportion of patients who underwent surgery), R0 rate, and treatment safety were analyzed retrospectively. Results A total of 36 patients were enrolled into the study, and 94.4% (34/36) completed the planned transformation treatment. The objective response rate was 71.4% (25/35), and 75% (27/36) of the patients who completed transformation treatment underwent surgery. For these surgical patients, 81.5% (22/27) obtained R0 resection, and 22.2% (6/22) had pathological complete response (pCR). During transformation treatment, 22.2% (8/36) patients had ≥ grade 3 complications. There were no reoperations or perioperative deaths. After surgery, 29.6% (8/27) had ≥ grade 3 complications. Conclusions Esophagectomy after immunotherapy is safe with acceptable complications. Compared with chemotherapy alone, chemotherapy combined with immunotherapy had a more favorable transformation effect for patients with unresectable esophageal cancer., Thirty‐six patients were enrolled. All patients received preoperative immunotherapy and 94.4% (34/36) completed the planned transformation treatment. The objective response rate was 71.4% (25/35), and 75% (27/36) of the patients who completed transformation treatment underwent surgery. For these surgical patients, 81.5% (22/27) obtained R0 resection, and 22.2% (6/22) had pathological complete response (pCR) as confirmed by postoperative pathological report.

Duodenal gastrointestinal stromal tumors (GISTs) constitute a small rare subset. This study aims to analyze the prognostic differences between duodenal and jejunoileal GISTs and evaluate the clinical treatment and prognostic characteristics of patients with duodenal GISTs.Data of patients with primary duodenal or jejunoileal GISTs were collected. Patients were matched through propensity score matching (PSM). Perioperative and long-term outcomes of patients with duodenal GISTs were compared based on surgical approach.Altogether, 101 duodenal and 219 jejunoileal GISTs were identified. In patients with duodenal GISTs, 79 (78%) underwent local resection (LR) and 22 (22%) underwent pancreaticoduodenectomy (PD). Patients undergoing PD had a longer postoperation stay (18.5 vs 13 days, P = 0.001) and more complications (Clavien-Dindo I-II complications for PD vs LR, 31.8 vs 15.2%; Clavien-Dindo III-V complications for PD vs LR, 22.7 vs. 2.5%; P 0.001). There was no difference in recurrence-free survival (RFS) (P = 0.8) or overall survival (OS) (P = 0.9) when comparing patients who underwent LR versus PD. Multivariable analysis showed that tumor size 5 cm was the only independent predictor of shorter RFS (P = 0.004) and OS (P = 0.012). After matching, there was no significant difference in RFS and OS between patients with duodenal versus jejunoileal GISTs (both P 0.05).The prognosis of duodenal and jejunoileal GISTs are similar. Recurrence and OS of duodenal GISTs primarily depend on tumor size. For duodenal GISTs, LR is associated with comparable long-term survival when compared to PD, but with superior short-term outcomes.

Bioorthogonal control of metal ion sensors for imaging metal ions in living cells is important for better understanding of the distribution and fluctuation of metal ions. While bioorthogonal control using external stimuli such as light has been reported, these stimuli are not suitable for investigating many biological systems where light penetration is limited or quantum yield of activation is low. To overcome this limitation, we herein report the endogenous and bioorthogonal activation of a DNAzyme fluorescent sensor containing an 18-base pair (bp) recognition site of a homing endonuclease (I-SceI), since the recognition site of this length is found by chance only once in 7×10(10) bp of genomic sequences, it can thus form a near bioorthogonal pair with I-SceI for DNAzyme activation with minimal effect on living cells. The formation of the recognition site through double stranded DNA hybridization prevents the formation of an active DNAzyme initially. Once I-SceI is expressed inside cells, it cleaves at the recognition site, which allows the DNAzyme to adopt its active conformation. The activated DNAzyme sensor is then able to specifically catalyze cleavage of a substrate strand in the presence of Mg(2+) to release the fluorophore-labeled DNA fragment and produce a fluorescent turn-on signal for Mg(2+). Using this method, we demonstrate the use of I-SceI to activate the 10–23 DNAzyme for imaging of Mg(2+) in HeLa cells with endogenous and bioorthogonal control.

BACKGROUND Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer and most clinically curable patients are diagnosed with locally advanced disease. While the efficacy of preoperative treatment is relatively clear and well characterized, the effect of postoperative treatment, especially postoperative chemotherapy, remains controversial, and its role in the treatment strategy is obscure. We conducted an updated meta-analysis to include recent developments. METHODS A comprehensive search in the PubMed, Embase, and Cochrane databases was performed to identify studies published from the inception of each database to February 2018. The overall survival (OS) and disease-free survival (DFS) rates of patients treated with and without postoperative chemotherapy were analyzed and compared. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the associations between postoperative chemotherapy and patient survival. Potential publication bias was assessed using Egger's line regression test. RESULTS A total of nine studies, including three randomized controlled trials and six retrospective studies, were retrieved from the databases, comprising a total of 1684 cases. The results showed that postoperative chemotherapy could improve OS (HR 0.78, 95% CI 0.66-0.91; P = 0.002) and DFS (HR 0.72, 95% CI 0.6-0.86; P < 0.001). CONCLUSIONS The current meta-analysis supports postoperative chemotherapy as an independent favorable prognostic factor for ESCC, which could improve both OS and DFS.

Background The current study aimed to determine the oncological efficacy and surgical safety of multiple pulmonary resections (MPRs) after prior curative surgery for local regional recurrent or second primary lung cancers. Methods All cases of lung cancer included in our prospective database between January 2000 and July 2015 were retrospectively reviewed. The oncological efficacy endpoints for synchronous and metachronous MPR were five-year overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) rates after the second surgery. The surgical safety endpoints were postoperative mortality and complications (Clavien-Dindo classification) within 30 days. Results In total, 67 MPR cases were identified. There were no significant differences in the five-year OS and DFS between the synchronous MPR group (n = 50) and the propensity score-matched solitary major pulmonary resection group (n = 250) (5-year OS 84.5% vs. 69.0%, log rank P = 0.112; DFS 64.4% vs. 58.0%, log rank P = 0.278). The five-year OS and PFS of the metachronous MPR group (n = 17) were significantly better than those in the non-surgical control group (n = 19) (5-year OS 94.1% vs. 50.7%, log rank P = 0.005; 5-year PFS 53.9% vs. 10.5%, log rank P = 0.020). No postoperative mortality or severe complications occurred in the MPR group. Conclusion The oncological efficacy of MPR is superior to the non-surgical approach for the management of local regional recurrent or second primary lung cancer, with comparable postoperative mortality and complications.

Clarifying the hidden but intrinsic feature of single nanoparticles by nanoelectrochemistry could help understand its potential for diverse applications. The uncontrolled interface and bandwidth limitation in the electrochemical measurement put the obstacle in single particle collision. Here, we demonstrate a well-defined 30 nm nanopore electrode with a rapid chemical-electrochemical fabrication method which provides a high reproducibility in both size and performance. A capacitance-based detection mechanism is demonstrated to achieve a high current resolution of 0.6 pA ±0.1 pA (RMS) and a high the temporal resolution of 0.01 ms. By utilizing this electrode, the dynamic interactions of every single particle in the mixture could be directly read during the collision process. The collision frequency is two orders of magnitude higher than previous reports, which helps reveal the hidden features of nanoparticles during the complex and multidimensional interaction processes.

Aims Human papillomavirus (HPV)-related carcinoma with adenoid cystic-like features is a newly described entity of the sinonasal tract. In this study, we evaluated histomorphology, immunophenotype and molecular testing to identify potentially helpful features in distinguishing it from classic adenoid cystic carcinoma (AdCC). Methods and results We retrospectively collected five HPV-related carcinomas with adenoid cystic-like features and 14 AdCCs of the sinonasal tract. All histological slides were retrieved for morphological evaluation. As comparing with AdCC, HPV-related carcinomas with adenoid cystic-like features were associated with squamous dysplasia of surface epithelium (80% versus 0%, P < 0.01) and the presence of a solid growth pattern (100% versus 29%, P = 0.01), but less densely hyalinized tumour stroma (20% versus 86%, P = 0.02). Squamous differentiation in the invasive tumour was seen in three HPV-related carcinomas with adenoid cystic-like features, two of them showing abrupt keratinization and one with scattered non-keratinizing squamous nests. Diffuse p16 staining in ≥75% of tumour cells was noted in all HPV-related carcinomas with adenoid cystic-like features but in only one AdCC (100% versus 7%, P < 0.01). High-risk HPV testing gave positive results in all HPV-related carcinomas with adenoid cystic-like features (four associated with type 33 and one associated with type 16) but not in AdCCs. MYB rearrangement was tested in four HPV-related carcinomas with adenoid cystic-like features, and all were negative. Conclusions This study has further clarified the histological spectrum of this tumour type, and reports the first HPV type 16-related case. Diffuse p16 staining followed by HPV molecular testing is useful in distinguishing HPV-related carcinomas with adenoid cystic features from classic AdCCs.

Inducible co-expression of multiple genes is often needed in research. Here we describe a single-vector-based Tet-On inducible system for co-expression of two transgenes. The two transgenes (DsRed1 and eGFP as model genes) and reverse tetracycline-controlled transactivator were separated by internal ribosomal entry sites and 2A sequences, and their transcription was controlled by the same tetracycline responsive element. Two novel vectors with different internal ribosomal entry sites and 2A positions on the vectors were constructed. The DsRed1 and eGFP in cells transduced with both vectors are undetectable in the absence of doxycycline and can be efficiently induced in the presence of doxycycline in vitro and in vivo. These two vectors can be useful tools when regulated co-expression of two ecotopic genes is needed.

Bone morphogenetic proteins (BMPs) are TGF-β family member proteins that have therapeutic potential. The amount of BMPs from natural resources is limited, and the production of biologically active BMPs in heterologous protein expression systems remains an obstacle for their clinical application. In this study, the DNA sequence of human BMP4 mature domain (hBMP4) was optimized according to the codon relative synonymous codon usage values in Pichia pastoris, and the A+T content in the sequence after optimization was within the range of 30% to 55%. In Pichia pastoris cultured in shake-flask, the expression level of hBMP4 protein from the optimized sequence (48 mg/L) increased fourfold in comparison with that from the native sequence (12 mg/L). Recombinant hBMP4 protein was purified by SP Sepharose and heparin affinity chromatography. The biological activities of recombinant hBMP4 were examined by measuring proliferation stimulation in cells and induction of ectopic cartilage formation in mouse models. Our results demonstrated that the optimized DNA sequence could significantly enhance hBMP4 protein expression in Pichia pastoris compared with the native sequence and produce biologically active recombinant hBMP4; this indicates the potential of this optimized sequence for bulk production of hBMP4 protein in future clinical applications.

Venus surface age suggests that there may have an extensive resurfacing of its lithosphere in the latest geological history period. Such global resurfacing is closely related to its interior thermal evolution. Base on the physical property and thermal parameters of the Venus and the theory of mantle convection, and considering the control function of the phase transition boundary in mantle convection, we calculate the thermal evolution history of Venus. The results show that Venus' thermal evolution is a non-monotonic cooling process. In this process, Venus' mantle convection displays an overturn with a quasi-periodicity. Being various thermal parameters, the mantle overturning would appear in three different modes, that is, the steadily changing mode, the gradually enhancing mode and the gradually weakening mode. But, we are not sure which mode is the true way in the Venus' thermal evolution. In addition, we take cognizance of that the punctuated turn over and avalanche effect in phase transition layer may play a key role for the Venus' resurfacing and lithosphere rebuilding in about 500 Ma intervals.

Gastrointestinal tract complications after abdominal aortic aneurysm (AAA) repair are well known. The reported frequency ranges from 6.6% to 21%. However, the incidence of duodenal obstruction following AAA has probably been underestimated. This report concerns a 78-year-old male who was admitted for elective repair of an infrarenal AAA. On the ninth postoperative day, the patient presented with large quantities of bile-stained vomitus despite passing flatus per rectum. Metoclopramide and ranitidine were given under the initial impression of paralytic ileus. However, the upper gastrointestinal obstruction persisted, and on day 12, computerized tomography (CT) revealed marked distension of the gastric tube and duodenum, down to the level of the third portion, with abrupt change of caliber at the point of the superior mesenteric artery (SMA). SMA syndrome was diagnosed. After nasogastric tube aspiration, parenteral nutrition, and 11 days of conservative treatment, abdominal CT and upper gastrointestinal series showed no apparent duodenal obstruction. The patient was discharged on the 29th postoperative day; follow-up abdominal CT 4 months later was unremarkable.

Qinghai-Xizang Plateau is produced by compression between the Indian plate in the south and the Eurasian plate in the north. The forces acting on the plate boundaries uplift the Qinghai-Xizang Plateau and increase its gravitational potential energy. With high gravitational potential energy, the Plateau tends to flow towards the lower elevation of lower potential energy for reaching an equilibrium state. However, constraints at both the south and the north boundaries of the Qinghai-Xizang Plateau limit such flow to east-west direction only. The interior part of the plateau of high potential energy between the Himalayas and the Kunlun Mountain is driven to extend toward the east direction and results in ductile deformations during the flow process. Using three different methods, we estimate the distribution of gravitational potential energy in the Qinghai-Xizang Plateau. The computed results show that given certain constraints on the rheology, the gravitational potential energy is sufficient to produce a wide variety of rates and styles of observed deformation.

Polypeptides are fascinating materials with unique properties for various biological materials. We highlight here recent advances in amino acid N-carboxyanhydrides (NCAs) and synthetic polypeptides from the aspects of chemistry, self-assembly and biological applications. New synthetic methodologies, mechanistic studies and optimization of polymerization conditions for the preparation of well-defined novel polypeptides are comprehensively reviewed and evaluated. Functional polypeptides, mostly prepared from novel NCA monomers, with ultra-stable helical conformation, stimuli-sensitive properties, or glycoprotein mimetics are summarized. We also highlight a number of interesting self-assembled structures of polypeptides in solid state and solution, with particular emphasis on those structures other than amphiphilic self-assembly. The biological applications of polypeptides in drug and gene delivery are also reviewed. Future directions and perspectives are discussed in the conclusion.

A basic question in the mechanics of ultra high pressure metamotphism (UHPM) formation is why low density continental crust can overcome buoyancy and be subducted into high density mantle more than 100km deep. 3-D finite element computation shows that subducting oceanic lithosphere can drag continental slivers up to 150km wide to great depth, to produce large scale UHPM belts which are relatively rare in the world. Smaller bodies of continental crust up to tens of kilometers in size can be also be taken to UHPM depth by subducting mantle, as evidenced by the presence of scattered UHPM rock occurrences in orogenic belts. Continental-continental collision does not allow continental crust subductioin to UHPM depth.

Based on observed data on orientation of stresses in Brazil, a genetic algorithm-finite element method (GA-FEM) is applied to inverse the boundary displacement and nodal forces within the plate. The inversion confirms previous studies that plate boundary actions are main factors controlling the regional stress field, and spreading forces of mountains and seashores are another important factor. The inversion further shows that vertical loading on plate can produce significant effects on horizontal stresses. In addition to the well-known east-west compression, it is found that north to south compression also exists in western Brazil, in agreement with recent GPS observations. GA-FEM is shown an effective way to solve inverse problems of partial differential equations.

Tunable dye laser excitation of carefully prepared samples of Rb. sphaeroides reaction centers provides richly detailed resonance Raman (RR) spectra of the bacteriopheophytins, H, and the accessory bacteriochlorophylls, B. These spectra demonstrate selective enhancement of the separate bacteriopheophytins on the active (H(L)) and inactive (H(M)) sides of the reaction centers. The spectra are assigned with the aid of normal coordinate analyses using force fields previously developed for porphyrins and reduced porphyrins. Comparison of the H(L) and H(M) vibrational mode frequencies reveals evidence for greater polarization of the acetyl substituent in H(L) than H(M). This polarization is expected to make H(L) easier to reduce, thereby contributing to the directionality of electron transfer from the special pair, P. In addition, the acetyl polarization of H(L) is increased at low temperature (100 K), helping to account for the increase in electron transfer rate. The polarizing field is suggested to arise from the Mg(2+) of the neighboring accessory bacteriochlorophyll, which is 4.9 A from the acetyl O atom. The 100 K spectra show sharpening and intensification of a number of RR bands, suggesting a narrowing of the conformational distribution of chromophores, which is consistent with the reported narrowing of the distribution in electron transfer rates. Excitation at 800 nm produces high-quality RR spectra of the accessory bacteriochlorophylls, and the spectral pattern is unaltered on tuning the excitation to 810 nm in resonance with the upper exciton transition of P. Either the resonance enhancement of P is weak, or the bacteriochlorophyll RR spectra are indistinguishable for P and B.

Porphyrins bearing a polyaromatic or a heterocyclic group are prepared to study their fundamental and photovoltaic properties.