Converting Plastic Wastes to Naphtha for Closing the Plastic Loop.

To solve the serious environmental problem and huge resource waste of plastic pollution, we report a tandem catalytic conversion of low-density polyethylene (LDPE) into naphtha, the key feedstock for renewable plastic production. Using ß zeolite and silicalite-1-encapsulated Pt nanoparticles (Pt@S-1), a naphtha yield of 89.5% is obtained with 96.8% selectivity of C5-C9 hydrocarbons at 250 °C. The acid sites crack long-chain LDPE into olefin intermediates, which diffuse within the channels of Pt@S-1 to encounter Pt nanoparticles. The hydrogenation over confined metal matches cracking steps by selectively shipping the olefins with right size, and the rapid diffusion boosts the formation of narrow-distributed alkanes. A conceptual upgrading indicates it is suitable for closing the plastic loop, with a significant energy saving of 15% and 30% reduced greenhouse gas emissions.

A pyroptosis-related gene signature predicts prognosis and immune microenvironment in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly malignant tumor with a very poor prognosis. Pyroptosis is an inflammatory form of cell death and plays an important role in cancer development. The prognostic value of pyroptosis-related genes (PRGs) in HCC has not been studied extensively. METHODS: Unsupervised consensus clustering analysis was performed to identify two subtypes based on the expression profiles of prognostic PRGs in the The Cancer Genome Atlas (TCGA) database, and the differences between the two subtypes were compared. A prognostic model based on four PRGs was established by further least absolute shrinkage and selection operator (LASSO) Cox regression analysis and multivariate Cox regression analysis. RESULTS: Two subtypes (clusters 1 and 2) were identified by consensus clustering based on prognostic PRGs in HCC. Survival outcomes, biological function, genomic alterations, immune cell infiltration, and immune checkpoint genes were compared between the subtypes. Cluster 2 had a worse survival outcome than cluster 1. Cluster 2 was enriched for hallmarks of cancer progression, TP53 mutation, tumor-promoting immune cells, and immune checkpoint genes, which may contribute to the poor prognosis. A prognostic risk signature that predicted the overall survival (OS) of patients was constructed and validated. Consequently, a risk score was calculated for each patient. Combined with the clinical characteristics, the risk score was found to be an independent prognostic factor for survival of HCC patients. Further analysis revealed that the risk score was closely associated with the levels of immune cell infiltration and the expression profiles of immune checkpoint genes. CONCLUSIONS: Collectively, our study established a prognostic risk signature for HCC and revealed a significant correlation between pyroptosis and the HCC immune microenvironment.

Laparoscopic versus open pancreatic resection for ductal adenocarcinoma: separate propensity score matching analyses of distal pancreatectomy and pancreaticoduodenectomy.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a leading causes of cancer mortality worldwide. Currently, laparoscopic pancreatic resection (LPR) is extensively applied to treat benign and low-grade diseases related to the pancreas. The viability and safety of LPR for PDAC needs to be understood better. Laparoscopic distal pancreatectomy (LDP) and pancreaticoduodenectomy (LPD) are the two main surgical approaches for PDAC. We performed separate propensity score matching (PSM) analyses to assess the surgical and oncological outcomes of LPR for PDAC by comparing LDP with open distal pancreatectomy (ODP) as well as LPD with open pancreaticoduodenectomy (OPD). METHODS: We assessed the data of patients who underwent distal pancreatectomy (DP) and pancreaticoduodenectomy (PD) for PDAC between January 2004 and February 2020 at our hospital. A one-to-one PSM was applied to prevent selection bias by accounting for factors such as age, sex, body mass index, and tumour size. The DP group included 86 LDP patients and 86 ODP patients, whereas the PD group included 101 LPD patients and 101 OPD patients. Baseline characteristics, intraoperative effects, postoperative recovery, and survival outcomes were compared. RESULTS: Compared to ODP, LDP was associated with shorter operative time, lesser blood loss, and similar overall morbidity. Of the 101 patients who underwent LPD, 10 patients (9.9%) required conversion to laparotomy. The short-term surgical advantage of LPD is not as apparent as that of LDP due to conversions. Compared with OPD, LPD was associated with longer operative time, lesser blood loss, and similar overall morbidity. For oncological and survival outcomes, there were no significant differences in tumour size, R0 resection rate, and tumour stage in both the DP and PD subgroups. However, laparoscopic procedures appear to have an advantage over open surgery in terms of retrieved lymph nodes (DP subgroup: 14.4 ± 5.2 vs. 11.7 ± 5.1, p = 0.03; PD subgroup 21.9 ± 6.6 vs. 18.9 ± 5.4, p = 0.07). These two groups did not show a significant difference in the pattern of recurrence and overall survival rate. CONCLUSIONS: Laparoscopic DP and PD are feasible and oncologically safe procedures for PDAC, with similar postoperative outcomes and long-term survival among patients who underwent open surgery.

Complete Genome Sequences of Leclercia sp. W6 and W17 Isolated from a Gastric Cancer Patient.

Leclercia sp. W6 and W17, which belong to the Enterobacteriaceae, were isolated from a stomach sample from a 78-year-old female gastric cancer patient, and genomic sequencing and analysis were performed. The genome of Leclercia sp. W6 consists of one chromosome with a size of 4,945,486 bp, while that of Leclercia sp. W17 contains one chromosome and two plasmids with a total size of 5,125,645 bp. Average nucleotide identity (ANI) calculations indicated that strains W6 and W17 exhibited similarities < 91.0% to other strains within the Enterobacteriaceae, except for six Leclercia strains. Phylogenomic analysis based on core-genome showed that strains W6 and W17 belong to the genus Leclercia, and phylogenetic analysis based on ANI values revealed that strains W6 and W17 formed an independent clade from those six Leclercia strains. Furthermore, comparative genomic analysis revealed that strains W6 and W17 had 5086 orthologous clusters (OCs) in their pan-genomes, and 59 exclusive OCs which were absent in their closest relatives. Genomic annotations revealed that the genomes of strains W6 and W17 encoded genes related to multidrug resistance clusters, multiple antibiotic resistance loci, and multidrug efflux pumps and had an identical urease gene cluster and a dissimilatory nitrate reduction pathway. Bioinformatic analyses indicated that strains W6 and W17 represented a novel species within the genus Leclercia. Genomic annotations revealed that these strains encoded genes related to multidrug resistance, nitrate reduction, and urease activity, which contribute to gastric malignant transformation. This will broaden our knowledge of the genetic mechanisms of the Enterobacteriaceae and help improve the clinical conditions of gastric cancer patients.

Cellular pharmacokinetics and pharmacodynamics mechanisms of ginkgo diterpene lactone and its modulation of P-glycoprotein expression in human SH-SY5Y cells.

Ginkgo diterpene lactone (GDL) is the raw material for ginkgo diterpene lactone meglumine injection, which is used for treating cerebral ischemia. The aims of this study were to explore the cellular pharmacokinetics of GDL in whole cells and subcellular fractions, and detect cellular pharmacodynamics on the human SH-SY5Y cells induced by oxygen-glucose deprivation and reoxygenation (OGD/R). Firstly, a simple, sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for assessing the amount of ginkgolide A (GA), B (GB) and K (GK) in cellular/subcellular samples. Then, phosphatidylserine and mitochondria membrane potential were assayed to evaluate the extent of apoptosis effect. The study showed that the cellular/subcellular accumulation of GA and GB were increased in a concentration-dependent manner; the levels of GA and GB in cytosol were the highest among these subcellular organelles. Meanwhile, GDL also attenuated the OGD/R-induced increases in the percentage of apoptotic and mitochondria membrane potential. In addition, verapamil increased the rate and amount of GA and GB entering cellular/subcellular compartments through inhibition of P-glycoprotein activity, and promoted the protective effect of GDL. The present study reports the cellular pharmacokinetics profiles of GA and GB in normal and OGD/R-induced SH-SY5Y cells in vitro for the first time, which provided valuable information for clinical safety application.

Intra-corporeal hand-sewn esophagojejunostomy is a safe and feasible procedure for totally laparoscopic total gastrectomy: short-term outcomes in 100 consecutive patients.

BACKGROUND: An optimal method for intracorporeal esophagojejunostomy has not yet been standardized. This study sought to introduce intracorporeal hand-sewn end-to-side esophagojejunostomy after totally laparoscopic total gastrectomy. METHODS: The author conducted a consecutive series of 100 intracorporeal hand-sewn esophagojejunostomies after totally laparoscopic total gastrectomy for upper third gastric cancer from September 2012 to December 2016. RESULTS: All patients were successfully operated on without conversion to open- or laparoscope-assisted surgery. The mean reconstruction time was 45 min, and the time until first flatus was 4 days. The time to start a soft diet was 7 days. The length of postoperative hospital stay was 8 days. The overall postoperative morbidity was 8%, including one anastomotic leak, and the mortality was zero. The median follow-up duration was 13 months; no anastomotic strictures were encountered. CONCLUSIONS: Intracorporeal hand-sewn end-to-side esophagojejunostomy after totally laparoscopic total gastrectomy is a safe and feasible procedure. This method can identify negative margins with intraoperative frozen sections before reconstruction and could be a good option for performing intracorporeal esophagojejunostomy with an advanced endoscopic suture technique.

Actibacterium pelagium sp. nov., a novel alphaproteobacterium, and emended description of the genus Actibacterium.

A Gram-stain-negative, non-motile, rod-shaped bacterium, designated JN33T, was isolated from seawater collected from the western Pacific Ocean. Strain JN33T was positive for hydrolysis of aesculin and gelatin. On the basis of 16S rRNA gene sequence analysis, strain JN33T showed high 16S rRNA gene sequence similarity to Actibacterium atlanticum 22II-S11-z10T (97.3 %), A. mucosum KCTC 23349T (96.6 %) and A. ureilyticum LS-811T (95.7 %) and exhibited less than 97.0 % 16S rRNA gene sequence similarity with respect to the other type strains within the family Rhodobacteraceae. Phylogenetic analysis revealed that strain JN33T fell within the cluster of the genus Actibacterium. The average nucleotide identity and in silico DNA-DNA hybridization values between strain JN33T and the type strains of Actibacterium species were 73.1-73.8 % and 19.8-20.1 %, respectively. The sole respiratory quinone was ubiquinone 10 (Q-10). The principal fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and C16 : 0. The major polar lipids were phosphatidylglycerol, one unidentified phospholipid and two unidentified aminolipids. The DNA G+C content was 57.8 mol%. Distinctly different phylogenetic characteristics, chemotaxonomic differences, as well as phenotypic properties, revealed that strain JN33T could be differentiated from the Actibacterium species with validly published names. Therefore, it is proposed that strain JN33T represents a novel species of the genus Actibacterium, for which the name Actibacterium pelagium sp. nov. (type strain, JN33T=CGMCC 1.16012T=KCTC 52653T) is proposed.

Comparison of clinical outcomes and quality of life between laparoscopic and open central pancreatectomy with pancreaticojejunostomy.

BACKGROUND: The studies comparing laparoscopic and open central pancreatectomy with pancreaticojejunostomy are limited. This study aimed to compare clinical outcomes and quality of life of patients undergoing laparoscopic and open central pancreatectomy with pancreaticojejunostomy. METHODS: Between December 1997 and December 2015, patients who underwent central pancreatectomy with pancreaticojejunostomy were reviewed. Patients were divided into 2 groups as laparoscopic central pancreatectomy (LCP) and open central pancreatectomy (OCP). Data considered for comparison analysis were patient demographics, intraoperative variables, morbidity, postoperative hospital stay, mortality, pathologic findings, and quality of life (SF-36 questionnaire). RESULTS: Thirty-six patients (17 LCP and 19 OCP) were included in the final analysis. Baseline characteristics were similar in the 2 groups. The operating time (280.4 ± 33.6 vs. 290.5 ± 62.5 min, p = 0.455) were similar between two groups. LCP group showed significantly lower estimated blood loss (76.4 ± 70.3 vs. 390.3 ± 279.0 ml, p = 0.001), shorter first flatus time (2.4 ± 0.9 vs. 3.9 ± 1.3 days, p = 0.001), and shorter diet start time (4.1 ± 2.2 vs. 6.1 ± 2.4 days, p = 0.030). However, the postoperative hospital stay was not significantly different between two groups (15.6 ± 12.1 vs. 24.0 ± 27.5 days, p = 0.347). Postoperative outcomes, including morbidity (58.8 vs. 52.6%, p = 0.749), pancreatic fistula rates (≥grade B: 17.6 vs. 36.8%, p = 0.106), and mortality, were similar in the 2 groups. The median follow-up period was 45 months (range 4-216 months). No local recurrence or distant metastasis was detected in either group. On the follow-up survey, the total quality of life score (702.9 ± 47.9 vs. 671.8 ± 94.1), physical health score (353.9 ± 24.8 vs. 326.6 ± 67.6) and mental health score (349.0 ± 26.5 vs. 345.2 ± 34.6) were higher in the LCP group compared with the OCP group. However, these differences were not statistically significant (p > 0.05). The score in role physical (100 vs. 73.1 ± 4.8, p = 0.042) was significantly higher in LCP group, and not statistically significant in other areas (p > 0.05). CONCLUSIONS: LCP with pancreaticojejunostomy is safe and feasible for benign or borderline malignant lesions in the pancreatic neck and proximal body. Compared to OCP, LCP is associated with lower estimated blood loss, faster recovery, and better quality of life.

Laparoscopic ligation of celiac trunk and splenic artery aneurysms with function preservation.

Celiac trunk aneurysms (CTAs) are rare and usually asymptomatic. Although most of these aneurysms can be treated with percutaneous embolization, some uncommon locations of the aneurysm may make this approach impossible. We report a patient with a celiac trunk aneurysm (CTA) and a proximal splenic artery aneurysm (SAA). Due to the size and location of these two aneurysms, after multidisciplinary discussion, endovascular management was considered inappropriate and they were treated by laparoscopic ligation of the two aneurysms and revascularization. This procedure offers good postoperative recovery with good preservation of the visceral function. Some collateral vessels in the viscera were obvious on postoperative day 7.

Laparoscopic versus open enucleation for pancreatic neoplasms: clinical outcomes and pancreatic function analysis.

BACKGROUND: The studies comparing laparoscopic enucleation (LE) with open enucleation (OE) are limited. This study aimed to compare perioperative outcomes of patients undergoing LE and OE and to assess the pancreatic function after LE. METHODS: Between February 2001 and July 2014, patients who underwent enucleation were reviewed. Patients were divided into two groups as LE and OE. Data considered for comparison analysis were patient demographics, intraoperative variables, morbidity, postoperative hospital stay, mortality, pathologic findings, and long-term follow-up (including pancreatic function). RESULTS: Thirty-seven patients (15 LE and 22 OE) were included in the final analysis. Baseline characteristics were similar in the two groups. LE group showed significantly shorter operating time (118.2 ± 33.1 vs. 155.2 ± 44.3 min, p = 0.009), lower estimated blood loss (80.0 ± 71.2 vs. 195.5 ± 103.4 ml, p = 0.001), shorter first flatus time (1.8 ± 1.0 vs. 3.4 ± 1.8 days, p = 0.004), shorter diet start time (2.4 ± 1.0 vs. 4.4 ± 2.0 days, p = 0.001), shorter postoperative hospital stay (7.9 ± 3.4 vs. 11.2 ± 5.7 days, p = 0.046). Postoperative outcomes, including morbidity (40.0 vs. 45.5 %, p = 1.000), grade B/C pancreatic fistula rates (20.0 vs. 13.6 %, p = 0.874), and mortality, were similar in the two groups. The median follow-up period was 47 months (range 7-163 months). No local recurrence or distant metastasis was detected in either group. Only one patient (4.8 %) underwent OE developed new-onset diabetes, in comparison with none in the LE group. One patient (7.1 %) had weight loss and received pancreatic enzyme supplementation in the LE group, in comparison with two patients (9.5 %) in the OE group. CONCLUSIONS: LE is a safe and feasible technique for the benign or low malignant-potential pancreatic neoplasms. Compared to OE, LE had shorter operating time, lower estimated blood loss, and faster recovery. LE could preserve the pancreatic function as the OE.

Comparison of short-term surgical outcomes between totally laparoscopic and laparoscopic-assisted distal gastrectomy for gastric cancer: a 10-y single-center experience with meta-analysis.

BACKGROUND: Laparoscopic-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) are two commonly used methods of laparoscopic gastrectomy for gastric cancer. This study aimed to compare the short-term surgical outcomes of these two methods. METHODS: A prospectively maintained gastric cancer database between October 2004 and February 2014 was reviewed and 115 patients underwent LADG and 198 patients underwent TLDG were included. The clinical characteristics and perioperative clinical outcomes of two groups were compared. Moreover, a systematic review and meta-analysis were conducted. RESULTS: The mean operation time and blood loss were similar in two groups, as was the number of retrieved lymph nodes. There was no significant difference in time to first flatus, the time to restart oral intake, the length of the hospital stay after surgery, and postoperative complications. The meta-analysis revealed no significant differences in the operative time, surgical margin, time to first flatus, length of hospital stay, mortality, overall, and anastomosis-related complications among the groups. However, the intraoperative blood loss was lower in TLDG (weighted mean difference = 21.50 mL; 95% confidence interval: 9.79-33.22; P < 0.01), and number of retrieved lymph nodes was higher in TLDG (weighted mean difference = -1.56; 95% confidence interval: -2.69 to -0.44; P < 0.01). CONCLUSIONS: TLDG is safe and feasible compared with LADG. However, it is difficult to identify the clinical advantages of TLDG over LADG based on our study. Thus, the choice of surgical approach mainly depends on the patient conditions and the preference of the patients or surgeons.

Laparoscopic versus open wedge resection for gastrointestinal stromal tumors of the stomach: a single-center 8-year retrospective cohort study of 156 patients with long-term follow-up.

BACKGROUND: The aim of this study was to compared laparoscopic (LWR) and open wedge resection (OWR) for the treatment of gastric gastrointestinal stromal tumors (GISTs). METHODS: The data of 156 consecutive GISTs patients underwent LWR or OWR between January 2006 and December 2013 were collected retrospectively. The surgical outcomes and the long-term survival rates were compared. Besides, a rapid systematic review and meta-analysis were conducted. RESULTS: Clinicopathological characteristics of the patients were similar between the two groups. The LWR group was associated with less intraoperative blood loss (67.3 vs. 142.7 ml, P < 0.001), earlier postoperative flatus (2.3 vs. 3.2 days, P < 0.001), earlier oral intake (3.2 vs. 4.1 days, P < 0.001) and shorter postoperative hospital stay (6.0 vs. 8.0 days, P = 0.001). The incidence of postoperative complications was lower in LWR group but did not reach statistical significance (4/90, 4.4% vs. 8/66, 12.1%, P = 0.12). No significant difference was observed in 3-year relapse-free survival rate between the two groups (98.6% vs. 96.4%, P > 0.05). The meta-analysis revealed similar results except less overall complications in the LWR group (RR = 0.49, 95% CI, 0.25 to 0.95, P = 0.04). And the recurrence risk was similar in two group (RR = 0.80, 95% CI, 0.28 to 2.27, P > 0.05). CONCLUSIONS: LWR is a technically and oncologically safe and feasible approach for gastric GISTs compared with OWR. Moreover, LWR appears to be a preferable choice with mini-invasive benefits.

Totally laparoscopic distal gastrectomy with D2 lymphadenectomy and Billroth II gastrojejunostomy for gastric cancer: short- and medium-term results of 139 consecutive cases from a single institution.

OBJECTIVE: The goal of this study was to investigate the feasibility, safety, and associated 3-year survival outcomes of the totally laparoscopic distal gastrectomy (TLDG) for the treatment of gastric cancer. METHODS: Herein, we analyzed the clinical data from 139 consecutive patients with gastric cancer who received TLDG at our institution from March of 2007 to March of 2013. RESULTS: TLDG was successfully carried out in 139 patients; no cases were converted to open surgery. The mean operation time was 228.6 ± 51.0 minutes, mean blood loss was 131.2 ± 85.2 mL, and mean number of dissected lymph nodes was 31.1 ± 9.0. The average time to flatus, time to fluid diet, and length of hospital stay were 3.6 ± 1.1 days, 4.8 ± 1.6 days, and 9.8 ± 4.0 days, respectively. The postoperative morbidity was 10.1%. A total of 135 patients were followed for a subsequent 1-73 months (median, 24.0 months). The 3-year disease-free survival (DFS) and overall survival (OS) rates were 82.3% and 82.9%, respectively. When divided by stage, the 3-year DFS for stage I, II, and III were 100%, 86.2%, and 48.8%, respectively; and the 3-year OS for stage I, II, and III were 98.0%, 92.3%, and 51.6%, respectively. CONCLUSIONS: In this preliminary report, TLDG was found to be a safe, feasible, and efficacious procedure for the treatment of gastric cancer with encouraging 3-year overall and stage-by-stage survival rates.

ZC3H13-mediated N6-methyladenosine modification of PHF10 is impaired by fisetin which inhibits the DNA damage response in pancreatic cancer.

DNA damage repair is a major barrier for chemotherapy efficacy of pancreatic ductal adenocarcinoma (PDAC), including the efficacy of platinum-based and gemcitabine/nab-paclitaxel treatments. N6-methyladenosine modifications (m6A) have recently been reported to play a role in homologous recombination (HR) repair of DNA double strand breaks (DSBs); however, the mechanism of action remains unknown. Our previous work indicated that fisetin may be a promising anti-tumour agent that induces DNA damage. In this study, we reported that fisetin induced DSBs and suppressed HR repair through m6A modification in PDAC cells. The m6A writer ZC3H13 and PHF10, which is a subunit of the PBAF chromatin remodelling complex, were identified as the main molecules affected by fisetin treatment. To our knowledge, it's the first time that PHF10 was found and involved in the DNA damage response. PHF10 loss-of-function resulted in elevated recruitment of γH2AX, RAD51, and 53BP1 to DSB sites and decreased HR repair efficiency. Moreover, ZC3H13 knockdown downregulated the m6A methylation of PHF10 and decreased PHF10 translation in a YTHDF1-dependent manner. In conclusion, our study demonstrates that fisetin enhanced DSBs via ZC3Hl3-mediated m6A modification of PHF10, which may provide insight into novel therapeutic approaches for PDAC.

Reduning Injection prevents carrageenan-induced inflammation in rats by serum and urine metabolomics analysis.

Objective: To elucidate the anti-inflammatory mechanism of Reduning Injection (RDN) by analyzing the potential biomarkers and metabolic pathways of the carrageenan-induced inflammatory model from the overall metabolic level. Methods: Rat inflammatory model was established by carrageenan. UPLC-Q-TOF/MS was used to detect and analyze changes of endogenous metabolites in the serum and urine of carrageenan-induced inflammatory rats. Combined with multivariate analysis and databases analysis, inflammatory-related potential biomarkers were screened and identified to analyze possible metabolic pathways. The reliability and biological significance of these biomarkers was verified by metabolic network analysis and correlation analysis with pharmacodynamic indicators. Results: A total of 16 potential biomarkers were screened and identified by multivariate analysis and metabolite databases, among which 13 species could be adjusted by RDN. The metabolism pathway analysis revealed that histidine metabolism, sphingolipid metabolism, and tyrosine metabolism were greatly disturbed. Their biomarkers involved urocanic acid, sphingosine, and norepinephrine, all of which showed a callback trend after RDN treatment. The three biomarkers had a certain correlation with some known inflammatory-related small molecules (histamine, arachidonic acid, Leukotriene B4, and PGE2) and pharmacodynamic indicators (IL-6, IL-1ß, PGE2 and TNF-α), which indicated that the selected biomarkers had certain reliability and biological significance. Conclusion: RDN has a good regulation of the metabolic disorder of endogenous components in carrageenan-induced inflammatory rats. And its anti-inflammatory mechanism is mainly related to the regulation of amino acid and lipid metabolism. This research method is conducive to the interpretation of the overall pharmacological mechanism of Chinese medicine.

Transcriptional Start Site Coverage Analysis in Plasma Cell-Free DNA Reveals Disease Severity and Tissue Specificity of COVID-19 Patients.

Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. A deep understanding of the variation of biological characteristics in severe COVID-19 patients is crucial for the detection of individuals at high risk of critical condition for the clinical management of the disease. Herein, by profiling the gene expression spectrum deduced from DNA coverage in regions surrounding transcriptional start site in plasma cell-free DNA (cfDNA) of COVID-19 patients, we deciphered the altered biological processes in the severe cases and demonstrated the feasibility of cfDNA in measuring the COVID-19 progression. The up- and downregulated genes in the plasma of severe patient were found to be closely related to the biological processes and functions affected by COVID-19 progression. More importantly, with the analysis of transcriptome data of blood cells and lung cells from control group and cases with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, we revealed that the upregulated genes were predominantly involved in the viral and antiviral activity in blood cells, reflecting the intense viral replication and the active reaction of immune system in the severe patients. Pathway analysis of downregulated genes in plasma DNA and lung cells also demonstrated the diminished adenosine triphosphate synthesis function in lung cells, which was evidenced to correlate with the severe COVID-19 symptoms, such as a cytokine storm and acute respiratory distress. Overall, this study revealed tissue involvement, provided insights into the mechanism of COVID-19 progression, and highlighted the utility of cfDNA as a noninvasive biomarker for disease severity inspections.

Serum and urine metabolomics based on UPLC-Q-TOF/MS reveals the antipyretic mechanism of Reduning injection in a rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Reduning injection (RDN), a patented traditional Chinese medicine, has the obvious antipyretic effect and has been widely used in China. Although some previous studies proved its antipyretic effect by animal efficacy experiment or clinical observation, its holistic mechanism in vivo was still unclear. AIM OF THE STUDY: To comprehensively elucidate the antipyretic mechanism of RDN, the investigation of fever-related potential biomarkers and metabolic pathways in the rat fever model is described in this paper. MATERIALS AND METHODS: Rat fever model was established by dry yeast. A large number of endogenous metabolites in serum and urine were detected by UPLC-Q-TOF/MS, and fever-related potential biomarkers were screened and identified by multivariate analysis and metabolite databases. The reliability and biological significance of the largely disturbed biomarkers was verified by the metabolic network and the correlation with pharmacodynamic indicators, which contained IL-1ß, IL-6, TNF-α, PGE2 and cAMP. RESULTS: The established UPLC-Q-TOF/MS analytical method afforded satisfactory results in terms of precision, repeatability and stability, which met the requirements of biological sample determination. A total of 32 potential biomarkers associated with fever were screened and identified, among which 22 species could be adjusted by RDN. The metabolism pathway analysis revealed that valine, leucine and isoleucine biosynthesis, and sphingolipid metabolism were greatly disturbed. Their biomarkers involved L-leucine, L-valine, sphinganine and phytosphingosine, all of which showed a callback trend after RDN was given. These 4 biomarkers had a certain correlation with some known fever-related small molecules and pharmacodynamic indicators, which indicated that the selected fever-related biomarkers had certain reliability and biological significance. CONCLUSIONS: RDN has a good regulation of the metabolic disorder of endogenous components in dry yeast-induced fever rats. Its antipyretic mechanism is mainly related to the regulation of amino acid, lipid and energy metabolism. The study is useful to better understand and analyze the pharmacodynamic mechanism of complex systems, such as traditional Chinese medicine.

Laparoscopic versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: a single-center propensity score matching study.

Laparoscopic distal pancreatectomy (LDP) for benign and low-grade malignant pancreatic diseases has been increasingly utilized. However, the use of LDP for pancreatic ductal adenocarcinoma (PDAC) remains controversial and has not been widely accepted. In this study, the outcomes of LDP versus conventional open distal pancreatectomy (ODP) for left-sided PDAC were examined. A retrospective review of patients who underwent LDP or ODP for left-sided PDAC between January 2010 and January 2019 was conducted. One-to-one propensity score matching (PSM) was used to minimize selection biases by balancing factors including age, sex, ASA grade, tumor size, and combined resection. Demographic data, their pathological and short-term clinical parameters, and long-term oncological outcomes were compared between the LDP and ODP groups. A total of 197 patients with PDAC were enrolled. There were 115 (58.4%) patients in the LDP group and 82 (41.6%) patients in the ODP group. After 1:1 PSM, 66 well-matched patients in each group were evaluated. The LDP group had lesser blood loss (195 vs. 210 mL, p < 0.01), shorter operative time (193.6 vs. 217.5 min; p = 0.02), and shorter hospital stay (12 vs. 15 days, p < 0.01), whereas the overall complication rates were comparable between groups (10.6% vs.16.7%, p = 0.31). There were no significant differences between the LDP and ODP groups regarding 3-year recurrence-free or overall survival rate (p = 0.89 and p = 0.33, respectively). LDP in the treatment of left-sided PDAC is a technically safe, feasible and favorable approach in short-term surgical outcomes. Moreover, patients undergoing LDP than ODP for PDAC had comparable oncological metrics and similar middle-term survival rate.

Circular RNA hsa_circ_000984 promotes colon cancer growth and metastasis by sponging miR-106b.

Circular RNAs (circRNAs) as a novel type of noncoding RNAs (ncRNAs) are widely studied in the development of human various diseases, including cancer. Here, we found circular RNA hsa_circ_000984 encoded by the CDK6 gene was remarkably upregulated in the tissues of colorectal cancer (CRC) patients and in the CRC cell lines. Moreover, high expression level of hsa_circ_000984 was significantly associated with advanced colorectal cancer. Further analysis revealed that hsa_circ_000984 knockdown could inhibit cell proliferation, migration, invasion in vitro and tumor formation in vivo in CRC cell lines. Mechanically, we found that hsa_circ_000984 may act as a competing endogenous RNA (ceRNA) by competitively binding miR-106b and effectively upregulate the expression of CDK6, thereby inducing a series of malignant phenotypes of tumor cells. Taken together, these observations suggest that the hsa_circ_000984 could mediate the expression of gene CDK6 by acting as a ceRNA, which may contribute to a better understanding of between the regulatory miRNA network and CRC pathogenesis.