Blood leukocytes as a non-invasive diagnostic tool for thyroid nodules: a prospective cohort study.

BACKGROUND: Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy. METHODS: This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes. RESULTS: The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies. CONCLUSIONS: This is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China.

Extended S2 diagnosis of mode degradation in fiber components through group delay stretching.

The separate diagnosis of mode degradation in few-mode fiber components (FMFCs) is a challenging task due to the reciprocal mode cross talk. In this work, we propose the group delay stretching, combined with the extended spatially and spectrally (S2) resolved imaging technique, to decouple and analyze the mode coupling within the body of the FMFC with short-length pigtails. Through stretching the mode delay by a delay fiber, the degraded modes related to different origins are effectively separated, and the extended S2 technique quantifies the individual modal weight for each component. Experiments on different types of FMFCs have verified the validity of our method. This method paves the way for optimizing and manipulating the fiber components in the dimensionality of modes.

Pneumothorax and pulmonary hemorrhage after C-arm cone-beam computed tomography-guided percutaneous transthoracic lung biopsy: incidence, clinical significance, and correlation.

OBJECTIVE: This study aimed to assess the incidence and clinical significance of pneumothorax (PTX) and pulmonary hemorrhage (PH) after percutaneous transthoracic lung biopsy (PTLB) guided by C-arm cone-beam computed tomography (CBCT). Furthermore, this study aimed to examine the relationships between PTX and PH with demographics, clinical characteristics, imaging, and PTLB parameters. METHODS: A retrospective analysis was conducted on 192 patients who underwent PTLB at our hospital between January 2019 and October 2022. Incidences of PTX and PH were recorded. PTX was considered clinically significant if treated with chest tube insertion (CTI), and PH if treated with bronchoscopes or endovascular treatments. The various factors on PTX and PH were analyzed using the Chi-squared test and Student t-test. Logistic regression analyses were then used to determine these factors on the correlation to develop PTX and PH. RESULTS: PTX occurred in 67/192 cases (34.9%); CTI was required in 5/67 (7.5%). PH occurred in 63/192 cases (32.8%) and none of these cases required bronchoscopes or endovascular treatments. Lesion diameter (ORPTX = 0.822; ORPH = 0.785), presence of pulmonary emphysema (ORPH = 2.148), the number of samples (ORPH = 1.834), the use of gelfoam (ORPTX = 0.474; ORPH = 0.341) and ablation (ORPTX = 2.351; ORPH = 3.443) showed statistically significant correlation to PTX and PH. CONCLUSIONS: CBCT-guided PTLB is a safe and effective method for performing lung biopsies. The use of gelfoam has been shown to reduce the occurrence of PTX and PH. However, caution should be exercised when combining radiofrequency ablation with PTLB, as it may increase the risk of PTX and PH.

Transient Absorption Spectroscopic Investigation of the Photocyclization-Deprotection Reaction of 3',5'-Dimethoxybenzoin Fluoride.

The 3',5'-dimethoxybenzoin (DMB) system has been widely investigated as a photoremovable protecting group (PRPG) for the elimination of various functional groups and has been applied in many fields. The photolysis of DMB fluoride leads to a highly efficient photocyclization-deprotection reaction, resulting in a high yield of 3',5'-dimethoxybenzofuran (DMBF) in a MeCN solution, while there is a competitive reaction that produces DMB in an aqueous solution. The yield of DMB increased as the volume ratio of water increased. To understand the solvent effect of the photolysis of selected DMB-based compounds, a combination of femtosecond to nanosecond transient absorption spectroscopies (fs-TA and ns-TA), nanosecond time-resolved resonance Raman spectroscopy (ns-TR3) and quantum chemical calculation was employed to study the photophysical and photochemical reaction mechanisms of DMB fluoride in different solutions. Facilitated by the bichromophoric nature of DMB fluoride with electron-donating and -withdrawing chromophores, the cyclized intermediates could be found in a pure MeCN solution. The deprotection of a cyclic biradical intermediate results in the simultaneous formation of DMBF and a cyclic cation species. On the other hand, in aqueous solution, fs-TA experiments revealed that α-keto cations could be observed after excitation directly, which could easily produce the DMB through the addition of a hydroxyl within 8.7 ps. This work provides comprehensive photo-deactivation mechanisms of DMB fluoride in MeCN and aqueous conditions and provides critical insights regarding the biomedical application of DMB-based PRPG compounds.

[Research Progress in the Role of Liquid-Liquid Phase Separation in Human Cancer]. / 液-æ¶²ç›¸åˆ†ç¦»åœ¨è‚¿ç˜¤ä¸­ä½œç”¨çš„ç ”ç©¶æ–°è¿›å±•.

Liquid-liquid phase separation (LLPS) is a reversible process, during which biological macromolecules, including proteins and nucleic acids, condense into liquid membraneless organelles under the influence of weak multivalent interactions. Currently, fluorescence recovery after photobleaching is the primary method used to detect the phase separation of biological macromolecules. Recent studies have revealed the link between abnormal LLPS and the pathogenesis and development of various human cancers. Through phase separation or abnormal phase separation, tumor-related biological macromolecules, such as mRNA, long noncoding RNAs (lncRNAs), and tumor-related proteins, can affect transcriptional translation and DNA damage repair, regulate the autophagy and ferroptosis functions of cells, and thus regulate the development of various tumors. In this review, we summarized the latest research findings on the mechanism of LLPS in the pathogenesis and progression of tumors and elaborated on the promotion or inhibition of autophagy, tumor immunity, DNA damage repair, and cell ferroptosis after abnormal phase separation of biomolecules, including mRNA, lncRNA, and proteins, which subsequently affects the pathogenesis and progression of tumors. According to published findings, many biological macromolecules can regulate transcriptional translation, expression, post-transcriptional modification, cell signal transduction, and other biological processes through phase separation. Therefore, further expansion of the research field of phase separation and in-depth investigation of its molecular mechanisms and regulatory processes hold extensive research potential.

Tetraborated Intrinsically Axial Chiral Multi-resonance Thermally Activated Delayed Fluorescence Materials.

Chiral multi-resonance thermally activated delayed fluorescence (CP-MR-TADF) materials hold promise for circularly polarized organic light-emitting diodes (CP-OLEDs) and 3D displays. Herein, we present two pairs of tetraborated intrinsically axial CP-MR-TADF materials, R/S-BDBF-BOH and R/S-BDBT-BOH, with conjugation-extended bidibenzo[b,d]furan and bidibenzo[b,d]thiophene as chiral sources, which effectively participate in the distribution of the frontier molecular orbitals. Due to the heavy-atom effect, sulfur atoms are introduced to accelerate the reverse intersystem crossing process and increase the efficiency of molecules. R/S-BDBF-BOH and R/S-BDBT-BOH manifest ultra-pure blue emission with a maximum at 458/459 nm with a full width at half maximum of 27 nm, photoluminescence quantum yields of 90 %/91 %, and dissymmetry factors (|gPL|) of 6.8×10-4/8.5×10-4, respectively. Correspondingly, the CP-OLEDs exhibit good performances with an external quantum efficiency of 30.1 % and |gEL| factors of 1.2×10-3.

Regulator of G-protein signaling 14 protects the liver from ischemia-reperfusion injury by suppressing TGF-ß-activated kinase 1 activation.

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion injury (IRI) is a common complication of hepatectomy and liver transplantation. However, the mechanisms underlying hepatic IRI have not been fully elucidated. Regulator of G-protein signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates the G-protein and mitogen-activated protein kinase (MAPK) signaling pathways. However, the role of RGS14 in hepatic IRI remains unclear. APPROACH AND RESULTS: We found that RGS14 expression increased in mice subjected to hepatic ischemia-reperfusion (IR) surgery and during hypoxia reoxygenation in hepatocytes. We constructed global RGS14 knockout (RGS14-KO) and hepatocyte-specific RGS14 transgenic (RGS14-TG) mice to establish 70% hepatic IRI models. Histological hematoxylin and eosin staining, levels of alanine aminotransferase and aspartate aminotransferase, expression of inflammatory factors, and apoptosis were used to assess liver damage and function in these models. We found that RGS14 deficiency significantly aggravated IR-induced liver injury and activated hepatic inflammatory responses and apoptosis in vivo and in vitro. Conversely, RGS14 overexpression exerted the opposite effect of the RGS14-deficient models. Phosphorylation of TGF-ß-activated kinase 1 (TAK1) and its downstream effectors c-Jun N-terminal kinase (JNK) and p38 increased in the liver tissues of RGS14-KO mice but was repressed in those of RGS14-TG mice. Furthermore, inhibition of TAK1 phosphorylation rescued the effect of RGS14 deficiency on JNK and p38 activation, thus blocking the inflammatory responses and apoptosis. CONCLUSIONS: RGS14 plays a protective role in hepatic IR by inhibiting activation of the TAK1-JNK/p38 signaling pathway. This may be a potential therapeutic strategy for reducing incidences of hepatic IRI in the future.

Towards a tapered Yb-doped fiber-based narrow linewidth single-mode fiber laser with a high signal to Raman ratio.

We demonstrate an all-fiber high-power narrow-linewidth fiber laser based on a homemade tapered Yb-doped fiber (T-YDF). The laser performance is investigated and systematically compared with different seed powers and pump manners. The experimental results reveal that the injected seed power requires a trade-off designed to take into account the impact of spectral broadening, nonlinear effects, and transverse mode instability (TMI). Compared with the co-pump manner, the counter-pump manner performs well in inhibiting nonlinearities, spectral broadening, and improving the TMI threshold. Under the counter-pump manner, this narrow-linewidth T-YDF amplifier realized a 2.09 kW output power with a 3 dB spectral linewidth of ∼0.34 nm, a beam quality of M2∼1.28 and a high Raman suppression ratio over 53.5 dB, the highest reported power for such a T-YDF-based narrow-linewidth single-mode laser, to the best of our knowledge. This work provides a promising pathway towards implementing monolithic high-power narrow-linewidth single-mode fiber lasers.

10 kW tandem pumping fiber amplifier with good beam quality based on tapered ytterbium-doped fiber.

In this paper, we established a high power tandem pumped fiber amplifier based on tapered ytterbium-doped fiber (TYDF). The TYDF is developed in-house with a core/inner cladding diameter of 30/250 µm at the small-core region and 48/400 µm at the large-core region. The key parameters of the amplifier in a co-pumped and counter-pumped configuration are experimentally investigated, such as slope efficiency, stimulated Raman scattering (SRS) threshold, and beam quality evolution. Up to 10.28 kW laser free of SRS or transverse mode instability is obtained from the counter-pumped amplifier, and the beam quality factor M2 is 2.29, which is significantly improved compared with the 48/400 µm uniform YDF. To the best of our knowledge, this is the highest average output power achieved so far based on the TYDF. This work could provide a solution for balancing the SRS suppression and high order modes control in high power tandem pumped YDF lasers.

Seeing the strong suppression of higher order modes in single trench fiber using the S2 technique.

The single trench fiber (STF) is a promising fiber design for mode area scaling and higher order mode (HOM) suppression. In this Letter, we experimentally demonstrate the strong HOM-suppression in a homemade STF using the spatially and spectrally resolved imaging (S2) technique. This STF has a 20-µm core and its performance is compared to a conventional step-index fiber with almost the same parameter. Results show that the bending loss of the HOM in STF is 8-times larger than conventional fiber at a bend radius of 7 cm. In addition, when severe coupling mismatch is introduced at the input end of the fiber, the STF can keep the fundamental-mode output while the conventional fiber cannot. To the best of our knowledge, this is the first time to experimentally analyze the HOM content in an STF and compare its performance with that of a conventional fiber. Our results indicate the great potential of the STF for filtering the HOM in fiber laser applications.

Preoperative transarterial chemoembolization with drug-eluting beads (DEB-TACE) in patients undergoing conversional hepatectomy: a propensity-score matching analysis.

OBJECTIVES: Patients with colorectal liver metastases (CRLM) who underwent hepatic resection after conversion therapy had a high recurrence rate of nearly 90%. Preoperative DEB-TACE has the potential to prevent postoperative recurrence which has not been elucidated. The objective of this study was to evaluate the safety and efficacy of preoperative DEB-TACE. MATERIALS AND METHODS: Patients with CRLM who underwent liver resection from June 1, 2016, to June 30, 2021, were collected and those who received conversional hepatectomy were included in this study. Patients with preoperative DEB-TACE were propensity-score matched in a 1:1 ratio to patients without preoperative DEB-TACE. Short-term outcomes and recurrence-free survival (RFS) were compared between the two groups. RESULTS: After PSM, 44 patients were included in each group. The toxicities of DEB-TACE were mild and could be managed by conservative treatment. Overall response rate (ORR) of conversion therapy (75.0% vs. 81.2%, p = 0.437) and postoperative complication of hepatic resection (27.3% vs. 20.5%, p = 0.453) were similar between the two groups. The median RFS of the DEB-TACE group (10.7 months, 95%CI: 6.6-14.8 months) was significantly longer than that of the control group (8.1 months, 95%CI: 3.4-12.8 months) (HR: 0.60, 95%CI: 0.37-0.95, p = 0.027). CONCLUSIONS: In patients who became resectable after conversion therapy, preoperative DEB-TACE might be a safe option to achieve longer RFS. KEY POINTS: • This is a propensity-score matching study comparing patients who underwent conversional hepatectomy with or without preoperative DEB-TACE. • The preoperative DEB-TACE was safe and with mild toxicities (without toxicities more than CTCAE grade 3). • The preoperative DEB-TACE significantly prolonged the RFS of those patients who underwent conversional hepatectomy (10.7 vs. 8.1 months, p = 0.027).

The prognostic role of the AST/ALT ratio in hepatocellular carcinoma patients receiving thermal ablation combined with simultaneous TACE.

BACKGROUND: To evaluate the prognostic value of the pre-treatment aspartate transaminase (AST)/alanine transaminase (ALT) ratio in hepatocellular carcinoma (HCC) patients receiving radiofrequency ablation (RFA)/microwave ablation (MWA) combined with simultaneous TACE. METHODS: The data for 117 patients were retrospectively analyzed in this study. The endpoint of prognosis was overall survival (OS). The Youden index was used to choose the optimal cut-off value of the pre-treatment AST/ALT ratio for OS prediction. Univariate and multivariate analyses were used to identify independent risk factors, then integrated to establish the nomogram. RESULTS: The AST/ALT ratio cut-off value for OS prediction was 0.89, and patients with a higher AST/ALT ratio had poorer OS. The median OS for the high-value AST/ALT group was not reached, while the median OS for the low-value AST/ALT group was 48.5 months (P = 0.0047). The univariate and multivariate analysis showed that AST/ALT ratio, AFP, and tumor numbers were independent prognostic indicators for OS. The integrated nomogram showed higher predictive accuracy for OS (C-index 0.674, 95%CI: 0.600-0.748). CONCLUSIONS: The preoperative AST/ALT ratio could be a prognostic indicator for HCC patients receiving thermal ablation combined with simultaneous TACE.

Long-term efficacy and safety of anticoagulant for cavernous transformation of the portal vein cirrhotic patient with extrahepatic portal vein obstruction.

BACKGROUND/AIMS: Cavernous transformation of the portal vein (CTPV) in cirrhotic patients with extrahepatic portal vein obstruction (EHPVO) was a relatively rare disease and had no consensus on the treatment. Our study aimed to explore the value of anticoagulation with warfarin treatment for CTPV cirrhotic patients with EHPVO. METHODS: From January 2015 to December 2019, the clinical characteristics of cirrhotic patients who were diagnosed as CTPV with EHPVO were retrospectively analyzed. Eligible patients were distributed into the anticoagulation group (n = 46) and control group (n = 38). The change of portal vein thrombosis, hepatic decompensation, survival and adverse events were evaluated between the two groups. RESULTS: The median follow-up of our patients was 51 months in the anticoagulation group and 44 months in the control group. The progress rate of the portal vein was higher in patients from the control groups (n = 12) than in patients from the anticoagulation group (n = 4, p = 0.008). There was no significant difference between the partial recanalization rate and stable rate between the two groups. Patients in anticoagulation group developed less hepatic decompensation than those in control group (13.0% vs 34.2%, p = 0.021). The Kaplan-Meier curve showed that patients in the anticoagulation group had a better prognosis than patients in the control group (P < 0.022). There were no serious complications due to warfarin treatment. CONCLUSION: For CTPV cirrhotic patients with EHPVO, anticoagulation with warfarin treatment was effective and safe. Anticoagulants could prevent portal vein thrombosis progression, hepatic decompensation and death. In addition, our results showed little benefit of anticoagulants on thrombosis recanalization.

A new alternative technique for the guidance of transjugular intrahepatic portosystemic shunt creation using DSA overlay reference.

BACKGROUND: Portal vein puncture (PVP) is a critical step during transjugular intrahepatic portosystemic shunt (TIPS) and correlates to several complications. Techniques guiding PVP are needed. PURPOSE: To evaluate the safety, feasibility, and efficiency of digital subtraction angiography (DSA) overlay reference during TIPS creation and compare it with transhepatic portal vein (THPV) guiding. MATERIAL AND METHODS: The clinical records of 185 patients at three medical centers who underwent TIPS placement were reviewed. Portal vein access was guided by THPV guiding in 120 cases and DSA overlay reference in 60 cases. The number of punctures, portal vein entry time, procedural adverse events, technical and hemodynamic success rate were analyzed to compare the safety, feasibility, and efficiency of the two methods. RESULTS: The median numbers of punctures in group 1 and group 2 were 2 (1-4) and 2 (1-5), respectively (P = 0.094). There was no statistical difference between two groups in needle passes. The median portal vein entry time of group 1 was 12 min (8-16 min) and 13 min (8-16 min) in group 2. No significant difference was found in the PVP time (P = 0.802). Arterioportal fistula formation occurred in 15 patients in group 1; two patients in group 2 had hepatic artery injury. The patients in group 2 had lower rates of procedural adverse events (P = 0.047). Median dose area product of G1 was lower than G2 statistically (P<0.001). There was no significant difference in total fluoroscopy time (P = 0.856). CONCLUSION: DSA overlay reference has lower procedural adverse events rates compared with THPV guiding TIPS. It seems to be a safe and effective method for guiding PVP.

[Therapeutic effect of recombinant human growth hormone on children with growth hormone deficiency and different pituitary developmental conditions: a prospective study]. / é‡ç»„äººç”Ÿé•¿æ¿€ç´ æ²»ç–—ä¸åŒåž‚ä½“å‘è‚²çŠ¶å†µç”Ÿé•¿æ¿€ç´ ç¼ºä¹ç—‡æ‚£å„¿ç–—æ•ˆçš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions. METHODS: A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups. RESULTS: After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05). CONCLUSIONS: In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.

Confined-doped active fiber enabled all-fiber high-power single-frequency laser.

In this paper, we investigate the performances of an in-house fabricated confined-doped active fiber in the applications of all-fiber high-power single-frequency amplifiers. A 210-W single-frequency single-mode fiber laser is obtained directly, which confirms the excellent performance of the confined-doped active fiber for high-power single-mode operation. To further demonstrate the power scalability of the fiber amplifier, the strategy of applying a temperature gradient along the active fiber is investigated numerically and experimentally, and an up to ∼75% enhancement of the stimulated Brillouin scattering (SBS) threshold is achieved. As a result, a 368-W single-frequency fiber laser is obtained with the beam quality factor of Mx2 = 1.19, My2 = 1.26. Overall, the technique of the confined-doped active fiber provides a promising approach to scale the output power of single-frequency single-mode fiber lasers.

Hypoxia blocks ferroptosis of hepatocellular carcinoma via suppression of METTL14 triggered YTHDF2-dependent silencing of SLC7A11.

Residue hepatocellular carcinoma (HCC) cells enduring hypoxic environment triggered by interventional embolization obtain more malignant potential with little clarified mechanism. The N6 -methyladenosine (m6 A) biological activity plays essential roles in diverse physiological processes. However, its role under hypoxic condition remains largely unexplored. RT-qPCR and Western blot were used to evaluate METTL14 expression in hypoxic HCC cells. MDA assay and electronic microscopy photography were used to evaluate ferroptosis. The correlation between SLC7A11 and METTL14 was conducted by bioinformatical analysis. Flow cytometry was used to verify the effect of SLC7A11 on ROS production. Cell counting kit-8 assay was performed to detect cells proliferation ability. Hypoxia triggered suppression of METTL14 in a HIF-1α-dependent manner potently abrogated ferroptosis of HCC cells. Mechanistic investigation identified SLC7A11 was a direct target of METTL14. Both in vitro and in vivo assay demonstrated that METTL14 induced m6 A modification at 5'UTR of SLC7A11 mRNA, which in turn underwent degradation relied on the YTHDF2-dependent pathway. Importantly, ectopic expression of SLC7A11 strongly blocked METTL14-induced tumour-suppressive effect in hypoxic HCC. Our investigations lay the emphasis on the hypoxia-regulated ferroptosis in HCC cells and identify the HIF-1α /METTL14/YTHDF2/SLC7A11 axis as a potential therapeutic target for the HCC interventional embolization treatment.

Preoperative Hepatic and Regional Arterial Chemotherapy in Patients Who Underwent Curative Colorectal Cancer Resection: A Prospective, Multi-center, Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of the addition of preoperative hepatic and regional arterial chemotherapy (PHRAC) on prognosis of stage II and III colorectal cancer (CRC) in a multicenter setting. SUMMARY OF BACKGROUND DATA: Our previous single-center pilot trial suggested that PHRAC in combination with surgical resection could reduce the occurrence of liver metastasis (LM) and improve survival in CRC patients. METHODS: A prospective multi-center randomized controlled trial was conducted from December 2008 to December 2012 at 5 hospitals in China. Eligible patients with clinical stage II or III CRC who underwent curative resection were randomized to receive PHRAC plus adjuvant therapy (PHRAC arm) or adjuvant therapy alone (control arm). The primary endpoint was DFS. Secondary endpoints were cumulative LM rates, overall survival (OS), and safety (NCT00643877). RESULTS: A total of 688 patients from 5 centers in China were randomly assigned (1:1) to each arm. The five-year DFS rate was 77% in the PHRAC arm and 65% in the control arm (HR = 0.61, 95% CI 0.46-0.81; P = 0.001). The 5-year LM rates were 7% and 16% in the PHRAC and control arms, respectively (HR = 0.37, 95% CI 0.22-0.63; P < 0.001). The 5-year OS rate was 84% in the PHRAC arm and 76% in the control arm (HR = 0.61, 95% CI 0.43-0.86; P = 0.005). There were no significant differences regarding treatment related morbidity or mortality between the two arms. CONCLUSIONS: The addition of PHRAC could improve DFS in patients with stage II and III CRC. It reduced the incidence of LM and improved OS without compromising patient safety. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00643877.

METTL3/IGF2BP1/CD47 contributes to the sublethal heat treatment induced mesenchymal transition in HCC.

Microwave ablation is a first-line treatment of small hepatocellular carcinoma (HCC), while incomplete ablation induces recurrence and metastasis. However, its underlying mechanism remains largely unexplored. Here we reported that sublethal heat treatment (46 °C) strongly promoted migration and EMT transition in HCC cells. Mechanistic investigation revealed that compared with 37 °C, HCC cells treated with 46 °C expressed higher level of CD47. Knockdown of CD47 significantly attenuated sublethal heat treatment stimulated migration and EMT transition. In addition, METTL3 which is the key enzyme of m6A modification was also induced by 46 °C treatment and triggered CD47 expression in HCC cells. Moreover, CD47 mRNA degradation was further proved to be stabled in the IGF2BP1-dependent manner. Importantly, sublethal heat treatment stimulated CD47 expression and EMT transition were also confirmed in patient-derived organoid. Taken together, our study suggests that METTL3/IGF2BP1/CD47 mediated EMT transition contributes to the incomplete ablation induced metastasis in HCC cells. Moreover, these findings identify the METTL3/IGF2BP1/CD47 axis as a potential therapeutic target for the microwave ablation and shed new lights on the crosstalk between incomplete heat ablation and RNA methylation.

Leakage channels enabled multi-resonant all-solid photonic bandgap fiber for effective single-mode propagation.

All-solid photonic bandgap fiber (AS-PBGF) has been fully demonstrated to be a promising candidate of large-mode-area fiber for its mode-dependent selectivity and spectral filtering mechanism. In the present work, the concepts of multiple-resonant coupling and leakage channels are taken into consideration simultaneously for mode area scaling of AS-PBGF. The single-mode performance and bending resistance of a modified structure, called leakage channels enabled multi-resonant AS-PBGF (LC-PBGF), are evaluated numerically. Robust single-mode transmission is guaranteed by a specially designed microstructure cladding with only four layers of germanium-doped rods. Multi-resonant cores in the inner layers and leakage channels in the outermost layer, resulting from missing rods in the microstructure cladding, are employed to generate modal dissipation of high-order modes under bent configuration. The missing germanium-doped rods in each layer are properly designed to eliminate the dependence on bending direction, leading to differential bending loss between fundamental mode and high-order-modes with high loss ratio. In addition, some typical derivative structures based on the LC-PBGF concept have also been proved to have great potential for effective single-mode operation.