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Abstract Dental pulp stem cells (DPSC) have shown osteogenic and bone regenerative potential. Improving the in situ bone regeneration potential of DPSC is crucial for their application as seed cells during bone defect reconstruction in clinics. This study aimed to develop DPSC-derived organoid-like microspheroids as effective seeds for bone tissue engineering applications. DPSC osteogenic microspheroids (70 μm diameter) were cultured in a polydimethylsiloxane-mold-based agarose-gel microwell-culture-system with or without cannabidiol (CBD)-treatment. Results of in vitro studies showed higher osteogenic differentiation potential of microspheroids compared with 2D-cultured-DPSC. CBD treatment further improved the osteogenic differentiation potential of microspheroids. The effect of CBD treatment in the osteogenic differentiation of microspheroids was more pronounced compared with that of CBD-treated 2D-cultured-DPSC. Microspheroids showed a higher degree of bone regeneration in nude mice calvarial bone defect compared to 2D-cultured-DPSC. CBD-treated microspheroids showed the most robust in situ bone regenerative potential compared with microspheroids or CBD-treated 2D-cultured-DPSC. According to mRNA sequencing, bioinformatic analysis, and confirmation study, the higher osteogenic potential of CBD-treated microspheroids was mainly attributed to WNT6 upregulation. Taken together, DPSC microspheroids have robust osteogenic potential and can effectively translate the effect of in vitro osteoinductive stimulation during in situ bone regeneration, indicating their application potential during bone defect reconstruction in clinics.

Abstract Background Implantable vagus nerve stimulation is a promising approach for restoring autonomic cardiovascular functions after heart transplantation. For successful treatment a system should have multiple electrodes to deliver precise stimulation and complex neuromodulation patterns. Methods This paper presents an implantable multi-channel stimulation system for vagal-cardiac neuromodulation studies in swine species. The system comprises an active electrode array implant percutaneously connected to an external wearable controller. The active electrode array implant has an integrated stimulator ASIC mounted on a ceramic substrate connected to an intraneural electrode array via micro-rivet bonding. The implant is silicone encapsulated for biocompatibility and implanted lifetime. The stimulation parameters are remotely transmitted via a Bluetooth telemetry link. Results The size of the encapsulated active electrode array implant is 8 mm × 10 mm × 3 mm. The stimulator ASIC has 10-bit current amplitude resolution and 16 independent output channels, each capable of delivering up to 550 µA stimulus current and a maximum voltage of 20 V. The active electrode array implant was subjected to in vitro accelerated lifetime testing at 70 °C for 7 days with no degradation in performance. After over 2 h continuous stimulation, the surface temperature change of the implant was less than 0.5 °C. In addition, in vivo testing on the sciatic nerve of a male Göttingen minipig demonstrated that the implant could effectively elicit an EMG response that grew progressively stronger on increasing the amplitude of the stimulation. Conclusions The multi-channel stimulator is suitable for long term implantation. It shows potential as a useful tool in vagal-cardiac neuromodulation studies in animal models for restoring autonomic cardiovascular functions after heart transplantation.

A deep understanding of the effects of the inorganic characteristics of Xinjiang coals on combustion particulate generation is of great significance for their clean and efficient utilization. This work investigated the inorganic characteristics of Wucaiwan coal (WCW), Wanxiang coal (WX), Tianchi coal (TC), and Xiheishan coal (XHS) and the their relationship with the production of ultrafine particulates during combustion. The results show that the four Xinjiang coals are mainly lignites with low ash and sulfur contents. Coal ashes are enriched in basic elements. Among them, the content of Na2O (3.58%−7.13%) is commonly higher than that of conventional utility coals. The ashes of WCW and WX coals have higher contents of CaO (> 33%), but low contents of SiO2 and Al2O3. WX coal is particularly characterized by high Na and Cl. The Na in coal is primarily water soluble(62.3%−90.6%). The K is mainly HCl insoluble. The Fe occurs primarily as HCl soluble and insoluble forms. And the distribution of Ca and Mg in different forms varies according to coal types. The composition of ultrafine particulate matter from Xinjiang coal combustion is dominated by Na, K, Cl, and S. The particle size range of the ultrafine particulate matter is accurately defined by using the condition that the mass fraction of Na2O+K2O+Cl+SO3 is higher than 50%. The ultrafine particulate matter of WCW, TC and XHS coals has similar particle size ranges (≤0.07 μm); while the ultrafine particulate matter of WX coal, which has the highest content of Na in the water-soluble form, has a wider particle size range (≤0.76 μm). The generation of ultrafine particulate matter (y) is found to be highly linearly and positively correlated with the total amount of water-soluble (Na+K) (x) in the coal, with the relationship equation y = 0.528x−0.239 and the correlation coefficient of 0.948.

Summary: Background: Both defects in mismatch repair (dMMR) and high microsatellite instability (MSI-H) have been recognised as crucial biomarkers that guide treatment strategies and disease management in colorectal cancer (CRC). As MMR and MSI tests are being widely conducted, an increasing number of MSI-H tumours have been identified in CRCs with mismatch repair proficiency (pMMR). The objective of this study was to assess the clinical features of patients with pMMR/MSI-H CRC and elucidate the underlying molecular mechanism in these cases. Methods: From January 2015 to December 2018, 1684 cases of pMMR and 401 dMMR CRCs were enrolled. Of those patients, 93 pMMR/MSI-H were identified. The clinical phenotypes and prognosis were analysed. Frozen and paraffin-embedded tissue were available in 35 patients with pMMR/MSI-H, for which comprehensive genomic and transcriptomic analyses were performed. Findings: In comparison to pMMR/MSS CRCs, pMMR/MSI-H CRCs exhibited significantly less tumour progression and better long-term prognosis. The pMMR/MSI-H cohorts displayed a higher presence of CD8+ T cells and NK cells when compared to the pMMR/MSS group. Mutational signature analysis revealed that nearly all samples exhibited deficiencies in MMR genes, and we also identified deleterious mutations in MSH3-K383fs. Interpretation: This study revealed pMMR/MSI-H CRC as a distinct subgroup within CRC, which manifests diverse clinicopathological features and long-term prognostic outcomes. Distinct features in the tumour immune-microenvironment were observed in pMMR/MSI-H CRCs. Pathogenic deleterious mutations in MSH3-K383fs were frequently detected, suggesting another potential biomarker for identifying MSI-H. Funding: This work was supported by the Science and Technology Commission of Shanghai Municipality (20DZ1100101).

Introduction The preliminary result of the TORCH trial has shown a promising complete response (CR) for managing locally advanced rectal cancer with neoadjuvant short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor. For locally advanced colon cancer (LACC) with bulky nodal disease and/or clinically T4, neoadjuvant chemotherapy followed by colectomy with en bloc removal of regional lymph nodes is the suggested treatment. However, the CR rate is less than 5%. TORCH-C will aim to investigate neoadjuvant SCRT combined with chemotherapy and PD-1 inhibitor in LACC.Methods and analysis TORCH-C is a randomised, prospective, multicentre, double-arm, open, phase II trial of SCRT combined with chemotherapy and immunotherapy in LACC with microsatellite stable (MSS) patients and cT4 or bulky nodes. Eligible patients will be identified by the multidisciplinary team. 120 patients will be randomised 1:1 to the intervention or control arm. The patients in the control arm will receive four cycles of capecitabine plus oxaliplatin (CAPOX). The patients in the intervention arm will receive SCRT, followed by four cycles of CAPOX and PD-1 inhibitor (serplulimab). Both arms will receive curative surgery, followed by four cycles of CAPOX. The primary endpoint is pathological complete regression.TORCH-C (TORCH-colon) trial aims to investigate whether the combination of immunotherapy and chemoradiotherapy improves the treatment effect in LACC with MSS. TORCH-C will establish the TORCH platform, a key part of our long-term strategy to develop neoadjuvant treatment for colorectal cancer.Ethics and dissemination This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (approval number: 2211265-12).Trial registration number NCT05732493

Abstract Background Restoration of salivary gland function in Sjogren’s syndrome (SS) is still a challenge. Dental pulp stem cells (DPSCs) derived exosomes had shown anti-inflammatory, anti-oxidative, immunomodulatory, and tissue function restorative abilities. However, the salivary gland function restoration potential of DPSCs-derived exosomes (DPSC-Exos) during SS has not been investigated yet. Methods DPSC-Exos was isolated by ultracentrifugation methods and characterized. Salivary gland epithelial cells (SGEC) were treated with interferon-gamma (IFN-γ) to mimic SS in vitro and cultured with or without DPSC-Exos. SGEC survival and aquaporin 5 (AQP5) expression were analyzed. mRNA sequencing and bioinformatics analysis were performed in IFN-γ vs. DPSC-Exos+ IFN-γ treated SGEC. Non-obese diabetic (NOD)/ltj female mice (SS model), were intravenously administered with DPSC-Exos, and salivary gland functions and SS pathogenicity were analyzed. Furthermore, the mRNA sequencing and bioinformatics predicted mechanism of the therapeutic effect of DPSC-Exos was further investigated both in vitro and in vivo using RT-qPCR, Western blot, immunohistochemistry, immunofluorescence, flowcytometry analysis. Results DPSC-Exos partially rescued IFN-γ triggered SGEC death. IFN-γ inhibited AQP5 expression in SGEC and DPSC-Exos reversed this effect. Transcriptome analysis showed GPER was the upregulated DEG in DPSC-Exos-treated SGEC with a positive correlation with salivary secretion-related DEGs. Pathway enrichment analysis revealed that DEGs were mainly attributed to estrogen 16 alpha-hydroxylase activity, extracellular exosome function, cAMP signaling, salivary secretion, and estrogen signaling. Intravenous injection of DPSC-Exos in NOD/ltj mice alleviated the SS syndrome as indicated by the increased salivary flow rate, attenuated glandular inflammation, and increased AQP5 expression. GPER was also upregulated in the salivary gland of DPSC-Exos-treated NOD/ltj mice compared with the PBS-treated NOD/ltj mice. IFN-γ+DPSC-Exos-treated SGEC showed higher expression of AQP5, p-PKA, cAMP, and intracellular Ca2+ levels compared with IFN-γ-treated SGEC. These effects were reversed by the inhibition of GPER. Conclusions Our results showed that DPSC-Exos revitalize salivary gland epithelial cell function during SS via the GPER-mediated cAMP/PKA/CREB pathway suggesting the possible therapeutic potential of DPSC-Exos in SS-treatment.

Photodetectors based on two-dimensional materials exhibit excellent performance including high specific detectivity and fast response times. However, the polarization detection performance remains to be improved. Here, we propose a strategy to improve the polarization sensitivity of TlPt2S3-based photodetectors by defect engineering based on density functional theory (DFT) calculations and investigate their optoelectronic properties using quantum transport simulations at 0.2 V bias. Theoretical calculations show that the monolayer TlPt2S3 achieves a multifunctional output of the optoelectronic device and obtains a larger photocurrent and high extinction ratio by defect engineering under linearly polarized light irradiation. These results indicate that TlPt2S3 is expected to be one of the candidate materials for future optoelectronics and polarized light devices.

Abstract Background To study the pattern and treatment outcome of rectal cancer (RC) with concurrent locoregional recurrence (LR) and distant metastasis (DM) after total mesorectal excision (TME) and to identify patient-, disease-, and treatment-related factors associated with differences in prognosis after concurrent LR and DM. Methods RC patients who were diagnosed with concurrent LR and DM after TME from May 2015 to June 2019 were included in our study. All patients received single or multiple treatment modalities under the guidance of multidisciplinary team (MDT) of colorectal cancer in Fudan University Shanghai Cancer Center. The prognostic value of various clinicopathological factors for survival were calculated by Kaplan–Meier curves and Cox regression analyses. Results A total of 74 RC patients with concurrent LR and DM who had undergone TME with a median follow-up of 27 months were eligible for analysis. The median survival of the included patients was 34 months, and 30 patients (41%) died. Fifty-nine patients (80%) underwent comprehensive treatments. Patients with oligometastatic disease (OMD) achieved no evidence of disease (NED) status more frequently than those with multiple metastases (P = 0.003). In the univariate analysis, patients achieving NED, diagnosed with OMD and five or less peritoneal metastases tended to have longer survival after LR and DM diagnosis (P

Abstract Early detection can benefit cancer patients with more effective treatments and better prognosis, but existing early screening tests are limited, especially for multi-cancer detection. This study investigated the most prevalent and lethal cancer types, including primary liver cancer (PLC), colorectal adenocarcinoma (CRC), and lung adenocarcinoma (LUAD). Leveraging the emerging cell-free DNA (cfDNA) fragmentomics, we developed a robust machine learning model for multi-cancer early detection. 1,214 participants, including 381 PLC, 298 CRC, 292 LUAD patients, and 243 healthy volunteers, were enrolled. The majority of patients (N = 971) were at early stages (stage 0, N = 34; stage I, N = 799). The participants were randomly divided into a training cohort and a test cohort in a 1:1 ratio while maintaining the ratio for the major histology subtypes. An ensemble stacked machine learning approach was developed using multiple plasma cfDNA fragmentomic features. The model was trained solely in the training cohort and then evaluated in the test cohort. Our model showed an Area Under the Curve (AUC) of 0.983 for differentiating cancer patients from healthy individuals. At 95.0% specificity, the sensitivity of detecting all cancer reached 95.5%, while 100%, 94.6%, and 90.4% for PLC, CRC, and LUAD, individually. The cancer origin model demonstrated an overall 93.1% accuracy for predicting cancer origin in the test cohort (97.4%, 94.3%, and 85.6% for PLC, CRC, and LUAD, respectively). Our model sensitivity is consistently high for early-stage and small-size tumors. Furthermore, its detection and origin classification power remained superior when reducing sequencing depth to 1× (cancer detection: ≥ 91.5% sensitivity at 95.0% specificity; cancer origin: ≥ 91.6% accuracy). In conclusion, we have incorporated plasma cfDNA fragmentomics into the ensemble stacked model and established an ultrasensitive assay for multi-cancer early detection, shedding light on developing cancer early screening in clinical practice.

Although the physicochemical properties of gallium selenide (GaSe) have been widely investigated, the property and application exploration of GaSe‐coupled fiber devices are still in its infancy. There are obvious challenges, namely, selecting from multiple GaSe phases and effectively coupling to the unique fiber structure. Herein, lab‐on‐fiber (LOF) based on optimized GaSe is proposed to be used for robust femtosecond pulse generation and fiber‐compatible photodetection. First, based on density functional theory (DFT) calculations, ε‐GaSe is selected as a preferable model material for its suitable band structures, low work function, and high damage threshold. Benefiting from the fiber‐compatible ε‐GaSe combined with micro–nano processing, stable femtosecond soliton pulse (≈303 fs, 16.67 MHz, 51.64 dB) output and multiwavelength (520, 808, and 1550 nm) detection are realized in LOF. These results pave the way for optics research of polyphase semiconductors and design of integrated all‐fiber devices.

While genetic factors were associated with over 30% of colorectal cancer (CRC) patients, mutations in CRC-susceptibility genes were identified in only 5% to 10% of these patients. Besides, previous studies on hereditary CRC were largely designed to analyze germline mutations in patients with single genetic high-risk factor, which limited understanding of the association between genotype and phenotypes. From January 2015 to December 2018, we retrospectively enrolled 2,181 patients from 8,270 consecutive CRC cases, covering 5 categories of genetic high-risk factors. Leukocyte genomic DNA was analyzed for germline mutations in cancer predisposition genes. The germline mutations under each category were detected and analyzed in association with CRC susceptibility, clinical phenotypes, and prognoses. A total of 462 pathogenic variants were detected in 19.3% of enrolled CRC patients. Mismatch repair gene mutation was identified in 9.1% of patients, most prevalent across all high-risk groups. Homologous recombination (HR) gene mutations were detected in 6.5% of cases, penetrated in early-onset and extra-colonic cancer risk groups. Mutations in HR genes, including BARD1, RAD50, and ATM, were found to increase CRC risk with odds ratios of 2.8-, 3.1-, and 3.1-fold, respectively. CRC patients with distinct germline mutations manifested heterogeneous phenotypes in clinicopathology and long-term prognoses. Thus, germline mutation screenings should be performed for CRC patients with any of those genetic risk factors. This study also reveals that HR gene mutations may be another major driver for increased CRC risk.

Abstract Previous studies on liquid biopsy-based early detection of advanced colorectal adenoma (advCRA) or adenocarcinoma (CRC) were limited by low sensitivity. We performed a prospective study to establish an integrated model using fragmentomic profiles of plasma cell-free DNA (cfDNA) for accurately and cost-effectively detecting early-stage CRC and advCRA. The training cohort enrolled 310 participants, including 149 early-stage CRC patients, 46 advCRA patients and 115 healthy controls. Plasma cfDNA samples were prepared for whole-genome sequencing. An ensemble stacked model differentiating healthy controls from advCRA/early-stage CRC patients was trained using five machine learning models and five cfDNA fragmentomic features based on the training cohort. The model was subsequently validated using an independent test cohort (N = 311; including 149 early-stage CRC, 46 advCRA and 116 healthy controls). Our model showed an area under the curve (AUC) of 0.988 for differentiating advCRA/early-stage CRC patients from healthy individuals in an independent test cohort. The model performed even better for identifying early-stage CRC (AUC 0.990) compared to advCRA (AUC 0.982). At 94.8% specificity, the sensitivities for detecting advCRA and early-stage CRC reached 95.7% and 98.0% (0: 94.1%; I: 98.5%), respectively. Promisingly, the detection sensitivity has reached 100% and 97.6% in early-stage CRC patients with negative fecal occult or CEA blood test results, respectively. Finally, our model maintained promising performances (AUC: 0.982, 94.4% sensitivity at 94.8% specificity) even when sequencing depth was down-sampled to 1X. Our integrated predictive model demonstrated an unprecedented detection sensitivity for advCRA and early-stage CRC, shedding light on more accurate noninvasive CRC screening in clinical practice.

Abstract There is no effective method to predict chemotherapy response and postoperative prognosis of colorectal cancer liver metastasis (CRLM) patients. Patient‐derived organoid (PDO) has become an important preclinical model. Herein, a living biobank with 50 CRLM organoids derived from primary tumors and paired liver metastatic lesions is successfully constructed. CRLM PDOs from the multiomics levels (histopathology, genome, transcriptome and single‐cell sequencing) are comprehensively analyzed and confirmed that this organoid platform for CRLM could capture intra‐ and interpatient heterogeneity. The chemosensitivity data in vitro reveal the potential value of clinical application for PDOs to predict chemotherapy response (FOLFOX or FOLFIRI) and clinical prognosis of CRLM patients. Taken together, CRLM PDOs can be utilized to deliver a potential application for personalized medicine.

The magnetic nanomaterial Mn3Si2Te6 is a promising option for spin-dependent electronic and magneto-optoelectronic devices. However, its application in nonlinear optics remains fanciful. Here, we demonstrate a pulsed Er-doped fiber laser (EDFL) based on a novel quasi-2D Mn3Si2Te6 saturable absorber (SA) with low pump power at 1.5 μm. The high-quality Mn3Si2Te6 crystals were synthesized by the self-flux method, and the ultrathin Mn3Si2Te6 nanoflakes were prepared by a simple mechanical exfoliation procedure. To the best of our knowledge, this is the first time laser pulses have been generated using quasi-2D Mn3Si2Te6. A stable pulsed laser at 1562 nm with a low threshold pump power of 60 mW was produced by integrating the Mn3Si2Te6 SA into an EDFL cavity. The maximum power of the output pulse is 783 μW. The repetition rate can vary from 24.16 to 44.44 kHz, with corresponding pulse durations of 5.64 to 3.41 µs. Our results indicate that the quasi-2D Mn3Si2Te6 is a promising material for application in ultrafast photonics.

Physiological and psychophysical methods allow for an extended investigation of ascending (afferent) neural pathways from the ear to the brain in mammals, and their role in enhancing signals in noise. However, there is increased interest in descending (efferent) neural fibers in the mammalian auditory pathway. This efferent pathway operates via the olivocochlear system, modifying auditory processing by cochlear innervation and enhancing human ability to detect sounds in noisy backgrounds. Effective speech intelligibility may depend on a complex interaction between efferent time-constants and types of background noise. In this study, an auditory model with efferent-inspired processing provided the front-end to an automatic-speech-recognition system (ASR), used as a tool to evaluate speech recognition with changes in time-constants (50 to 2000 ms) and background noise type (unmodulated and modulated noise). With efferent activation, maximal speech recognition improvement (for both noise types) occurred for signal-to-noise ratios around 10 dB, characteristic of real-world speech-listening situations. Net speech improvement due to efferent activation (NSIEA) was smaller in modulated noise than in unmodulated noise. For unmodulated noise, NSIEA increased with increasing time-constant. For modulated noise, NSIEA increased for time-constants up to 200 ms but remained similar for longer time-constants, consistent with speech-envelope modulation times important to speech recognition in modulated noise. The model improves our understanding of the complex interactions involved in speech recognition in noise, and could be used to simulate the difficulties of speech perception in noise as a consequence of different types of hearing loss.

Pulsed fiber lasers, with high peak power and narrow pulse widths, have been proven to be an important tool for a variety of fields of application. In this work, frontier and hot topics in pulsed fiber lasers were analyzed with 11,064 articles. Benefitting from the scientometric analysis capabilities of CiteSpace, the analysis found that passively mode-locked fiber lasers with saturable absorbers (SAs) based on two-dimensional (2D) materials have become a hot research topic in the field of pulsed fiber lasers due to the advantages of self-starting operation, high stability, and good compatibility. The excellent nonlinear optical properties exhibited by 2D materials at nanometer-scale thicknesses have become a particularly popular research topic; the research has paved the way for exploring its wider applications. We summarize the performance of several typical 2D materials in ultrafast fiber lasers, such as graphene, topological insulators (TIs), transition metal dichalcogenides (TMDs), and black phosphorus (BP). Meanwhile, we review and analyze the direction of the development of 2D SAs for ultrafast fiber lasers.

This article presents a versatile neurostimulation platform featuring a fully implantable multi-channel neural stimulator for chronic experimental studies with freely moving large animal models involving peripheral nerves. The implant is hermetically sealed in a ceramic enclosure and encapsulated in medical grade silicone rubber, and then underwent active tests at accelerated aging conditions at 100°C for 15 consecutive days. The stimulator microelectronics are implemented in a 0.6-μm CMOS technology, with a crosstalk reduction scheme to minimize cross-channel interference, and high-speed power and data telemetry for battery-less operation. A wearable transmitter equipped with a Bluetooth Low Energy radio link, and a custom graphical user interface provide real-time, remotely controlled stimulation. Three parallel stimulators provide independent stimulation on three channels, where each stimulator supports six stimulating sites and two return sites through multiplexing, hence the implant can facilitate stimulation at up to 36 different electrode pairs. The design of the electronics, method of hermetic packaging and electrical performance as well as in vitro testing with electrodes in saline are presented.

ObjectiveThis study aimed to compare the molecular, clinical, and pathological characteristics and pedigrees of familial colorectal cancer type X (FCCTX) with those of Lynch syndrome (LS) to provide a theoretical basis for the management of FCCTX.MethodsOverall, 46 cases of FCCTX and 47 LS probands and affected families were enrolled between June 2008 and September 2018 for this study. Multigene cancer panel tests that included 139 genes were performed for all patients, and variants in each group were described. The clinical, pathological, and pedigree characteristics were also compared between the two groups.ResultsIn total, 42 variants were detected in 27 (58.7%) cases in the FCCTX group, with BRCA1, BRCA2, POLE, POLD1, ATR, and ATM being the most frequently mutated genes. The mean onset age of colorectal cancer (CRC) was significantly older in the FCCTX group than in the LS group (53.57 ± 12.88 years vs. 44.36 ± 11.26 years, t = −9.204, p < 0.001). The proportion of patients with rectal cancer was also higher in the FCCTX group than in the LS group [43.5% (20/46) vs. 10.6% (5/47), χ2 = 12.823, p = 0.005]. Within a median follow-up time of 53.9 ± 37.0 months, the proportion of patients who developed metachronous CRC was significantly higher in the LS group than in the FCCTX group [34.0% (16/47) vs. 13.0% (6/46), χ2 = 5.676, p = 0.017]. When comparing pedigrees, older age at cancer onset and rectal cancer clustering were observed in the FCCTX families. A higher prevalence in male patients was also observed in the FCCTX families.ConclusionFCCTX is an entity distinct from LS, but its genetic etiology remains unknown. A larger multigene panel would be recommended for determining the underlying pathogenic variants. Considering the pathology and moderate penetrance of the CRC link to FCCTX, less stringent surgical treatments and colonoscopy surveillance would be preferable. Rectum preference is a typical feature of FCCTX. Colonoscopy surveillance in FCCTX families could be less intensive, and more attention should be given to male members.

Gallium sulfide (GaS), with a hexagonal structure, has received extensive attention due to its graphene-like structure and derived optical properties. Here, high-quality GaS was obtained via chemical vapor synthesis and then prepared as a saturable absorber by the stamp-assisted localization-transfer technique onto fiber end face. The stability of the material and the laser damage threshold are maintained due to the optimized thickness and the cavity integration form. The potential of the GaS for nonlinear optics is explored by constructing a GaS-based Erbium-doped mode-locked fiber laser. Stable femtosecond (~448 fs) mode-locking operation of the single pulse train is achieved, and the robust mode-locked operation (>30 days) was recorded. Experimental results show the potential of GaS for multi-functional ultrafast high-power lasers and promote continuous research on graphene-like materials in nonlinear optics and photonics.

In this study, we compared the molecular, clinical, and pathological characteristics, as well as pedigrees, between patients with Lynch-like syndrome (LLS) and confirmed Lynch syndrome (LS) to develop appropriate management strategies for patients with LLS and their affected family members. Between June 2008 and September 2018, 81 patients with LLS and 47 patients with LS who developed colorectal cancer (CRC) were enrolled in this study. Multigene panel testing included 139 genes and was performed for all patients. The variants identified in each group were described, and clinicopathological characteristics and pedigrees were compared between the two groups. In the LLS group, a total of 52 variants were detected in 44 (54.3%) patients. Among the 52 variants, 17 were variants of unknown significance in mismatch repair genes, and the other most frequently mutated genes were MUYTH, POLE, BRCA2, and GJB2. The proportion of early-onset patients was significantly higher among the LS probands than among the LLS probands (74.5 and 53.1%, respectively; χ2 = 5.712, P = 0.017). On the other hand, the proportion of primary CRC developed in the rectum was higher in the LLS group than in the LS group (25.9 and 10.6%, respectively; χ2 = 2.358, P = 0.046). There were no significant differences in the occurrence of metachronous CRC (P = 0.632) and extra-colorectal cancer (extra-CRC) (P = 0.145) between the two groups. However, analysis of pedigrees showed that more patients developed CRC in the LS families (P = 0.013), whereas more patients with extra-CRC were observed in the LLS families (P = 0.045). A higher prevalence of male patients was observed in the LLS families (P = 0.036). In conclusion, LLS should be classified as a mixed entity, containing cases of LS, other hereditary cancer syndromes, and sporadic CRC. The high risks of CRC and extra-CRCs, which were found in this study, suggest tailored management policy and surveillance should be formulated based on individual and family risk. The surveillance regimen can be based on the presence of confirmed pathogenic/likely pathogenic germline variant(s) and family history.

Abstract Background Colorectal cancer (CRC) patients diagnosed with Lynch syndrome (LS) are recommended genetic testing. Increasing numbers of germline variants involved in homologous recombination have been identified in suspected LS patients. This study compared phenotypic the characteristics of suspected LS patients carrying BRCA and BRCA‐like variants with those of LS patients. Methods Forty‐two patients carrying pathogenic variants of DNA mismatch repair (MMR) genes (MMR group), 9 carrying BRCA variants, and 11 carrying BRCA‐like variants (BRCA/BRCA‐like group) who met LS clinical criteria were enrolled in this study. Clinical characteristics, pedigrees, and survival rates were compared and BRCA variants were analyzed. Results The earliest CRC‐onset age and tumor differentiation were higher in the BRCA/BRCA‐like group than in the MMR group. Metachronous CRCs were more numerous in the MMR group, resulting in a higher progression‐free survival rate in the BRCA/BRCA‐like group. Extra‐colorectal cancers were more frequently observed in the BRCA/BRCA‐like group. BRCA2 and BRCA1 variants were clustered in exons 11 and 4/7, respectively. Conclusion BRCA and BRCA‐like variants in CRC patients with LS showed moderate penetrance. BRCA/BRCA‐like variant carriers had a higher risk for extra‐colorectal cancers. Surveillance of susceptible organs other than the intestine should be performed for probands and affected family members.

Abstract Background Thyroid metastases from colorectal cancer (CRC) are rare, both in clinical practice and in the literature; hence, their diagnosis, appropriate treatment, and prognostic factors require further investigations. Methods A retrospective analysis was performed for four cases of thyroid metastases from CRC, treated in our center between January 2005 and December 2015, and the relevant literature was searched using PubMed, resulting in the identification of 17 patients with detailed information available. The clinical data and follow-up information of our patients and the previously reported cases were collected and compared. Results The median age of the 21 patients was 59 years (44.5 and 66 years for our patients and the previously reported cases, respectively). Fifteen (71.4%) primary tumors were distributed throughout the distal colon or rectum (75% [3/4] in our center and 70.5% [12/17] in the previously reported cases). According to our analysis, we found that 81.0% of patients (17/21) showed concomitant lung metastasis. Among them, all four patients in our center showed lung metastasis, and 75% (3/4) developed thyroid metastases after the lung metastasis. In the previously reported cases, the corresponding proportions were 76.5 and 76.5% (13/17) of patients, respectively. The median time after primary tumor diagnosis to thyroid metastasis development was 28 months (26 months in our center and 35 months in the previously reported cases). One patient with advanced CRC in our center died 5 months after the thyroid metastasis was identified, while the remaining three patients are currently alive (longest follow-up time, 27 months). The median survival time after thyroid metastasis during 3 years of follow-up of the previously reported 17 patients was 12 months. There was no difference in the overall survival between patients treated non-surgically (8/21) and patients undergoing thyroidectomy alone or thyroidectomy with adjuvant therapy (13/21) (p = 0.388). In addition, we found that the overall survival of the patients whose other metastases were treated with radical treatment was superior to that in those treated with palliative treatment (p = 0.022). Conclusions Thyroid metastases from CRC are rare in clinical practice and are a manifestation of advanced CRC. The prognosis of patients with thyroid metastases from CRC is related to various factors, including the grade of malignancy of the primary lesion, the presence of other metastases, and whether the metastases are timely diagnosed and a radical treatment strategy is employed.