Background:In patients with hepatocellular carcinoma (HCC), the prognostic role of tumor-infiltrating lymphocytes (TILs) for survival is still controversial. A meta-analysis was performed to investigate the prognostic effect of TILs in HCC.Methods:We identify studies from PubMed, Embase, and the Cochrane Library to evaluate the prognostic value of TILs in patients with HCC. A meta-analysis was conducted to estimate overall survival and disease-free survival. The hazard ratio (HR) and 95% confidence interval (CI) were calculated employing fixed-effect or random-effect models depending on the heterogeneity of the included trials.Results:A total of 7905 patients from 46 observational studies were enrolled. For TILs subsets, the density of CD8+, FOXP3+, CD3+, and Granzyme B+ lymphocytes was significantly associated with improved survival (P < .05). The density of FOXP3+ TILs in intratumor (IT) was the most significant prognostic marker (pooled HR = 1.894; 95% CI = 1.659–2.164; P < .001). Patients with high infiltration of CD8+ TILs in IT (pooled HR = 0.676; 95% CI = 0.540–0.845; P = .001) or in margin of tumor (MT) (pooled HR = 0.577; 95% CI = 0.437–0.760; P < .001) had better OS. The pooled analysis revealed that high density of Granzyme B+ T-lymphocytes in IT was statistically significant associated with better OS (pooled HR = 0.621; 95% CI = 0.516–0.748; P < .001) and DFS (pooled HR = 0.678; 95% CI = 0.563–0.815; P < .001). It was interesting that high density of CD3+ in IT foreboded worse OS (pooled HR = 1.008; 95% CI = 1.000–1.015; P = .037), but better DFS (pooled HR = 0.596; 95% CI = 0.374–0.948; P = .029).Conclusion:Our findings suggested that some TIL subsets could serve as prognostic biomarkers in HCC. High-quality randomized controlled trials are needed to determine if these TILs could serve as targets for immunotherapy in HCC.

Background:In patients with hepatocellular carcinoma (HCC), the clinicopathologic and prognostic roles of tumor-infiltrating CD8+ T cells for survival are still controversial. A meta-analysis was performed to resolve this issue.Methods:We identified studies from PubMed, Embase, and the Cochrane Library to evaluate the clinicopathologic and prognostic value of tumor-infiltrating CD8+ T cells in patients with HCC. A meta-analysis was conducted to estimate clinicopathologic characteristics, overall survival (OS), and disease-free survival. The hazard ratio (HR) and 95% confidence interval (CI) were calculated employing fixed-effect or random-effect models depending on the heterogeneity of the included trials.Results:A total of 3509 patients from 21 observational studies were enrolled. The meta-analysis revealed that high levels of intratumoral CD8+ tumor-infiltrating lymphocytes (TILs) were associated with better OS (OS; HR = 0.676, P = .001) and disease-free survival (disease-free survival [DFS]; HR = 0.712, P = .002). The pooled analysis also demonstrated high density of infiltration of CD8+ TILs in margin of tumor (MT) was statistically significant associated with better OS (HR = 0.577; P <.001). Moreover, the patients with low CD8+ TILs infiltration had negative HBSAg (OR = 1.67, P = .02), large tumor size (OR = 1.74, P <.01), and later TNM stage (OR = 1.70, P <.01).Conclusions:Our findings suggested that low levels of CD8+ TILs predict large tumor size, later TNM stage and might be a promising prognostic factor of HCC especially for Asian patients. High-quality randomized controlled trials are needed to determine if CD8+ TILs could serve as targets for immunotherapy in hepatocellular carcinoma.

PurposeTumor-associated macrophages (TAMs) deserve more focus because of its clinicopathologic and prognostic roles in solid tumors. However, the prognostic value of TAMs in patients with hepatocellular carcinoma (HCC) is still controversial. We performed a meta-analysis to resolve the issue.MethodsWe selected relevant studies from the Cochrane Library, Embase and PubMed databases. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated employing fixed-effect or random-effect models depending on the heterogeneity of the included trials. Moreover, we also performed subgroup analysis, cumulative meta-analysis, sensitivity analysis, and bias analysis (Egger’s test).ResultsA total of 20 observational studies with 4297 patients were enrolled. For TAMs subsets, high density of CD68+ TAMs in either intratumor (IT) (pooled HR = 1.417; 95% CI = 1.092–1.839; P = 0.009) or peritumor (PT) (pooled HR = 1.393; 95% CI = 1.022–1.899; P = 0.036) was associated with a poor OS. High density of CD68+ TAMs in IT was also associated with high AFP value, large tumor size, absent encapsulation, present vascular invasion, and later tumor-nodes-metastasis (TNM) stage. High density of CD163+ macrophages in serum was associated with a poor OS (pooled HR = 5.698; 95% CI = 3.062–10.603; P < 0.001). High density of CD204+ TAMs in IT was associated with a poor OS (pooled HR = 1.947; 95% CI = 1.387–2.733; P < 0.001. High density of CD206+ TAMs in IT was associated with a poor OS (pooled HR = 1.723; 95% CI = 1.308–2.270; P < 0.001) and DFS (pooled HR = 1.711; 95% CI = 1.214–2.412; P = 0.002). However, high density of CD169+ TAMs in IT was associated with a good OS (pooled HR = 0.471; 95% CI = 0.343–0.647; P = 0.037).ConclusionsTAMs could serve as independent predictive indicators and therapeutic targets for HCC. Further trials are needed to elucidate the exact relationship and the underlying mechanism.

Color change during flower opening is common; however, little is understood on the biochemical and molecular basis related. Lilac (Syringa oblata), a well-known woody ornamental plant with obvious petal color changes, is an ideal model. Here, we presented chromosome-scale genome assembly for lilac, resolved the flavonoids metabolism, and identified key genes and potential regulatory networks related to petal color change. The genome assembly is 1.05 Gb anchored onto 23 chromosomes, with a BUSCO score of 96.6%. Whole-genome duplication (WGD) event shared within Oleaceae was revealed. Metabolome quantification identified delphinidin-3-O-rutinoside (Dp3Ru) and cyanidin-3-O-rutinoside (Cy3Ru) as the major pigments; gene co-expression networks indicated WRKY an essential regulation factor at the early flowering stage, ERF more important in the color transition period (from violet to light nearly white), while the MBW complex participated in the entire process. Our results provide a foundation for functional study and molecular breeding in lilac.

Background:The conventional Billroth I anastomosis (cBIA) after laparoscopic distal gastrectomy (LDG) is performed through circular staple extracorporeally. Now, delta-shaped anastomosis (DA), which is performed using a linear stapler intracorporeally, becomes popular. We conducted a meta-analysis to compare the effectiveness and safety between the 2 techniques.Methods:A systematic literature search was performed using PubMed, Ovid, and the Cochrane Library Central. Participants of any age and sex, who underwent DA, or cBIA after LDG, were considered following inclusion criteria.Results:A total of 11 articles, published between 2010 and 2017, fulfilled the selection criteria. The total sample size of these studies was 2729 cases, including DA group 1008 cases and cBIA group 1721 cases. Compared to cBIA group, patients in DA group had less blood loss (mean deviation [MD] = −0.68, 95% confidence interval [CI] = −0.15 to −0.31, P < .001), fewer administration of analgesics (MD = −0.82, 95% CI = −1.58 to −0.05, P = .04), lower NRS score on POD 1 (MD = −0.84, 95% CI = −1.34 to −0.33, P = .001), lower NRS score on POD 3 (MD = −0.38, 95% CI = −0.50 to −0.26, P < .001). Furthermore, compared to cBIA group, obese patients in DA group had fewer total number of complications (MD = 0.46, 95% CI = 0.22 to 0.95, P = .04), shorter postoperative hospital stays (MD = −0.73, 95% CI = −1.18 to −0.28, P = .001), earlier first flatus (MD = −0.30, 95% CI = −0.50 to −0.10, P = .004), fewer administration of analgesics (MD = −1.08, 95% CI = −1.61 to −0.55, P < .001), lower NRS score on POD 1 (MD = −0.68, 95% CI = −0.99 to −0.37, P < .001) and lower NRS score on POD 3 (MD = −0.63, 95% CI = −0.86 to −0.40, P < .001).Conclusions:Compared with cBIA, DA is a safe and feasible procedure, with similar surgical outcomes and postoperative complications. In terms of postoperative recovery, DA is less invasive with quicker resume than cBIA, especially for the obese patients.

Summary Quercus dentata Thunb., a dominant forest tree species in northern China, has significant ecological and ornamental value due to its adaptability and beautiful autumn coloration, with color changes from green to yellow into red resulting from the autumnal shifts in leaf pigmentation. However, the key genes and molecular regulatory mechanisms for leaf color transition remain to be investigated. First, we presented a high‐quality chromosome‐scale assembly for Q. dentata. This 893.54 Mb sized genome (contig N50 = 4.21 Mb, scaffold N50 = 75.55 Mb; 2n = 24) harbors 31 584 protein‐coding genes. Second, our metabolome analyses uncovered pelargonidin‐3‐O‐glucoside, cyanidin‐3‐O‐arabinoside, and cyanidin‐3‐O‐glucoside as the main pigments involved in leaf color transition. Third, gene co‐expression further identified the MYB‐bHLH‐WD40 (MBW) transcription activation complex as central to anthocyanin biosynthesis regulation. Notably, transcription factor (TF) QdNAC (QD08G038820) was highly co‐expressed with this MBW complex and may regulate anthocyanin accumulation and chlorophyll degradation during leaf senescence through direct interaction with another TF, QdMYB (QD01G020890), as revealed by our further protein–protein and DNA–protein interaction assays. Our high‐quality genome assembly, metabolome, and transcriptome resources further enrich Quercus genomics and will facilitate upcoming exploration of ornamental values and environmental adaptability in this important genus.

Precise predictive tools are critical for choosing the individualized treatment protocols and follow-up procedures for patients with gastric cancer (GC). In this study, we aimed to evaluate and validate the prognostic abilities of preoperative nutrition and immunity parameters in GC after curative R0 resection. We established two nomograms based on 437 patients who underwent curative radical gastrectomy for gastric cancer to predict the postoperative overall survival (OS) and recurrence-free survival (RFS), and then compared the predictive accuracy and discriminative ability of the nomograms with the TNM stage systems for GC. An internal validation cohort of 141 patients and an external validation cohort of 116 patients were used to validate the result. The independent predictive factors for OS or RFS, including T stage, N stage, differentiated degree, neutrophil monocyte lymphocyte ratio (NMLR) and albumin globulin ratio (AGR) were used to establish the 2 nomograms. The C-index of the OS nomogram was 0.802, which was higher than that of the AGR, the NMLR and the TNM stage. The C-index of the RFS nomogram was 0.850, which was higher than that of the AGR, the NMLR and the TNM stage. Analogously, the areas under the receiver operating characteristics curves (AUROCs, 0.920 for OS and 0.897 for RFS, respectively) of the two nomograms were higher than that of the NMLR, the AGR and the TNM stage. In the internal validation cohort, the C-indexes of the OS and RFS nomograms were 0.812 and 0.826, respectively. In the external validation cohort, the C-indexes of the OS and RFS nomograms were 0.866 and 0.880, respectively. The proposed nomograms including nutrition and immunity parameters were proved to have excellent predictive ability in survival and recurrence for patients with GC after R0 resection.

Background: The optimal extent of therapeutic lateral neck dissection (LND) in the management of N1b papillary thyroid microcarcinoma (PTMC) is still under debate in clinical practice. In this light, our study aims to explore the incidence, patterns, and predictive factors of the lateral multiple-level metastasis in N1b PTMC patients. Methods: The clinical records of 142 patients diagnosed with N1b PTMC who underwent therapeutic LND from July 2015 to November 2018 at our institution were retrospectively reviewed. Univariate and multivariate analyses were conducted to examine the predictive factors associated with lateral multiple-level metastasis. The recurrence-free survival was analyzed and confirmed by Kaplan–Meier plots and log-rank test. Results: The overall frequency of lateral multiple-level metastasis was 50.7% in N1b PTMC patients, and two-level to four-level simultaneous metastasis were present in 26.8, 17.6, and 6.3% patients, respectively. Extrathyroidal extension (ETE) (OR = 5.79, 95% CI, 1.36–24.59; P = 0.017) and the central metastatic lymph node ratio (CLNR) with values equal or higher than 0.61 (OR = 6.18, 95% CI, 2.53–15.09; P < 0.001) served as independent predictors of multiple-level metastasis in N1b PTMC patients. Moreover, locoregional recurrence was significantly higher in the selective neck dissection (SND) group compared to the modified radical neck dissection (MRND) one (HR = 3.65, 95% CI, 1.11–12.00; P = 0.03). Conclusion: Our results show that the lateral multiple-level metastasis was relatively common, and we suggest MRND to be considered for N1b PTMC patients with ETE or CLNR equal or higher than 0.61.