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Gastric cancer is a heterogeneous disease which requires a multimodal approach of management. The Department of Gastrointestinal Surgery at Changhai Hospital, a tertiary hospital in Shanghai, established the gastric cancer multidisciplinary team (MDT) clinic based on the guidance of MDT culture in the year of 2017. Our MDT discussion followed a weekly consultation model, with the full-board discussion held once a month, and mini-board communication and discussion made once a week. The stages of MDT management are: pre-operative treatment plan and preparation, post-operative treatment plan, and follow-up treatment and evaluation. As of March 2021, a total of 296 patients visited the MDT clinic. Majority of the patients were gastric carcinoma patients (273/296, 92.2%). Here, we shared our gastric cancer MDT experiences and summarized our strengths and proposed directions for improvement.

We theoretically study the nature of parametrically driven dissipative Kerr soliton (PD-DKS) in a doubly resonant degenerate micro-optical parametric oscillator (DR-DμOPO) with the cooperation of χ (2) and χ (3) nonlinearities. Lifting the assumption of close-to-zero group velocity mismatch (GVM) that requires extensive dispersion engineering, we show that there is a threshold GVM above which single PD-DKS in DR-DμOPO can be generated deterministically. We find that the exact PD-DKS generation dynamics can be divided into two distinctive regimes depending on the phase matching condition. In both regimes, the perturbative effective third-order nonlinearity resulting from the cascaded quadratic process is responsible for the soliton annihilation and the deterministic single PD-DKS generation. We also develop the experimental design guidelines for accessing such deterministic single PD-DKS state. The working principle can be applied to different material platforms as a competitive ultrashort pulse and broadband frequency comb source architecture at the mid-infrared spectral range.

The catalyst pore structure is important to accommodate deposits in the hydrotreatment processes. In the current study, urchin alumina with large pore mouths was successfully synthesized by template free method, and was used as catalyst support for the hydrodesulfurization (HDS) of Siberian crude oil. Commercial alumina was used as reference. The catalysts were characterized by XRD, N2 physisorption, TPR, NH3-TPD, SEM, and was evaluated in a trickle-bed reactor. The urchin alumina exhibits smaller surface area and larger average pore diameter than the commercial alumina. NiMo/ur-Al2O3 shows similar activity and better stability within the long-term HDS run of 100 h. After the HDS test, the weight loss of coke over NiMo/ur-Al2O3 is about half of that over NiMo/com-Al2O3; however, the urchin morphology of NiMo/ur-Al2O3 is not retained due to the high pressure during the reaction. The better performance in carbon resistance is consistent with the “chestnut bur” catalyst reported by IFP; this work supplements the synthesis detail and characterizations for the urchin-alumina supported catalyst, and provides important information for industrial hydrotreatment catalyst development.

The Hedgehog (HH) signaling pathway plays important roles in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment (TME). Aberrant HH signaling activation may accelerate the growth of gastrointestinal tumors and lead to tumor immune tolerance and drug resistance. The interaction between HH signaling and the TME is intimately involved in these processes, for example, tumor growth, tumor immune tolerance, inflammation, and drug resistance. Evidence indicates that inflammatory factors in the TME, such as interleukin 6 (IL-6) and interferon-γ (IFN-γ), macrophages, and T cell-dependent immune responses, play a vital role in tumor growth by affecting the HH signaling pathway. Moreover, inhibition of proliferating cancer-associated fibroblasts (CAFs) and inflammatory factors can normalize the TME by suppressing HH signaling. Furthermore, aberrant HH signaling activation is favorable to both the proliferation of cancer stem cells (CSCs) and the drug resistance of gastrointestinal tumors. This review discusses the current understanding of the role and mechanism of aberrant HH signaling activation in gastrointestinal carcinogenesis, the gastrointestinal TME, tumor immune tolerance and drug resistance and highlights the underlying therapeutic opportunities., Graphical abstract Hedgehog pathway (HH) is one of the most important modulators of gastrointestinal cancer. This review concludes the role of HH pathway in gastrointestinal carcinogenesis as well as the development of tumor microenvironment, which indicates the mechanisms of immune tolerance and drug resistance in gastrointestinal cancers and highlights the potential therapeutics.Image 1

We identify the role of transverse modes in causing temporal instability in an all-solid-state laser system and thus propose a new method to trigger deterministic optical rogue waves. Experimental investigations show that the near-degenerate transverse modes with mode frequency difference close to the relaxation oscillation frequency is responsible for the rogue waves. By tilting the reflective mirror, the transverse modes beating frequency decreases and gets close to relaxation oscillation frequency, thus the system exhibits self-pulsing behavior and rarely-arising giant pulses. The statistical distribution of the pulse intensity deviates from the exponential statistics to the L-shaped distributions with long tails, indicating the appearance of optical rogue waves. The conclusion can be extended to other Class-B lasers where the population inversion cannot be eliminated adiabatically.

Dissipative Kerr soliton (DKS) frequency combs – also known as microcombs – have arguably created a new field in cavity nonlinear photonics, with a strong cross-fertilization between theoretical, experimental, and technological research. Spatiotemporal mode-locking (STML) not only add new degrees of freedom to ultrafast laser technology, but also provide new insights for implementing analogue computers and heuristic optimizers with photonics. Here, we combine the principles of DKS and STML for the first time to demonstrate the STML DKS by developing an unexplored ultrahigh-quality-factor Fabry–Pérot microresonator based on graded index multimode fiber (GRIN-MMF). Using the intermodal stimulated Brillouin scattering, we can selectively excite either the eigenmode DKS or the STML DKS. Furthermore, we demonstrate an ultralow noise microcomb that enhances the photonic flywheel performance in both the fundamental comb linewidth and DKS timing jitter. The demonstrated fundamental comb linewidth of 400 mHz and DKS timing jitter of 500 attosecond (averaging times up to 25 μs) represent improvements of 25x and 2.5x, respectively, from the state-of-the-art. Our results show the potential of GRIN-MMF FP microresonators as an ideal testbed for high-dimensional nonlinear cavity dynamics and photonic flywheel with ultrahigh coherence and ultralow timing jitter.

Dissipative Kerr soliton (DKS) microcomb has emerged as an enabling technology that revolutionizes a wide range of applications in both basic science and technological innovation. Reliable turnkey operation with sub-optical-cycle and sub-femtosecond timing jitter is key to the success of many intriguing microcomb applications at the intersection of ultrafast optics and microwave electronics. Here we propose a novel approach to demonstrate the first turnkey Brillouin-DKS frequency comb. Our approach with a Chimera cavity offers essential benefits that are not attainable previously, including phase insensitivity, self-healing capability, deterministic selection of DKS state, and access to the ultralow noise comb state. The demonstrated turnkey Brillouin-DKS frequency comb achieves a fundamental comb linewidth of 100 mHz and DKS timing jitter of 1 femtosecond for averaging times up to 56 µs. The approach is universal and generalizable to various device platforms for user-friendly and field-deployable comb devices.

We theoretically unveil the mode-locking principle in microresonator-filtered laser cavities and predict chirped bright soliton with normal-dispersion microresonators. With ultrahigh-speed time magnifier, we experimentally observe real-time soliton rain harmonics and the first soliton Newton's cradle.

We demonstrate the first intermodal cascaded SBS up to three orders and corresponding Brillouin-Kerr soliton microcombs in a multimode fiber FP microresonator, along with the coexisting Raman combs and Turing pattern for the pump mode.

We demonstrate a photonic microwave synthesizer based on microresonator-filtered fiber lasers with two co-lasing laser frequencies. Low phase noise is achieved at 10.088 GHz due to common-mode noise suppression, comparable to the state-of-art.

Kerr microcombs hold the promise of bringing frequency combs onto the chip and into a variety of applications requiring low size, weight, power, and cost. However, reliable Kerr microcomb generation is hindered by the thermal effect and multistability of dissipative Kerr solitons (DKSs). Past approaches toward Kerr microcomb reliability include either deterministic single-soliton generation or self-starting soliton behavior but not both. Here we describe a regime of DKSs that is both deterministic and self-starting, in which only a single soliton can stably exist. We term this new DKS regime “monostable DKSs” (MS-DKSs) as all other optical behaviors, such as continuous-wave-only and multiple solitons, are fundamentally forbidden by the design. We establish a graphical model to describe MS-DKSs and discuss the design principles of MS-DKSs. We numerically demonstrate the MS-DKS behavior in an example periodically poled lithium niobate microring resonator.

Optical frequency comb, with precisely controlled spectral lines spanning a broad range, has been the key enabling technology for many scientific breakthroughs. In addition to the traditional implementation based on modelocked lasers, photonic frequency microcombs based on dissipative Kerr and quadratic cavity solitons in high-Q microresonators have become invaluable in applications requiring compact footprint, low cost, good energy efficiency, large comb spacing, and access to nonconventional spectral regions. In this review, we comprehensively examine the recent progress of photonic frequency microcombs and discuss how various phenomena can be utilized to enhance the microcomb performances that benefit a plethora of applications including optical atomic clockwork, optical frequency synthesizer, precision spectroscopy, astrospectrograph calibration, biomedical imaging, optical communications, coherent ranging, and quantum information science.

Background Peritoneal dialysis (PD) is a safe and home-based treatment for end-stage renal disease (ESRD) patients. The direct thermal damage of abdominal organs is very rare. Case presentation We report a peritoneal dialysis patient presented abdominal pain and feculent effluent 3 weeks after he instilled hot dialysis solution. In spite of emergency exploratory laparotomy and active treatment, the patient died of septic shock. Biopsy revealed necrosis and perforation of the intestines. Conclusions Delayed bowel perforation by hot fluid is very rare. Standardized performance is of the first importance for peritoneal dialysis patients.

Sub-hertz fundamental linewidth soliton microcombs consisting of multiple eigenmodes are demonstrated in an ultra-high-Q graded-index fiber FP microresonator. The feedback-free SBS-assisted comb generation and stabilization enables ultralow-noise microwave generation.

We analytically and numerically unveil the existence condition of symbiotic solitons in doubly resonant non-degenerate optical parametric oscillators. Resonant signal and idler with terahertz comb bandwidth and femtosecond pulse duration in the mid-infrared are attainable through this symbiotic soliton mode-locking technique. The group velocity mismatches between the three interacting waves are the dominant cause of the symbiotic soliton perturbation, and their effects are numerically investigated in detail. The principle can be applied to commonly used mid-infrared material platforms, making it a competitive ultrashort pulse and broadband comb source architecture.

Background Analysis of the risk factors associated with functional delayed gastric emptying after distal gastric cancer surgery to provide a basis for further reduction of the incidence of this complication. Methods Total of 1382 patients with distal gastric cancer from January 2016 to October 2018 were enrolled. Correlation analysis was performed in 53 patients with FDGE by logistic regression. Subgroup risk analysis was performed in 114 patients with preoperative pyloric obstruction. A Pearson Chi-square analysis was used to compare categorical variables between normal distribution groups. Meanwhile, a t test was used to compare continuous variables between groups. Odds ratio (OR) was used for comparison of the two groups, and it was summarized with its 95% confidence interval (CI) and p value using logistic regression. Result In multivariable analysis, age (OR 1.081, 95% CI, 1.047–1.117), BMI (OR 1.233, 95% CI, 1.116–1.363), preoperative pyloric obstruction (OR 3.831, 95% CI, 1.829–8.023), smaller volume of residual stomach (OR 1.838, 95% CI, 1.325–6.080), and anastomosis in greater curvature perpendicular (OR 3.385, 95% CI, 1.632–7.019) and in greater curvature parallel (OR 2.375, 95% CI, 0.963–5.861) were independent risk factors of FDGE. In the preoperative pyloric obstruction group, higher BMI (OR 1.309, 95% CI, 1.086–1.579) and preoperative obstruction time (OR 1.054, 95% CI, 1.003–1.108) were independent risk factors of FDGE and preoperative gastrointestinal decompression (OR 0.231, 95% CI, 0.068–0.785) was independent protective factor of FDGE. Conclusion Adequate gastrointestinal decompression should be performed before the operation to reduce the incidence of postoperative gastroparesis in patients with preoperative pyloric obstruction. We also could improve the surgical methods to reduce the occurrence of FDGE, such as controlling the size of the residual stomach, ensuring blood supply. Especially selecting an appropriate stapler and anastomosis during the anastomosis process, the occurrence of FDGE can be reduced.

Gastric cancer (GC) has a high incidence and mortality rate. If discovered late, GC tends to have a poor prognosis. Improvements in the prognostic accuracy of GC through combined analysis of multiple relevant genes and clinical factors may solve this problem. In the present study, GSE62254 (including 300 GC tissues), obtained from the Gene Expression Omnibus database, was used as a training set, and the mRNA‑sequencing data of GC (including 384 GC tissues) downloaded from the Cancer Genome Atlas database served as a validation set. Based on the t‑test and Wilcoxon test, the significantly differentially expressed genes (DEGs) were obtained by screening the intersecting DEGs. The prognosis-associated genes and clinical factors were identified using Cox regression analysis in the R survival package. The optimal prognosis‑associated pathways were examined using the Cox‑proportional hazards (Cox‑PH) model in the R penalized package. Finally, risk prediction models were constructed and validated using the Cox‑PH model and the Kaplan‑Meier method, respectively. There were a total of 382 significant DEGs, including 268 upregulated genes and 114 downregulated genes. A total of 50 prognosis‑associated genes were identified, 16 optimal prognosis‑associated pathways (including mitochondrial pathway and the tyrosine‑protein kinase JAK‑signal transducer and activator of transcription signaling pathway, which involve caspase 7, phosphoinositide‑3‑kinase regulatory subunit 3, peroxisome proliferator‑activated receptor γ and collagen triple helix repeat containing 1) and four prognosis‑associated clinical factors [including Pathologic_N, Pathologic_stage, mutL homolog 1 (MLH1) mutation and recurrence]. The pathway‑ and clinical‑factor‑based risk prediction model exhibited marked prognostic accuracy. The clinical‑factor‑based risk prediction model with improved P‑values for prognosis prediction may be superior to the pathway‑based risk prediction model in predicting the prognosis of GC patients.

We first demonstrate the laser performance of a compact 2.06- $\mu$ m Ho: YLF laser wing pumped by a fiber-coupled laser diode, which is insensitive to the polarization state of pump source. A maximum output power of 1.44 W, corresponding to a slope efficiency of 41.25%, is obtained. The optimized beam quality factor reaches 2.52 when the output power is about 1 W. Multi-peak laser spectra are observed in the range of 2064.5–2066.6 nm. The output power fluctuation is greatly reduced to about 0.57% of the average power in 50 min. The degree of polarization reaches the level of 96%. The performance in power stability and overall compact structure indicates that diode wing-pumped Ho: YLF laser has great value in gas sensing and precise medical treatment that require a relative high stable output laser.

In this paper, a semiconductor laser-pumped high-brightness $1.56~\mu \text{m}$ polarization-entangled photon pairs with a 30-mm-length PPKTP down-converter inside a Sagnac-type interferometer is firstly demonstrate. Large active-area InGaAs/InP-based single photon detectors and step-index multi-mode fiber collection are attempted to evaluate the brightness and entanglement quality. The maximum spectral brightness is about $1.33\times 10^{5}$ pairs( $\text{s}\ast $ mW $\ast $ nm) $^{-1}$ with a pump power of 200 mW and a spectral bandwidth of 1.34 nm. Under the condition of maximum entanglement brightness, polarization visibility of 96.08%±1.62% is obtained in the diagonal orthogonal basis. The quantum state tomography also shows a high fidelity of 97% for the ideal Bell states. Meanwhile, the CHSH-type Bell inequality is violated with a value of 2.8196±0.0098 ( $96~\sigma$ ). Both the performance in brightness and entanglement quality indicate that the current $1.56~\mu \text{m}$ polarization-entangled source has great potential in free-space quantum key distribution or quantum communication.

In this paper, pulsed output with pulse-widths approaching the round-trip time were generated by utilizing a cavity-less high-gain Nd:GdVO

Background Gastric cancer (GC) is a leading cause of cancer deaths, and an increased number of GC patients adopt to next-generation sequencing (NGS) to identify tumor genomic alterations for precision medicine. Methods In this study, we established a hybridization capture-based NGS panel including 612 cancer-associated genes, and collected sequencing data of tumors and matched bloods from 153 gastric cancer patients. We performed comprehensive analysis of these sequencing and clinical data. Results 35 significantly mutated genes were identified such as TP53, AKAP9, DRD2, PTEN, CDH1, LRP2 et al. Among them, 29 genes were novel significantly mutated genes compared with TCGA study. TP53 is the top frequently mutated gene, and tends to mutate in male (p = 0.025) patients and patients whose tumor located in cardia (p = 0.011). High tumor mutation burden (TMB) gathered in TP53 wild-type tumors (p = 0.045). TMB was also significantly associated with DNA damage repair (DDR) genes genotype (p = 0.047), Lauren classification (p = 1.5e−5), differentiation (1.9e−7), and HER2 status (p = 0.023). 38.31% of gastric cancer patients harbored at least one actionable alteration according to OncoKB database. Conclusions We drew a comprehensive mutational landscape of 153 gastric tumors and demonstrated utility of target next-generation sequencing to guide clinical management. Electronic supplementary material The online version of this article (10.1186/s12967-019-1941-0) contains supplementary material, which is available to authorized users.

The roles of cancer-associated fibroblasts (CAFs) in progression of gastric cancer (GC) are far from well illustration. Here, we show that CAFs can trigger the proliferation and decrease the doxorubicin (Dox) sensitivity of GC cells via secretion of Nodal, one embryonic morphogen that can promote malignancy of various cancers. The neutralization antibody of Nodal can attenuate CAFs-induced cell proliferation. Further, CAFs can activate the Smad2/3 signal, which further increase the phosphorylation and nuclear localization of Akt, in GC cells. While anti-Nodal can abolish the CAFs-induced activation of Smad2/3/Akt signals. Further, both inhibitors of Smad2/3 and Akt can attenuate CAFs-induced proliferation of GC cells. All these data suggest that CAFs can increase the malignancy of GC cells via Nodal-induced activation of Smad2/3/Akt signals. It indicates that CAFs/Nodal signals might be a potential new target of clinical interventions for GC patients. SIGNIFICANCE OF THE STUDY: The roles about CAFs in progression of GC are not well illustrated. Our present study reveals that CAFs can increase the proliferation and decrease the Dox sensitivity of GC cells via secretion of Nodal. The secreted Nodal further activated Samd2/3/Akt signals to trigger the GC progression. It suggests that targeted inhibition CAFs/Nodal might be a potential approach for GC therapy.

Additional file 2. The proportion of mutations of 35 significantly mutated genes.

We present the first design and analysis of a solid-state Mamyshev oscillator. We utilize the phase-mismatched cascaded quadratic nonlinear process in a periodically poled lithium niobate waveguide to generate substantial spectral broadening for Mamyshev mode locking. The extensive spectral broadening bridges the two narrowband gain media in the two arms of the same cavity, leading to a broadband mode locking not attainable with either gain medium alone. Two pulses are coupled out of the cavity, and each of the output pulses carries a pulse energy of 25.3 nJ at a repetition rate of 100 MHz. The 10 dB bandwidth of 2.1 THz supports a transform-limited pulse duration of 322 fs, more than 5 times shorter than what can be achieved with either gain medium alone. Finally, effects of group velocity mismatch, group velocity dispersion, and nonlinear saturation on the performance of Mamyshev mode locking are numerically discussed in detail.

In this paper, laser pulses with pulse-widths approach to the round-trip time are generated by utilizing a cavityless high gain Nd:GdVO4 bounce geometry. By adopting an EOQ (electro-optics Q-switch), pulse-widths of 1.36 ns, 1.82 ns, and 2.39 ns are achieved at three effective cavity lengths respectively. All these pulse-widths are close to the round-trip time of corresponding effective cavity lengths. Moreover, the output power reaches watt-level and the repetition rate is kHz-level, meanwhile the M2 factor is less than 1.3. Spectrally, the laser has a continuous spectrum with 10 dB linewidth of 0.2 nm., Comment: 7 pages

In this paper, factors influencing the performance of high-gain Nd:YVO4 amplifiers are analyzed and a schematic map of the relationships between different factors is given. A model, including the pump absorption saturation effect and overlap efficiency along the beam propagation direction, as well as non-radiative decays due to high doping concentration, is developed. The performance of laser amplifier is studied by changing doping concentration, pump beam quality, and focal size of pump laser. To get high gain, samples with low doping concentration should cooperate with long crystals and laser diodes with good beam quality. Based on the model, the focal radius of pump laser could be optimized for different doping concentrations and beam qualities of pump laser. Experiments were conducted and the results agreed well with the simulated ones. Moreover, a single-stage and single-pass amplifier was realized, achieving a small-signal gain of 51 dB.

In this paper, the theoretical quantitative energy-level character and the experimental laser performance of resonantly fiber-coupled diode-pumped Ho3+: YLiF4 (Ho: YLF) laser are first presented. More precise 2.7-level character of diode-pumped Ho: YLF laser can be acquired with our theoretical analysis. With the experimental study, a maximum slope efficiency of 88.5%, corresponding to an output power of 1.85 W, was obtained. In actively Q-switched operation, a maximum pulse energy of 0.3 mJ was achieved at the repetition frequency of 5 kHz with a minimum pulse duration of 160 ns. At a maximum repetition frequency of 100 kHz, a pulse energy of $16~\mu \text{J}$ was achieved with a pulse duration of 816 ns. Both the performance in continuous-wave and Q-switched regimes indicates that the current resonantly fiber-coupled diode-pumped Ho: YLF laser has great potential in certain conditions that require several watts of average output power.

Gastric cancer (GC) in young patients is thought to exhibit a worse prognosis due to specific clinicopathologic characteristics and delayed diagnosis; however, the data are controversial. This study aimed to analyse the clinicopathologic characteristics and prognostic factors of GC in young patients and to determine whether GC is a different clinical entity in younger vs. older patients.Clinical data of 3930 gastric cancer patients who underwent radical gastrectomy were retrospectively analysed and divided into two age groups. The younger group consisted of 342 cases of patients aged 40 years or younger at the time of surgery, and the older group included 3588 cases of patients older than 40 years. Clinicopathologic characteristics were compared using Pearson's χ(2) or Fisher's exact tests, and survival curves were constructed using the Kaplan-Meier method.Clinicopathologic characteristics of the younger group exhibited a predominance of females (p 0.001), diffuse stomach lesions (p = 0.014), signet-ring cell type (p 0.001), poorly differentiated histological tumours (p 0.001), Borrmann type IV (p 0.001), mixed Lauren's classification types (p = 0.004), and recurrence rate in the gastric remnant (p 0.001). The overall 5-year survival rates in the younger group and older group were 60.8% and 53.7%, respectively (p = 0.017). When stratified by TNM stage, the younger group exhibited enhanced 5-year survival at stage IV compared with the older group (26.9% VS. 10.3%, p = 0.003).Although younger patients with GC exhibit more aggressive cancer patterns and higher recurrence rate in the gastric remnant, the overall 5-year survival rate may be better than older patients.

An electrooptically Q-switched Nd:YLF laser end-pumped by an 880-nm laser diode with high energy and short pulsewidth at 1 kHz is demonstrated. The asymmetry of the focal lengths of thermal lens along the $a$ -axis and $c$ -axis is observed, and the cylindrical lens is used to compensate for the thermal lens effect along the $a$ -axis. We experimentally studied the performance of the Nd:YLF laser with different combinations of the output coupler transmission $T$ and the focal length $f$ of cylindrical lens. With $T=40\%$ and $f=300\ \text{mm}$ , 9.5-mJ pulse energy, 9.5-ns pulsewidth, and beam quality factors of $M_{x}^{2}=1.74$ and $M_{y}^{2}=1.97$ are obtained. Moreover, the relationships between the pulse width and pump power as well as beam transverse mode were experimentally studied and discussed.

In this paper, a wavelength-locked 878.6-nm pumped acoustic-optically Q-switched Nd:YVO4 laser is presented. A master oscillator power amplifier configuration with two-stage amplifiers is employed to scale the output power. Both the oscillator and the power amplifiers are directly pumped by a wavelength-locked 878.6-nm laser diode, reducing the thermal load of the laser crystal. The maximal output power is 120.8 W at the repetition rate of 100 kHz, with the M2 factor of 1.31 and 1.30 in two directions. The maximal pulse energy of 4.85 mJ and the shortest pulsewidth of 15 ns are achieved at the repetition rate of 20 kHz, with near diffraction limited output. The global optical-optical efficiencies are 37.7% and 47% at the repetition rate of 20 and 100 kHz, respectively. The laser has excellent output stability in a specific range of time and temperature. The output power is very stable during the five operating hours, and it is insensitive to the temperature variation of the water chiller from 15 °C to 35 °C.

We demonstrate a 1064 nm, mJ-level, sub-nanosecond end-pumped Q-switched laser with weak feedback and high gain. We obtain the pulse duration of 449.7 ps, namely 1.2 times of the round-trip time, as well as the maximum energy of 0.26 mJ at the repetition rate of 1 kHz. The pulse energy is further scaled to 3.6 mJ by a double-passed amplifier, resulting in the peak power of 8.1 MW at the highest repetition rate of 2 kHz. Moreover, both the classical Q-switching theory and weak-feedback Q-switching theory are utilized to analyze the experimental results. The simulated results support that the Q-switched lasers with weak feedback and high gain, is effective for approaching single roundtrip time, which is the pulse duration limit. Smaller pulse duration is expected by virtue of this simple and compact configuration.

By identifying the similarities between the coupled-wave equations and the parametrically driven nonlinear Schr\"odinger equation, we unveil the existence condition of the quadratic soliton mode-locked degenerate optical parametric oscillator in the previously unexplored parameter space of near-zero group velocity mismatch. We study the nature of the quadratic solitons and divide their dynamics into two distinctive branches depending on the system parameters. We find the nonlinear interaction between the resonant pump and signal results in phenomena that resemble the dispersive two-photon absorption and the dispersive Kerr effect. Origin of the quadratic soliton perturbation is identified and strategy to mitigate its detrimental effect is developed. Terahertz comb bandwidth and femtosecond pulse duration are attainable in an example periodically poled lithium niobate waveguide resonator in the short-wave infrared and an example orientation-patterned gallium arsenide free-space cavity in the long-wave infrared. The quadratic soliton mode-locking principle can be extended to other material platforms, making it a competitive ultrashort pulse and broadband comb source architecture at the mid-infrared.

Background The progression-free survival (PFS) is not optimal when imatinib was recommended for treatment of gastrointestinal stromal tumor (GIST) undergoing surgery after tumor local or multifocal progression. Methods We evaluate PFS of patients undergoing R0 resection or optimal cytoreductive surgery followed by sunitinib therapy compared with imatinib after tumor unifocal or multifocal progression. Results From January 2006 to June 2017, ninety-seven patients from thirteen medical centers were enrolled. Fifty-six patients continued imatinib therapy and 41 patients switched sunitinib treatment directly after R0 resection or optimal cytoreductive surgery. The PFS of sunitinib group was longer than that of imatinib group (30.0 months vs 12.0 months, p = 0.009). In subgroup analysis, the PFS of the sunitinib and imatinib groups were 25.5 months and 12.0 months in patients with tumor multifocal progression (p = 0.008), and 39.0 months and 13.0 months in patients with unifocal progression (p = 0.156), respectively. PFS of postoperative sunitinib group was also superior to the total PFS of postoperative imatinib group (PFS of postoperative imatinib plus PFS of subsequent sunitinib therapy (30.0 months vs 21.0 months, p = 0.012). The overall survival in the sunitinib and imatinib groups were 37.0 months and 33.0 months, respectively (p = 0.794). Conclusions Surgery followed by sunitinib in GIST patients with unifocal or multifocal progression on imatinib may improve PFS, compared with surgery followed by imatinib.