Individualized management of immunosuppressants in liver transplant recipients by using a novel immune score system.

BACKGROUND: There is no reliable means to evaluate the immune status of liver transplant recipients. We proposed a novel score model, namely Mingdao immune cell analysis and Mingdao immune score system, to quantify the immunity. METHODS: Data from those who underwent a single liver transplant between January 2017 and June 2020 at Beijing Chaoyang Hospital, were collected. In addition, healthy volunteers were also enrolled. The score model was based on the immune cell populations determined by flow cytometry. RESULTS: There were a total of 376 healthy controls with 376 tests and 148 liver transplant recipients with 284 tests in this study. Evaluated by Mingdao immune cell analysis and Mingdao immune score system, the mean scores of healthy controls were near zero suggesting a balanced immune system. In contrast, the mean scores of liver transplant recipients were negative both before and after surgery indicating a compromised immune system. When liver transplant recipients were given a reduced or routine first dose according to their preoperative score, they had similar recovery of liver function. Moreover, liver transplant recipients with increased scores ≥ 5 were associated with elevated aspartate transaminase and alanine amiotransferase. Finally, on multivariate analysis the score model was the only significant independent risk factor for clinical acute rejection (P = 0.021; Odds ratio, 0.913; 95% confidence interval, 0.845-0.987). CONCLUSION: The novel score model could be used as an indicator to reflect immunity and to regulate immunosuppressants in liver transplant recipients after surgery.

Thermoregulatory pathway underlying the pyrogenic effects of prostaglandin E2 in the lateral parabrachial nucleus of male rats.

It has been shown that prostaglandin (PG) E2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE2 in male rats. The core temperature (Tcore) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE2. We demonstrated that EP3 receptor was a pivotal receptor for PGE2-induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE2, respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE2; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (IA) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE2; however, the IA current density was significantly increased by PGE2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of IA currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.

Can soil health in degraded woodlands of a semi-arid environment improve after thirty years?

In natural habitats, especially in arid and semi-arid areas that are fragile ecosystems, vegetation degradation is one of the most important factors affecting the variability of soil health. Studying physicochemical and biological parameters that serve as indicators of soil health offers important information on the potential risk of land degradation and the progression of changes in soil performance and health during recovery periods. This study specifically examines the impact of vegetation degradation on soil health indicators and the duration needed to improve the physical, chemical, and biological parameters in a semi-arid mountainous area site types with the dominance of Quercus macranthera Fisch & C.A. Mey and Carpinus orientalis Miller in northern Iran. In different years (2003, 2013, and 2023), litter and soil samples (at depths of 0-10, 10-20, and 20-30 cm) were collected in different types of degraded sites. Additionally, in 2023, a non-degraded site was chosen as a control and similar samples were collected. A total of 48 litter (12 samples for each of the study site types) and 144 soil (4 study site types × 3 depths × 12 samples) samples were collected. In order to investigate the spatial changes of soil basal respiration (or CO2 emission), which is involved in global warming, from each site type, 50 soil samples were taken along two 250-meter transects. The findings showed that litter P and Mg contents in the non-degraded site were 1.6 times higher than in degraded site types (2003). Following vegetation degradation, soil fertility indicators decreased by 2-4 times. The biota population was lower by about 80 % under the degraded site types (2003) than in the non-degraded site, and the density of fungi and bacteria in the degraded site types was almost half that of the non-degraded site types. Geostatistics showed the high variance (linear model) of CO2 emissions in areas without degradation. In addition, vegetation degradation significantly reduced soil carbon and nitrogen mineralization. Although soil health indicators under the degraded vegetation have improved over time (30 years), results showed that even thirty years is not enough for the full recovery of a degraded ecosystem, and more time is needed for the degraded area to reach the same conditions as the non-degraded site. Considering the time required for natural restoration in degraded site types, it is necessary to prioritize the conservation of vegetation and improve the ecosystem restoration process with adequate interventions.

Impact of the diagnosis of metabolic dysfunction-associated fatty liver disease and non-alcoholic fatty liver disease in patients undergoing liver transplantation for hepatocellular carcinoma.

Purpose: Whether the diagnosis of non-alcoholic fatty liver disease or metabolic dysfunction-associated fatty disease has a different impact on liver transplant recipients with hepatocellular carcinoma is not yet clear. Methods: Data from a two-center retrospective cohort study were collected to compare and investigate the differences between non-alcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease in clinicopathologic parameters and prognosis among liver transplant recipients with hepatocellular carcinoma. Results: A total of 268 liver transplant recipients with hepatocellular carcinoma were included. The prevalence among pre- and post-transplant metabolic dysfunction-associated fatty liver disease was 10.82% and 30.22%, while for non-alcoholic fatty liver disease, it was 7.09% and 26.87%, respectively. The clinicopathological parameters were similar between the two pre-transplant groups. In contrast, the post-transplant group with metabolic dysfunction-associated fatty liver disease exhibited a higher prevalence of diabetes mellitus and a greater body mass index. However, the other parameters were similar between the two post-transplant groups (p > 0.05). Factors such as the largest tumor size > 4 cm, microvascular invasion, lack of tumor capsule, post-transplant metabolic dysfunction-associated fatty liver disease, and decreased post-transplant lymphocyte percentage were related to an increased risk of recurrence. Conclusion: In patients undergone liver transplantation for hepatocellular carcinoma, the diagnosis of metabolic dysfunction-associated fatty disease is more strongly associated with metabolic abnormalities than the diagnosis of non-alcoholic fatty liver disease and is an independent predictor of hepatocellular carcinoma recurrence.

Diagnosis of pulmonary hemorrhagic leptospirosis complicated by invasive pulmonary aspergillosis complemented by metagenomic next-generation sequencing: a case report.

Background: Leptospirosis is a bacterial zoonosis with variable clinical manifestations. Pulmonary diffuse hemorrhagic leptospirosis often occurs rapidly and, when not promptly diagnosed and treated, it can be life-threatening. Aspergillus flavus is an opportunistic fungus that is commonly seen in immunosuppressed patients. Invasive pulmonary aspergillosis also progresses rapidly. This case study describes a patient with severe pneumonia caused by pulmonary hemorrhagic leptospirosis combined with invasive pulmonary aspergillosis. We have found almost no clinical reports to date on these two diseases occurring in the same patient. Case presentation: A 73-year-old male arrived at our hospital complaining of fever, general malaise, and hemoptysis that had lasted 4 days. The patient was initially diagnosed with severe pneumonia in the emergency department, but he did not respond well to empiric antibiotics. Subsequently, the patient's condition worsened and was transferred to the ICU ward after emergency tracheal intubation and invasive ventilator. In the ICU, antibacterial drugs were adjusted to treat bacteria and fungi extensively. Although the inflammatory indices decreased, the patient still had recurrent fever, and a series of etiological tests were negative. Finally, metagenomic next-generation sequencing (mNGS) of bronchial alveolar lavage fluid detected Leptospira interrogans and Aspergillus flavus. After targeted treatment with penicillin G and voriconazole, the patient's condition improved rapidly, and he was eventually transferred out of the ICU and recovered. Conclusion: Early recognition and diagnosis of leptospirosis is difficult, especially when a patient is co-infected with other pathogens. The use of mNGS to detect pathogens in bronchial alveolar lavage fluid is conducive to early diagnosis and treatment of the disease, and may significantly improve the prognosis in severe cases.

Granzyme B+ B cells detected by single-cell sequencing are associated with prognosis in patients with intrahepatic cholangiocarcinoma following liver transplantation.

B cells possess anti-tumor functions mediated by granzyme B, in addition to their role in antigen presentation and antibody production. However, the variations in granzyme B+ B cells between tumor and non-tumor tissues have been largely unexplored. Therefore, we integrated 25 samples from the Gene Expression Omnibus database and analyzed the tumor immune microenvironment. The findings uncovered significant inter- and intra-tumoral heterogeneity. Notably, single-cell data showed higher proportions of granzyme B+ B cells in tumor samples compared to control samples, and these levels were positively associated with disease-free survival. The elevated levels of granzyme B+ B cells in tumor samples resulted from tumor cell chemotaxis through the MIF- (CD74 + CXCR4) signaling pathway. Furthermore, the anti-tumor function of granzyme B+ B cells in tumor samples was adversely affected, potentially providing an explanation for tumor progression. These findings regarding granzyme B+ B cells were further validated in an independent clinic cohort of 40 liver transplant recipients with intrahepatic cholangiocarcinoma. Our study unveils an interaction between granzyme B+ B cells and intrahepatic cholangiocarcinoma, opening up potential avenues for the development of novel therapeutic strategies against this disease.

Impact of metabolic dysfunction-associated fatty liver disease on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease was proposed by international consensus to redefine the metabolic abnormal condition. However, its impact on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma has not been explored. METHODS: A two-center retrospective cohort study on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma was performed to analyze the impact of metabolic dysfunction-associated fatty liver disease on the clinicopathologic parameters and prognosis. RESULTS: There were 201 liver transplant recipients enrolled from two hospitals in our study. The pre- and post-transplant prevalences of metabolic dysfunction-associated fatty liver disease were 9.95% and 28.86%, respectively. The clinicopathological parameters revealed a similarity between patients with and without pre-transplant metabolic dysfunction-associated fatty liver disease. In contrast, the group with post-transplant metabolic dysfunction-associated fatty liver disease was linked with older age, a higher hepatitis recurrence rate and incidence of cardiovascular disease, usage of calcineurin inhibitors, a greater body mass index and waist circumference, lower albumin and high-density lipoprotein cholesterol levels, and poorer tumor-free survival and overall survival. The multivariate analysis showed the largest tumor size >4 cm (95% confidence intervals: 0.06~0.63, p = 0.006), microvascular invasion (95% confidence intervals: 1.61~14.92, p = 0.005), post-transplant metabolic dysfunction-associated fatty liver disease (95% confidence intervals: 1.40~10.60, p = 0.009), and calcineurin inhibitors-based regimen (95% confidence intervals: 0.33~0.96, p = 0.036) were the independent risk factors for recurrent hepatocellular carcinoma. CONCLUSIONS: Our study suggests that post-transplant metabolic dysfunction-associated fatty liver disease is more closely to metabolic abnormalities and that it can help identify liver transplant recipients at high risk of recurrent hepatocellular carcinoma.

Tumor-microenvironment responsive nano-carrier system for therapy of prostate cancer.

Poor selectivity, low bioavailability and serious systemic side-effects have limited the application of traditional chemotherapy method for treatment of prostate cancer. Stimuli-responsive drug delivery systems for chemotherapy are mainly based on the unique characteristics of tumor microenvironment. In this study, the GSH-sensitive poly-TTG-SS@DTX NPs (DTX-loaded poly-Tetraethylene glycol nanoparticles) were designed and synthesized, which were characterized with nanosized diameter (92.8 ± 2.5 nm) and negatively charged surface charge (-24.7 ± 5.56 mV). Experiments in vitro showed that poly-TTG-SS@DTX NPs had good compatibility to healthy cells and strong anti-tumor effect because of rapid and sustained drug release of DTX from poly-TTG-SS@DTX NPs under the tumor-microenvironment condition. The cellular activity remained greater than 90% when the concentration of poly-TTG-SS NPs reached as high as 100 µg/mL treated on healthy cells. The killing effect of DTX loading NPs group on C4-2 cells was stronger than that of free anti-tumor drug and free DTX combined with the blank nano-carrier (25.21% vs 19.93% vs 20.96%). In conclusion, poly-TTG-SS@DTX NPs may provide a new therapeutic strategy for the chemotherapy of prostate cancer.

Revised Thyroid Imaging Reporting and Data System (TIRADS): imitating the American College of Radiology TIRADS, a single-center retrospective study.

Background: The incidence of thyroid lumps is more and more high in population, and most biopsies of thyroid nodules are benign. To develop a practical risk stratification system based on five ultrasound features to stratify the malignancy risk of thyroid neoplasms. Methods: This retrospective investigation enrolled 999 consecutive patients with 1,236 thyroid nodules who underwent ultrasound screening. Fine-needle aspiration and/or surgery was performed, and pathology results were obtained at the Seventh Affiliated Hospital of Sun Yat-sen University in Shenzhen, China, which is a tertiary referral center, from May 2018 to February 2022. Each thyroid nodule's score was calculated based on five ultrasound features: composition, echogenicity, shape, margin, and echogenic foci. Additionally, each nodule's malignancy rate was calculated. The chi-square test was used to test whether the malignancy rate was different among the three subcategories (scores of 4-6, 7-8, and 9 or more) of thyroid nodules. We proposed the revised Thyroid Imaging Reporting and Data System (R-TIRADS), and its sensitivity and specificity were compared to the two existing systems [the American College of Radiology TIRADS (ACR TIRADS) and the Korean Society of Thyroid Radiology TIRADS (K-TIRADS)]. Results: The final dataset consisted of 425 nodules from 370 patients. The malignancy rates of three subcategories [malignancy rate: 28.8% (scores from 4-6), 64.7% (scores from 7-8), and 84.2% (scores of 9 or more)] were significantly different (P<0.01). The unnecessary biopsy rates of the three systems (ACR TIRADS, R-TIRADS, and K-TIRADS) were 28.7%, 25.2%, and 14.8%, respectively. The R-TIRADS presented better diagnostic performance than the ACR TIRADS or K-TIRADS [area under the curve: 0.79 (95% CI: 0.74-0.83) vs. 0.69 (95% CI: 0.64-0.75), P=0.046; 0.79 (95% CI: 0.74-0.83) vs. 0.66 (95% CI: 0.60-0.71), P=0.041, respectively]. The R-TIRADS had the highest sensitivity [0.746 (95% CI: 0.689-0.803)], followed by the K-TIRADS [0.399 (95% CI: 0.335-0.463), P=0.000] and ACR TIRADS [0.377 (95% CI: 0.314-0.441), P=0.000]. Conclusions: The R-TIRADS enables radiologists to diagnose thyroid nodules efficiently, and the number of unnecessary fine-needle aspirations can be considerably reduced.

Retrospective study to assess the effect of epidural analgesia on labor progress and women's pelvic floor muscle from the perspective of electromyography.

OBJECTIVE: Epidural analgesia has been widely used as a form of pain relief during labor and its safety has been gradually recognized. However, few studies of the effect of epidural analgesia on the pelvic floor are known. Thus, we aim to analyze the effect of epidural analgesia on labor progress and women's pelvic floor muscle from the perspective of electromyography systematically. In addition, obstetric risk factors for dysfunction of pelvic floor muscle after vaginal delivery were also evaluated. METHODS: Childbirth data of 124 primiparas who gave first birth vaginally in our hospital and their pelvic floor function assessment results at postpartum 7 weeks were retrospectively collected. Pelvic floor muscle electromyogram screenings were performed by a biofeedback electro-stimulant therapy instrument. RESULTS: There was no significant difference in the percentage of episiotomy, forceps, artificial rupturing membrane, and the application of oxytocin, except perineal laceration. Woman who implemented epidural analgesia experienced a longer stage of labor. Statistically, there was no significant difference in the total score and pelvic floor muscle strength. The risk factors for the value of the pre-rest phase include the age of pregnant women, the fetal weight, and the length of the second stage while the value of the post-rest phase was only associated with the fetal weight and the length of the second stage. In addition, the value of type I muscles was associated with the gravida and fetal weight while the value of type II muscles was only associated with forceps. The sustained contraction was correlated with the gravida and the total scores had a significant correlation with forceps. CONCLUSION: Epidural analgesia during labor is approved to be a safe and effective procedure to relieve pain with very low side effects on the mode of labor and pelvic floor muscle. The assessment of pelvic floor muscle before pregnancy is beneficial in guiding the better protection of pelvic floor muscle function. According to the evaluation results, the doctors can control the associated risk factors as much as possible to reduce the injury of pregnancy and parturition to the pelvic floor.

Circulating tumor cells in peripheral blood as a diagnostic biomarker of breast cancer: A meta-analysis.

Purpose: Studies have reported that breast cancer (BC) patients' circulating tumor cells (CTCs) have varying results for their diagnostic role. Thus, we conducted a meta-analysis to systematically assess the accuracy of CTCs in the diagnosis of BC. Methods: A meta-analysis was conducted to evaluate the overall accuracy of CTC detection. A pooled analysis of sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic advantage ratio (DOR) was used to measure diagnostic accuracy. In addition, the area under the summary receiver operating characteristic curve (AUC) was used to discriminate BC from non-BC. An analysis of the threshold effect was calculated using the Spearman correlation coefficient. We calculated the Q and I2 statistics to determine whether the studies were heterogeneous. Sensitivity analysis was performed by removing studies one by one. Publication bias was assessed by Deeks' funnel plot asymmetry test. Results: Studies from the PubMed, Cochrane Library, Embase, Web of Science, Wanfang, Vip, and CNKI databases were collected for diagnosing BC from January 2000 to April March 2023. Finally, 8 publications were retrieved in total containing 2014 cases involved in the study. Based on a random-effects model, it was found that the pooled SEN was 0.69 (0.55 - 0.80), SPE was 0.93 (0.60 - 0.99), PLR was 9.5 (1.4 - 65.9), NLR was 0.33 (0.23 - 0.48), DOR was 29 (4 - 205) and the AUC of the summary receiver operating characteristic (SROC) curve was 0.81 (0.77 - 0.84). Some heterogeneity was found in the article, but there was no threshold effect to account for it (P = 0.27). Deek's funnel plot asymmetry test indicated that no publication bias was observed in this meta-analysis (P = 0.52). Conclusion: The results of this meta-analysis confirmed that CTCs were an important component of noninvasive methods of confirming BC with SEN of 0.69 (0.55 - 0.80), SPE of 0.93 (0.60 - 0.99) and AUC of 0.81 (0.77 - 0.84).

Sex effects on carcass characteristics, meat quality traits and meat amino acid and fatty acid compositions in a novel Duroc line pig.

In-depth studies of carcass characters and meat quality could provide insight both for breeding improvement and food development in pigs. Breed and gender are two main factors affected the carcass and meat altitude, which plays important roles in pork industry. The aim of this study was to evaluate the sex effects on carcass characteristics and meat quality traits in a novel Duroc strain pig crossbred from French line, American line and Canadian line pigs. A total of 30 pigs (15 surgical-castrated males and 15 females) with similar birthweight (1.8 ± 0.13 kg) was used in experiment. During the experiment period, all pigs were fed same commercial diets. Overall, female pigs observed higher (p < 0.05) carcass weight, slaughter backfat, loin muscle area, loin muscle depth, carcass yield, pH on 45 min, meat histidine and essential amino acid (AA) compositions, and eicosenoic, unsaturation and free fatty acids (FA) compositions compared with meat from castrated males. Whereas, castrated males' meat showed better altitude (p < 0.05) on meat lightness, meat moisture content percentage, total umami AA and stearic acid and saturated FA compositions than those from female ones. In conclusion, the results of this study provide evidence on the sex effects on meat quality and carcass parameters in Duroc strain pigs. Furthermore, this study also give a reference on the relationship between sex and carcass and meat characteristics in Durco strain pigs.

Ultrasound-based artificial intelligence in gastroenterology and hepatology.

Artificial intelligence (AI), especially deep learning, is gaining extensive attention for its excellent performance in medical image analysis. It can automatically make a quantitative assessment of complex medical images and help doctors to make more accurate diagnoses. In recent years, AI based on ultrasound has been shown to be very helpful in diffuse liver diseases and focal liver lesions, such as analyzing the severity of nonalcoholic fatty liver and the stage of liver fibrosis, identifying benign and malignant liver lesions, predicting the microvascular invasion of hepatocellular carcinoma, curative transarterial chemoembolization effect, and prognoses after thermal ablation. Moreover, AI based on endoscopic ultrasonography has been applied in some gastrointestinal diseases, such as distinguishing gastric mesenchymal tumors, detection of pancreatic cancer and intraductal papillary mucinous neoplasms, and predicting the preoperative tumor deposits in rectal cancer. This review focused on the basic technical knowledge about AI and the clinical application of AI in ultrasound of liver and gastroenterology diseases. Lastly, we discuss the challenges and future perspectives of AI.

Development and validation of nomograms for predicting survival in patients with de novo metastatic triple-negative breast cancer.

Metastatic triple-negative breast cancer (mTNBC) is a heterogeneous disease with a poor prognosis. Individualized survival prediction tool is useful for this population. We constructed the predicted nomograms for breast cancer-specific survival (BCSS) and overall survival (OS) using the data identified from the Surveillance, Epidemiology, and End Results database. The Concordance index (C-index), the area under the time-dependent receiver operating characteristic curve (AUC) and the calibration curves were used for the discrimination and calibration of the nomograms in the training and validation cohorts, respectively. 1962 mTNBC patients with a median follow-up was 13 months (interquartile range, 6-22 months), 1639 (83.54%) cases died of any cause, and 1469 (74.87%) died of breast cancer. Nine and ten independent prognostic factors for BCSS and OS were identified and integrated to construct the nomograms, respectively. The C-indexes of the nomogram for BCSS and OS were 0.694 (95% CI 0.676-0.712) and 0.699 (95% CI 0.679-0.715) in the training cohort, and 0.699 (95% CI 0.686-0.712) and 0.697 (95% CI 0.679-0.715) in the validation cohort, respectively. The AUC values of the nomograms to predict 1-, 2-, and 3-year BCSS and OS indicated good specificity and sensitivity in internal and external validation. The calibration curves showed a favorable consistency between the actual and the predicted survival in the training and validation cohorts. These nomograms based on clinicopathological factors and treatment could reliably predict the survival of mTNBC patient. This may be a useful tool for individualized healthcare decision-making.

Micropeptide PACMP inhibition elicits synthetic lethal effects by decreasing CtIP and poly(ADP-ribosyl)ation.

Synthetic lethality through combinatorial targeting DNA damage response (DDR) pathways provides exciting anticancer therapeutic benefit. Currently, the long noncoding RNAs (lncRNAs) have been implicated in tumor drug resistance; however, their potential significance in DDR is still largely unknown. Here, we report that a human lncRNA, CTD-2256P15.2, encodes a micropeptide, named PAR-amplifying and CtIP-maintaining micropeptide (PACMP), with a dual function to maintain CtIP abundance and promote poly(ADP-ribosyl)ation. PACMP not only prevents CtIP from ubiquitination through inhibiting the CtIP-KLHL15 association but also directly binds DNA damage-induced poly(ADP-ribose) chains to enhance PARP1-dependent poly(ADP-ribosyl)ation. Targeting PACMP alone inhibits tumor growth by causing a synthetic lethal interaction between CtIP and PARP inhibitions and confers sensitivity to PARP/ATR/CDK4/6 inhibitors, ionizing radiation, epirubicin, and camptothecin. Our findings reveal that a lncRNA-derived micropeptide regulates cancer progression and drug resistance by modulating DDR, whose inhibition could be employed to augment the existing anticancer therapeutic strategies.

Evaluation of dietary Perilla frutescens seed on performance and carcass quality in finishing castrated male Songliao black pigs.

OBJECTIVES: This study was conducted to investigate the effects of dietary supplementation of Perilla frutescens seed (PFS) on growth performance, blood profiles, meat quality and meat nutrient characteristics in finishing castrated male Songliao black pigs. METHODS: A total of 80 castrated male Songliao black pigs with an average initial body weight (BW) of 84.1 ± 2.1 kg were used in a 75 days feeding trial. All pigs were randomly assigned into four dietary treatments: CON, basal diet; PFS3.0, basal diet + 3.0% of PFS; PFS6.0, basal diet + 6.0% of PFS and PFS9.0, basal diet + 9.0% of PFS. RESULTS: As a result of this experiment, dietary supplementation of PFS improved the growth performance parameters, blood albumin and blood lipid parameters. Whereas, on FBW, average daily feed intake and average daily gain there showed a non-dose-dependent manner that pigs in PFS9.0 had lowest performance compared with other two PFS treatments. Furthermore, meat colour of yellowness, pH, cook meat rate, moisture, crude protein and crude fat were increased by PFS addition. However, lower growth performance was observed in PFS9.0 group. As well as, dietary inclusion of PFS also alters the meat amino acid composition and meat fatty acids composition. Particularly, umami amino acid contents and polyunsaturated fatty acid were all enhanced by PFS addition. CONCLUSIONS: In summary, dietary supplementation of PFS have beneficial effects on the performance and meat quality and nutritional values in Songliao black pigs.

Plasmacytoid dendritic cells mediate the tolerogenic effect of CD8+regulatory T cells in a rat tolerant liver transplantation model.

BACKGROUND: Tolerance is more easily induced in liver transplant models than in other organs; CD8+CD45RClowregulatory T cells (Tregs) have been shown to induce tolerance in heart allografts. Whether CD8+CD45RClowTregs could induce tolerance in a liver transplant model and how dendritic cells (DCs) mediate the CD8+CD45RClowTregs effect remains to be investigated. METHODS: A rat liver transplantation model was established and used to test tolerance and acute rejection compared to control groups. Liver function and histopathological changes of allograft were examined by enzyme-linked immunosorbent assay (ELISA) and haematoxylin and eosin (H&E) staining, respectively. The distribution and proportion of CD8+CD45RClowTregs and plasmacytoid dendritic cells (pDCs) in the allografts and spleen were determined using flow cytometry. Cytokine secretion levels were determined using ELISA and real-time quantitative PCR (qRT-PCR). RESULTS: The rat liver transplantation model was well established, with a success rate of 93.3% (28/30). The mean survival time of the tolerant and acute-rejection rats were 156 and 14 days, respectively. The proportions of CD8+CD45RClowTegs were higher in the allografts of tolerant rats than in those of acute-rejection rats (33.1 ± 4.3 and 12.4 ± 4.6, respectively; P = 0.04). Significant accumulation of pDCs was observed in tolerant liver graft rats compared to that in acute-rejection rats (1.46 ± 0.23 and 0.80 ± 0.20, respectively; P = 0.02). Importantly, CD8+CD45RClowTregs were positively associated with the frequency of pDCs (P = 0.001, r2 = 0.775). The protein and mRNA expression of IL-10 and TGF-ß in the allograft group were increased, possibly being responsible for tolerance induction. CONCLUSION: CD8+CD45RClowT cells interact with pDCs through the induction of IL-10 and TGF-ß expression and are responsible for inducing immune tolerance in rat liver transplantation.

TNF-α and HMGB1: New Biomarkers of Acute Pulmonary Embolism.

OBJECTIVE: Inflammatory mediators have been implicated in the pathophysiology of acute pulmonary embolism (PE). However, the role of inflammatory mediator activation in the development of pulmonary embolism remains elusive. Here, we determined the reliability of the plasma levels of inflammatory markers tumor necrosis factor-alpha (TNF-α) and high mobility histone 1 (HMGB1) as diagnostic biomarkers of PE. METHODS: Eighty-seven patients with PE and ninety-two healthy adults were enrolled. Plasma levels of TNF-α and HMGB1 were measured before and after anticoagulation treatment using conventional commercialized ELISA. RESULTS: The mean concentrations of plasma TNF-α and HMGB1 in patients with PE before anticoagulation treatment were 3.36- and 2.54-fold higher than those in controls (p<0.0001), respectively. Similar results were obtained in patients with PE before anticoagulation treatment, in which plasma levels of TNF-α and HMGB1 were 3.99- and 1.99-fold higher (p<0.0001), respectively, than in PE patients after anticoagulation treatment. Among the two potential markers, TNF-α performed best in distinguishing patients with PE from controls. A significant positive correlation was found between the two markers' concentrations. CONCLUSIONS: These findings suggest that the plasma levels of TNF-α and HMGB1 may serve as potential biomarkers for PE.

Extended lymphadenectomy benefits patients with borderline resectable pancreatic head cancer-a single-center retrospective study.

BACKGROUND: Whether standard lymphadenectomy or extended lymphadenectomy should be performed is still under debate during pancreaticoduodenectomy (PD). We aimed to compare their morbidity and mortality rates among patients with pancreatic head cancer (PHC). METHODS: In this retrospective study, a total of 322 patients were enrolled. According to the scope of intraoperative lymph node dissection, patients were divided into extended lymphadenectomy group (n=120) and standard lymphadenectomy group (n=202). Based on the resectability of the tumor, there were 198 cases of resectable PHC and 124 cases of borderline resectable PHC, respectively, in which further stratified analysis was carried out according to the extent of lymph node dissection. RESULTS: All patients completed the operation successfully, with a perioperative morbidity rate of 27.9% and mortality rate of 0.9%. As for the overall patients, patients in the extended lymphadenectomy group had higher neutrophil-to-lymphocyte ratio (NLR), longer operation time, more intraoperative blood loss, lymph node dissection and patients with borderline resectable pancreatic head cancer (BRPHC) (P<0.05). The 1-, 2- and 3-year overall survival rates of patients with extended lymphadenectomy and standard lymphadenectomy were 71.9%, 50.6%, 30.0% and 70.0%, 32.9%, 21.5%, respectively (P=0.068). With regards to patients with BRPHC, the number of lymph node dissection in the extended lymphadenectomy group was more (P<0.05), and the 1-, 2- and 3-year overall survival rates of patients with extended lymphadenectomy and standard lymphadenectomy were 60.7%, 43.3%, 27.4% and 43.2%, 17.7%, 17.7%, respectively (P=0.007). CONCLUSIONS: Patients with BRPHC tended to have vast lymph node metastasis. Extended lymphadenectomy can improve their long-term survival.

DeepSE: Detecting super-enhancers among typical enhancers using only sequence feature embeddings.

Super-enhancer (SE) is a cluster of active typical enhancers (TE) with high levels of the Mediator complex, master transcriptional factors, and chromatin regulators. SEs play a key role in the control of cell identity and disease. Traditionally, scientists used a variety of high-throughput data of different transcriptional factors or chromatin marks to distinguish SEs from TEs. This kind of experimental methods are usually costly and time-consuming. In this paper, we proposed a model DeepSE, which is based on a deep convolutional neural network model, to distinguish the SEs from TEs. DeepSE represent the DNA sequences using the dna2vec feature embeddings. With only the DNA sequence information, DeepSE outperformed all state-of-the-art methods. In addition, DeepSE can be generalized well across different cell lines, which implied that cell-type specific SEs may share hidden sequence patterns across different cell lines. The source code and data are stored in GitHub (https://github.com/QiaoyingJi/DeepSE).