USP11 regulates proliferation and apoptosis of human spermatogonial stem cells via HOXC5-mediated canonical WNT/ß-catenin signaling pathway.

Spermatogonial stem cells (SSCs) are capable of transmitting genetic information to the next generations and they are the initial cells for spermatogenesis. Nevertheless, it remains largely unknown about key genes and signaling pathways that regulate fate determinations of human SSCs and male infertility. In this study, we explored the expression, function, and mechanism of USP11 in controlling the proliferation and apoptosis of human SSCs as well as the association between its abnormality and azoospermia. We found that USP11 was predominantly expressed in human SSCs as shown by database analysis and immunohistochemistry. USP11 silencing led to decreases in proliferation and DNA synthesis and an enhancement in apoptosis of human SSCs. RNA-sequencing identified HOXC5 as a target of USP11 in human SSCs. Double immunofluorescence, Co-immunoprecipitation (Co-IP), and molecular docking demonstrated an interaction between USP11 and HOXC5 in human SSCs. HOXC5 knockdown suppressed the growth of human SSCs and increased apoptosis via the classical WNT/ß-catenin pathway. In contrast, HOXC5 overexpression reversed the effect of proliferation and apoptosis induced by USP11 silencing. Significantly, lower levels of USP11 expression were observed in the testicular tissues of patients with spermatogenic disorders. Collectively, these results implicate that USP11 regulates the fate decisions of human SSCs through the HOXC5/WNT/ß-catenin pathway. This study thus provides novel insights into understanding molecular mechanisms underlying human spermatogenesis and the etiology of azoospermia and it offers new targets for gene therapy of male infertility.

Laparoscopic Anatomical Cranial Sub-segmentectomy of Segment VII (S7) with Super-Selective Intra-arterial Nano-ICG Positive Staining-Guided Trans-Parenchymal Approach.

BACKGROUND: With introduction of "cone unit," which is the smallest resectable anatomical area supplied by a tertiary branch of Glissonean pedicle, more precise subsegmental anatomical resection has been proposed.1 Super-selective intra-arterial ICG staining, delivering ICG and lipiodol mixing to arterial branch using interventional radiology, has been proved feasibility especially for complicated anatomy.2-6 It was difficult to uniformly mix water-soluble ICG with lipophilic lipiodol, rendering to inconsistency development of liver segment between angiography and laparoscopy. Nano-ICG is a uniform mixing of ICG and lipiodol.7 We demonstrated an exclusive "two-step" method to perform LAR for cranial S7 via super-selective intra-arterial nano-ICG staining guidance. METHODS: A 70-year-old male was admitted. CT scan showed tumor was located in cranial S7 with 2.1*1.9 cm. Preoperative AFP was 4.66 ng/ml and PIVKA-II was 2332 mAU/ml. The liver function was Child-Pugh class A and ICG-15R was 7.8%. Given that tumor was confined to cranial S7, precise anatomical sub-segmentectomy was warranted. This study was approved by the West China Hospital, Sichuan University Ethics Committee (approval number: 2023-2327). RESULTS: The operation was performed "two step." "First step" was super-selective intra-arterial nano-ICG embolization in intervention room, while "second step" was performed in operation room. ICG demarcation line was clearly identified even after 7 hr. After full mobilization of right hemiliver, we performed transparenchymal approach to find and clamp pedicle of cranial S7 under fluorescence guidance. Operation time was 150 min with 20 ml of blood loss with uneventful course. CONCLUSIONS: Although LAR of S7 remains challenging, super-selective intra-arterial nano-ICG positive staining guidance might be a feasible and safe option.

CDCA5-EEF1A1 interaction promotes progression of clear cell renal cell carcinoma by regulating mTOR signaling.

BACKGROUND: Cell division cycle associated 5 (CDCA5) plays ontogenetic role in various human cancers. However, its specific function and regulatory mechanism in ccRCC remain uncertain. METHODS: Immunohistochemistry and western blots were performed to investigate the expression of CDCA5 in ccRCC tissues. Genetic knockdown and upregulation of CDCA5 were performed to investigate its functional roles in ccRCC proliferation, migration, apoptosis and sunitinib resistance. Furthermore, Co-IP assay and LC-MS/MS were performed to investigate the underlying mechanisms. RESULTS: We found that CDCA5 expression is frequently upregulated in ccRCC tumors and is associated with poor prognosis of ccRCC patients. Functionally, CDCA5 promotes proliferation, migration, and sunitinib resistance, while inhibiting apoptosis in ccRCC cells. In vivo mouse xenograft model confirms that silencing of CDCA5 drastically inhibits the growth of ccRCC. Mechanistically, we discovered that CDCA5 interacts with Eukaryotic Translation Elongation Factor 1 Alpha 1 (EEF1A1) to regulate mTOR signaling pathway, thereby promoting ccRCC progression. CONCLUSIONS: Taken together, our results demonstrate the significant role of CDCA5 in ccRCC progression. The findings may provide insights for the development of new treatment strategies targeting CDCA5 for ccRCC patients.

CircPTEN suppresses human clear cell renal carcinoma progression and resistance to mTOR inhibitors by targeting epigenetic modification.

Renal cell carcinoma (RCC) is known to be the most commonly diagnosed kidney cancer. Clear cell RCC (ccRCC) represents approximately 85 % of diagnosed RCC cases. Targeted therapeutics, such as multi-targeted tyrosine kinase inhibitors (TKI) and mTOR inhibitors, are widely used in ccRCC therapy. However, patients treated with mTOR and TKI inhibitors easily acquire drug resistance, making the therapy less effective. Here, we demonstrated that circPTEN inhibits the expression of its parental gene PTEN by reducing methylation of the PTEN promotor and inhibits GLUT1 expression by reducing m6A methylation of GLUT1, which suppresses ccRCC progression and resistance to mTOR inhibitors.

Impact of imaging-diagnosed sarcopenia on outcomes in patients with biliary tract cancer after surgical resection: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Sarcopenia has been associated with poor prognosis in patients with malignant tumors. However, its impact on the outcomes of patients with biliary tract cancer (BTC) undergoing surgical resection remains unclear and warrants further review. This study aims to summarize the available evidence on this issue. METHODS: A systematic search was conducted in PubMed, Embase, Web of Science, and the Cochrane Library for eligible studies up to March 10, 2024. We extracted data on overall survival (OS), recurrence free survival (RFS), and postoperative major complications from the included studies as the outcomes of interest. Following data synthesis and analysis, we assessed the heterogeneity and performed subgroup analyses. Additionally, the potential for publication bias was evaluated. RESULTS: A total of 26 studies involving 4292 BTC patients were ultimately retrieved. The findings indicated that sarcopenia was significantly associated with reduced OS in BTC patients after surgery (adjusted HR: 2.03, 95% CI: 1.65-2.48, P < 0.001, I2 = 57.4%). Moreover, sarcopenia may also be linked to poorer RFS (adjusted HR: 2.15, 95% CI: 1.79-2.59, P < 0.001, I2 = 0%) and increased postoperative major complications (OR: 1.22, 95% CI 1.02-1.47, P = 0.033, I2 = 29.2%) as well. Notably, no significant publication bias was detected through funnel plots and Egger's tests. CONCLUSION: Sarcopenia is associated with poorer OS in BTC patients following surgery. Additionally, it may serve as a prognostic indicator for poorer RFS and increased postoperative major complications. Further studies are warrant to standardize existing definitions and validate these findings.

Special issue "The advance of solid tumor research in China": Presurgical therapy in the management of local retroperitoneal recurrence of renal cell carcinoma after radical nephrectomy.

Local retroperitoneal recurrence (RPR) after radical nephrectomy (RN) is rare in patients with renal cell carcinoma (RCC); however, it is associated with poor prognosis and lacks standard treatment. Our study aimed to assess oncological outcomes and prognostic factors of patients that underwent targeted therapy for RPR after RN, and to evaluate the role of presurgical targeted therapy in this context. This was a retrospective multicenter study of 85 patients with RPR treated with targeted therapy for RPR after RN (July 2008-October 2020). Clinical and pathological characteristics were reported using descriptive statistics. Cancer-specific survival (CSS) was examined using the Cox proportional hazards model. The median follow-up time was 50 months (95% confidence interval [CI]: 33.3-66.7) after the RPR diagnosis. The median CSS was 96 months in the presurgical targeted therapy followed by surgical resection group and 42 months (95% CI: 28.8-55.2) in the targeted therapy alone group (P = .0011). In multivariate analysis, International Metastatic RCC Database Consortium classification intermediate/poor risk, number of recurrence lesions and surgical resection were independent predictors of CSS. Presurgical targeted therapy may increase the feasibility of tumor resection for RPR after RN. Patients who underwent surgical resection following presurgical targeted therapy had better CSS than those treated with targeted therapy alone.

IL-6-induced cGGNBP2 encodes a protein to promote cell growth and metastasis in intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: IL-6-induced tumor progression has been well established through the induction of antiapoptotic and proliferative genes. However, whether other mechanisms such as IL-6 regulation of circular RNAs (circRNAs) may also contribute to tumor development remains unknown. APPROACH AND RESULTS: High-throughput RNA sequencing was used to identify the differentially expressed circRNAs on IL-6 stimulation in intrahepatic cholangiocarcinoma (ICC) cells. CircRNA GGNBP2 (derived from ggnbp2 gene, termed as cGGNBP2) was up-regulated by IL-6 treatment in a time and concentration-dependent manner. The biogenesis of cGGNBP2 was regulated by RNA-binding protein DEx-H Box Helicase 9, which was also mediated by IL-6 exposure. Mass spectrometry and western blotting identified a protein cGGNBP2-184aa encoded by cGGNBP2. cGGNBP2-184aa promoted ICC cell proliferation and metastasis in vitro and in vivo. Mechanistically, cGGNBP2-184aa directly interacted with signal transducers and activators of transduction-3 (STAT3), phosphorylated STAT3Tyr705 , and played a positive regulatory role in modulating IL-6/STAT3 signaling. IL-6/cGGNBP2-184aa/STAT3 formed a positive feedback loop to sustain constitutive activation of IL-6/STAT3 signaling. Elevated cGGNBP2 expression was correlated with poor prognosis of patients with ICC and was identified as an independent risk factor for patient prognosis. CONCLUSIONS: Our study demonstrates that cGGNBP2-184aa, a protein encoded by IL-6-induced cGGNBP2, formed a positive feedback loop to facilitate ICC progression and may serve as an auxiliary target for clinical IL-6/STAT3-targeting treatments in ICC.

Laparoscopic Anatomical Resection of Paracaval Portion of Caudate Lobe and Segment 8 for HCC in an HCV-Related Cirrhotic Patient.

BACKGROUND: Laparoscopic anatomical resection of caudate lobe remains poorly described due to deep location and connection with major vascular structures. The anterior transparenchymal approach might be safter and provide a better surgical view in cirrhotic cases.1,2 This report demonstrated this approach for anatomic laparoscopic resection of paracaval portion and segment eight (S8) for HCC in an HCV-related cirrhotic patient. METHODS: A 58-year-old man was admitted. The preoperative magnetic resonance imaging indicated that the mass with pseudo capsule was located in paracaval portion and S8 closed to IVC, RHV, and MHV with atrophic left lobe. The preoperative ICG-15R test was 16.2%. In this regard, right hemihepatectomy combined with caudate resection was aborted. We decided to perform an anatomical resection via anterior transparenchymal approach to reserve liver parenchyma as much as possible.3,4 RESULTS: After right lobe mobilization and cholecystectomy, the anterior transparenchymal approach was performed along Rex-Cantlie line by using Harmonic (Johnson & Johnson, USA). With the dissection and clamping of the Glissonean pedicles of S8, anatomical segmentectomy was performed according to the ischemic line and parenchymal transection was performed along hepatic veins. Finally, paracaval portion combined with S8 was en bloc resected. The operating time was 300 minutes with 150 ml of blood loss. The histopathologic report demonstrated the mass as HCC with negative resection margin. Furthermore, it showed a medium-to-high differentiation with no MVI and no microscopic satellite. CONCLUSIONS: The anterior transparenchymal approach for anatomic laparoscopic resection of paracaval portion and S8 might be a feasible and safe option for severe cirrhotic cases.

Safety and efficacy of laparoscopic transperitoneal versus retroperitoneal resection for benign retroperitoneal tumors: a retrospective cohort study.

BACKGROUND AND OBJECTIVE: Benign retroperitoneal tumors (BRTs) are clinically rare solid tumors. This study aimed to compare the safety and efficacy of laparoscopic transperitoneal versus retroperitoneal resection for BRTs. METHODS: The clinical data of 43 patients who had pathologically confirmed BRTs and underwent laparoscopic resection in a single center from January 2019 to May 2022 were retrospectively analyzed. Patients were divided into two groups according to the surgical methods: the Transperitoneal approach group (n = 24) and the Retroperitoneal approach group (n = 19). The clinical characteristics and perioperative data between the two groups were compared. The baseline data and surgical variables were analyzed to determine the impact of different surgical approaches on the treatment outcomes of BRTs. RESULTS: No significant difference was observed between the two groups in gender, age, body mass index, the American Society of Anesthesiologists score, presence of underlying diseases, tumor size, tumor position, operation duration, intraoperative hemorrhage, postoperative hospital stay, intestinal function recovery time, and postoperative complication rate. The conversion rate from laparoscopic to open surgery was significantly lower in the Transperitoneal approach group than in the Retroperitoneal approach group (1/24 vs. 5/19, χ2 = 4.333, P = 0.037). Tumor size was an independent influencing factor for the effect of surgery (odds ratio = 1.869, 95% confidence interval = 1.135-3.078, P = 0.014) and had a larger efficacy on the retroperitoneal group (odds ratio = 3.740, 95% confidence interval = 1.044-13.394, P = 0.043). CONCLUSION: The laparoscopic transperitoneal approach has the inherent advantages of anatomical hierarchies and surgical space, providing a better optical perspective of the targeted mass and improved bleeding control. This approach may have better efficacy than the retroperitoneal approach, especially in cases of a large tumor or when the tumor is located near important blood vessels.

Broadband and CMOS-compatible polarization splitter and rotator built on a silicon nitride-on-silicon multilayer platform.

A broadband and CMOS-compatible polarization beam splitter and rotator (PSR) built on the silicon nitride-on-silicon multilayer platform is presented. The PSR is realized by cascading a polarization beam splitter and a polarization rotator, which are both subtly constructed with an asymmetrical directional coupler waveguide structure. The advantage of this device is that the function of PSR can be directly realized in the SiN layer, providing a promising solution to the polarization diversity schemes in SiN photonic circuits. The chip is expected to have high power handling capability as the light is input from the SiN waveguide. The use of silicon dioxide as the upper cladding of the device ensures its compatibility with the metal back-end-of-line process. By optimizing the structure parameters, a polarization conversion loss lower than 1 dB and cross talk larger than 27.6 dB can be obtained for TM-TE mode conversion over a wavelength range of 1450 to 1600 nm. For TE mode, the insertion loss is lower than 0.26 dB and cross talk is larger than 25.3 dB over the same wavelength range. The proposed device has good potential in diversifying the functionalities of the multilayer photonic chip with high integration density.

CircNFIB inhibits tumor growth and metastasis through suppressing MEK1/ERK signaling in intrahepatic cholangiocarcinoma.

BACKGROUND: Considerable evidence shows that circular RNAs (circRNAs) play an important role in tumor development. However, their function in intrahepatic cholangiocarcinoma (ICC) metastasis and the underlying mechanisms are incompletely understood. METHODS: circNFIB (hsa_circ_0086376, termed as cNFIB hereafter) was identified in human ICC tissues through circRNAs sequencing. The biological role of cNFIB was determined in vitro and in vivo by gain or loss of functional experiments. Fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to analyze the interaction of cNFIB with dual specificity mitogen-activated protein kinase kinase1 (MEK1). Duolink in situ proximity ligation assay (PLA) and coimmunoprecipitation (co-IP) assay were used to investigate the effects of cNFIB on the interaction between MEK1 and mitogen-activated protein kinase 2 (ERK2). Finally, a series of in vitro and in vivo experiments were performed to explore the influences of cNFIB on the anti-tumor activity of trametinib (a MEK inhibitor). RESULTS: cNFIB was significantly down-regulated in human ICC tissues with postoperative metastases. The loss of cNFIB was highly associated with aggressive characteristics and predicted unfavorable prognosis in ICC patients. Functional studies revealed that cNFIB inhibited the proliferation and metastasis of ICC cells in vitro and in vivo. Mechanistically, cNFIB competitively interacted with MEK1, which induced the dissociation between MEK1 and ERK2, thereby resulting in the suppression of ERK signaling and tumor metastasis. Moreover, we found that ICC cells with high levels of cNFIB held the potential to delay the trametinib resistance. Consistently, in vivo and in vitro studies demonstrated that cotreatment with trametinib and lentivirus vector encoding cNFIB showed greater inhibitory effect than isolated trametinib treatment. CONCLUSIONS: Our findings identified that cNFIB played a key role in ICC growth and metastasis by regulating MEK1/ERK signaling. Given the efficacy of cNFIB modulation on ICC suppression and trametinib sensitivity, cNFIB appears to be a potential therapeutic molecule for ICC treatment.

Bio-Based Aerogel Based on Bamboo, Waste Paper, and Reduced Graphene Oxide for Oil/Water Separation.

In recent years, the discharge of industrial waste oil has increased and offshore oil leakage has occurred frequently, and thus water pollution has become a worldwide problem that attracts much attention. In this regard, a kind of oil-absorbing material with high oil-absorbing property and good mechanical property is urgently needed. Here, we reported a new type of aerogels with three-dimensional layered voids using natural bamboo powder, waste paper (WP), and graphene oxide (GO) as raw materials. The obtained aerogel had high adsorption capacity (87-121 g/g), compressibility, and high elasticity, which can separate oil from water and selectively absorb oil. This study provides not only a new treatment in agricultural waste treatment but also a facile, green, and low-cost approach to synthesize high-performance graphene-based oil absorbers, which might give us an effective solution for oil pollution of water resources worldwide.

Second-line treatment with axitinib plus toripalimab in metastatic renal cell carcinoma: a retrospective multicenter study.

Aim: To evaluate the efficacy and safety of second-line treatment with axitinib plus toripalimab in patients with metastatic renal cell carcinoma and failure of VEGFR tyrosine kinase inhibitors. Methods: Data were collected restropectively. Kaplan-Meier analysis and Cox proportional hazards model determined the efficacy outcomes. Results: In 57 patients, objective response rate was 31.6% and median progression-free survival (PFS) was 11.7 months, while median overall survival was not reached. Median PFS was not reached in favorable-risk patients, whereas PFS of 11.0 and 7.8 months were observed in intermediate- and poor-risk patients, respectively (p = 0.011). The treatment-related toxicities were mild in nature. Conclusion: Second-line therapy with axitinib plus toripalimab provided durable response rate, longer PFS and a tolerable safety profile.

Renal cell carcinoma is the most common type of kidney cancer. In cases of metastatic RCC, the combination of axitinib (a VEGFR tyrosine kinase inhibitor) and toripalimab (a recombinant humanized anti-PD-L1 monoclonal antibody) may be beneficial. We investigated the efficacy and safety of second-line treatment with axitinib plus toripalimab in patients with metastatic renal cell carcinoma and anti-VEGFR tyrosine kinase inhibitor therapy failure. Data on patients treated with axitinib plus toripalimab were collected retrospectively and we evaluated the response rate, survival status and toxicities. In total, 31.6% of patients responded to the treatment, with a median progression-free survival of 11.7 months. The combination therapy was safe, with hypertension being the most common grade ≥3 adverse event.

Trocar layouts in laparoscopic liver surgery.

BACKGROUND: Since the first laparoscopic wedge resection reported by Reich, laparoscopic liver resection (LLR) has been progressively developed, acquiring safety and feasibility. The time has witnessed a milestone leap for laparoscopic hepatectomy from pure laparoscopic partial hepatectomy to anatomical hepatectomy and from minor liver resection to major liver resection. The numerous previous studies have paid more attention to the short-time and long-time surgical outcomes caused by surgical techniques corresponding to various segments and approaches. However, focus on trocar layouts remains poorly described, but it plays an indispensable role in surgical process. METHODS: We have searched PubMed for English language articles with the key words "trocar," "laparoscopic liver resection," and "liver resection approaches." RESULTS: This review highlighted each type of trocar layouts corresponding to specific circumstances, including targeted resection segments with various approaches. Notably, surgeon preferences and patients body habitus affect the trocar layouts to some extent as well. CONCLUSIONS: Although there were fewer researches focus on trocar layouts, they determine the operation field and manipulation space and be likely to have an impact on outcomes of surgery. Therefore, further studies are warranted to firm the role of trocar layouts in LLR.

CMOS-compatible, broadband, and polarization-independent edge coupler for efficient chip coupling with standard single-mode fiber.

A CMOS-compatible, broadband, and polarization-independent edge coupler for efficient chip coupling with standard single-mode fiber is proposed. Three layers of a silicon nitride waveguide array with the same structures are used in the top oxide cladding of the chip to achieve high coupling efficiency and to simplify the mode transformation structure. Optimal total coupling loss at the wavelength of 1550 nm, -0.49dB for TE mode polarization and -0.92dB for TM mode polarization is obtained. The -1dB bandwidth is beyond 160 nm for TE mode polarization and ∼130nm for TM mode polarization, respectively. A significant reduction in the packaging cost of silicon photonic chips is anticipated. Meanwhile, the structure holds vast potential for on-chip three-dimensional photonic integrations or fiber-to-chip, chip-to-chip optical interconnections.

Thermal ablation assisted laparoscopic partial nephrectomy for clinical T1b renal tumors.

OBJECTIVE: To report our preliminary results of thermal ablation, including microwave and radiofrequency ablation assisted laparoscopic partial nephrectomy for cT1b renal tumors. MATERIAL AND METHODS: A total of 56 patients with cT1b renal tumors who underwent microwave ablation or radiofrequency ablation assisted laparoscopic partial nephrectomy between January 2014 and May 2018 were enrolled. Thirty of them underwent microwave ablation assisted laparoscopic partial nephrectomy (MWA-LPN group), and the other 26 received radiofrequency ablation assisted laparoscopic partial nephrectomy (RFA-LPN group). Baseline, perioperative and follow-up data were compared between the two groups. RESULTS: There were no statistical differences with respect to patients' gender, age, tumor size, RENAL score, BMI and estimated glomerular filtration rate between the MWA-LPN and RFA-LPN group, nor were any differences observed in warm ischemia time, post-operative complications and hospital stay. Patients in the MWA-LPN group had shorter median operative time (p = .012), less estimated blood loss (p = .023). Median follow-up was 36 months (range 12-64). Three-year cancer-specific and progression-free survival was 100% and 96.4%. The overall kidney recurrence rate was 3.6% in the present study. CONCLUSIONS: Thermal ablation assisted laparoscopic partial nephrectomy is a safe, effective nephron-sparing treatment which provides acceptable results for selective cT1b renal tumors.

High-Performance Three-Dimensional Aerogel Based on Hydrothermal Pomelo Peel and Reduced Graphene Oxide as an Efficient Adsorbent for Water/Oil Separation.

In this study, HPP-RGO aerogels, which were based on a hydrothermal pomelo peel (HPP) and reduced graphene oxide (RGO), were fabricated by using a green and eco-friendly two-step hydrothermal method. The characterization results showed that the HPP-RGO aerogel was endowed with extremely low density, high specific area, robust thermal stability, good mechanical property, stable acid-alkali resistance, superior recyclability, and excellent hydrophobicity and lipophilicity. Remarkably, the typical 40%-HPP-RGO aerogel presented a preferable adsorption capacity (45-80 g·g-1). Moreover, continuous water/oil separation was achieved via the water ring vacuum pump. The successful preparation of the HPP-RGO aerogel endows the pomelo peel with high value-added properties and improves the comprehensive utilization of agricultural wastes. Furthermore, it would open up bright prospects for the field of oil adsorption and water/oil separation.

Individual or combined transcatheter arterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma: a time-to-event meta-analysis.

BACKGROUND: There is still some debate as to whether transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA) is better than TACE or RFA alone. This meta-analysis aimed to compare the efficacy and safety of TACE plus RFA for hepatocellular carcinoma (HCC) with RFA or TACE alone. METHODS: We searched PubMed, MEDLINE, Embase, Cochrane Library, and CNKI (China National Knowledge Infrastructure) for all relevant randomized controlled trials and retrospective studies reporting overall survival (OS), recurrence-free survival (RFS), and complications of TACE plus RFA for HCC, compared with RFA or TACE alone. RESULTS: Twenty-one studies involving 3413 patients were included. TACE combined with RFA was associated with better OS (hazard ratio [HR]=0.62, 95% confidence intervals [CI] = 0.55-0.71, P < 0.001) and RFS (HR = 0.52, 95% CI = 0.39-0.69, P < 0.001) than TACE alone; compared with RFA alone, TACE plus RFA resulted in longer OS (HR = 0.63, 95% CI = 0.53-0.75, P < 0.001) and RFS (HR = 0.60, 95% CI = 0.51-0.71, P < 0.001). Subgroup analyses by tumor size also showed that combined treatment resulted in better OS and RFS compared with RFA alone in patients with HCC larger than 3 cm. Combined treatment resulted in similar rate of major complications compared with TACE or RFA alone (OR = 1.78, 95% CI = 0.99-3.20, P = 0.05; OR = 1.00, 95% CI = 0.42-2.38, P = 1.00, respectively). CONCLUSIONS: TACE combined with RFA was more effective for HCC than TACE alone. For patients with a tumor larger than 3 cm, the combined treatment also achieved a better effect than RFA alone.

Development and validation of a novel nomogram predicting 10-year actual survival after curative hepatectomy for hepatocellular carcinoma.

INTRODUCTION: Although hepatectomy is a curative treatment modality for hepatocellular carcinoma (HCC), the associated 10-year long-term actual survival are rarely reported. This study aims to develop and validate a predictive nomogram for 10-year actual survivors with HCC. MATERIALS AND METHODS: From 2004 to 2009, 753 patients with curative hepatectomy for HCC (development set, n = 325; validation set, n = 428) were included. In development set, comparison of clinic-pathological data was made between patients surviving ≥10 years and those surviving <10 years. Good independent prognostic factors identified by multivariate analysis were involved in a nomogram development, which was validated internally and externally using validation set. RESULTS: On multivariate analysis, five independent good prognostic factors for 10-year survival were identified, including young age (OR = 0.943), good ASA status (≤2) (OR = 2.794), higher albumin level (OR = 1.116), solitary tumor (OR = 2.531) and absence of microvascular invasion (OR = 3.367). A novel nomogram was constructed with C-index of 0.801 (95% CI 0.762-0.864). A cut-off point of 167.5 had a sensitivity of 0.794 and specificity of 0.730. Internal validation using bootstrap sampling and external validation using validation set revealed C-index of 0.792 (95% CI, 0.741-0.853) and 0.761 (95% CI, 0.718-0.817). CONCLUSION: A novel nomogram for 10-year HCC survivor using age, ASA status, preoperative albumin, tumor number and presence of microvascular tumor invasion was developed and validated with high accuracy.

Analysis of Copy Number Variations by Low-Depth Whole-Genome Sequencing in Fetuses with Congenital Cardiovascular Malformations.

Congenital cardiovascular malformations (CVMs) due to genomic mutations bring a greater risk of morbidity and comorbidity and increase the risks related to heart surgery. However, reports on CVMs induced by genomic mutations based on actual clinical data are still limited. In this study, 181 fetuses were screened by fetal echocardiography for prenatal diagnosis of congenital heart disease, including 146 cases without ultrasound extracardiac findings (Group A) and 35 cases with ultrasound extracardiac findings (Group B). All cases were analyzed by clinical data, karyotyping, and low-depth whole-genome sequencing. The rates of chromosomal abnormalities in Groups A and B were 4.8% (7/146) and 37.1% (13/35), respectively. There was a significant difference in the incidence of chromosomal abnormalities between Groups A and B (p < 0.001). In Group A, CNV-seq identified copy number variations (CNVs) in an additional 9.6% (14/146) of cases with normal karyotypes, including 7 pathogenic CNVs and 7 variations of uncertain clinical significance. In Group B, one pathogenic CNV was identified in a case with normal karyotype. Chromosomal abnormality is one of the most common causes of CVM with extracardiac defects. Low-depth whole-genome sequencing could effectively become a first approach for CNV diagnosis in fetuses with CVMs.